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Role of phospholipase C-gamma1 in insulin-like growth factor I-induced muscle differentiation of H9c2 cardiac myoblasts. Insulin-like growth factor-I (IGF-I) regulates muscle differentiation through phosphatidylinositol 3-kinase (PI 3-kinase). Also it was recently reported that PI 3-kinase is involved in the activation of phospholipase C-gamma1 (PLC-gamma1). We investigated whether PLC-gamma1 therefore plays a role in IGF-I-induced muscle differentiation using H9c2 rat cardiac myoblasts as a model. IGF-I was able to activate PLC-gamma1 via both PI 3-kinase-dependent and tyrosine phosphorylation-dependent mechanisms in this model. However, PI 3-kinase appeared to play a more important role than tyrosine phosphorylation in IGF-I activation of PLC-gamma1. In addition, PLC-gamma1 activation was independent of Akt/protein kinase B (Akt/PKB). Importantly, PLC-gamma1 was involved in IGF-I-induced muscle differentiation in parallel with Akt/PKB. Taken together, these results suggest that IGF-I regulation of muscle differentiation is dependent on the activation of PLC-gamma1 and Akt/PKB, both of which are downstream mediators of PI 3-kinase.

Stage I/II follicular lymphoma: spread of bcl-2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy. Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl-2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66.6%). After treatment, in 9/15 Bcl-2/IgH positive evaluable patients, a disappearance of Bcl-2/IgH+ cells was observed, which persisted after a median follow-up of 43.5 months (range 11-70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl-2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl-2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR.

U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade. We investigated the potentiating effect of U-46619, a synthetic analogue of thromboxane A(2) (TXA(2)), on the adrenergic responses in human saphenous vein. Saphenous vein rings were obtained from 35 patients undergoing coronary artery bypass surgery. The rings were suspended in organ bath chambers for isometric recording of tension. U-46619 (10(-10)-3 x 10(-7) mol/l) produced concentration-dependent and endothelium-independent contractile responses. U-46619 (10(-10) mol/l) potentiated the contractions elicited by electrical stimulation and potassium chloride, and produced leftward shifts of the concentration-response curve for noradrenaline. The TXA(2) receptor antagonist SQ-30741 (10(-8) mol/l) prevented the potentiation evoked by U-46619. The dihydropyridine calcium antagonist nifedipine (10(-6) mol/l) did not affect the potentiation of electrical stimulation and noradrenaline induced by U-46619, but abolished the potentiation of U-46619 on KCl-induced contractions. U-46619 facilitates sympathetic neurotransmission and potentiates constrictor effects of noradrenaline in human saphenous veins through stimulation of TXA(2) receptors. These effects are independent of calcium entry through dihydropyridine calcium channels.

Retinochoroidal collateral veins protect against anterior segment neovascularization after central retinal vein occlusion. To test the hypothesis that retinochoroidal collateral veins (RCVs), or alternatively, retinociliary or optociliary shunts/collaterals/veins or opticociliary anastomoses, act protectively against the development of anterior segment neovascularization (ASN) following central retinal vein occlusion (CRVO). Case-control retrospective medical record review of patients with CRVO. We identified 107 patients with CRVO, of whom 34 had developed ASN, by reviewing their medical records. After applying exclusion criteria, a case group and an age-, sex-, and visual acuity-matched control group were selected. We analyzed these groups for the presence or absence of RCVs and noted the time course involved in their development. Anterior segment neovascularization (including neovascularization of the iris and/or anterior chamber angle), neovascular glaucoma, and RCV development. Only 1 (5.4%) of 19 individuals who developed ASN did so in the presence of RCVs. In contrast, 11 (57.9%) of 19 individuals in the control group developed RCVs. Statistical analysis revealed that patients who developed ASN were roughly 25 times less likely to have had RCVs than individuals who never developed ASN (odds ratio = 24.74; P =.001). Retinochoroidal collateral veins are negatively associated with ASN post-CRVO and may function in a protective manner against such an outcome.

[Effect of myocardial ischemia on the phospholipid composition of cardiac tissue and mitochondria]. Concentration of lysophosphatidyl choline was slightly increased in heart tissue within 30 min after total rabbit myocardial ischemia and it was distinctly decreased within 1 hr as compared with control values. In the mitochondria within the initial periods (0.5 hr, 1 hr) of the ischemia concentration of lysophosphatidyl choline increased most markedly but the phospholipid content became similar to control level within 2 hrs. Alterations in the total phospholipid content whereas separate phospholipid fractions, lysophosphatidyl choline and cardiolipin, altered more distinctly in mitochondria. In ischemically impaired cell phospholipases appear to be initially involved in degradation of mitochondria phospholipids.

Xerostomia: 12-month changes in saliva production and its relationship to perception and performance of swallow function, oral intake, and diet after chemoradiation. Previous investigators have found permanent changes in saliva production after chemoradiation but have not examined these in relation to swallowing measures, diet changes, and patient comfort over time. Thirty patients with advanced stage cancer of the oropharynx treated with chemoradiation were followed with videofluoroscopic swallow studies, a measure of stimulated total saliva production, a questionnaire of their perception of dry mouth, and a questionnaire on the nature of their oral intake at pretreatment until 12 months after treatment. Saliva declined significantly from pretreatment to 12 months. Swallowing-related complaints increased significantly over the 12 months, especially in patients with lower saliva weights. Diet choices increased over time after treatment, except crunchy foods. Swallow measures did not relate to saliva weight. Reduced saliva weight does not correlate with slowed or inefficient swallow. Instead, reduced saliva weight seems to change patients' perceptions of their swallowing ability and, on that basis, their diet choices.

The versatility of the pump-perfused rat hindlimb preparation: examples relating to skeletal muscle function and energy metabolism. The pump-perfused rat hindlimb model, in various forms, has been in use for several decades. There are many applications for this model, owing to the ability to control the content and rate of perfusion. In the context of exercise physiology this model has been put to particularly good use. In this report we summarize some of the central surgical differences between different versions of the pump-perfused rat hindlimb model, including the double hindlimb + trunk, double hindlimb alone, single hindlimb, and distal hindlimb-alone models. We also summarize specific elements of the perfusion medium and measurement of force used in our lab during assessment of muscle metabolic and contractile responses, and illustrate some of the differences from the in vivo condition that merit consideration. We then provide specific examples of how the single pump-perfused hindlimb and distal hindlimb-alone versions of this model have been used to study muscle function and energy metabolism. In this context we show how this model can be used to permit the experimenter to manipulate and control the rate of O(2)delivery and to add specific compounds that inhibit a particular aspect of muscle metabolism, such that in combination with measurements of the flux of specific substances across the muscle and/or fast-freezing of muscle after contractions, more can be understood about the metabolic state of the contracting muscles.

[When can the treatment of isolated systolic hypertension be avoided?]. The treatment of isolated systolic hypertension (ISH) in the elderly reduces the cardiovascular (CV) risk, in particular in patients with diabetes or previous CV events. However, in the very old (> 80-85 years) the treatment of ISH may increase global mortality, although it still decreases the risk of stroke. The benefits of treatment on the risk of dementia remain uncertain. To verify the indication for therapy, the diagnosis of ISH should be confirmed by ambulatory blood pressure monitoring. Since the absolute benefit of treatment is related to its duration, a limited life expectancy may restrict the real impact of treatment. The advantages and limitations of anti-hypertensive therapy in the elderly should be discussed individually, respecting the patient's autonomy.

Collision-induced dissociation of valdecoxib metabolites: a novel rearrangement involving an isoxazole ring. Valdecoxib is a potent COX-2 inhibitor. During metabolism studies of valdecoxib by liquid chromatography/tandem mass spectrometry, we observed a novel mass spectral rearrangement involving an isoxazole ring for some of the metabolites in the negative ion mode. Accurate mass measurements were performed with quadrupole time-of-flight mass spectrometry to determine the elemental compositions of the fragments. Additionally, two types of stable-isotope labeled analogues were prepared to assist with the assignments of these fragments and possible mechanistic rearrangements resulting from collision-induced dissociation (CID). Detailed analyses of the CID mass spectra suggest that the fragmentation process involves a novel two-step rearrangement. The first step consists of an intramolecular SN2 reaction with a five-membered ring rearrangement to form an intermediate. The second step involves a four-membered ring intramolecular rearrangement followed by a cleavage of the N-O bond on the isoxazole ring to form a unique fragment ion at m/z 196. The same phenomenon was observed for a group of structurally related metabolites that also contain a 5-hydroxymethyl or 5-carboxylic acid moieties. A mechanism for the novel rearrangement involving an isoxazole ring is proposed.

Activation of primary T lymphocytes results in lysosome development and polarized granule exocytosis in CD4+ and CD8+ subsets, whereas expression of lytic molecules confers cytotoxicity to CD8+ T cells. Lytic granule exocytosis is the major cytotoxic mechanism used by CD8(+) cytotoxic lymphocytes. CD8(+) T cells acquire this effector function in the process characterized by lysosomal biogenesis, induction of expression of cytolytic molecules, and their selective sorting into the lysosomal vesicles. However, temporal relation of these differentiation stages during T cell activation has not been defined precisely. Also, although CD4(+) T cells typically do not express lytic molecules as a consequence of activation, and therefore, do not acquire granule exocytosis-mediated lytic function, it is not clear whether CD4(+) T cells are able to degranulate. By using in vitro TCR stimulation of primary mouse lymphocytes, we found that polyclonally activated CD4(+) T cells degranulate upon TCR ligation and polarize enlarged lysosomal granules in response to target cell recognition, despite the lack of granule exocytosis-mediated cytotoxicity. Upon TCR stimulation, resting CD8(+) T cells rapidly express lytic molecules and acquire potent lytic function early in activation. Maximal cytolytic potential, however, depends on enlargement of lysosomal granules during the subsequent activation stages. Thus, polyclonal TCR stimulation of resting T cells results in development of lysosomal granules and their release upon TCR engagement in CD4(+) and CD8(+) T cells, but only CD8(+) T cells acquire lytic function as a result of induction of expression of lytic molecules.

[Evaluation and analysis of facial somatosensory changes of chronic masticatory muscle pain patients with quantitative sensory testing]. To evaluate and analysis facial somatosensory changes of patients with chronic masticatory muscle pain (MMP) quantitatively. The seven parameters of standardized quantitative sensory testing (QST) protocol were used to test the pain sites, contralateral sites of masticatory muscles of 20 chronic MMP patients and the same sites of right masticatory muscles of 20 matched healthy controls. QST thresholds were compared within groups using paired t test and between groups using unpaired t test. Compared to the controls, all seven parameters of bilateral sides of patients had changed. Mainly cold detection thresholds [(-1.2±0.5) and (-1.7±0.9) °C] and cold pain thresholds [(27.6±2.3) and (27.0±2.0) °C] of pain and contralateral sides increased significantly, while warm detection thresholds [(2.0±1.1) and (2.1±1.2) °C], heat pain thresholds [(37.9±3.2) and (39.7±3.9) °C], and mechanical pain thresholds [(49.3±34.1) and (111.8±86.3) mN] of pain and contralateral sides decreased significantly (P<0.05). Mechanical detection thresholds of pain sites [(1.8±1.4) mN] significantly increased (P=0.01). Chronic MMP patients were detected thermal hyperesthesia, thermal hyperalgesia, and mechanical hyperalgesia. Mechanical hypoesthesia was found at the pain sites of masticatory muscles. Chronic MMP might influence the central modulation of trigeminal nerve system.

Botulinum toxin has an increased effect when targeted toward the muscle's endplate zone: a high-density surface EMG guided study. To compare the effect of endplate-targeted injections of a low Botulinum neurotoxin type A (BoNT-A) dose with that of injections at defined distances from the motor endplate zone. In eight healthy volunteers, the main endplate zones of the right and left extensor digitorum brevis (EDB) muscles were localized using high-density surface EMG. On the study side BoNT-A was injected at fixed distances from the endplate zone. On the control side, BoNT-A was administered into the endplate zone. Compound muscle action potential (CMAP) prior to the injection and 2, 12, and 24 weeks later were recorded. On the control side, the mean CMAP reduction 2 weeks after BoNT-A injection was 79.3%. The difference in CMAP reduction between both EDB muscles was significantly related to the injection distance from the endplate zone. Increasing the injection distance by 1cm reduced the effect of BoNT-A by 46%. Guided injection of a reduced BoNT-A dose into the muscle's endplate zone(s) is a promising strategy for optimizing the therapeutic effectiveness of BoNT-A and for minimizing side-effects such as unwanted weakness of adjacent muscles. Precise endplate-targeted injections increase the effect of BoNT-A and may thus prove to reduce required dosage and treatment costs.

Evidence of decarboxylation of lysine by mammalian ornithine decarboxylase. In enzymic preparations from mouse kidney stimulated with the anabolic steroid Durabolin (nandrolone phenpropionate) lysine and ornithine were shown to inhibit the decarboxylation of each other competitively. The Michaelis constants for the decarboxylations were approximately equal to the inhibition constants of the two amino acids. The pH optima of the decarboxylation of lysine and ornithine were found to be identical. Chromatographic studies of the enzyme preparation on a Sephadex G-150 Superfine column did not bring about a separation of the two enzyme activities. The ratio of the decarboxylating activities was practically the same during the elution. Lysine decarboxylating activity was also shown to be present in growth hormone stimulated rat liver. The results are in agreement with the assumption that the decarboxylation of lysine and ornithine is carried out by the same enzyme.

Cardiac troponin I is associated with severity of myxomatous mitral valve disease, age, and C-reactive protein in dogs. Concentrations of cardiac troponin I (cTnI) and C-reactive protein (CRP) might be associated with cardiac remodeling in dogs with myxomatous mitral valve disease (MMVD). Age- and sex-dependent variations in cTnI concentration have been described. To investigate whether plasma concentrations of cTnI and CRP are associated with severity of MMVD, and investigate potential associations of dog characteristics on cTnI and CRP concentrations. Eighty-one client-owned dogs with MMVD of varying severity. Dogs were prospectively recruited for the study. Dogs were classified according to severity of MMVD. Plasma cTnI was analyzed by a high sensitivity cTnI assay with a lower limit of detection of 0.001 ng/mL, and plasma CRP was analyzed by a canine-specific CRP ELISA. Higher cTnI concentrations were detected in dogs with moderate (0.014 [interquartile range 0.008-0.029] ng/mL, P = .0011) and severe (0.043 [0.031-0.087] ng/mL, P < .0001) MMVD, compared with healthy dogs (0.001 [0.001-0.004]ng/mL). Dogs with severe MMVD also had higher cTnI concentrations than dogs with mild (0.003 [0.001-0.024] ng/mL, P < .0001) and moderate (P = .0019) MMVD. There were significant associations of age, CRP, heart rate, and left ventricular end-diastolic diameter, on cTnI concentration C-reactive protein did not differ among severity groups, but was significantly associated with cTnI, breed, and systolic blood pressure on CRP concentration. Analysis of cTnI concentration has potential to increase knowledge of overall cardiac remodeling in dogs with MMVD. However, effect of age on cTnI needs consideration when assessing cTnI.

Monoclonal B-cells in blood in non-Hodgkin lymphoma. Correlation with clinical features and prognoses. Presence of monoclonal B-cells in peripheral blood (MBCB) was studied in 132 previously untreated patients with non-Hodgkin lymphoma classified according to the Kiel classification. Detection of B-cells was performed by immunofluorescence microscopy, using antibodies against immunoglobulin light chains. Thirty-six patients (27%) were found to have MBCB. In the subgroup of low grade lymphomas 25/75 (33%) and in high grade lymphomas, 11/57 (19%) had MBCB. Presence of MBCB was correlated to clinical stage and 81% of the patients with MBCB were in stage IV. Twenty-two out of 36 (61%) patients with MBCB had normal lymphocyte counts (less than 5.0 X 10(9]. MBCB indicated a less favourable prognosis, mainly due to the close association with stage IV. It was concluded that studies of MBCB by this simple method are useful in detecting 'subclinical' blood involvement and valuable in the initial staging procedure as well as in the follow-up of the patients.

Cryopreserved oocytes can serve as the treatment for secondary infertility: a novel model for egg donation. To report the use of previously cryopreserved oocytes for the treatment of secondary infertility. Case report. University-based IVF program. A 41-year-old woman with 18 months of secondary infertility and a previous history (age 38) of elective oocyte cryopreservation. Previously cryopreserved oocytes. Fertilization, embryo development, pregnancy, and outcome. The patient achieved pregnancy and delivery following thaw of oocytes electively cryopreserved 39 months before use. Before thawing the oocyte, the patient attempted pregnancy naturally for 12 months, followed by two unsuccessful clomiphene citrate ovulation induction cycles with intrauterine insemination and one fresh IVF cycle resulting in a chromosomally abnormal twin gestation that aborted. Although oocyte cryopreservation is still labeled an experimental procedure, this case demonstrates that oocyte cryopreservation used for electively deferred reproduction can subsequently serve in the treatment for secondary infertility when the patient becomes her own oocyte donor.

Factors relating to intelligence in treated cases of spina bifida cystica. Analysis of results on 83 survivors of spina bifida cystica showed the following: (1) in the seven children who had had central nervous system (CNS) infection, intelligence was impaired, six being severely retarded. (2) In the nine children who did not suffer CNS infection or require a shunt, intelligence was normal. The need for a shunt was related to radiological appearance (craniolacunae) and to the sensory level at birth. (3) In the 67 children who did not suffer CNS infection but did require a shunt, intelligence was related to sensory level found at birth and to thickness of the pallium measured within four weeks of birth. Their intelligence did not relate to the occipitofrontal circumference at birth, or to its increase before the insertion of the shunt. Intelligence did not relate to the function of the shunt at the time of assessment or to the number of times it had been revised.

[Conservative and surgical therapy of humerus fractures of the collum chiruricum]. 111 patients with humeral fractures of the surgical neck were examined 10 months after trauma. In cases of minor dislocation no significant difference between conservative and operative therapy could be observed, whereas in cases of major dislocation operative intervention lead to better functional results. Thus fractures of the surgical neck with major dislocation should be operated upon.

Biomineralization in the presence of calcium-binding phosphoprotein particles. The innermost shell lamella, which coats the inner surface of the shells in the estuarine clam Rangia cuneata, is a dynamic structure with a variable composition. In some populations the lamella is a phosphoprotein-rich structure devoid of crystalline mineral, and in others it is a glucosamine-rich structure often containing barite (BaSO4) inclusions. Mineral depositions was artificially stimulated in Rangia containing glucosamine-rich lamellae by scratching the inner shell surface. After stimulation, the lamellae were transformed into phosphoprotein-rich structures in which aragonite (CaCO3) was deposited. The mineral grew in spherulitic and dumbbell-shaped clusters characteristic of aragonite precipitated from strictly inorganic solutions. This study demonstrates that phosphoprotein particles accumulate in the innermost shell lamella during stimulated biomineralization but neither inhibit mineral deposition nor influence the crystal habits. Since phosphoprotein particles are high capacity calcium-binding proteins, they may be the source and transport vehicle for the calcium ions utilized in shell mineralization.

The interaction of chemicals during pregnancy: an update. The role of chemical interactions in the genesis of induced embryotoxicity in humans and in experimental animals is a point of current concern and interest. This review summarizes the current knowledge in this field and demonstrates that, under appropriate conditions, the observed results of chemical interactions can be explained, in part, through an understanding of the underlying pharmacokinetic and pharmacodynamic parameters. These define the concentration of the "primary" teratogen at its receptor site in cells and tissues that are particularly sensitive to its embryotoxic action. The interacting "secondary" or "coteratogen" is viewed as an agent that is capable of altering these parameters in a way that is correlated with an observed alteration in the embryotoxic response. A series of recent experiments (diazouracil: 5-fluouracil; hydroxyurea: 5-bromodeoxyuridine; caffeine: 5-bromodeoxyuridine; caffeine: phenytoin) are reported which demonstrate both the validity and the limitations of such an approach and attempt to interpret observations, which are primarily empirical in nature, in pharmacologic terms.

Mechanical-biological waste treatment and the associated occupational hygiene in Finland. A special feature of waste management in Finland has been the emphasis on the source separation of kitchen biowaste (catering waste); more than two-thirds of the Finnish population participates in this separation. Source-separated biowaste is usually treated by composting. The biowaste of about 5% of the population is handled by mechanical-biological treatment. A waste treatment plant at Mustasaari is the only plant in Finland using digestion for kitchen biowaste. For the protection of their employees, the plant owners commissioned a study on environmental factors and occupational hygiene in the plant area. During 1998-2000 the concentrations of dust, microbes and endotoxins and noise levels were investigated to identify possible problems at the plant. Three different work areas were investigated: the pre-processing and crushing hall, the bioreactor hall and the drying hall. Employees were asked about work-related health problems. Some problems with occupational hygiene were identified: concentrations of microbes and endotoxins may increase to levels harmful to health during waste crushing and in the bioreactor hall. Because employees complained of symptoms such as dry cough and rash or itching appearing once or twice a month, it is advisable to use respirator masks (class P3) during dusty working phases. The noise level in the drying hall exceeded the Finnish threshold value of 85 dBA. Qualitatively harmful factors for the health of employees are similar in all closed waste treatment plants in Finland. Quantitatively, however, the situation at the Mustasaari treatment plant is better than at some Finnish dry waste treatment plants. Therefore is reasonable to conclude that mechanical sorting, which produces a dry waste fraction for combustion and a biowaste fraction for anaerobic treatment, is in terms of occupational hygiene better for employees than combined aerobic treatment and dry waste treatment.

Usefulness of feature analysis of breast-specific gamma imaging for predicting malignancy. The purpose of this study was to investigate which feature of the breast-specific gamma imaging (BSGI) uptake in women who were recently diagnosed with breast cancer was associated with malignancy. Data on 231 newly diagnosed breast cancer patients who underwent preoperative BSGI were retrospectively reviewed. Feature analysis was done by classifying BSGI uptake into mass, non-mass, or focus/foci. Descriptors for mass, non-mass, or focus/foci were shape, distribution, number, and intensity. BSGI features of known malignancies and lesions that were additionally found by BSGI were correlated with mammographic breast density, histology, hormonal status, and clinical follow-up data obtained over at least 2 years. Among 372 breast lesions from 231 patients, 241 malignancies had been pathologically confirmed prior to BSGI and 131 additional lesions were found on BSGI. Irregular shape was more predictive of malignancy than oval shape (p=0.004) in mass uptake. Linear/ductal distribution was more predictive of malignancy than focal, regional, and segmental distribution (p<0.05) in non-mass uptake. Mammographic breast density was not associated with BSGI features. The lesion to normal ratio (LNR) was higher in the postmenopausal patients than that in the premenopausal patients (p=0.003). The feature analysis of radiotracer uptake in BSGI is useful in predicting whether breast lesions are malignant or benign. • The feature analysis of BSGI uptake is useful in predicting malignancy. • Irregular shape was predictive of malignancy in mass uptake. • Linear/ductal distribution was predictive of malignancy in non-mass uptake.

Uterine adenosarcomas: A dual-institution experience. There has been limited literature about treatment and follow-up strategies of uterine adenosarcomas because of their rare nature. For this study we retrospectively investigated the medical database of the two major womens' health hospitals in Turkey. A total of 15 patients were identified from the hospital's database. Median follow-up was 86.43 months for all patients. Seven out of 15 patients had recurrences during their follow-up. Among these 7 patients, 4 of them had stage IA disease. Median Disease Free Survival (DFS) and Overall Survival (OS) were calculated as 41.47 and 57.21 months, respectively. According to our study, polypoid tumours confined to the uterus with superficial myometrial invasion can be treated without comprehensive surgical staging. We believe that, publishing all the data in an organised manner even though they are small in size, gives us an opportunity to design meta-analysis for the development of more appropriate treatment strategies.

Evidence for an ATP-dependent bile acid transport protein other than the canalicular liver ecto-ATPase in rats. Canalicular secretion is rate limiting in overall blood-to-bile transport of bile acids. Studies using transfected cells have implicated the canalicular ecto-adenosine triphosphatase (ecto-ATPase) in adenosine triphosphate (ATP)-dependent bile acid transport. However, the structural features of this ecto-ATPase are not those anticipated for an in-to-out ATP-dependent transporter. The aim of this study was to explore the possible existence of an ATP-dependent bile acid transport mechanism distinct from ecto-ATPase. Bile acid transport activity and ecto-ATPase expression were analyzed in primary rat hepatocytes, rat hepatoma HTC cells, and specially adapted HTC (HTC-R) cells using plasma membrane vesicles and Northern blot, slot blot, ribonuclease protection assay, and Western blot analyses. Plasma membranes isolated from HTC-R cells exhibited ATP-dependent taurocholate transport, which was many-fold greater than that in HTC cells. Hepatocytes showed the highest transport rates. Protein and RNA analyses showed very low expression of ecto-ATPase in HTC and HTC-R cells compared with hepatocytes. There was no difference between the two cell types at both the RNA and protein level. These findings show the presence in HTC-R cells and, apparently in hepatocytes, of one or more proteins other than the ecto-ATPase that mediate ATP-dependent transport of bile acids.

Correlation between retinoid inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis and levels of retinoic acid binding proteins. A correlation was made between the ability of retinoids to suppress N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis and the levels of cytosolic retinoic acid binding proteins (cRABP) in the cytosol of MNU-induced mammary tumors. Although retinyl acetate and N-(4-hydroxyphenyl)-retinamide were found to be effective inhibitors of mammary carcinogenesis in intact hosts, both retinoids were significantly more active in ovariectomized rats than in intact animals. Quantitative analysis of cRABP in the tumors indicated that mammary cancers arising in animals which were ovariectomized one week after MNU administration contained significantly increased concentrations of cRABP compared to cancers appearing in intact rats. In addition, when animals bearing palpable mammary tumors were ovariectomized, the tumors which continued to grow contained significantly higher levels of cRABP than did tumors which stopped growing or regressed. These data suggest that the selective inhibition of ovarian hormone-independent mammary cancer by retinyl acetate and N-(4-hydroxyphenyl)retinamide may be mediated through an increased level of cRABP in tumor cells of ovariectomized hosts.

Effort thrombosis: recognition and management while underway. Effort thrombosis of the axillary and subclavian veins is an uncommon cause of upper extremity swelling. Prompt recognition and treatment of this disorder is important in order to minimize the complications of pulmonary embolism and postphlebitic syndrome that can occur with this condition. This can be very challenging while underway or in the field. A sailor who developed effort vein thrombosis while underway on board the aircraft carrier USS Abraham Lincoln is presented to review the presentation and management of this disorder, particularly as it applies to active duty military personnel.

Direct generation of starting points for freeform off-axis three-mirror imaging system design using neural network based deep-learning. In this paper, we propose a framework of starting points generation for freeform reflective triplet using back-propagation neural network based deep-learning. The network is trained using various system specifications and the corresponding surface data obtained by system evolution as the data set. Good starting points of specific system specifications for further optimization can be generated immediately using the obtained network in general. The feasibility of this design process is validated by designing the Wetherell-configuration freeform off-axis reflective triplet. The amount of time and human effort as well as the dependence on advanced design skills are significantly reduced. These results highlight the powerful ability of deep learning in the field of freeform imaging optical design.

[2- 14C]deoxyglucose uptake in rat visual system during flashing-diffuse and flashing-pattern stimulation over a 6 log range of luminance. The 2-deoxyglucose autoradiographic technique was used to assess the metabolic activity of cortical area 17, the dorsal and ventral lateral geniculate nuclei, the lateral posterior nucleus, and the superior colliculus, during 5-Hz flashing-pattern (montage of black and white square-wave gratings) and flashing-diffuse (eye covered with white mask) stimulation at three intensities over a 6 log range. In area 17 flashing-pattern was found to be equally effective at elevating uptake of the functional label over the photopic-scotopic range of luminance levels tested, whereas flashing-diffuse was ineffective. In subcortical nuclei, however, flashing-diffuse was no less effective than flashing-pattern and uptake of the label correlated positively with intensity level. The results suggest that the subcortical components of the visual system do play an important role in the processing of intensity information and that primary visual cortex does not.

Antibiotic Susceptibility Patterns of Mycobacterium tuberculosis Isolates from Guizhou Province of China Against 13 Antituberculosis Drugs. A total of 92 Mycobacterium tuberculosis isolates were collected from patients with pulmonary tuberculosis (TB) in the Zunyi region between 2011 and 2012. Collected isolates were used to determine antibiotic susceptibility patterns against 13 anti-TB drugs: 4 first-line and 9 second-line (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, para-aminosalicylic acid, amikacin, capreomycin, kanamycin, and prothionamide) drugs. Results showed that among 57 new cases of TB only 66.7% were susceptible to all four first-line anti-TB drugs and 64.9% were susceptible to fluoroquinolones and second-line injectables; 10.5% of new and 22.9% of previously treated cases were multidrug-resistant TB (MDR-TB); and 1.8% of new and 2.9% of previously treated cases were extensively drug-resistant TB (XDR-TB). In addition, 14.3% of MDR-TB cases (2 out of 14) were XDR-TB, which is higher than the average numbers in China (about 8%) and in the world (9.6%). This study confirms that primary transmission of drug-resistant TB, including MDR/XDR-TB, is a real threat to achieving effective control of drug-resistant TB in the Guizhou Province and indicates the necessity to determine antibiotic susceptibility patterns in patients with TB to improve treatment outcomes.

A generalizable energetics-based model of avian migration to facilitate continental-scale waterbird conservation. Conserving migratory birds is made especially difficult because of movement among spatially disparate locations across the annual cycle. In light of challenges presented by the scale and ecology of migratory birds, successful conservation requires integrating objectives, management, and monitoring across scales, from local management units to ecoregional and flyway administrative boundaries. We present an integrated approach using a spatially explicit energetic-based mechanistic bird migration model useful to conservation decision-making across disparate scales and locations. This model moves a Mallard-like bird (Anas platyrhynchos), through spring and fall migration as a function of caloric gains and losses across a continental-scale energy landscape. We predicted with this model that fall migration, where birds moved from breeding to wintering habitat, took a mean of 27.5 d of flight with a mean seasonal survivorship of 90.5% (95% Cl = 89.2%, 91.9%), whereas spring migration took a mean of 23.5 d of flight with mean seasonal survivorship of 93.6% (95% CI = 92.5%, 94.7%). Sensitivity analyses suggested that survival during migration was sensitive to flight speed, flight cost, the amount of energy the animal could carry, and the spatial pattern of energy availability, but generally insensitive to total energy availability per se. Nevertheless, continental patterns in the bird-use days occurred principally in relation to wetland cover and agricultural habitat in the fall. Bird-use days were highest in both spring and fall in the Mississippi Alluvial Valley and along the coast and near-shore environments of South Carolina. Spatial sensitivity analyses suggested that locations nearer to migratory endpoints were less important to survivorship; for instance, removing energy from a 1036 km2 stopover site at a time from the Atlantic Flyway suggested coastal areas between New Jersey and North Carolina, including the Chesapeake Bay and the North Carolina piedmont, are essential locations for efficient migration and increasing survivorship during spring migration but not locations in Ontario and Massachusetts. This sort of spatially explicit information may allow decision-makers to prioritize their conservation actions toward locations most influential to migratory success. Thus, this mechanistic model of avian migration provides a decision-analytic medium integrating the potential consequences of local actions to flyway-scale phenomena.

Curved space plasmonic optical elements. We have designed and experimentally studied non-planar curved space plasmonic optical elements. Three different smooth curved space plasmonic structures were studied: a dome that acts either as a focusing element or as a deflector for plasmonic beams, a cone that acts as a plasmonic prism, and a tapered book cover that alters the size of a plasmonic guided wave. The functional mechanism of these elements relies purely on the curvature-induced effective potential and does not require any additional dielectric layer for shaping the plasmonic beams. The curved space plasmonic elements open exciting new possibilities for guiding, focusing, deflecting, and controlling the propagation of plasmonic beams in a compact manner.

[Irreversible electroporation to treat prostate cancer (Nanoknife)]. Modern medicine tends to use minimally invasive treatments. Selected patients with prostate cancer may be treated using irreversible electroporation that involves the application of a NanoKnife device. The procedure directs short electrical pulses that open microscopic pores in the cells in the treatment area and effectively destroy cancer cells. This literature review outlines the history of irreversible electroporation, its use in surgery for treating cancers of the pancreas, liver, lung, kidney and brain. This technique is relatively new and is not yet applied in routine urologic practice, but has been increasingly used in Europe and North America and, no doubt, will find an appropriate utilization in Russia.

Flow cytometric analysis of within-strain variation in polysaccharide expression by Bacteroides fragilis by use of murine monoclonal antibodies. The reactivity of four different monoclonal antibodies (MAbs) with populations of Bacteroides fragilis NCTC 9343, enriched by density gradient centrifugation for a large capsule, small capsule and electron-dense layer (EDL) only visible by electronmicroscopy, was examined. The MAbs reacted strongly with polysaccharides present in both the large capsule- and EDL-enriched populations but not in the small capsule-enriched populations. The pattern of labelling was determined by immunoblotting, immunofluorescence and immuno-electronmicroscopy, and flow cytometry. The MAbs labelled cell membrane-associated epitopes in the large capsule- and EDL-enriched populations and cell-free material in the EDL population. By immunoblotting, ladders of repeating polysaccharide subunits were evident in the EDL population but not in the large capsule population. The proportion of cells labelled within each population was determined by flow cytometry. The reactivity of another MAb with the small capsule population was confirmed by flow cytometry. A qualitative indication of epitope expression was obtained by examination of the flow cytometric profiles. Differential expression of the same saccharide epitope was observed both between and within structurally distinct B. fragilis populations. The MAbs were species-specific and cross-reacted with several recent clinical isolates. These polysaccharides may be relevant to the virulence of B. fragilis.

A novel systematic approach to the evaluation of the fetal venous system. Sonographic evaluation of the fetal venous system in normal and abnormal conditions has drawn increasing interest in recent years. Whereas the assessment of the fetal heart and the related arteries is standardized using well-defined planes, the fetal venous system is still lacking a systematic approach. In this article we present a novel sonographic algorithm for a systematic examination of the fetal venous system using six planes of transverse and oblique views of the fetal abdomen and chest. These planes, using two-dimensional and color Doppler, enable a targeted demonstration of the typical veins to include the umbilical vein, ductus venosus, portal veins, hepatic veins, inferior vena cava, azygos vein, pulmonary veins, coronary sinus, superior vena cava and brachiocephalic vein. We postulate that integrating such a sequential stepwise algorithm for the evaluation of the venous system into targeted fetal cardiac imaging may improve the detection of isolated and combined anomalies of the fetal systemic and pulmonary veins.

Safe storage times for sterile dental packs. Safe storage times were evaluated for three sterile packaging materials that are commonly used in dentistry. No significant differences were found among packaging materials. Only three packs of 300 produced positive cultures during the 1-year test period. There were no time-related trends. The contamination levels found were within the range that has been reported to occur as a result of inadvertent contamination during unpackaging and transfer of sterile instruments. The findings of this study support the proposal that contamination is event related, not time related; that is, sterile instrument packs remain sterile for at least 1 year unless a specific event causes contamination.

Comparative cutting effectiveness of an ultrasonic diamond tip and a high-speed diamond bur. The aim of this in vitro study was to compare an ultrasonic diamond tip to a high-speed conventional diamond bur regarding the cutting effectiveness in enamel and dentin of human teeth. Twenty permanent molars were longitudinally sectioned in the buccal-lingual plane giving 40 specimens, 20 for enamel and 20 for dentin groups. One cavity was performed in each specimen using a spherical diamond tip (83231, CVDentus(R), CVDVale, São José dos Campos, SP, Brazil) coupled with an ultrasound device or a conventional spherical diamond bur (1013, KG Sorensen, São Paulo, Brazil)) coupled with a high-speed turbine. A modified measurement analysis using the Radiocef 4.0 software (Radiocef Memory) was applied to determine the width and the depth of the cavities on scanning electron microscopy (SEM) at x50 magnification micrographs. The features of the cavities and the characteristics of the cutting instruments were also examined under different magnifications by SEM. Statistical analysis by Kruskal-Wallis non-parametric and Dunn post hoc tests (P < or = 0.05) showed that cavities prepared in enamel and dentin with the ultrasonic diamond tip were shallower and narrower than those prepared with conventional diamond bur. The internal walls of cavities prepared in dentin by the ultrasonic diamond tip reproduced the superficial aspect of the diamond, however, scratches were observed in the internal walls of the dentin cut by high-speed conventional diamond bur. Both instruments were effective in enamel and dentin cutting; however, cavities prepared with a high-speed conventional diamond bur showed more invasive characteristics.

Production of a severe cystic fibrosis mutation in mice by gene targeting. We have used gene targeting in embryonic stem cells to introduce an HPRT mini-gene into the coding sequence of the murine cystic fibrosis gene (cftr). This insertion introduces a termination codon in frame with the cftr coding sequence to terminate prematurely the CFTR protein within the first nucleotide binding domain. Animals homozygous for the cftr disruption fail to thrive and display a range of symptoms including meconium ileus, distal intestinal obstructions, gastrointestinal mucus accumulation and blockage of pancreatic ducts. The animals also show lacrimal gland pathology. Tracheal and caecal transepithelial current measurements demonstrate the lack of a cAMP activatable Cl- channel. These animals will prove useful for the evaluation of new therapeutic drugs and gene therapy strategies.

Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening. As maternal age advances, the risk of fetal Down's syndrome increases. Pregnant women 35 years of age or older are routinely offered amniocentesis because of this risk. Recently, maternal serum markers have been reported to be useful in screening for Down's syndrome, primarily in younger women. We therefore investigated whether offering amniocentesis only to selected women 35 years of age or older who were identified by screening measurements in serum might prove a useful alternative to the current practice. We studied 5385 women with singleton pregnancies who were 35 years of age or older and were undergoing routine amniocentesis. Along with information about the pregnancy, we obtained a serum sample for measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Individual estimates of the risk of Down's syndrome in the fetus were calculated for each pregnancy before the karyotype was known. If amniocentesis had been reserved for the women calculated to have a risk greater than 1 in 200 of having a fetus with Down's syndrome, 48 of the 54 cases of Down's syndrome (89 percent) would have been identified, 25 percent of the unaffected pregnancies would also have been identified as being at high risk for Down's syndrome (false positives). Seven of 15 fetuses (47 percent) with other trisomies, 11 of 25 (44 percent) with sex aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities would also have been detected. In practice, such screening would have made 75 percent of the amniocentesis unnecessary, along with a proportion of the amniocentesis-associated fetal losses. If the cutoff for the risk of Down's syndrome were set higher than 1 in 200, both the rate of detection and the false positive rate would be lower. Conversely, these rates would be higher if the cutoff were set lower. Prenatal screening of serum to generate individual estimates of the risk of Down's syndrome in the fetus can provide a basis for decision making in the cases of women 35 years of age or older, as it does in younger pregnant women, and is an alternative to current testing practices.

[A by-pass to the internal jugular. An original method to salvage a dysfunctional vascular prosthesis in the arm for hemodialysis]. A case of PTFE straight prosthesis in arm, causing an ipsilateral subclavian vein thrombosis, is presented. An original method of treatment (by-pass to internal jugular) allowed to save the vascular access for hemodialysis.

Treatment of skin and soft-tissue infections. Bacterial infections of the skin range from mild pyodermas to life-threatening necrotizing infections. Pyodermas are most often due to Staphylococcus aureus or beta-hemolytic Streptococcus sp, whereas infections associated with skin ulcers of the extremities, infections following trauma or surgery, and histotoxic necrotizing infections may involve a large number of additional pathogens, including Enterobacteriaceae, Pseudomonas sp, enterococci, and anaerobes. Management of bacterial skin and soft-tissue infections includes appropriate surgical drainage or excision of infected tissue and antimicrobial therapy. The combination of piperacillin and the beta-lactamase inhibitor tazobactam is a newly released antimicrobial, which has excellent in vitro activity against the vast majority of pathogens involved in skin infections. Two multicenter studies recently evaluated the efficacy and safety of piperacillin/tazobactam in the therapy of skin and soft-tissue infections in hospitalized patients. Piperacillin/tazobactam was well tolerated and demonstrated high clinical efficacy for the treatment of these infections.

Work time required to perform diagnostic and interventional pediatric cardiac catheterizations. This study was designed to determine the time required to perform pediatric diagnostic and interventional heart catheterizations. These data are the first published information evaluating such work times.

Localization of transglutaminase in hippocampal neurons: implications for Alzheimer's disease. The purpose of this investigation was to identify and localize tissue transglutaminase (TGase) within neurons from the hippocampi of normal aged individuals and of those with confirmed Alzheimer's disease (AD). This enzyme may be a factor in the molecular mechanisms of neurodegeneration and formation of insoluble macromolecular complexes found in the neurons of normal aged and AD brain tissue. An antibody made to the extracellular TGase, coagulation factor XIIIa, was found to be specific for purified intracellular guinea pig liver tissue TGase. The specificity for liver tissue TGase has enabled us to identify tissue TGase(s) within rat hippocampal neurons and within neurons from normal aged and AD hippocampal tissues. Degenerating neurons from the AD hippocampus, compared to neurons from the normal aged hippocampus, exhibited increased immunoreactivity for TGase and demonstrated co-labeling for PHF1 and anti-TGase. Our results suggest that TGase may be associated with the neurofibrillary degeneration observed in AD, thereby implicating TGase as a potential factor in the pathogenesis of Alzheimer's disease.

How to help patients understand and conquer grief. Avoiding depression in the midst of sadness. Grief is a painful yet normal process that many patients do not fully understand or appreciate. Any person may be at risk for depression as a result of grief-inducing events. Early, organized intervention by primary care physicians can help patients return to full emotional health and maintain self-esteem. When the behavioral markers that measure the intensity of grief are named and used as a scale by which to measure progress, grief reactions can be jointly managed by patient and physician in brief counseling sessions over a reasonable period of time. I believe this is an efficient, effective, and valuable service to patients.

Clinical trial of recombinant leukocyte A interferon as initial therapy for favorable histology non-Hodgkin's lymphomas and chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group pilot study. Twenty patients with disseminated favorable histology non-Hodgkin's lymphomas (16 patients) or chronic lymphocytic leukemia (four patients) who had not received previous chemotherapy were treated with recombinant leukocyte A interferon (IFL-rA) (Hoffmann-La Roche, Nutley, NJ). Treatment was administered in a moderate dose (12 X 10(6) U/m2) by intramuscular (IM) injection three times weekly for 8 weeks, followed by weekly maintenance therapy for an additional 16 weeks in patients responding to therapy. Five patients with stable disease at 8 weeks received four additional weeks of three-times-weekly treatment at an escalated dose (25 X 10(6) U/m2). Interferon was tolerated without severe toxicity by most patients, although treatment was discontinued prematurely due to side effects in four patients. Objective tumor responses (one complete response [CR] and six partial responses [PRs]) were seen in seven of 16 patients with lymphoma (44%). One of four patients with chronic lymphocytic leukemia also experienced a PR. Median time-to-progression from initiation of therapy among responding patients was 26 + weeks (range, 7 + to 84 + weeks). This study has demonstrated single agent antitumor activity of IFL-rA given in a tolerable outpatient dosage regimen in patients with advanced favorable histology non-Hodgkin's lymphomas, and serves as a basis for further trials of IFL-rA combined with chemotherapy as initial therapy for such patients in the future.

Routine performance of endomyocardial biopsy decreases the incidence of orthotopic heart transplant for myocarditis. In critically ill children presenting with dilated cardiomyopathy (DCM), the presence of myocarditis predicts an improved chance of myocardial recovery. Noninvasive differentiation of myocarditis from other causes of DCM is difficult. However, sensitivity of endomyocardial biopsy has been questioned. We reviewed clinical, echocardiographic, catheterization, and pathology data from all children admitted to the intensive care unit with DCM undergoing orthotopic heart transplantation since the inception of our transplant program in 1987 and all patients with definitively diagnosed myocarditis presenting since 1996. Thirty-six patients with DCM underwent orthotopic heart transplantation. Cellular infiltrate was present in 3 of 36 (8.3%) explanted specimens. Pre-transplant biopsy was performed in 81%. No explanted heart demonstrated infiltrates after a negative biopsy. One biopsy was positive with negative explant histology after transplant 6 months later. No patient with biopsy-proven myocarditis died while listed for transplantation. Eleven additional patients with myocarditis did not undergo transplant. Ten have survived and experienced complete (n = 9) or near complete (n = 1) recovery of myocardial function. One patient died shortly after presentation from fulminant myocarditis. The 10 transplant-free survivors could not be easily distinguished from our transplant cohort by clinical features at presentation. The incidence of cellular infiltrate in explanted hearts was significantly lower than that previously reported. Potentially, our aggressive myocarditis diagnostic protocol was useful in therapeutic stratification as a cohort of myocarditis patients avoided transplant and experienced complete recovery of myocardial function despite being difficult to distinguish clinically from our DCM transplant cohort at presentation.

Understanding medication compliance and persistence from an economics perspective. An increased understanding of the reasons for noncompliance and lack of persistence with prescribed medication is an important step to improve treatment effectiveness, and thus patient health. Explanations have been attempted from epidemiological, sociological, and psychological perspectives. Economic models (utility maximization, time preferences, health capital, bilateral bargaining, stated preference, and prospect theory) may contribute to the understanding of medication-taking behavior. Economic models are applied to medication noncompliance. Traditional consumer choice models under a budget constraint do apply to medication-taking behavior in that increased prices cause decreased utilization. Nevertheless, empiric evidence suggests that budget constraints are not the only factor affecting consumer choice around medicines. Examination of time preference models suggests that the intuitive association between time preference and medication compliance has not been investigated extensively, and has not been proven empirically. The health capital model has theoretical relevance, but has not been applied to compliance. Bilateral bargaining may present an alternative model to concordance of the patient-prescriber relationship, taking account of game-playing by either party. Nevertheless, there is limited empiric evidence to test its usefulness. Stated preference methods have been applied most extensively to medicines use. Evidence suggests that patients' preferences are consistently affected by side effects, and that preferences change over time, with age and experience. Prospect theory attempts to explain how new information changes risk perceptions and associated behavior but has not been applied empirically to medication use. Economic models of behavior may contribute to the understanding of medication use, but more empiric work is needed to assess their applicability.

[Postoperative pain assessment in special patient groups: part II. Children with cognitive impairment]. Postoperative pain assessment in children with cognitive impairment poses major challenges to healthcare professionals.Children with moderate to severe cognitive impairment are generally unable to communicate effectively and to self-report the level of pain. Difficulties assessing pain have led to their exclusion from clinical trials and rendered them vulnerable to insufficient treatment of pain.The realization of pain is a particularly important step forward for a better care of children with cognitive impairment.Scales based on a child's own perception of pain and its severity play a limited role in this vulnerable population and pain assessment tools which rely on observing pain behavior are essential. The r-FLACC, which is reliable and valid, includes specific behavioral descriptors and can be used simply and effectively postoperatively in clinical practice. Our task has to be assessing pain as a routine procedure in cognitively impaired children as a keystone for an improved and successful pain management in this very sensitive patient population.

Eight-fold path to attain laparoscopic totally extraperitoneal (TEP) hernia repair Nirvana - a standardized technique to reduce the learning curve of surgical residents. Laparoscopic totally extraperitoneal (TEP) hernia repair remains technically challenging due to the steep learning curve and unfamiliar territory. This paper describes an eight-step standardized technique of laparoscopic TEP hernia repair that is easily reproducible, thus reducing the learning curve. The eight steps are as follows: (a) creation of the pneumo pre-peritoneal space; (b) identify the pubis symphysis; (c) identify the inferior epigastric vessels; (d) lateral to medial dissection of the hernia sac; (e) identification of cord structures and triangle of doom/pain; (f) herniotomy; (g) parietalization of the hernia sac; (h) placement and fixation of the mesh. The learning curve of laparoscopic TEP can be decreased by proctoring, standardization of the procedure and having a formal set of operative steps that residents can follow and easily repeat.

Tumor targeting HPMA-porphyrin-99mTc copolymer molecular imaging agent. Porphyrins typically show preferential uptake and retention by tumor tissues via receptor-mediated endocytosis of low-density lipoproteins. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific targeting porphyrin HPMA [HPMA: N-(2-hydroxypropyl)methacrylamide] copolymer tracer poly(HPMA)-porphyrin-DTPA-(99m)Tc (DTPA: diethylenetriaminepentaacetic acid), nonspecific targeting HPMA copolymer tracer poly(HPMA)-DTPA-(99m)Tc, and nontargeting tracer DTPA-(99m)Tc are described in this study. The results showed that the cellular accumulation of poly(HPMA)-porphyrin-DTPA-(99m)Tc complex was found to be time-dependent. The uptake of poly(HPMA)-porphyrin-DTPA-(99m)Tc was significantly higher than that of poly(HPMA)-DTPA-(99m)Tc, indicating that uptake of the poly(HPMA)-porphyrin-DTPA-(99m)Tc was active binding. The uptake of poly(HPMA)-DTPA-(99m)Tc was significantly higher than that of DTPA-(99m)Tc, suggesting that uptake of the poly(HPMA)-DTPA-(99m)Tc was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p < 0.001) tumor localization for poly(HPMA)-porphyrin-DTPA-(99m)Tc (5.18 ± 0.50% ID/g [percentage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-(99m)Tc (2.69 ± 0.15% ID/g) and DTPA-(99m)Tc (0.83 ± 0.03% ID/g). Moreover, higher T/B for poly(HPMA)-porphyrin-DTPA-(99m)Tc indicated reduced extravasation of the targeted polymeric conjugates in normal tissues. Thus, the poly(HPMA)-porphyrin-DTPA-(99m)Tc is a potential macromolecular tumor targeting molecular agent.

Antimutagenesis by factors affecting DNA repair in bacteria. The term 'antimutagen' was originally used to describe an agent that reduces the apparent yield of spontaneous and/or induced mutations, regardless of the mechanisms involved. The 'antimutagens' include 'desmutagens' and 'bio-antimutagens'. In this article, our attention was focused on the bio-antimutagens affecting DNA repair in bacteria. Cobaltous chloride reduced the frequency of mutations in Escherichia coli induced by MNNG. The possibility that metal compound inhibits the growth of mutagen-treated cells was examined. The results clearly showed that the antimutagen surely reduces the mutation rate. The target of cobaltous chloride was found to be cellular factors including Rec A. Vanillin and cinnamaldehyde had strong antimutagenic activities against UV, 4NQO and AF-2. They stimulated Rec A-dependent recombination repair functions in the mutagen-treated cells. Among plant materials, tannins possess antimutagenic activity against UV-induced mutations in E. coli. It has been found that tannic acid stimulates the excision repair encoded by the uvrA gene thereby reducing the yield of mutants. Substances which are antimutagenic in bacterial systems also had antimutagenic activity in cultured mammalian cell systems. Vanillin reduced the frequency of mutagen-induced chromosomal aberrations.

Flip-Flop Phenomenon in Epidural Sufentanil Pharmacokinetics: A Population Study in Children and Infants. The aims of this study were to develop a population pharmacokinetic model of sufentanil coadministered with 0.2% ropivacaine as an epidural infusion in infants and describe the sufentanil absorption profile from epidural space. Data from 2 previously published studies were merged for analysis-20 infants aged 3-36 months receiving sufentanil as an epidural infusion and 41 children 0-17 years old receiving sufentanil as a long-term intravenous infusion. A population nonlinear mixed-effects model was built in NONMEM. Sufentanil pharmacokinetics were described by a 2-compartment model with first-order absorption. The effect of body size on all volume and clearance parameters was included in the model according to allometric scaling with theoretical exponents. The maturation process of metabolic clearance was described by the Hill model. During the model-building process the population was divided into 2 fractions with different typical values of metabolic clearance (CL1 and CL2). The typical values of systemic clearance scaled to a 70-kg patient for the 2 subpopulations were CL1 = 52.6 L/h and CL2 = 158 L/h. The parameters of the Hill function were 54.9 weeks for the postmenstrual age of 50% clearance maturation and 0.802 for the Hill coefficient. The typical values of distribution clearance and volumes of the central and peripheral compartments for a patient with a weight of 70 kg were Q = 40.5 L/h, VC = 7.63 L, and VT = 473 L, respectively. The value of the absorption rate constant from the epidural space was 0.0459/h, which suggests flip-flop pharmacokinetics of sufentanil after epidural administration.

Distinguishability for magnetic resonance-electrical impedance tomography (MR-EIT). A distinguishability measure is defined for magnetic resonance-electrical impedance tomography (MR-EIT) based on magnetic flux density measurements. This general definition is valid for 2D and 3D structures of any shape. As a specific case, a 2D cylindrical body with concentric inhomogeneity is considered and a bound of the distinguishability is analytically formulated. Distinguishabilities obtained with potential and magnetic flux density measurements are compared.

Extracellular superoxide dismutase in tissues from obese (ob/ob) mice. We have examined the protein content and gene expression of three superoxide dismutase (SOD) isoenzymes in eight tissues from obese ob/ob mice, particularly placing the focus on extracellular-SOD (EC-SOD) in the white adipose tissue (WAT). Obesity significantly increased EC-SOD level in liver, kidney, testis, gastrocnemius muscle, WAT, brown adipose tissue (BAT), and plasma, but significantly decreased the isoenzyme level in lung. Tumor necrosis factor-alpha and interleukin-1beta contents in WAT were significantly higher in obese mice than in lean control mice. Immunohistochemically, both WAT and BAT from obese mice could be stained deeply with anti-mouse EC-SOD antibody compared with those from lean mice. Each primary culture per se almost time-dependently enhanced EC-SOD production, and overtly expressed its mRNA. The loss of heparin-binding affinity of EC-SOD type C with high affinity for heparin occurred in kidney of obese mice. These results suggest that the physiological importance of this SOD isoenzyme in WAT may be a compensatory adaptation to oxidative stress.

Psychosocial risk factors, weight changes and risk of obesity: the Copenhagen City Heart Study. The aim of the study was to establish the effects of a range of psychosocial factors on weight changes and risk of obesity. The study population consisted of the 4,753 participants in the third (1991-1994) and fourth wave (2001-2003) of the Copenhagen City Heart Study, Denmark. At baseline the participants were asked comprehensive questions on major life events, work stress, vital exhaustion, social network, economic hardship, and intake of sleep medication. Weight and height were measured by health professionals. Weight changes and incident obesity was used as outcome measures. The participants on average gained 2 kg of weight and 8% became obese during follow-up. The experience of major life events in childhood, work life and adult life was associated with weight gain and obesity in women, but not in men. Vital exhaustion was associated with weight gain in a dose-response manner in men (P = 0.002) and younger women (P = 0.02). Persons with high vital exhaustion gained approximately 2 kg more during follow-up compared to those with no vital exhaustion. Women with high vital exhaustion were also more likely to become obese during follow-up (OR = 2.39; 95% CI: 1.14-5.03). There were no clear patterns in the associations between social network, economic hardship and weight gain or obesity. The number of psychosocial risk factors, as an indicator for clustering, was not associated with weight gain or obesity. In conclusion, major life events and vital exhaustion seem to play a role for weight gain and risk of obesity, especially in women.

Scaling up the production of colloidal nanocrystals: should we increase or decrease the reaction volume? Recent progress in facet-controlled syntheses has started to produce nanocrystals with great promise as the next-generation catalysts for a variety of applications. To move from academic studies to industrial applications, however, one has to address the issue of scaling up a synthesis that has been commonly conducted in a batch format. There are two opposite approaches to scaling up the production of colloidal nanocrystals: increasing and decreasing the reaction volume. Contrary to conventional wisdom, continuous flow synthesis based on droplets is expected to provide a more practical platform for scaling up the synthesis. Here we highlight recent progress in using droplet reactors for the synthesis of colloidal noble-metal nanocrystals with controlled sizes and shapes, with an aim towards high-volume production.

Cancer therapeutics based on BCL-2 functional conversion.

Organic anion-transporting polypeptides: a novel approach for cancer therapy. Organic anion-transporting polypeptides (OATPs) encoded by the SLCO genes constitute an important transporter superfamily that mediates transmembrane transport of various clinical drugs and endogenous nutrients. Eleven human OATPs with different transport functions are expressed in various tissues. Bile acids, steroid hormone conjugates, prostaglandins, testosterone and thyroid hormones that promote cell proliferation are typical substrates of OATPs. Many important clinical drugs have been identified as substrates of OATP1B1, OATP1B3, OATP2B1 and OATP1A2. Liver-specific OATP1B1 and OATP1B3 as well as testis-specific OATP6A1 are expressed in malignancies and can act as biomarkers for many tumours. Various studies have shown the associations of genetic polymorphisms in OATP genes with the uptake pharmacokinetics of their substrates. Because of their abundant expression in tumours and their high transport activity for many cancer drugs, OATPs should be considered as important therapeutic targets in anti-cancer drug design.

Drug-resistant tuberculosis in human immunodeficiency virus infected persons in Italy. The Italian Drug-Resistant Tuberculosis Study Group. To describe the prevalence and epidemiological-clinical characteristics of tuberculosis (TB) resistance to first-line drugs in Italian human immunodeficiency virus (HIV)-infected subjects. Prospective, observational multicenter (25 Centers of Infectious Diseases) study. Mycobacterium tuberculosis strains from 167 HIV co-infected subjects with TB (149 new cases, 18 relapses) were tested at a central laboratory for susceptibility to rifampin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E) and streptomycin (S) and for DNA fingerprint type. Drug susceptibility results were related to patients' epidemiological, clinical and laboratory features. Drug resistance patterns among new TB cases were as follows: R = 1%, Z = 6%, S = 8%, H + S = 3%, S + Z = 4%. TB resistant to at least R + H (MDR-TB) was detected in 36% of new cases due to an MDR-TB outbreak which was the largest thus far in Europe, involving 7/25 participating institutions, and was demonstrated by conventional and molecular epidemiology evidence. With multivariate analysis, MDR-TB was associated with hospital exposure to MDR-TB (OR = 39.3, P < 0.001) and previous use of anti-TB drugs (OR = 9.8, P = 0.008). As drug-resistant tuberculosis in Italy is thus far relatively scarce, detection of a large MDR-TB epidemic among HIV-infected subjects was alarming. Aggressive control measures are urgently needed to prevent the spread of MDR-TB throughout the country and among the general population.

Antagonistic intestinal microflora produces antimicrobial substance inhibitory to Pseudomonas species and other spoilage organisms. Chicken intestine harbors a vast number of bacterial strains. In the present study, antimicrobial substance produced by lactic acid bacteria (LAB) isolated from the gastrointestinal tract of healthy chicken was detected, characterized, and purified. Based on 16S rRNA sequencing, the bacteria were identified as Lactobacillus plantarum vN. The antimicrobial substance produced by this bacterium was designated vN-1 and exhibited a broad-spectrum of activity against many important pathogenic and spoilage microorganisms, including Pseudomonas aeruginosa, Staphylococcus aureus, Micrococcus luteus, Salmonella Typhimurium, and Erwinia amylovova. vN-1 was determined to be thermostable, insensitive to pH values ranging from 2.0 to 8.0, resistant to various organic solvents and to enzymatic inactivation. The inhibition kinetics displayed a bactericidal mode of action. This study revealed an antimicrobial substance with low molecular mass of less than 1 kDa as determined by ultrafiltration and having features not previously reported for LAB isolated from chicken intestines. The detection of this antimicrobial substance addresses an important aspect of biotechnological control agents of spoilage caused by Pseudomonas spp. and promises the possibility for preservation of refrigerated poultry meat. Practical Application: The newly characterized antimicrobial substance and designated as vN-1 may have the potential to be used in food preservation.

The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. Resistance to zidovudine (3'-azido-3'-deoxythymidine, AZT) by the human immunodeficiency virus, type 1, requires multiple amino acid substitutions such as D67N/K70R/T215F/K219Q in the viral reverse transcriptase (RT). In this background of AZT resistance, additional "suppressive" substitutions such as Y181C restore sensitivity to AZT. In order to characterize the mechanism of this AZT resistance suppression, the Y181C substitution was introduced into both wild-type and AZT-resistant reverse transcriptase. The introduction of the Y181C substitution suppresses the increased repair (or unblocking) of the AZTMP-terminated primer provided by the AZT resistance substitutions in RT using either DNA or RNA templates, independently from the RT RNase H activity. Contrary to wild-type RT, the low level of unblocking activity is not due to inhibition by the next correct nucleotide binding to the RT/AZTMP-terminated primer complex. When Y181C is added to the AZT resistance substitutions, ATP binds with less affinity to the AZTMP-terminated primer-RT binary complex. These results provide an insight into one possible molecular mechanism of re-sensitization of AZT-resistant viruses by suppressive substitutions.

Successful use of somatostatin in a case of neonatal chylothorax. A 2-week-old infant status postrepair of gastroschisis had spontaneous bilateral chylothoraces necessitating thoracostomy drainage. Voluminous chylous drainage persisted despite cessation of enteral feedings. On administration of the somatostatin analogue octreotide, pleural drainage diminished markedly and ceased entirely within 4 days. These results, along with reported successes in treatment of chylothorax after thoracic surgery, support the prospective investigation of somatostatin use in problematic chylothorax.

Application of polymerase chain reaction fingerprinting to differentiate Ornithobacterium rhinotracheale isolates. Ornithobacterium rhinotracheale (ORT) is an infectious respiratory pathogen of chickens, turkeys, and wild birds. There are 18 serotypes of ORT reported worldwide. In this study, enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction and random amplified polymorphic DNA assay with Universal M13 primer-based fingerprinting techniques were investigated for their ability to differentiate ORT isolates. The authors examined 50 field isolates and 8 reference strains of ORT for their genetic differences. The fingerprint patterns were compared with serotyping results of ORT by the agar gel precipitation test. M13 fingerprinting revealed different patterns for 6 reference serotypes of ORT that were tested, namely, C, D, E, I, J, and K. Ornithobacterium rhinotracheale reference serotypes A and F yielded indistinguishable fingerprints with M13 fingerprinting. The ERIC 1R technique discerned only 5 of the 8 reference serotypes of ORT. Distinct fingerprints were also found within the ORT serotypes with both techniques. From 58 isolates of ORT that were fingerprinted belonging to 8 ORT serotypes, 10 different fingerprints were obtained with M13 fingerprinting and 6 different fingerprints were obtained with ERIC 1R fingerprinting. M13 fingerprinting technique was found to be more discriminative in differentiating ORT isolates than the ERIC 1R fingerprinting technique. These results suggest that fingerprinting techniques may be a more discerning tool for characterizing ORT isolates than the serological test using the agar gel precipitation test. This fingerprinting technique could potentially be a valuable tool in identifying an isolate from a clinical outbreak of ORT infection for development of an autogenous vaccine.

[Histological and molecular-biological markers of malignancy in different variants of thyroid papillary carcinoma]. Material for this study from 61 patients (thyroid papillary carcinoma) is shown to represent a heterogenic group of tumors differing from each other morphologically, molecular-biologically and histogenetically. The most malignant were long-cell and B-cell variants and the least malignant--a follicular variant. 81% of the tumors had neuro-endocrine differentiation and their malignant potential was higher compared to tumors without this differentiation.

The lack of benefit of a combination of an angiotensin receptor blocker and calcium channel blocker on contrast-induced nephropathy in patients with chronic kidney disease. Contrast-induced nephropathy (CIN) is a relatively common and serious complication, which occurs after the administration of contrast materials to patients. Although the pathophysiology of CIN is not exactly understood, ischemia of the medulla, oxidative stress, and direct toxicity of the contrast material are some of the factors that are implicated for the pathogenesis of CIN. To date, the only therapy that reduces the risk of CIN is volume expansion. There are conflicting results about the roles of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) in studies on CIN. For this reason the aim of this study was to compare the efficiency of the prophylactic use of amlodipine/valsartan plus hydration versus hydration only for the prevention of CIN in patients undergoing coronary angiography (CAG). We prospectively enrolled 90 patients whose baseline serum creatinine levels were under 2.1 mg/dL and who were scheduled for CAG. Patients were divided into two groups. Group I (n = 45), consisted of patients who received amlodipine/valsartan plus hydration, group II (n = 45) consisted of patients who received only hydration. The patients in group I were given amlodipine/valsartan 5/160 mg once a day for a total of 3 days, starting one day before CAG and continuing on the day of and the day after the procedure. A 1 mL/kg/h sodium chloride infusion was administered for a total of 24 h, starting 12 h before the procedure and 12 h after, in all patients. The baseline serum creatinine (Scre) level was obtained before the procedure and repeated 48 h after. CIN was defined as an increase of ≥0.5 mg/dL or an increase of >25% in baseline Scre on the second day after CAG. The baseline clinical characteristics of the treatment groups were similar. Baseline Scre was 1.13 ± 0.33 in group I and 1.07 ± 0.23 mg/dL in group II (p = 0.31). There was a significant difference between the Scre levels 48 h after CAG between the two groups (1.18 ± 0.33-1.05 ± 0.23) (p = 0.03). The reason for this was the increase of Scre in group I. CIN occurred in 17.8% (8/45) of patients in group I and in 6.7% (3/45) of patients in group II (p = 0.197). In the diabetic subgroup, CIN occurred in 10.5% (2/19) of patients taking amlodipine/valsartan and in none of the patients in group II (p = 0.486). The Mehran scores of the patients who developed CIN were significantly higher than those patients who did not develop CIN. Amlodipine/valsartan therapy plus hydration did not reduce the risk of CIN in chronic kidney disease (CKD) Stage 2 patients who underwent elective CAG using a low-osmolar nonionic contrast medium. This is because there was a decrease in the glomerular filtration rate (GFR) using the Levey Modification of Diet in Renal Disease (MDRD) formula in the amlodipine/valsartan group and CIN occurred at a higher frequency in this group; ARBs and CCBs may be withheld before CAG in high-risk patients.

Prognostic Value of Pretreatment Lymphocyte-to-Monocyte Ratio in Non-Small Cell Lung Cancer: A Meta-Analysis. Past evidence has shown that lymphocyte-to-monocyte ratio (LMR) could be considered as a potential prognostic factor in non-small cell lung cancer (NSCLC). We conducted the current meta-analysis based on published studies to elucidate the prognostic value of pretreatment LMR on survival outcomes in NSCLC. Comprehensive searches of available electronic databases were implemented to identify potentially related studies that focused on the role of pretreatment LMR in predicting the prognosis of NSCLC patients. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association of pretreatment LMR with overall survival (OS) and progression-free survival (PFS). A total of 20 articles including 8,304 patients were analyzed. Compared with patients with higher LMR, patients with lower LMR had poorer OS (HR = 1.63, 95% CI: 1.44-1.85, p < 0.001) and PFS (HR = 1.49, 95% CI: 1.25-1.77, p < 0.001). The subgroup analysis outcomes were similar to the overall analysis. Pretreatment LMR may be a useful prognostic marker in patients with NSCLC. However, more well-designed studies are warranted to confirm our findings.

Single chamber microbial fuel cell with spiral anode for dairy wastewater treatment. This study reports on the fabrication of a novel annular single chamber microbial fuel cell (ASCMFC) with spiral anode. The stainless steel mesh anode with graphite coating was used as anode. Dairy wastewater, containing complex organic matter, was used as substrate. ASCMFC had been operated for 450 h and results indicated a high open circuit voltage (about 810 mV) compared with previously published results. The maximum power density of 20.2 W/m(3) obtained in this study is significantly greater than the power densities reported in previous studies. Besides, a maximum coulombic efficiency of 26.87% with 91% COD removal was achieved. Good bacterial adhesion on the spiral anode is clearly shown in SEM micrographs. High power density and a successful performance in wastewater treatment in ASCMFC suggest it as a promising alternative to conventional MFCs for power generation and wastewater treatment. ASCMFC performance as a power generator was characterized based on polarization behavior and cell potentials.

Studies on the analgesic and anti-inflammatory effects of Sideritis candicans Ait. var. eriocephala Webb aerial part. Different extracts and fractions from Sideritis candicans Ait. var. eriocephala Webb aerial part were investigated for their analgesic, anti-inflammatory and antimicrobial activities in mice. Results indicated that the extracts assayed showed anti-nociceptive activities because they were able to reduce the nociceptive response to chemical pain stimuli, such as in the acetic acid-induced writhing test. Moreover the extracts also possessed anti-inflammatory activity against carrageenan-induced paw oedema and TPA-induced ear oedema, being the chloroform fraction the most active. Further fractionation and analysis of this fraction revealed that the analgesic and anti-inflammatory activities found could be related in part to the presence of phytosterols, alpha and beta amyrin triterpenic derivatives and ent-kaurene type diterpenes in this species, since some of these compounds are endowed with these activities.

Cytostatic Agents in the Management of Malignant Gliomas. BACKGROUND: Cytotoxic therapy for malignant gliomas is limited by poor delivery and drug resistance, and local therapy is ineffective in managing migratory cells. However, recent developments in malignant glioma therapy involve trials of cytostatic rather than conventional cytotoxic agents. METHODS: The biology of the brain extracellular matrix, tumor invasion, and angiogenesis are reviewed, and the cytostatic agents that inhibit matrix metalloproteinases, angiogenesis, cell proliferation, and signal transduction are discussed, as well as studies of the angiogenic and migratory capacity of malignant brain tumors. RESULTS: Two specific and interrelated areas, anti-invasion (migration) and anti-angiogenesis, are potential areas to develop new treatment strategies. Tumor invasion and angiogenesis are important components of the spread and biologic effects of malignant gliomas. Several proteinase inhibitors are in clinical trial, as well as anti-angiogenic agents and signal transduction cascade inhibitors. CONCLUSIONS: Biologic control of brain tumor cell populations may offer a new management approach to add to currently available management options for malignant brain tumors.

Differential expression of genes encoding calmodulin-binding proteins in response to bacterial pathogens and inducers of defense responses. Calmodulin (CaM) plays an important role in sensing and transducing changes in cellular Ca2+ concentration in response to several biotic and abiotic stresses. Although CaM is implicated in plant-pathogen interactions, its molecular targets and their role in defense signaling pathway(s) are poorly understood. To elucidate the signaling pathways that link CaM to defense responses, we screened a cDNA library constructed from bean leaves undergoing a hypersensitive response (HR) with radiolabeled CaM isoforms. A total of 26 putative CBPs were identified. Sequencing of the cDNAs revealed that they represent 8 different genes. They are homologues of previously identified CaM-binding proteins (CBPs) in other systems. However, some CBPs are novel members of known CBP families. The proteins encoded by these clones bound CaM in a Ca2+-dependent manner. To determine if these CBPs are involved in plant defense responses, we analyzed their expression in bean leaves inoculated with compatible, incompatible and nonpathogenic bacterial strains. Expression of three CBPs including an isoform of cyclic nucleotide-gated channels (PvCNGC-A) and two hypothetical proteins (PvCBP60-C and PvCBP60-D) was induced whereas the expression of two other isoforms of CNGCs (PvCNGC-B and PvCNGC-C) was repressed in response to incompatible pathogens. The expression of the rest, a small auxin up RNA (PvSAUR1) and two hypothetical proteins (PvCBP60-A and PvCBP60-B), was not changed. The expression of most of the pathogen-regulated genes was also affected by salicylic acid, jasmonic acid, hydrogen peroxide and a fungal elicitor, which are known to induce defense responses. Our results strongly suggest that at least five bean CBPs are involved in plant defense responses.

Georges Guillain's neurologic exploration of America. This is a study of the status of American neurology at the beginning of the 20th century as perceived by European neurologist Georges Guillain. Guillain trained in Paris, the international "Mecca" of neurology at that time. Whereas many Americans traveled and studied in Europe, very few European neurologists made the reverse journey to the United States. In 1902 Georges Guillain, age 26, traveled to the United States with the specific aim of evaluating neurologic services in America. Recent access to Guillain's personal travel journal and an article in French that he wrote after his return to Europe provide first-hand documentation of American neurology at the turn of the century from a European perspective. Using introductory references from his teacher, Pierre Marie, Guillain visited New York, Chicago, Boston, Philadelphia, and Baltimore. He studied hospitals, outpatient departments, laboratories, and universities, comparing them with institutions in his native France and other European capitals. Guillain was particularly struck by the creative energy of American neurologists, the broad-ranging programs in research and patient care, and the strong financial support provided by local philanthropists, universities, and governments. Guillain clearly foresaw the rising international role of American neurology and the prominence it would gain by the end of his career in the 1950s.

Clinicopathological characterization of TSH-producing adenomas: special reference to TSH-immunoreactive but clinically non-functioning adenomas. Thyrotropin (thyroid-stimulating hormone (TSH))-producing pituitary adenomas have been known to be quite variable in clinical features covering from typical functioning TSH-producing adenomas (FTSHomas) associated with hyperthyroidism to clinically silent TSH cell adenomas (STAs) that are apparently unassociated with hyperthyroidism. It is important to distinguish STAs from other types of clinically non-functioning adenomas for adequate postoperative managements. However, because of rareness of TSH-producing adenomas, their histopathological features linking to the clinical manifestations have not been well characterized. Herein, we investigated clinical and histopathological findings to characterize 29 TSH-producing adenomas including 20 FTSHomas and nine STAs. Clinical symptoms of the patients with STAs included headache, visual defect, vertigo, and nausea. All STAs and 19 FTSHomas were macroadenoma. The average tumor size of STAs was significantly larger than that of FTSHomas (P < 0.05). The invasiveness was detected in 33% STAs and in 20% FTSHomas. Both STAs and FTSHomas showed a variety of morphological features and immunohistochemical profiles. Chromophobic polygonal or short-spindled tumor cells usually proliferated in a diffuse pattern, while they exhibited globoid or whorl-like appearance with intertwined cytoplasmic processes in both subgroups. Stromal fibrosis and calcification were often noted. Their nuclei were somehow pleomorphic. Ultrastructural features of all four STAs examined were similar to those of normal thyrotrophs. Thus, STAs and FTSHomas were indistinguishable by histology alone. Immunohistochemically, the number of TSH-positive cells in individual FTSHomas was highly various. Six tumors showed only a few TSH-positive cells (1-5%), and three were negative for TSH by conventional method without antigen retrieval. After proteinase K treatment, these tumors turned out TSH positive. As defined, STAs were TSH positive in more than 20% of tumor cells and three of them in more than 50%. Growth hormone- and/or prolactin-positive cells were detected in 55% STAs and 63% FTSHomas. Both pituitary-specific transcription factor 1 and GATA-binding protein 2 were expressed in all STAs and 20 FTSHomas. Membranous somatostatin receptor (SSTR)-2A immunoreactivity was found in 89% STAs and 94% FTSHomas, whereas SSTR5 was positive in 78% of both STAs and FTSHomas. MIB-1 labeling index was related to tumor invasiveness and tumor size (P < 0.05, P = 0.09, respectively). Thus, although both STAs and FTSHomas showed unique histopathological features distinct from other type adenomas, these two subgroups were indistinguishable by histopathology. Immunohistochemistry for TSH by use of antigen retrieval, transcription factors, and SSTRs may be useful to confirm STAs and to determine the postoperative therapy among various kinds of clinically non-functioning adenomas.

Neopterin and kynurenine-tryptophan ratio as predictors of coronary events in older adults, the Hordaland Health Study. Immune system activation is involved in atherosclerosis. Neopterin production and tryptophan catabolism through the kynurenine pathway, measured by the kynurenine-tryptophan ratio (KTR), are induced by interferon gamma, thus both are considered markers of cell mediated immune activation. This study prospectively investigated their predictive value on acute coronary events among Norwegian community-dwelling older adults without previous coronary heart disease. 1112 men and 1631 women, 71-74 years old were examined during 1997-99 as part of the Hordaland Health Study. They were followed until an acute coronary event (defined as unstable angina, non-fatal or fatal acute myocardial infarction or sudden death) or December 31, 2006. Kaplan-Meier hazard curves were constructed for quartiles of plasma neopterin and KTR. Cox proportional hazards models adjusted for sex, body mass index, smoking, hypertension, renal function and cholesterol were used to examine the relation between neopterin and KTR quartiles and the study endpoint. Median (interquartile range) values were 8.6 (7.2-10.4) nmol/L for neopterin and 25.8 (25.3-31.1) nmol/μmol for KTR. During the follow up, 265 participants had at least one acute coronary event. Increased baseline levels of plasma neopterin and KTR were associated with continuous increased risk of developing the study endpoint (P-values for trend <0.001 and 0.019, respectively). Adjusted hazard ratios comparing the fourth quartile to the first were 1.65 (95% CI; 1.11-2.47; P=0.013) for neopterin and 1.57 (95% CI 1.03-2.39; P=0.036) for KTR. Plasma neopterin and KTR levels predict acute coronary events in older adults without previous coronary heart disease.

Open trials in cutaneous malignant melanoma. Surgery is still the primary treatment for cutaneous malignant melanoma. During the last 15 years randomized studies have given information on how to excise and we know now that thin melanomas (up to 2.0 mm in thickness) can be treated with 1-2 cm excision margins. Whether this is also true for thicker melanomas is not known and the only way to obtain more knowledge is to participate in prospective randomized studies. These have to be large due to the expected low difference in outcome or no difference in outcome between groups. The studies also involve adjuvant treatment of different types. No treatment in series, with large numbers and long follow-up, has shown improved overall survival compared with the control arm when different adjuvant therapies are given. Palliative treatment of disseminated melanoma has shown increasing response rates with combination chemotherapy and/or treatment with immune response modifiers but more data are needed. Clinicians with responsibility for patients with malignant melanoma and with an interest in improving outcome and quality of life should participate in ongoing clinical trials. Only with large prospective randomized trials of the design described in this article, will our knowledge increase for the benefit of our patients.

Tissue regeneration in bone defects adjacent to endosseous implants: an experimental pilot study. Extraction socket defects or alveolar ridge defects may limit or restrict placement of implants. The present study assessed the efficacy of inducing bone formation with demineralized freeze-dried bone (DFDB), osteoinduction with hydroxyapatite (HA), and guided bone regeneration with expanded polytetrafluoroethylene (e-PTFE) in bone defects adjacent to endosseous implants in an animal model. Twenty-four implants were placed in the long bones of 3 pigs. After preparation of 24 cylindric acute defects adjacent to the coronal 5 mm of each implant, 18 of the defects were treated by DFDB, HA, or e-PTFE. The 6 remaining defects healed spontaneously with no treatment (controls). In each pig, one tibia received 4 commercially pure titanium screw implants (3.75 mm x 15 mm), while the contralateral tibia received 4 HA-coated cylindric implants (3.25 mm x 15 mm). Bone formation in response to the 3 treatments and control cases was evaluated using computer-assisted densitometric image analysis. The results showed that a higher density of tissue formed under e-PTFE membranes. A significantly greater increase in bone density was noticed in bone defects treated with an e-PTFE membrane vs DFDB (P = 0.04), in e-PTFE vs control sites (P = 0.04), and in defects treated with HA vs DFDB (P = 0.04) in HA-coated implants. In titanium implants the differences observed were not significant. It was also observed that bone regeneration in defects treated with HA differs with the type of implant used (titanium vs HA-coated implants), but such differences were not significant.

When law is not law: setting aside legal provisions during declared emergencies. During an emergency, laws designed for normal operations and circumstances may sometimes hinder response efforts, potentially endangering the public's health rather than protecting it. Pursuant to declared states of emergency, however, officials may be authorized to waive or suspend some provisions of state law to address emergency conditions. Such authority can play a critical role in response efforts, but this authority varies significantly between states. States should carefully consider how their existing laws may affect response during a declared emergency and whether adoption of waiver authority would improve their legal structure. Where waiver provisions are in place, officials should ensure they understand its proper scope and utility.

High-throughput production of prokaryotic membrane proteins. Membrane proteins constitute ~30% of prokaryotic and eukaryotic genomes but comprise a small fraction of the entries in protein structural databases. A number of features of membrane proteins render them challenging targets for the structural biologist, among which the most important is the difficulty in obtaining sufficient quantities of purified protein. We are exploring procedures to express and purify large numbers of prokaryotic membrane proteins. A set of 280 membrane proteins from Escherichia coli and Thermotoga maritima, a thermophile, was cloned and tested for expression in Escherichia coli. Under a set of standard conditions, expression could be detected in the membrane fraction for approximately 30% of the cloned targets. About 22 of the highest expressing membrane proteins were purified, typically in just two chromatographic steps. There was a clear correlation between the number of predicted transmembrane domains in a given target and its propensity to express and purify. Accordingly, the vast majority of successfully expressed and purified proteins had six or fewer transmembrane domains. We did not observe any clear advantage to the use of thermophilic targets. Two of the purified membrane proteins formed crystals. By comparison with protein production efforts for soluble proteins, where approximately 70% of cloned targets express and approximately 25% can be readily purified for structural studies [Christendat et al. (2000) Nat. Struct. Biol., 7, 903], our results demonstrate that a similar approach will succeed for membrane proteins, albeit with an expected higher attrition rate.

Sonographically guided caudal epidural steroid injections. Caudal epidural steroid injections are used for the symptomatic treatment of radicular lumbosacral pain syndromes, but incorrect injection placement has been recognized as a common problem with the routinely used unguided technique. We aimed to explore the use of sonography to facilitate this procedure. In patients with clinically unreliable anatomic landmarks, high-resolution real-time sonography was used to identify those landmarks and to assist in correct needle placement. Sonography enabled localization of the sacral hiatus landmarks. We found this method particularly useful for guiding needle placement in patients with moderate obesity. Real-time sonography can facilitate caudal epidural steroid injections.

Training physicians to conduct physical activity counseling. In accordance with the U.S. Preventive Services Task Force recommendations, the current pilot study tests the feasibility and efficacy of a physician-delivered physical activity counseling intervention. A sequential comparison group design was used to examine change in self-reported physical activity between experimental (counseling and self-help materials) and control (usual care) patients at base-line and 6 weeks after the initial office visit. Patients in both groups were contacted by telephone 2 weeks after their office visit and asked about the physical activity counseling at their most recent physician visit. Experimental patients also received a follow-up appointment to discuss physical activity with their physician 4 weeks after their initial visit. Counseling was feasible for physicians to do and produced short-term increases in physical activity levels. Both groups increased their physical activity, but the increase in physical activity was greater for patients who reported receiving a greater number of counseling messages. Physician-delivered physical activity interventions may be an effective way to achieve wide-spread improvements in the physical activity of middle-aged and older adults.

[Complete thoracoscopic lobectomy with systematic nodal dissection via 5 ports for lung cancer]. We herein report a procedure for thoracoscopic lobectomy with mediastinal dissection for primary lung cancer using 5 access ports. A thoracoscope is inserted through an access port on the mid-axillary line in the 6th intercostal space. The availability of 4 instruments through 4 ports makes it easy to divide bronchus and pulmonary vessels and to dissect mediastinal lymph nodes. Between April 2005 and March 2007, 88 patients with clinical stage I/II primary lung cancer underwent this thoracoscopic procedure. Mean (+/- SD) operation time was 148 +/- 42 minutes and mean (+/- SD) blood loss was 166 +/- 148 ml. No local recurrence was found in patients with pathologic stage I/II diseases, whereas ipsilateral mediastinal lymphadenopathy occurred in 2 with pathologic stage III A disease during the mean post-opetrative period of 518 +/- 200 days. The thoracoscopic surgery for lung cancer presented here was seen to be a feasible procedure and has the advantage of reducing operative time.

Elevated expression of human papillomavirus antigen in brain tissue of patients with Rasmussen's encephalitis. To investigate the expression of human papillomavirus (HPV)-specific antigen in the brain tissue of patients with Rasmussen's Encephalitis (RE) and its possible link to the clinical manifestation of RE. The correlation between RE and HPV antigen expression in brain tissue sections was investigated using immunohistochemical (IHC) staining, pathological examination, MRI and clinical manifestations. HPV antigen expression was elevated in three out of four patients with RE, whereas there were no detectable HPV antigens in six control patients. Significant staining for HPV antigen was located mainly around or in the nucleus and cytoplasm of neurons. Among these RE patients, three with elevated expression of HPV antigens had obvious hemisphere atrophy, whereas the patient with negative staining for HPV antigens had mild atrophy. Elevated expression of HPV antigens was observed in the brain tissue of RE patients, which may correlate with hemisphere atrophy. Thus, our results may suggest that HPV infection or being a carrier of HPV may play a role in the initiation and progression of RE.

[Dysthymic disorder and depressive personality]. Depressive personality is a clinic category of Kurt Schneider psychopathic personalities. Despite definition of DSM III Axe II personality disorders criteria is Kurt Schneider' definition of psychopathic personalities, no depressive personality disorders is mentionned in Axe II. Axe I dysthymic disorder is a chronic state of depression with depressive traits. The hypothesis that some depressive personality disorders are included in this category cannot be rejected. More generally, DSM III classification regulation discriminate states, but, less operationally, traits which include affective variables with questionnable inter-rating reliability.

The macroglial cells of the leech are molecularly heterogeneous. Monoclonal antibodies derived from fusions employing either whole leech nerve cords or fractionated proteins (gel bands) bind to the macroglial cells of the nerve cord. Three different antibodies bind to either one, two, or three of the four macroglial cell types in the leech CNS, serving as markers and showing that these four cell types, which differ primarily by anatomical position, all differ molecularly as well. Conventional microscopy confirms the existence of a novel macroglial cell type first noted because it binds antibody. Western (immunoblot) blot analyses demonstrate a polypeptide antigen of 77 kD in the macroglial cells of the connectives and a 130-kD polypeptide antigen associated with the macroglial cells of the connectives, of the root nerves, and of the ganglionic neuropil. The extensive molecular heterogeneity of leech neurons demonstrated by monoclonal antibody techniques is shared by macroglia.

PET-measured responses of MBF to cold pressor testing correlate with indices of coronary vasomotion on quantitative coronary angiography. The aims of this study were to determine whether responses in myocardial blood flow (MBF) to the cold pressor testing (CPT) method noninvasively with PET correlate with an established and validated index of flow-dependent coronary vasomotion on quantitative angiography. Fifty-six patients (57 +/- 6 y; 16 with hypertension, 10 with hypercholesterolemia, 8 smokers, and 22 without coronary risk factors) with normal coronary angiograms were studied. Biplanar end-diastolic images of a selected proximal segment of the left anterior descending artery (LAD) (n = 27) or left circumflex artery (LCx) (n = 29) were evaluated with quantitative coronary angiography in order to determine the CPT-induced changes of epicardial luminal area (LA, mm(2)). Within 20 d of coronary angiography, MBF in the LAD, LCx, and right coronary artery territory was measured with (13)N-ammonia and PET at baseline and during CPT. CPT induced on both study days comparable percent changes in the rate x pressure product (%DeltaRPP, 37% +/- 13% and 40% +/- 17%; P = not significant [NS]). For the entire study group, the epicardial LA decreased from 5.07 +/- 1.02 to 4.88 +/- 1.04 mm(2) (DeltaLA, -0.20 +/- 0.89 mm(2)) or by -2.19% +/- 17%, while MBF in the corresponding epicardial vessel segment increased from 0.76 +/- 0.16 to 1.03 +/- 0.33 mL x min(-1) x g(-1) (DeltaMBF, 0.27 +/- 0.25 mL x min(-1) x g(-1)) or 36% +/- 31% (P <or= 0.0001). However, in normal controls without coronary risk factors (n = 22), the epicardial LA increased from 5.01 +/- 1.07 to 5.88 +/- 0.89 mm(2) (19.06% +/- 8.9%) and MBF increased from 0.77 +/- 0.16 to 1.34 +/- 0.34 mL x min(-1) x g(-1) (74.08% +/- 23.5%) during CPT, whereas patients with coronary risk factors (n = 34) revealed a decrease of epicardial LA from 5.13 +/- 1.48 to 4.24 +/- 1.12 mm(2) (-15.94% +/- 12.2%) and a diminished MBF increase (from 0.76 +/- 0.20 to 0.83 +/- 0.25 mL x min(-1) x g(-1) or 10.91% +/- 19.8%) as compared with controls (P < 0.0001, respectively), despite comparable changes in the RPP (P = NS). In addition, there was a significant correlation (r = 0.87; P <or= 0.0001) between CPT-related percent changes in LA on quantitative angiography and in MBF as measured with PET. The observed close correlation between an angiographically established parameter of flow-dependent and, most likely, endothelium-mediated coronary vasomotion and PET-measured MBF further supports the validity and value of MBF responses to CPT as a noninvasively available index of coronary circulatory function.

Generation of VNTRs and heteroplasmy by sequence turnover in the mitochondrial control region of two elephant seal species. We describe an unusual repetitive DNA region located in the 3' end of the light (L)-strand in the mitochondrial control region of two elephant seal species. The array of tandem repeats shows both VNTR (variable-number tandem repeat) and sequence variation and is absent from 12 compared mammalian species, except for the occurrence in the same location of a distinct repetitive region in rabbit mtDNA and a similar repeat in the harbor seal. The sequence composition and arrangement of the repeats differ considerably between the northern elephant seal (Mirounga angustirostris) and the southern species (M. leonina) despite an estimated divergence time of 1 MY (based on an mtDNA-RNA gene and the nonrepetitive control region). Analysis of repeat sequence relationships within and between species indicate that divergence in sequence and structure of repeats has involved both slippage-like and unequal crossingover processes of turnover, generating very high levels of divergence and heteroplasmy.

Non-invasive assessment of liver fibrosis in patients after the Fontan operation. This study analyzed the change in liver fibrosis markers after the Fontan operation and investigated their clinical usefulness as an index of congestive liver fibrosis. The study enrolled 24 patients who underwent the Fontan operation between January 1994 and December 2008. We subdivided the postoperative period into four intervals and then compared the hepatological markers during each. Eighteen patients underwent postoperative cardiac catheterization and the correlation between hepatological markers and the inferior vena cava (IVC) pressure was analyzed. The mean age of the patients was 138.6 months and the mean interval between the Fontan operation and the examination was 97.8 months. Type IV collagen was extremely high in every interval (I, 286 ± 93; II, 265 ± 93; III, 305 ± 143; IV, 206 ± 70), while none of the laboratory variables changed significantly in each interval. A significant positive correlation was observed between type IV collagen and the IVC pressure, but no significant correlation with any other hepatological marker was detected. No specific parameter that reflects the progress in liver fibrosis was identified in this study. The possibility exists that type IV collagen reflects the degree of hepatic congestion.

Engineerable generation of quadratic solitons in synthetic phase matching. We show that the efficiency and the mismatch bandwidth of quadratic soliton formation under conditions of second-harmonic generation can be enhanced in an important way in synthetic phase-matching profiles. Soliton excitation in smooth but arbitrary profiles is shown to be well described by a reduced variational approach. The potential of abrupt, nonadiabatic profiles for improved soliton formation is numerically revealed.

Radiographic workload and use factors for orthopedic facilities. Observations of technique factors at 9 radiographic installations dedicated to orthopedic radiography have been made. Monthly area radiation measurements with thermoluminescent dosimeters were made at three of these facilities. The results of these observations and measurements suggest that current NCRP recommended assumptions utilized in protective barrier computations result in considerably more shielding than is necessary. We observed an average workload of 224 mA min/wk and a maximum weekly average of 670 mA min/wk. The use factor for the chest wall averaged 5%. That for all other vertical barriers was less than 1%. The average operating potential was 75 kVp. Room radiation measurements confirm the suggestion that at least two of the walls and the control booth barrier in an orthopedic radiographic facility may be considered secondary barriers.

[A comparison of measurements made with Goldmann's application tonometer and Draeger's hand applanation tonometer (author's transl)]. The hand held applanationstonometer Draeger gives reliable measurements of intraocular pressure, they correspond of those from Goldmann applanationstonometer. The eventual value deviations of i. o. pressure at the beginning of the tests are not caused by the instrument but mainly by the effect of repeated applanation tonometry.

Carbon use efficiencies and allocation strategies in Prochlorococcus marinus strain PCC 9511 during nitrogen-limited growth. We studied cell properties including carbon allocation dynamics in the globally abundant and important cyanobacterium Prochlorococcus marinus strain PCC 9511 grown at three different growth rates in nitrogen-limited continuous cultures. With increasing nitrogen limitation, cellular divinyl chlorophyll a and the functional absorption cross section of Photosystem II decreased, although maximal photosynthetic efficiency of PSII remained unaltered across all N-limited growth rates. Chl-specific gross and net carbon primary production were also invariant with nutrient-limited growth rate, but only 20% of Chl-specific gross carbon primary production was retained in the biomass across all growth rates. In nitrogen-replete cells, 60% of the assimilated carbon was incorporated into the protein pool while only 30% was incorporated into carbohydrates. As N limitation increased, new carbon became evenly distributed between these two pools. While many of these physiological traits are similar to those measured in other algae, there are also distinct differences, particularly the lower overall efficiency of carbon utilization. The latter provides new information needed for understanding and estimating primary production, particularly in the nutrient-limited tropical oceans where P. marinus dominates phytoplankton community composition.

Population surveys compared with wastewater analysis for monitoring illicit drug consumption in Italy in 2010-2014. Monitoring consumption by population surveys (PS) is an important way to challenge the spread of illicit drugs (ID). To improve the information, we explored a complementary method, particularly wastewater analysis (WWA). We estimated the prevalence of use by PS, and the consumption by WWA, of cocaine, opioids, cannabis, methamphetamine and MDMA (ecstasy) from 2010 to 2014 in Italy and compared the results. According to PS, cannabis and cocaine were the ID most used in Italy (last month prevalence 3.0% and 0.43% respectively in 2010) followed by opioids (0.17%) and amphetamines (0.14%). WWA gave similar findings, with cannabis consumption (4.35 g THC/day/1000 inhabitants) exceeding cocaine (0.78 g), heroin (0.092 g), methamphetamine and MDMA (0.103 g). The time trend investigated by PS showed significant decreases for all ID from 2010 to 2012. WWA also indicated a reduction of consumption for methamphetamine (p<0.0001) and heroin (p<0.01). Both methods showed an increase for cannabis in 2014 (p<0.001) with the other ID unchanged. Spatial investigations by WWA showed that cannabis and cocaine were consumed significantly more in central Italy than in the north and south. PS indicated the same but only for cannabis. WWA was helpful to study weekly patterns of consumption, showing increases in cocaine and MDMA at weekends. PS and WWA were confirmed as complementary methods and when used together improved the information on ID use in Italy. We suggest that the combined use of the two approaches can give better information on ID use in the population.

Sex pheromone of the pink bollworm moth: biological masking by its geometrical isomer. A mixture of the cis and trans forms of propylure (10-propyl-trans-5,9-tridecadienyl acetate), the sex pheromone of the female pink bollworm moth, has been separated into its pure isomers by thin-layer chromatography. The cis isomer inhibits or masks the activity of the trans isomer, as little as 15 percent of the cis isomer being sufficient to completely nullify the activity of the trans isomer.

Strategies to prevent death by suicide: meta-analysis of randomised controlled trials. BackgroundFew randomised controlled trials (RCTs) have shown decreases in suicide.AimsTo identify interventions for preventing suicide.MethodWe searched EMBASE and Medline from inception until 31 December 2015. We included RCTs comparing prevention strategies with control. We pooled odds ratios (ORs) for suicide using the Peto method.ResultsAmong 8647 citations, 72 RCTs and 6 pooled analyses met inclusion criteria. Three RCTs (n = 2028) found that the World Health Organization (WHO) brief intervention and contact (BIC) was associated with significantly lower odds of suicide (OR = 0.20, 95% CI 0.09-0.42). Six RCTs (n = 1040) of cognitive-behavioural therapy (CBT) for suicide prevention and six RCTs of lithium (n = 619) yielded non-significant findings (OR = 0.34, 95% CI 0.12-1.03 and OR = 0.23, 95% CI 0.05-1.02, respectively).ConclusionsThe WHO BIC is a promising suicide prevention strategy. No other intervention showed a statistically significant effect in reducing suicide.

[Submucosal symptomatic leiomyoma treated with transcatheter uterine artery embolisation--case report]. The paper describes case of a patient (43 year old) suffering from submucosal symptomatic leiomyoma. She was treated with transcatheter uterine artery embolization. After a 3 month follow-up the patient was asymptomatic and a great reduction of leiomyoma was seen in MR.

Potent antagonism of Escherichia coli, Bacteroides ovatus, Fusobacterium varium, and Enterococcus faecalis, alone or in combination, for enteropathogens in anaerobic continuous flow cultures. Interactions between representative strains of four predominant resident bacteria of the human colon, Escherichia coli, Enterococcus faecalis, Bacteroides ovatus, and Fusobacterium varium, and strains of seven enteropathogens, Yersinia enterocolitica, Shigella flexneri, Salmonella typhimurium, Vibrio parahaemolyticus, V. cholerae serogroup non O1, Staphylococcus aureus, and Clostridium perfringens, were examined in studies with an anaerobic continuous flow culture system and medium resembling the content of the mouse caecum (MCM). Potent unilateral antagonism attributable to synergic activities of the resident bacteria against the enteropathogens was evident. The four resident bacteria persisted at levels of c. 10(6) cfu/ml or more in single and in any mixed cultures of the resident species. The seven enteropathogens also persisted in single cultures. In contrast, Y. enterocolitica was excluded in several days in mixed cultures with each of the four resident bacteria. Sh. Flexneri and Staph. aureus were excluded in the presence of E. coli alone. C. perfringens, V. parahaemolyticus and V. cholerae serogroup non O1 were excluded in the presence of E. coli with B. ovatus and, in some cases, with additional species. S. typhimurium was the most resistant; only c. 10(2)-fold reduction of the population level was observed in mixed culture with all four of the resident species. When the amounts of some components in the medium, such as peptone and yeast extract, were increased, C. perfringens grew and persisted even in the presence of the four resident bacteria. Sh. flexneri, in contrast decreased steadily, even in enriched media.

[Significance of endogenous glutathione in realizing the oxygen effect in bone marrow cells]. It has been established using hemopoietic bone marrow cells or EHrlich ascites carcinoma cells that endogenous glutathione affects the realization of only those lesions which appear in response to an increase in radioresistance, for example during anoxia. The involvement of glutathione in the realization of the oxygen effect is not limited to the time of irradiation. The effect of glutathione extends to the postirradiation period i. e., it is not determined only by the competition with oxygen for target radicals.

Mossy fiber synaptic reorganization in the epileptic human temporal lobe. The distribution of the mossy fiber synaptic terminals was examined using the Timm histochemical method in surgically excised hippocampus and dentate gyrus from patients who underwent lobectomy of the anterior part of the temporal lobe for refractory partial complex epilepsy. The dentate gyrus of epileptic patients demonstrated intense Timm granules and abundant mossy fiber synaptic terminals in the supragranular region and the inner molecular layer. In contrast, the dentate gyrus of presenescent nonepileptic primates demonstrated no Timm granules in the supragranular region. In nonepileptic senescent primates, occasional very sparse supragranular Timm granules were results are morphological evidence of mossy fiber synaptic reorganization in the temporal lobe of epileptic humans, and suggest the intriguing possibility that mossy fiber sprouting and synaptic reorganization induced by repeated partial complex seizures may play a role in human epilepsy.

Mechanisms of cavitation and the formation of stable bubbles on the Björk-Shiley Monostrut prosthetic heart valve. Transcranial Doppler studies performed on patients with the Björk-Shiley Monostrut mechanical heart valve have detected signals typical of gaseous emboli. In this study, a high-speed digital imaging system was used to examine the closure event of the Björk-Shiley Monostrut valve in vitro. Observations support the hypothesis that cavitation occurs before the formation of stable gas bubbles. Bubble cavitation occurs at the instant of valve closure and lasts on the order of 0.3 ms. The rebounding motion of the occluder initiates the development of a vortex which induces vortex cavitation. Vortex cavitation begins approximately 0.5 ms after impact of the occluder and the valve housing (approximately 0.2 ms after bubble cavitation has subsided), and lasts for approximately 1 ms. The formation of stable bubbles occurs later, along the center of the vortex that persists throughout much of the first rebound. It is hypothesized that the low-pressure region at the center of the vortex contributes to the formation of stable bubbles by collecting expanded nuclei that arise from both bubble and vortex cavitation, and providing a low-pressure environment in which the nuclei combine and continue to grow.

Characterization and mechanisms of action of novel NaV1.5 channel mutations associated with Brugada syndrome. Brugada syndrome is a heterogeneous heart rhythm disorder characterized by an atypical right bundle block pattern with ST-segment elevation and T-wave inversion in the right precordial leads. Loss-of-function mutations in SCN5A encoding the cardiac sodium channel Na(V)1.5 are associated with Brugada syndrome. We found novel mutations in SCN5A in 2 different families diagnosed with Brugada syndrome and investigated how those affected Na(V)1.5 channel function. We performed genetic testing of the probands' genomic DNA. After site-directed mutagenesis and transfection, whole-cell currents were recorded for Na(V)1.5 wild type and mutants heterologously expressed in Chinese hamster ovary-K1 cells. Proband 1 had two novel Na(V)1.5 mutations: Na(V)1.5-R811H and Na(V)1.5-R620H. The Na(V)1.5-R811H mutation showed a significant loss of function in peak Na(+) current density and alteration of biophysical kinetic parameters (inactivation and recovery from inactivation), whereas Na(V)1.5-R620H had no significant effect on the current. Proband 2 had a novel Na(V)1.5-S1218I mutation. Na(V)1.5-S1218I had complete loss of function, and 1:1 expression of Na(V)1.5-wild type and Na(V)1.5-S1218I mimicking the heterozygous state revealed a 50% reduction in current compared with wild type, suggesting a functional haploinsufficiency in the patient. Na(V)1.5-S1218I and R811H are novel loss-of-function mutations in the SCN5A gene causing Brugada syndrome.

Energetics and Control of Ultracold Isotope-Exchange Reactions between Heteronuclear Dimers in External Fields. We show that isotope-exchange reactions between ground-state alkali-metal, alkaline-earth-metal, and lanthanide heteronuclear dimers consisting of two isotopes of the same atom are exothermic with an energy change in the range of 1-8000 MHz, thus resulting in cold or ultracold products. For these chemical reactions, there are only one rovibrational and at most several hyperfine possible product states. The number and energetics of open and closed reactive channels can be controlled by the laser and magnetic fields. We suggest a laser-induced isotope- and state-selective Stark shift control to tune the exothermic isotope-exchange reactions to become endothermic, thus providing the ground for testing models of the chemical reactivity. The present proposal opens the way for studying the state-to-state dynamics of ultracold chemical reactions beyond the universal limit with a meaningful control over the quantum states of both reactants and products.

[The role of cerebral arteriosclerosis in the etiology of trigeminal neuralgia]. Out of 125 observations, trigeminal++ neuralgia in 43 patients ran its course in association with cerebral atherosclerosis. The rheoencephalographic investigations made in O-M leads and the data of rheofaciograms with the use of the nitroglycerin test confirmed that.