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Treatment of cryptorchidism with a potent analog of gonadotropin-releasing hormone. Pernasal therapy of cryptorchidism with D-Leu6-des-Gly10-gonadotropin-releasing hormone ethylamide (D-Leu6-des-Gly10-GnRH-EA), a potent, long-acting GnRH analog, was attempted. Eleven prepubertal cryptorchid boys received between 25 microgram once daily and 25 to 50 microgram twice daily for 5 to 12 weeks. Complete testicular descent was achieved in 4 of the 11 boys. GnRH tests (1.5 microgram/kg intravenously), conducted in six boys before treatment, after 4 weeks of treatment, and in 2 boys 3 months after treatment, did not reveal changes in gonadotropin secretion indicative of precocious puberty or of decreased hypophyseal sensitivity to GnRH. Antibodies to the GnRH analog or to GnRH could not be detected.

Mast cell degranulation and elastolysis in the early stage of striae distensae. The lesions of nine patients with early striae distensae (SD) during puberty were examined by light and electron microscopy. Specific changes were seen in very early stage SD, and in clinically uninvolved skin 0.5 to 3 cm remote from the edge of the long axis of the SD lesions. Sequential changes of elastolysis accompanied by mast cell degranulation appeared first, followed by an influx of activated macrophages that enveloped fragmented elastic fibers. The relationships among elastic fibers, mast cells, and macrophages seen in the present work suggest their critical roles in the process of SD formation, especially in the early stage. Our results also indicate that the elastic fiber is the primary target of the pathological process, and the abnormalities extend as far as 3 cm beyond the lesion into normal skin.

Cytotoxicity of Mannich bases of alpha-arylidene-beta-ketoesters and related compounds against EMT6 mammary carcinoma cells. A number of Mannich bases 2 derived from alpha-arylidene-beta-ketoesters, some corresponding deaminated products 3, and a thiol adduct 5 were prepared. High resolution 1H NMR spectroscopy revealed that, in solution, most of the bases 2 existed principally in acyclic forms, but that all members of this series underwent some intramolecular cyclization. The compounds 2, 3 and 5 possessed activity against EMT6 mammary carcinoma cells. The Mannich bases 2a-e had the highest cytotoxicity. Topliss analysis of these compounds revealed an E4 parameter dependency, in which intramolecular cyclization was minimal. The Mannich base 2f--which existed principally in the cyclic forms 6 in deuterium oxide, the deamination products, and a thiol adduct had approximately one-sixth of the activity of 2a-e.

Differences in surface membrane ecto-ATPase and ecto-AMPase in normal and malignant cells. I. Decrease in ecto-ATPase in myeloid leukemic cells and the independent regulation of ecto-ATPase and ecto-AMPase. The hydrolysis of ATP and AMP by enzymes located on the external side of the plasma membrane (ecto-ATPase and ecto-AMPase) was studied in mouse myeloid leukemic cells, normal early myeloid cells, and normal mature granulocytes and macrophages. Nine clones of myeloid leukemic cells were used belonging to three groups that differ in their ability to be induced to differentiate by the differentiation-inducing protein MGI. These three groups consisted of MGI+D+ that can be induced to undergo complete differentiation, MGI+D- that can be induced to partially differentiate and MGI-D- with no induction of differentiation. The ecto-ATPase activity of normal early myeloid cells was similar to that of normal mature granulocytes and macrophages and higher than that of any of the leukemic cells. Among the leukemic cells, the MGI-D- cells had the highest level of ecto-ATPase activity. The behaviour of ecto-AMPase differed from that of ecto-ATPase. Some MGI-D- clones had a higher ecto-AMPase activity than normal cells and MGI+D- and MGI+D+ cells showed no detectable activity. Neither the ecto-ATP-ase nor ecto-AMPase activities changed after induction of differentiation in normal early myeloid or MGI+D+ leukemic cells. The results indicate that the myeloid leukemic cells had a decreased ability to hydrolyse external ATP, that there can be an independent regulation of ecto-ATPase and ecto-AMPase and that neither of these enzyme activities changed during differentiation.

Enhancing effect of partial cystectomy on rat urinary bladder carcinogenesis. The effects of 5% and 50% partial cystectomies on bladder tumorigenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) were investigated in Wistar rats by examining the histological findings and cell proliferative activity. The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in-vitro labeling technique. After eight weeks of treatment with drinking water containing 0.05% BBN, 5% or 50% partial cystectomy was performed at the end of week 16, and the resected bladder was sutured with dexon or silk. There was no difference in the incidence of papillary or nodular (PN) hyperplasia between the control and partial cystectomy groups. However, the incidence of cancer in the group given partial cystectomy was much higher than that in the control. All the cancers in the control group were grade-1 superficial tumors, whereas grade-2 or invasive tumor was observed in six of 40 animals in the partial cystectomy group. The 31.0% labeling index of cancer in the partial cystectomy group was greater than the 24.1% in the control group. There was also a significant difference in the number of BrdUrd-labeled cells in PN hyperplasia between the control and partial cystectomy groups. These findings indicate that partial cystectomy enhances BBN-initiated bladder carcinogenesis and the increase in DNA synthesis found in PN hyperplasia and cancer may be associated with the induction of bladder tumors.

Pathology manpower needs in the United States. By means of a set of questionnaires, the Joint ASCP/CAP Task Force on Manpower survey of fact and opinion regarding manpower problems and needs of pathology in the United States was completed. The response from pathologists approached 75%. From this survey, there appears to emerge an accurate picture of the number of pathologists in solo or group practice in the United States in terms of board certification and age group; so that over a five-year period, there will be a net addition of approximately 1,800 pathologists from 500--700 residents completing their training annually. This survey showed a demand of 22% of pathology practices seeking to fill funded positions with a projected need within the next five years of approximately 2,700 to meet primarily expanded patient loads. The number of pathologists in the graduate medical education "pipeline" revealed 2,153 residents with about 76% of the residency positions filled. A match of approximately 2,153 residents entering pathology practice against 2,160 vacancies anticipated in the next four years was identified. However, it is likely that there will continue to be a modest deficit of pathologists five years from now in view of the possibility that not all will enter practice. In conclusion, the demand for pathologists and supply from residency programs seem to match well in numbers so that supply and demand for pathology manpower are in approximate balance.

Effects of human antisperm antibodies on development of preimplantation embryos. The effects of antisperm antibodies (ASAs) present in sera of immunoinfertile patients and vasectomized men were investigated on preimplantation embryonic development in mice. Of the nine immunoinfertile sera tested, two were effective in inhibiting blastulation rates of in vitro cultured murine 2-cell embryos (p less than .05 to .002). Similarly, sera from two of the three vasectomized men were capable of affecting early embryonic development in mice (p less than .05 to .002). Specificities of the embryotoxic effects of ASAs were further confirmed by culturing embryos in the presence of affinity-purified monovalent Fab' antibodies isolated from these sera. Fab' antibodies from only one of the two immunoinfertile patients whose sera affected blastulation rates, and from one of the three vasectomized men were effective in influencing blastulation rates of in vitro cultured 2-cell murine embryos (p less than .05 to .001), mainly due to an arrest of development at 2 to 8-cell and morula stages. In the Western blot procedure, none of the immunoinfertile Fab' antibodies recognized any specific band on blots of extracts from murine ova or 2-cell embryos. However, all the immunoinfertile Fab', but not fertile control Fab', specifically recognized a protein band in the M(r) 25 +/- 2 kD region, on the Western blots of extract from murine blastocyst stage embryos. In addition, Fab' from one immunoinfertile serum, which inhibited embryonic development, reacted specifically with a protein band in the lower molecular range (approximate M(r) 12 kD) on Western blot involving exact from blastocysts. Fab' antibodies of sera from vasectomized men did not react with any specific protein band on blots of extracts from murine ova, 2-cell embryo, or blastocyst. These results suggest that ASAs from some immunoinfertile patients and vasectomized men, especially those reacting with 12-kD blastocyst protein, are capable of affecting preimplantation embryonic development in mice, and thus may contribute toward immunologically medicated infertility both at fertilization and postfertilization stages.

The influence of primary unilateral cleft lip repair on facila growth. The lip pressure exerted by the repaired cleft lip was studied in 35 rabbits during a 20-week period. Animals were divided into four groups. Two of them were controls, and in the other two, two different surgical procedures were used for the lip repair. The results of this study indicate that there was reduction in lip pressure resulting from the surgically induced cleft lip, alveolus, and palate. Substantial increases in lip pressure were shown in both groups in which lip repair was completed. The influence of primary unilateral cleft lip repair on the facial growth of rabbits in this study will be presented in Part II of this report.

[Chromatin staining with thallium in NK/Ly ascites tumors of various ages]. Staining of the chromatin in the NK/Ly ascitic tumour was studied by electron microscopy using Mentré's thallium method. Investigations were carried out on the 2., 7., 9., and 14th days after the transplantation of the tumour. It was established, that the chromatin of the nuclei of the proliferating--2 days old--tumour cells occurs in dispers form. Later the temp of the growth decreases and as the consequence of the aggregation of the chromatin electrodense areas are formed. Authors assume, that on the base of the morphological alterations transformation of diffuse chromatin into aggregated one depression of the gene-substance might lie.

New aspects of the tolerance of retinol in humans. A review is given of the evaluation of 517 cases of acute vitamin A intoxication and chronic hypervitaminosis A. Whereas acute vitamin A intoxication has lost numerical importance during the past 15 years, chronic hypervitaminosis-A, especially that caused by self-medication, has provoked world-wide discussion concerning the safety of retinol intake. Evaluation of the 132 cases of chronic hypervitaminosis-A showed that approximately one quarter cannot be considered as genuine cases, whereas the rest is divided almost equally between vitamin A prescription and self-medication. A significant positive correlation could be shown between the dose administered and the duration of treatment. Moreover, with comparable doses the symptoms of chronic hypervitaminosis-A appear significantly earlier (by a factor of 6) after emulsified or equivalent preparations than after oily emulsions because of their better absorbability. As soon as the liver vitamin A storage capacity is exhausted, hypervitaminosis-A symptoms appear and the liver vitamin A concentration is at least 10-fold the normal. The calculated vitamin A concentration in the liver of the individual cases of hypervitaminosis-A is highly correlated with the daily intake of vitamin A per kg of body-weight and its duration.

Effect of subinhibitory concentrations of clindamycin and trospectomycin on the adherence of Staphylococcus epidermidis in an in vitro model of vascular catheter colonization. Septicemia, often due to Staphylococcus epidermidis, is a life-threatening complication associated with indwelling vascular catheters. An important factor in the development of such infections is glycocalix, or slime. An in vitro model that mimics intravenous delivery systems in humans was developed. It consisted of a modified Robbins device containing slices of silicone catheters in the removable ports, through which S. epidermidis diluted in 5% dextrose-normal saline with 10% heat-inactivated normal human serum was run, with and without clindamycin and trospectomycin. S. epidermidis was recovered from all catheters in the absence of antibiotics; no growth was detected with antibiotics. Scanning electron microscopy demonstrated significant reduction in glycocalix and no visible organisms with all concentrations except 0.5 micrograms/ml trospectomycin and 1 microgram/ml clindamycin; for those, a moderate amount of glycocalix and a few bacteria were seen. Thus, subinhibitory levels of trospectomycin and clindamycin may have a role in the prevention of microbial adherence to vascular catheters.

Pulmonary pseudocysts in newborn infants with respiratory distress syndrome. Twelve neonates who developed intrathoracic cystlike structures ("pseudocysts") are described. All infants had clinical and radiographic respiratory distress syndrome and all were treated with assisted ventilation. Pulmonary interstitial emphysema preceded the development of the pseudocysts in all cases. The pseudocysts appeared between 0 and 6 days of life (average, 2.4 days), and radiographically documented disappearance occurred in 10 patients at 3--18 days old (average, 7.0 days). Two patients had persisting pseudocysts at 8 and 25 days of age, and no subsequent radiographs. In no case did these structures persist symptomatically or require surgical intervention such as has been described with patients in other series. In two cases, abrupt disappearance of the pseudocysts was accompanied by increased extraalveolar gas in other locations. Eight patients developed radiographic bronchopulmonary dysplasia, which was severe in two of the cases.

[Formation of superoxide radicals in membranes of subcellular organelles in regenerating liver]. A correlation between the changes in the rates of superoxide radical generation, upsilon, in microsomes, mitochondria, and nuclei and the Cu, Zn- and Mn-SOD activities in rat liver during the first 5 days after partial hepatectomy, has been studied. Level of upsilon in microsomal and mitochondrial membranes in the regeneration process was reduced. The Cu, Zn- and Mn-SOD activities changed in an extreme and antibate manner: the former was characterized by a minimum, whereas the latter-by a maximum with an extreme on the 3rd day after surgery. Analysis of the correlation between the values of upsilon in the nuclear membranes and cell cycle stages (on a literary basis) revealed that the upsilon was decreased 2 times on the stage of DNA synthesis. When mitosis was at maximum, upsilon showed a 4-5-fold increase in comparison with the control, the Cu, Zn-SOD activity being essentially unchanged. A role of SOD and O2-. in cell division is postulated. O2-. is assumed to play a role in gene expression, disassembly, and regeneration of the nuclear membrane; that of SOD is thought to consist in regulation of the proliferative activity.

Cloning and in vivo and in vitro regulation of cyclic AMP-dependent carbon starvation genes from Escherichia coli. The regulation of three Escherichia coli carbon starvation (cst) genes fused to lacZ was examined. Expression of these genes is induced by starvation for a carbon source. The role of carbon and cyclic AMP (cAMP) availability and of an altered-function crp mutation were investigated for their effect on cst expression in vivo. The experiments indicated that cAMP concentrations controlled the absolute expression of one cst fusion, but the other two cst fusions were dependent upon some component not present in exponentially growing cells under conditions of glucose excess, even when cAMP was added. To examine the regulation of these genes in further detail, the three cst::lacZ fusions were cloned on multicopy plasmids. All three cst::lacZ fusions retained their inducible regulatory phenotype in the multicopy state. Analysis of the expression of the cloned cst::lacZ fusions in an in vitro-coupled transcription-translation cell-free system demonstrated that the predominant promoter(s) present on each cloned DNA was dependent on sigma 70 for expression. In vitro cAMP titration curves indicated that this molecule was necessary and sufficient for the expression of one fusion but not sufficient for the second fusion, while the third fusion exhibited constitutive levels of expression in vitro. The results are discussed in the context of the E. coli carbon starvation response.

Endogenous opioids may be involved in idazoxan-induced food intake. In this study it has been shown that the unexpected increase in food consumption, produced by the alpha 2-adrenoceptor antagonist idazoxan (10 mg/kg, i.p.) in rats, was significantly attenuated by small doses of the opioid antagonist (-)-naloxone (0.1, 1 mg/kg, i.p.) and totally inhibited by a small dose of naltrexone (1 mg/kg, i.p.). On the other hand, idazoxan-induced feeding was not affected by (+)-naloxone (0.1, 1 mg/kg, i.p.), which is inactive at opioid receptors. In addition, idazoxan-induced food consumption was not blocked by the delta-opioid antagonist, naltrindole (0.1, 1 mg/kg, i.p.) nor by the mu/delta-antagonist, RX8008M (16-methyl cyprenorphine; 0.1, 1 mg/kg, i.p.), which clearly discriminates between mu/delta- and kappa-opioid receptor function in vivo. These findings suggest that idazoxan may lead to the release of endogenous opioid peptides, which subsequently stimulate feeding by activation of kappa-, as opposed to mu- or delta-opioid receptors. This response is unlikely to be due to alpha 2-adrenoceptor blockade, since other highly selective alpha 2-adrenoceptor antagonists do not increase food intake and, instead may reflect the high affinity of idazoxan for non-adrenoceptor idazoxan binding sites.

A study of some biological and socio-economic factors in low birth weight. Of 3841 children born alive in Malmö in Sweden in 1966, 188, 4.9% had a birth weight of larger than 2500 g. We studied these children with their families and a control in order to form an opinion on the role played by certain social and biological factors in the aetiology of LBW in a country with a relatively high average standard of living. Biological factors were analysed, such as the mother's age, parity, stature, and weight, as well as purely socio-economic factors such as the mother's civil staatus, the social group of the mother and father, income, mother's allowance in case of illness, social help or investigations regarding one or more members of the family, as well as the frequency of immigrants. The combined effect of various socio-economic factors was judged by help of a "social score". The results were analysed for 3 different groups of low birth weight, appropriate for gestational age, small for gestational age and multiple births. Judging from our investigation, biological factors probably play the greatest role in the question of LBW but these factors are difficult to distinguish from socio-economic factors which probably still play a certain role in the group preterm children, appropriate for gestational age.

B-scan ultrasonography in the diagnosis of atypical retinoblastomas. Contact B- scan ultrasonography (Bronson-Turner unit) was performed on fourteen patients with retinoblastoma. In ten cases, the patient presented with leukocoria, and ultrasonography was helpful in confirming the clinical diagnosis. In four atypical cases contact B-scan ultrasonography was instrumental in making the diagnosis. The ultrasonographic pattern for retinoblastoma is characteristic but not pathognomic. There is a solid intraocular echo corresponding to the tumor and within it are numerous dense focal echoes which persist at lower sensitivities, suggesting calcification. Calcification was demonstrated ultrasonographically and confirmed histologically in all four of these atypical cases, but routine skull x-rays failed to demonstrate calcium in three of the four children. Contact B- scan ultrasonography is a safe and simple procedure which may provide valuable diagnostic information in children with suspected retinoblastoma.

Acute effect of anterior temporal lobectomy on musical processing. Patients with intractable epilepsy treated by anterior temporal lobectomy (Right, RT, n = 12; Left, LT, n = 9) and healthy controls (n = 12) with no musical training were prospectively evaluated with a standardized battery, including the Musical Aptitude Profile and the Seashore Tonal Memory Test. Before surgery, patients performed below controls (P less than 0.001), but there were no differences between RT and LT patients. After resection (2 weeks), RT patients showed a differential decline on tasks measuring perception of meter (P = 0.005) and tempo (P = 0.008) but not tonal processes. LT, and controls studied at the same time interval, showed no decline. The results support the role of the right hemisphere in specific aspects of musical processing.

Epidemiology, prevention, and prognostic factors in lung cancer. Recent studies confirm that the only effective strategy for control of lung cancer is prevention, with abolition of smoking as the preliminary strategy. Lung cancer is beginning to decline in men, but is still rising in women, whose risk from cigarette smoking per amount smoked is now recognized to be similar to that of men. Passive smoke exposure increases risk in nonsmokers and probably smokers as well. Radon exposure increases risk but the effects in the general population are not quantified. Occupational factors continue to be evaluated while some dietary factors, especially from plant foods, are protective. There is probably a genetic contribution, but its nature is still under investigation. Prognostic factors are being evaluated with increased sophistication, with potential for contribution to stratification in clinical trials.

Alpha-fetoprotein levels in maternal plasma and amniotic fluid during prostaglandin-induced mid-trimester abortions: the relation to fetal distress and death. Alpha-fetoprotein (AFP) levels were measured in both plasma and amniotic fluid during 43 abortions induced with prostaglandin F2alpha (PGF2alpha) and their relationship to the induction-abortion interval and signs of fetal distress or intrauterine death examined. The mean plasma AFP levels showed a progressive rise after PGF2alpha administration but abnormally high levels were found infrequently until the time of delivery. Feto-maternal bleeding could explain the abnormally high plasma AFP levels which occurred early in a few cases. A shorter induction-abortion interval was found in patients with normal plasma AFP levels. Neither fetal distress nor intrauterine death were associated with abnormally high plasma AFP levels. No change in AFP levels in amniotic fluid was found.

Phenotypical and functional characterization of small intestinal TcR gamma delta + T cells in coeliac disease. Increased numbers of TcR gamma delta + T cells are present in the small intestinal epithelium of patients with coeliac disease (CoD). Their function, however, is unknown. In order to facilitate detailed functional studies, intestinal gamma delta T cells have been isolated from small intestinal biopsies of patients with CoD (n = 18) and controls (n = 14). As expected, increased numbers of V delta 1+ TcR gamma delta + T cells were detected in freshly isolated intraepithelial cell suspensions (IEL) from CoD patients. Also, in the in vitro expanded IEL T-cell populations from CoD patients the numbers of V delta 1+ TcR gamma delta + T cells were increased compared with similar cell cultures from control patients. From IEL cultures derived from six CoD patients, 107 T-cell clones were generated by limiting dilution and analysed. Sixty of these clones were either CD4 or CD8 positive TcR alpha beta + clones. The remaining 47 clones expressed the TcR gamma delta. Further phenotypical analysis of the gamma delta T-cell clones indicated that the TcR gamma delta + T-cell population in the small intestinal epithelium of CoD patients is heterogeneous: four TcR gamma delta phenotypes could be detected and, although the majority of the TcR gamma delta + T cells were CD4 CD8, gamma delta T-cell clones expressing either a CD8 alpha alpha homodimer, a CD8 alpha beta heterodimer or CD4 were also identified. In contrast to the TCR alpha beta + IEL, most TcR gamma delta + IEL were CD5 negative. Furthermore, biochemical analysis indicated that the increase in V delta 1+ gamma delta T cells in the small intestinal epithelium of CoD patients was not the result of a monoclonal expansion. The small intestinal epithelium-derived gamma delta T-cell clones were functional in vitro since the majority of these clones were able to lyse target cell lines such as K562. Molt4 and Daudi. These novel findings therefore indicate that the gamma delta T cells in the small intestine of CoD patients represent a heterogeneous population and that such cells are functional in vitro. The isolation and the in vitro propagation and cloning of these cells may open new avenues for the study of the putative immune mechanisms leading to coeliac disease.

Identification of two products of mitochondrial protein synthesis associated with mitochondrial adenosine triphosphatase from Neurospora crassa. Soluble mitochondrial ATPase (F1) isolated from Neurospora crassa is resolved by dodecylsulfate-gel electrophoresis into five polypeptide bands with apparent molecular weights of 59000, 55000, 36000, 15000 and 12000. At least nine further polypeptides remain associated with ATPase after disintegration of mitochondria with Triton X-100 as shown by the analysis of an immunoprecipitate obtained with antiserum to F1 ATPase. Two of the associated polypeptides with apparent molecular weights of 19000 and 11000 are translated on mitochondrial ribosomes, as demonstrated by incorporation in vivo of radioactive leucine in the presence of specific inhibitors of mitochondrial (chloramphenicol) and extramitochondrial (cycloheximide) protein synthesis. The appearance of mitochondrial translation products in the immunoprecipitated ATPase complex is inhibited by cycloheximide.. The same applies for some of the extramitochondrial translation products in the presence of chloramphenicol. This suggests that both types of polypeptides are necessary for the assembly of the ATPase complex

Cultured epidermal allografts as biological wound dressings. Recent advances in cell culture technology permit the generation of large stratified epithelial sheets appropriate for wound coverage. Autografts (sheets prepared from the patient's own skin) have proven life-saving in the treatment of large third-degree burns and have been successfully employed in the management of chronic ulcers. Allografts (sheets prepared from the skin of an unrelated donor) have also been used. In our experience, cultured allografts derived from neonatal foreskin provide a potent stimulus to healing in a variety of partial thickness wounds. Their application is a simple outpatient procedure which involves no discomfort for the patient. In contrast to autografting, no biopsy is necessary and use of cultured allogenic cells permits immediate grafts availability and possibility of stockpiling and preserving grafts for future use. Preparation of epithelial sheets suitable for grafting is also faster and easier with newborn than with adult donor cells. Newborn allografts have caused rapid healing of most previously refractory ulcers with long-term results comparable to those obtained with conventional split thickness grafting. We postulate that cultured allografts act by providing a temporary wound covering while releasing multiple cytokines that synergistically promote permanent reepitheliazation by previously quiescent host keratinocytes then stimulated to divide and migrate. Whether allografts are immunologically rejected in a clinically undetectable reaction or simply replaced stochastically by host keratinocytes is presently unknown.

Purification of human factor IX by chromatography of a coagulation factor concentrate. A purification procedure for, and some properties of, coagulation factor IX are described. The coagulation factor concentrate used for the treatment of hemophilia B patients was employed as the starting material. The isolation procedure consists of chromatography in DEAE-cellulose, two chromatographies in hydroxyapatite gel and two gel filtrations in Sephadex G-200. Only trace amounts of factors II, VII and X were present in the final preparation and the specific activity of factor IX was 159 corresponding 10,300 times purification from plasma. The molecular weight was estimated to be 76,000 in gel filtration and 86,000 in sodium dodecyl sulfate disc gel electrophoresis. Three activity peaks with pIs 4.15, 4.25 and 4.40 were obtained by isoelectric focusing.

Morphological changes in the rabbit ovary after active immunization to testosterone. The role of testosterone in follicular development was investigated by immunizing female rabbits (mean wt 1.4 kg) to testosterone-3-bovine serum albumin (T-3-BSA). Controls received BSA. Follicular diameters and histology, and ovarian and uterine weights were recorded at intervals up to 11 weeks. At 5 weeks T-3-BSA ovaries did not differ from controls in either histology or follicular diameter (number of follicles greater than or equal to 1.0 mm were 12.5 +/- 3.4 and 17.0 +/- 1.0 for BSA and T-3-BSA treated animals respectively). By 8 weeks T-3-BSA animals had multiple cystic and hemorrhagic follicles. T-3-BSA ovaries contained more follicles greater than or equal to 1.0 less than 1.5 mm (27.3 +/- 3.1 vs. 15.3 +/- 2.9, p less than 0.01) and greater than or equal 1.5 mm diameter (5.8 +/- 1.7 vs. 0.4 +/- 0.3, p less than 0.005). At 11 weeks T-3-BSA ovaries contained more follicles less than 1.5 mm in diameter (5.0 +/- 0.9 vs. 0.9 +/- 0.3, p less than 0.001). Increased vascularization, some thecal hypertrophy and marked interstitial cell hypertrophy were characteristic of the T-3-BSA ovaries at 8 and 11 weeks. These results suggest that testosterone has a role in the regulation of follicular development.

[Megacolon congenitum (Hirschsprung's disease) in adults]. Hirschsprung's disease is rare in adults and represents a unique problem in the diagnosis and therapy. The permanent symptoms of the disease are persistent chronic constipation and meteorism. The degree of constipation depends on the length and narrowing of the aganglionary segment, diet and compensatory capacities of the bowel. Already known characteristics of agangliosis (absence of ganglions cells in intramuscular and submucous plexus, changes in nerve fibers and increased cholinesterase activity of the parasympathetic nerve fibers) cause impairment in peristalsis of the aganglionary segment and insufficient relaxation of the internal anal sphincter. The result is a functional refractory constipation. The disease can be diagnosed on the basis of the history, RTG examination, electromanometry and histopathology. In the majority of cases RTG examination is very reliable if performed according to generally accepted criteria. It is important to reveal the narrowed aganglionary area by oblique and profile images during irrigoscopy and irrigography. The treatment is surgical. The preferred operations are those with a combined transabdominal-transanal approach. Such operations are the most successful in management of constipation and maintenance of contingency. The authors present three cases. Three patients were old between 21 and 23 years. Their stools ranged from 10 days to two months (a stool per 10 days to two months). The diagnosis was established for all three patients by RTG examinations and histopathological findings. All bore the operation very successfully. Three various operation techniques were used according to surgeon's choice.

Multiple forms of cytosol and membrane-bound protein kinase activity in human erythrocytes. Both cytosol and membranes of human erythrocytes display protein kinase activity towards exogenous protein substrates such as casein, phosvitin and histones. The histone kinase activity, unlike casein kinase, of both cytosol and membranes is increased by cyclic AMP. The protein kinase forms removed from the membranes with 0.7 M NaCl, phosphorylate only serine residues of both casein and histones through a mechanism cyclic AMP-independent. The protein kinase activity located in the cytosol (hemolysate) is due also to enzyme forms phosphorylating both serine and threonine residues of casein, in addition to forms phosphorylating only serine residues of casein and histones. Also the cytosol kinase forms, once partially purified by Sepharose 6B filtration, appear to be cyclic AMP-independent.

Physical characteristics of reticular content in the bovine and consequences on reticular outflow. Reticular content was sampled in cows before and 2 and 5 hours after they were fed various forages. Dry matter, particle size distribution, pH, osmotic pressure and viscosity of the liquid phase were measured. Consistency was also evaluated using purpose-built apparatus. The contents were fractionated by vertical distribution under gravity and by intermittent flow through an orifice into fractions containing different particle concentrations, to model reticular retention of large particles in rumen outflow. Retention occurs as a result of a combination of flotation carrying large particles back into the rumen, and filtration which prevents them leaving it. These processes are particularly effective after feeding, and with poor hay, and so help prolong fermentation time. The consistency of reticular content is relatively stable; it may be autoregulated by adjustment of feeding parameters in response to sensory receptor signals.

Twitch potentiation during fatiguing exercise in the elderly: the effects of training. Twitch potentiation was studied during a fatigue paradigm involving intermittent maximum voluntary contractions (MVCs) of the tibialis anterior muscle in the elderly and in young adults. Resting twitch torques were similar between groups, but twitch potentiation was significantly greater (241% vs 166%) in the young; the recovery of the twitch after fatigue was similar between groups. Contraction time, time to peak torque and half-relaxation time were all significantly slower in the elderly. Following 12 weeks of resistance training in the elderly, there was no significant change in the twitch contractile properties at rest, but there was a significant main effect of training on the degree of twitch potentiation during the same fatigue protocol (peak potentiation 192% post-training vs 165% pretraining). These data suggest that the mechanism(s) responsible for twitch potentiation following MVCs may be influenced by both aging and training.

An outbreak of organomercury poisoning among Iraqi farmers. An outbreak of organomercury poisoning due to the consumption of treated grain by farmers and their families occurred in Iraq in 1971-72. A total of 6530 cases were admitted to hospital and of these 459 died. However, there were many more with minor symptoms of poisoning who consulted outpatient departments. This outbreak constituted the largest poisoning epidemic ever recorded. No age was exempt and no pronounced sex difference was apparent. The latent period of up to 60 days between dosage and the onset of symptoms was probably the major factor contributing to the size of the epidemic. Measures taken to limit the outbreak are outlined.

[Dimethyl sulfoxide in the treatment of interstitial cystitis]. The paper presents the results obtained with endovesical dimethylsulphoxide in the treatment of interstitial cystitis in 30 women. Up to 80% patients showed clinical improvement with an average of 10 installations. Volume of maximal vesical capacity was increased in 24 patients (80%), the increase being greater than 100 cc in 10 cases. Presently, 24 (80%) patients remain under treatment, 14 with one instillation monthly and 10 once every six months. Six patients are fully asymptomatic without treatment after an average symptoms-free interval of 32 months. Since this is directly related to a decrease both in pain and miction frequency, the increase in vesical capacity appears to be a good improvement index. Dimethylsulphoxide in neither a healing nor a definite therapy but it seems to be effective in the management of this unknown disease.

The effect of various putative neurotransmitters on the release of corticotrophin releasing hormone from the hypothalamus of the rat in vitro. I. The effect of acetylcholine and noradrenaline. The effect of various putative neurotransmitters upon the release of corticotrophin releasing hormone (CRH) was investigated using the hypothalamus of the rat in vitro. Acetylcholine (1-5 pg) caused a dose-dependent release of CRH which was antagonized by hexamethonium (1-10ng) and partially antagonized by atropine (300 pg). Neither noradrenaline, dopamine nor histamine had any effect on the basal secretion of CRH. Noradrenaline (10 ng), however, was able to inhibit the release of CRH in response to acetylcholine (3 pg) and this action of noradrenaline was reduced by phentolamine (100 ng), an alpha adrenergic blocking agent.

Astrotactin provides a receptor system for CNS neuronal migration. CNS neuronal migration is a specialized form of cell motility that sets forth the laminar structure of cortical regions of brain. To define the neuronal receptor systems in glial-guided neuronal migration, an in vitro assay was developed for mouse cerebellar granule neurons, which provides simultaneous tracking of hundreds of migrating neurons. Three general classes of receptor systems were analyzed, the neuron-glial adhesion ligand astrotactin, the neural cell adhesion molecules of the IgG superfamily, N-CAM, L1 and TAG-1, and the beta 1 subunit of the integrin family. In the absence of immune activities, migrating cerebellar granule neurons had an average in vitro migration rate of 12 microns h-1, with individual neurons exhibiting migration rates over a range between 0 to 70 microns h-1. The addition of anti-astrotactin antibodies (or Fabs) significantly reduced the mean rate of neuronal migration by sixty-one percent, resulting in eighty percent of the neurons having migration rates below 8 microns h-1. By contrast, blocking antibodies (or Fabs) against L1, N-CAM, TAG-1 or beta 1 integrin, individually or in combination, did not reduce the rate of neuronal migration. By video-enhanced contrast differential interference contrast microscopy the effects of anti-astrotactin antibodies were seen to be rapid. Within fifteen minutes of antibody application, streaming of cytoplasmic organelles into the leading process arrested, the nucleus shifted from a caudal to a central position, and the extension of filopodia and lamellopodia along the leading process ceased. Correlated video and electron microscopy suggested that the mechanism of arrest by antiastrotactin antibodies involved the failure to form new adhesion sites along the leading process and the disorganization of cytoskeletal components. These results suggest astrotactin acts as a neuronal receptor for granule neuron migration along astroglial fibers.

Effects of antihypertensive agents on carotid pulse contour in humans. The aim of this study was to assess the influence of antihypertensive agents on arterial wave reflections (AWR) and carotid pulse pressure (PP) in humans. Twenty patients with hypertension (predominantly systolic) were studied. After one month of placebo therapy they were randomly assigned to atenolol (At) 50 mg/day or to nitrendipine (Ni) 40 mg/day. Carotid pressure waveform was recorded noninvasively by applanation tonometry using a Millar micromanometer-tipped probe. Arterial wave reflections were quantified as the ratio of the height of the late systolic peak (delta P) to the total height of carotid pulse pressure wave as an augmentation index (delta P/PP). Travel time of the reflected wave (delta tp) was timed from the foot of the pressure wave to the foot of the late systolic peak. Atenolol and Ni were equally effective in reducing sphygmomanometric brachial artery blood pressure (BP). Whereas At (p < 0.05) and Ni (p < 0.01) reduced the carotid PP, Ni (p < 0.01) but not At significantly reduced delta P/PP. Both agents increased the delta tp (p < 0.01) and decreased aortic PWV (p < 0.01). Nitrendipine was associated with a decrease in left ventricular ejection time (LVET) (p < 0.01), while At increased heart period (p < 0.01) and LVET. The LVET/delta tp ratio decreased after Ni (from 3.25 +/- 0.77 to 2.42 +/- 0.73; p < 0.01) but did not change after At. The study shows, that for the same effect on peripheral BP, Ni has a more pronounced effect on pressure wave in central arteries, resulting from an improvement in the timing between the ventricular ejection and AWRs.

Specific detection of Mycobacterium paratuberculosis by DNA hybridisation with a fragment of the insertion element IS900. This paper describes the evaluation of a newly developed DNA probe for Mycobacterium paratuberculosis. DNA probe PCR278 is a 278 bp fragment obtained by polymerase chain reaction (PCR) amplification of the 5'-region of IS900, an insertion element contained in the genome of M paratuberculosis. This DNA probe can specifically distinguish M paratuberculosis from a wide range of other organisms, including members of the M avium-M intracellulare complex. When used in conjunction with the PCR amplification technique DNA probe PCR278 could detect as little as 10 fg (equivalent to two genomes) starting material of M paratuberculosis genomic DNA. Use of PCR amplification assays based on IS900, for the detection of M paratuberculosis, and homologous IS elements found in disease isolates of M avium should greatly help our understanding of the role of these organisms in Crohn's disease and other chronic inflammatory disorders.

Antiproteolytic aldehydes and ketones: substituent and secondary deuterium isotope effects on equilibrium addition of water and other nucleophiles. Equilibrium constants for hydration of ketones, in dilute D2O solution at 34 degrees C, observed by proton magnetic resonance under conditions of slow exchange, were acetone 0.002, chloroacetone 0.08, 1,3-dichloroacetone 4.17, bromoacetone 0.07, and 1,3-dibromoacetone (an inhibitor of papain) 1.85. Neither acetamidoacetone nor N,N-diacetylaminoacetone showed evidence of appreciable hydration in dilute aqueous solution, nor was any hydrate detectable in solutions of tosylglycine chloromethyl ketone. Substitution of acetaldehyde with acylamido substituents, as in several potent reversible inhibitors of papain, was found to enhance its equilibrium constant for covalent hydration by an order of magnitude; these inhibitors are about 90% hydrated in dilute aqueous solution, and their affinity for proteases may have been underestimated accordingly. The effects of deuterium substitution at C-1 of acetaldehyde, on equilibrium addition of oxygen and sulfur nucleophiles, are substantial and vary with the nature of the nucleophile. These isotope effects may be useful as a mean of distinguishing between alternative structures of complexes formed between enzymes and aldehydes.

Unintended conception and unwanted fertility in Gondar, Ethiopia. This is a report on unintended conception and unwanted fertility in Gondar, Northwestern Ethiopia. The purpose of the study was to explore the extent of the problem and to inquire whether there is a need for fertility regulation. To this end, relatively numerous questions on reproductive history of women aged 15-49 have been raised. Results showed that the proportion of abortion to delivery was 0.3984 to 0.6016 and the ratio of unintended conception to intended conception was 0.4043 to 0.5957. The proportion of unwanted fertility to wanted was 0.4099 to 0.5901. Mean desired interpregnancy interval was substantially higher than actual interpregnancy interval. The relatively high rate of abortion, high proportion of unintended conception and unwanted fertility combined with the wide difference between desired interpregnancy interval and current interpregnancy interval all point to the need for a policy that increases the capacity to regulate fertility.

Absence of need for amniocentesis in patients with elevated levels of maternal serum alpha-fetoprotein and normal ultrasonographic examinations. Recent improvements in the accuracy of sonographic diagnosis of neural-tube and ventral-wall defects have raised a question about the wisdom of routinely offering amniocentesis to women who have elevated levels of maternal serum alpha-fetoprotein with a structurally normal fetus as determined by ultrasonography. We reviewed the ultrasound findings in 51 consecutive fetuses with spina bifida, encephalocele, gastroschisis, or omphalocele that were delivered or aborted at a single hospital, to estimate the sensitivity of ultrasonography for these diagnoses. In all cases, the mothers had undergone prenatal sonography at one facility between 16 and 24 weeks after the last menstrual period. We used these data to calculate the probability of an affected fetus in a women with a given level of maternal serum alpha-fetoprotein and a normal sonogram. These four types of anomalies were correctly identified in all 51 cases, yielding a sensitivity of 100 percent (95 percent confidence interval, 94 to 100 percent). Using the lower limit of this confidence interval, we calculated that the probability of an affected fetus ranges from 0.01 to 0.15 percent for maternal serum alpha-fetoprotein levels ranging from 2.0 to 3.5 times the median, respectively. This level of risk is less than the reported risk of abortion due to amniocentesis and may lead some women with elevated levels of alpha-fetoprotein to decide not to proceed with amniocentesis.

A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell cycle checkpoints can enhance cell survival and limit mutagenic events following DNA damage. Primary murine fibroblasts became deficient in a G1 checkpoint activated by ionizing radiation (IR) when both wild-type p53 alleles were disrupted. In addition, cells from patients with the radiosensitive, cancer-prone disease ataxia-telangiectasia (AT) lacked the IR-induced increase in p53 protein levels seen in normal cells. Finally, IR induction of the human GADD45 gene, an induction that is also defective in AT cells, was dependent on wild-type p53 function. Wild-type but not mutant p53 bound strongly to a conserved element in the GADD45 gene, and a p53-containing nuclear factor, which bound this element, was detected in extracts from irradiated cells. Thus, we identified three participants (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development.

Synthesis and evaluation of iodinated benzamide derivatives as selective and reversible monoamine oxidase B inhibitors. A new series of iodinated analogues of N-(2-aminoethyl)benzamide was synthesized and evaluated for inhibitory potency and specificity toward monoamine oxidase type-B (MAO-B). Among them, N-(2-aminoethyl)-2-chloro-4-iodobenzamide hydrochloride (2d) showed high inhibitory potency and selectivity against MAO-B. The type of MAO-B inhibition by 2d was non-competitive and the inhibition constant (Ki) was 0.80 microM. Strong and selective in vivo MAO-B inhibition by 2d was also confirmed. The brain MAO-B inhibition by 2d was reversible and the enzyme activity completely returned to the control value 24 h after administration. Compound 2d was, therefore, considered to be a candidate for advanced development as a radioiodinated ligand that may be useful for functional MAO-B studies in the living brain using single photon emission computer tomography.

[Changes in high amplification ECG during the 2 years following the acute phase of myocardial infarction]. Late potentials have been reported 1 to 15 days after the onset of myocardial infarction but the evolution during long-term follow-up is not so well known. In order to determine if the signal averaged electrocardiogram remained stable or if it was necessary to repeat the investigation during a period of 2 years, 90 patients underwent 2 recordings on average 3 weeks after the onset of the infarct and then 2 years later. After the first recording, 16 patients (18%) had late potentials. The second recording was performed under the same conditions by the same operator. Globally, the signal averaged electrocardiogram recorded by Simson's method remained remarkably stable (83/90). It was rare to observe late potentials occurring for the first time after the initial recording (4 cases, 5%) in this study. It was more common to observe their disappearance (3 cases, 19%). No explanation could be found except in one case. These possible long-term changes in the signal averaged electrocardiogram suggest that the investigation should only be repeated in patients with abnormalities on the initial recording. Some authors have reported a better prognosis in patients in whom late potentials disappeared but this was not verified in this study.

Tolerance of protein and lipid synthesis to mild hyperphenylalaninemia in developing rat brain. Chronic injection of low levels (1.5-2.5 mg/g body wt./day for 6-8 days) of L-phenylalanine which did not significantly affect body weight or brain to body weight ratios also did not significantly affect myelin accumulation or synthesis in developing rat brain. A single injection of L-phenylalanine (1 mg/g body wt.) significantly reduced in vivo protein synthesis by 10% in cerebral cortex of 7-day-old rats. Although transient reductions in protein synthesis are produced during low level daily injections, cumulative effects are not expressed in significant reductions in brain to body growth ratios. It is concluded that myelination is significantly inhibited in hyperphenylalaninemia only when other parameters of brain growth and development are affected.

[Echography of the operated breast]. Aim of the present study is to evaluate the results of quadrantectomy by means of mammography and sonography (US). A hundred and thirty-five quadrantectomized patients bearing a carcinoma were investigated; 97 of them are now undergoing TCT. Mammographic examinations were performed with last-generation units; US studies employed high-frequency probes greater than or equal to 7.5 MHz. Ten relapses (7.4%) were observed, all of them around the scar: clinical examination correctly detected 3 cases, mammography 8, and US 6; the latter technique identified in 1 further case a pathologic finding which had not been previously assessed as a neoplastic lesion. Our results suggest that clinical examination has poor diagnostic value, while mammography has high value (8/10 cases), especially in detecting neoplastic microcalcifications (3/10 cases). The structural opacity of the breast caused 2/10 mammographic false negatives; US correctly detected 6/10 relapses, but failed to identify 3 microcalcifications. The combined use of the two techniques allowed the respective mistakes to be amended. US has proven to be especially useful not only to integrate mammography in the diagnosis of tumor recurrences, but also to study postoperative fluid collections, which are usually missed by mammography.

The response of equine cortical bone to loading at strain rates experienced in vivo by the galloping horse. The behaviour of cortical bone under load is strain rate-dependent, i.e. it is dependent on the rate at which the load is applied. This is particularly relevant in the galloping horse since the strain rates experienced by the bone are far in excess of those recorded for any other species. In this study the effect of strain rates between 0.0001 and 1 sec-1 on the mechanical properties of equine cortical bone were assessed. Initially, increasing strain rates resulted in increased mechanical properties. Beyond a critical value, however, further increases in strain rate resulted in lower strain to failure and energy absorbing capacity. This critical rate occurred around 0.1 sec-1 which is within the in vivo range for a galloping racehorse. Analysis of the stress-strain curves revealed a transition in the type of deformation at this point from pseudo-ductile to brittle. Bones undergoing brittle deformation are more likely to fail under load, leading to catastrophic fracture and destruction of the animal.

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects. Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.

Suppression of c-myc and c-myb is tightly linked to terminal differentiation induced by IL6 or LIF and not growth inhibition in myeloid leukemia cells. Cell proliferation and differentiation are intimately related processes where the proto-oncogenes c-myc and c-myb have been implicated to play a role. Previously, we have shown that both c-myc and c-myb were induced in normal myeloid precursors when the cells were stimulated for growth, were expressed in the autonomously proliferating myeloid leukemic M1 cell line and were rapidly suppressed in both normal and M1 cells following induction of terminal differentiation associated with growth arrest. In order to distinguish molecular events associated with terminal differentiation versus those due to growth inhibition, as well as to increase our understanding of the role of the proto-oncogenes c-myc and c-myb in both of these cellular processes, in this work we have studied the expression of c-myc and c-myb in M1 cells induced for growth inhibition associated with terminal differentiation (via treatment with the physiological inducers IL6 or leukemia inhibitory factor mean value of LIF), partial differentiation (using IL1 or LPS) or no detectable differentiation properties (using IFN beta or IFN gamma). We show that, for all the treatments used in this study, down regulation of the proto-oncogenes c-myc and c-myb occurred only when M1 cells were stimulated to undergo terminal differentiation. In addition, we transfected the M1 cell line with a vector containing the c-myc gene under control of the beta-actin promoter, so that c-myc was no longer down regulated by IL6 or LIF. Previously, we have shown that in the presence of the myeloid differentiation inducers IL6 or LIF, these M1myc cells were blocked at an intermediate stage of myeloid differentiation and continued to proliferate. In sharp contrast to their altered response to IL6 or LIF, M1myc cells were as responsive as the parental M1 cells to growth suppression by the different antiproliferative compounds which do not induce terminal differentiation. Thus, continued expression of c-myc had no effect on growth suppression induced by IL1, IFN beta, IFN gamma and LPS. Taken together, these results indicate that c-myc and c-myb down regulation is not necessary for growth suppression, but down regulation of c-myc is, and c-myb may be, essential for terminal differentiation.

A simple purification method of Vibrio cholerae non-O1 hemagglutinin/protease by immunoaffinity column chromatography using a monoclonal antibody. A new simple purification method (I) for Vibrio cholerae non-O1 hemagglutinin/protease (NAG-HA/P) was developed. The method (I) requires only an immunoaffinity column chromatography using a monoclonal antibody against NAG-HA/P. The method (I) is much simpler than previously reported purification method (II) (Honda, T. et al, Infection and Immunity 57: 2799-2803, 1989) which required four or more complicated chromatographic procedures. Method (I) also gave an improved recovery rate (about 27%) compared with (II). The molecular weight of NAG-HA/P purified by method (I) was mainly 34 kilodaltons (kDa) with a little of 32 kDa, whereas that of NAG-HA/P purified by (II) was usually 32 kDa. Immunological analysis by the Ouchterlony double gel diffusion test and Western blotting test using polyclonal antibody against 32 kDa protein revealed that the 34 and 32 kDa proteins are immunologically indistinguishable and thus it is supposed that 34 K protein is an isoform or a preform of the 32 K protein.

Adenovirus 21 infection in an isolated antarctic station: transmission of the virus and susceptibility of the population. Natural dissemination of viral respiratory illness to susceptible men may occur with surprising difficulty. This was especially evident during a 1977 outbreak of adenovirus type 21 (Ad-21) at McMurdo Station, a US research base in Antarctica. The unique circumstances at McMurdo allowed 125 men from the US to join and intermingle with 75 men who had wintered for 6 months in complete isolation. For an additional 5-week (September 2 to October 4, 1977) isolation period, respiratory illness etiology and transmission were monitored in the combined population. A total of 89% of the population was susceptible (neutralizing antibody titer, less than 1:3) to Ad-21 but only 15.0% were infected. Illness spread very slowly (1.5 cases/100 persons/week) with no epidemic peak and was much less severe than Ad-21 outbreaks in other settings. The incidence of infection (17.3%) and illness (9.6%) was low even in men who had wintered over, with values very similar to those of the newcomers (13.9% and 8.9%, respectively). Thus, despite a harsh environment and frequent prolonged gatherings of susceptible personnel, even a respiratory virus type with known epidemic potential was surprisingly difficult to transmit.

The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. We have examined the distribution and time course of the microglial reaction in the rat dorsal hippocampus after 25-min transient forebrain ischemia (four-vessel occlusion model). Microglial cells were visualized in brain sections using lectin staining with the Griffonia simplicifolia B4-isolectin following intervals of reperfusion ranging from 20 min to 4 weeks. Increased staining of microglial cells was detected in the dentate hilus and area CA1 as early as 20 min after reperfusion. These same regions demonstrated more intense microglial staining after 24 h. The strongest microglial reaction was observed 4-6 days after reperfusion when reactive microglia were abundant throughout all laminae of CA1 and the dentate hilus. Following longer reperfusion intervals, the microglial reaction became less intense; however, it remained above normal levels until the end of the fourth week. At all time points examined, microglial reactivity in the CA3 pyramidal and dentate granule cell layers was considerably lower than that observed in CA1 and dentate hilus. Our results are consistent with the known serial pathological changes associated with cerebral ischemia, but, in addition, show that the examination of the microglial reaction provides an extremely sensitive indicator of subtle and morphologically nonapparent neuronal damage during the early stages of injury.

Early postnatal hyperthyroidism alters hippocampal circuitry and improves radial-maze learning in adult mice. Inbred mice show strain-specific differences in the hippocampal mossy fiber projection. These differences are most pronounced in the portion of the projection that forms synaptic connections with the basal dendrites of the CA3 pyramidal neurons [intra- and infrapyramidal mossy fiber (IIP-MF) projection]. We have previously demonstrated that the extent of the IIP-MF subfield is positively correlated with the capacity to perform a spatial radial-maze task and that an experimentally induced enlargement of the IIP-MFs, by means of postnatal thyroxine treatment, predicted the ability of adult two-way avoidance learning. In the present study, we tested whether this treatment would also influence radial-maze performance. Forty-five male mouse pups from the inbred strain DBA/2 (chosen because of scanty IIP-MF projection and poor radial-maze learning) were divided into three groups that received daily injections of either 2 micrograms L-thyroxine, an alkaline vehicle solution, or physiological saline. Treatment lasted from postnatal days 0 to 11. At the age of 3 months, these animals were tested in an eight-arm radial maze. The extent of their IIP-MF projections was measured by means of planimetry on Timm-stained sections. Thyroxine-treated animals made significantly fewer errors and had larger IIP-MF projections as compared to both control groups. Within each group, the individual variability of the IIP-MF projection was significantly and positively correlated with performance. We conclude that experimentally modified IIP-MF projections mediate processes underlying spatial working memory. It would appear that the hippocampal circuitry alterations induced by postnatal hyperthyroidism can counteract a hereditary lack of talent, albeit only partially and in selected populations.

Indications for enteric conversion after pancreas transplantation with bladder drainage. Bladder drainage has become the procedure of choice for 94% of transplant centers in North America. Bladder drainage is superior to other techniques as far as graft survival and technical success are concerned; however, the procedure is associated with significant urologic problems that might necessitate conversion to enteric drainage. This review summarizes the indications and results for enteric conversion at this institution. Between June 1982 and January 1992 a total of 240 pancreas transplantations were performed at our center. In 229 cases exocrine secretions were drained into the bladder. These cases were reviewed, and those with enteric conversions were further analyzed to delineate indications, complications, and results. Sixteen (7%) were converted to enteric drainage (side-to-side duodenojejunostomy). The reasons for conversion were urethral disruption (six), recurrent urine leaks (five), bleeding (four), and chronic urinary tract infection (one). Enteric conversions were performed between 1 1/2 and 32 months after the initial transplantation. With the exception of one anastomotic leak resulting in an intraabdominal abscess, no complications occurred. All patients undergoing enteric conversions had resolution of their problems and, in addition, were able to discontinue use of oral bicarbonate. We conclude that enteric conversion after pancreas transplantation with bladder drainage is safe and effective in the correction of urologic problems. Based on our experience, we recommend early enteric conversion if urologic problems do not resolve after an appropriate period of conservative therapy.

Plasma levels of antidiuretic hormone in patients receiving prolonged lithium therapy. Among 18 patients receiving prophylactic, long-term lithium treatment for manic-depressive psychosis, a high incidence of increased thirst and frequency of micturition (60-70 per cent) was noted on direct questioning. Symptoms arose at varying times after the start of lithium therapy; in no patient did symptoms antedate the use of the drug. Plasma levels of antidiuretic hormone were found, on average, to be higher than in normal control subjects for a given level of plasma osmolality, although the scatter of results was wide. It is suggested that elevation of antidiuretic hormone occurs as a compensatory mechansims for the polyuria which is a common feature of long-term lithium treatment. The more florid form of nephrogenic diabetes insipidus occasionally seen in lithium takers seems likely to be due to a different mechanism from the more common mild polyuria.

Treatment of chronic post partum endometritis in cattle with cloprostenol. Seven dairy cattle showing clinical post partum endometritis were monitored daily by rectal examination of uterus, ovaries and vagina and by sampling of jugular venous blood and uterine pus. The animals were treated by intramuscular injection of 500 microgram cloprostenol (ICI). All seven animals had an immediate reduction of plasma progesterone concentrations and showed oestrus within two to three days. In six cases the clinical endometritis resolved, with uterine involution, within seven days and uterine mucus sample showed no specific growth. One animal required a second cloprostenol injection 11 days after the first to achieve complete resolution. Subsequently, plasma progesterone levels rose in all animals but two cases later appeared to become anoestrous, perhaps due to pituitary insufficiency. In a further study of chronic endometritis in cattle in the field, 51 out of 56 animals treated in the presence of a corpus luteum showed oestrus within 14 days with resolution of the condition; five others did not respond. None of the three cases which had been treated in the absence of a corpus luteum showed any improvement. This lack of response was not unexpected and supports the view that the mode of action of cloprostenol in this treatment regime is to induce luteolysis. The mechanism of therapy and possible explanation for the occurrence of chronic endometritis are discussed.

Two unusual forms of human immunoglobulin E encoded by alternative RNA splicing of epsilon heavy chain membrane exons. We present evidence for RNA transcripts encoding two forms of human epsilon immunoglobulin (Ig) heavy chain that differ significantly from those of other isotypes. We previously demonstrated three human epsilon mRNA species, instead of the two, corresponding to membrane and secreted proteins, seen with other heavy chain transcripts. In human genomic DNA downstream of the C epsilon gene, we identified sequences homologous to the two putative murine exons M1 (encoding a hydrophobic, presumably transmembrane region) and M2 (encoding hydrophilic residues). To determine the structures of epsilon transcripts containing these sequences, we amplified epsilon-related RNAs with the reverse transcriptase polymerase chain reaction. RNA was examined from fresh human B cells stimulated to IgE production by interleukin 4 plus anti-CD40, as well as from the human IgE-producing line AF10. Instead of the single CH4-M1-M2 splice product predicted for murine membrane IgE, we found two other RNA species. One form has the structure CH4-M1'-M2, in which M1' includes the human sequence homologous to the murine M1 as well as a unique segment of 52 codons further upstream in the genomic sequence; this RNA species apparently encodes the IgE expressed on the membrane of IgE-producing lymphocytes. The other RNA has the structure CH4-M2', in which M2' is spliced in an alternative reading frame that includes an additional 109 codons downstream of the termination codon of the CH4-M1'-M2 form. Because the CH4-M2' mRNA form does not encode a hydrophobic segment, its translated product should be secreted. A secreted epsilon protein of approximately the size predicted for this form was identified by Western blotting. This novel IgE protein could play a significant and distinctive role in allergic disorders.

Combined genetic deficiency of C6 and C7 in man. By routine screening of sera, a subject was discovered who showed a sub-total deficiency of C6 and C7. No clinical disease was associated with this deficiency which was transmitted through the subject's family as a single genetic characteristic, the C6 deficiency being associated with a silent allele at the structural locus. The propositus was found to have low quantities of an abnormal C6 which was both antigenically deficient and smaller in size than normal C6 (110,000 daltons compared with 140,000 daltons) and small quantities of apparently normal C7. It is concluded that the most likely explanation for this defect is that the subject has a structural mutation in his C6 gene which produces hyopsynthesis not only of C6 but also of the closely linked gene for C7. These findings suggest the possibility that C6 and C7 may function as a single genetic unit and that the primary transcript copied from the genome includes information for both proteins.

Quantitative studies on the development of inoculated Brugia malayi microfilariae in Anopheles sinensis and Culex quinquefasciatus. Definite numbers of B. malayi mf were inoculated into An. sinensis and Cx. quinquefasciatus, and their subsequent development was observed. The relationships between the dosage and the L3 positive rate on the one hand and the average filarial maturity rate on the other were defined. At the same dosages of 4 and 10 mf/mosquito, the L3 positive rates and the average filarial maturity rates in An. sinensis were much higher than those in Cx. quinquefasciatus (p less than 0.01). It was demonstrated that the immune response to filariae of the mosquitos was the main factor resulting in these differences. The intensity of the immune response not only varied with the species, but also declined with the aging of mosquitos. The results of our experiment might be useful to studies on the dynamics of filariasis transmission and the interaction between filariae and their insect hosts.

Follow-up study of camp marathon group psychotherapy for adolescents with emotional disturbances. Every summer since 1972, the Department of Psychiatry at Fukuoka University has been holding the Camp Marathon Group Psychotherapy (MGP) for adolescents with emotional disturbances. This time we conducted a follow-up survey on 114 camp attendees from 1978 to 1985. Questionnaires were mailed out and we received 56 replies, that is a response rate of 49.1%. The average observation period of the follow-up was 4 years. The results were as follows: Thirty-six cases or 64.3% were making satisfactory progress at the time of the survey. Eight or 14.3% showed no change or showed worsening conditions. Seven or 12.5% cases developed into schizophrenia. Based on these results, we studied roughly what role MGP plays in the therapy of adolescents with emotional disturbances.

Squamous epithelial cancer in metaplastic pleura following extrapleural pneumothorax for pulmonary tuberculosis. During the period 1947-1955, 148 patients underwent extrapleural pneumolysis for pulmonary tuberculosis in Stockholm City Chest Hospital at Söderby. In 121 tuberculosis healed following operation. Ten of these later developed pain and a feeling of tension on the operated side and were operated upon with evacuation of the extrapleural sac. In four of them a highly differentiated keratinizing aquamous cell carcinoma had developed. In addition, two more cases of carinomas of the same type operated on at other hospitals are described. Five of the six patients died of cancer. Squamous cell carcinoma occurring in metaplastic mesothelial cells has hitherto not been reported on and the phenomenon is discussed and compared with the more common scar cancers within lung tissue caused by damage from tuberculosis.

Individual trajectories of cognitive decline in patients with dementia of the Alzheimer type. The course of decline was studied in 16 patients with probable or definite dementia of the Alzheimer type (DAT) over 2.7 to 6.8 years from first to last evaluation. Overall severity of dementia was measured with the Wechsler Adult Intelligence Scale (WAIS), the Dementia Rating Scale (DRS), and the Mini-Mental State Examination (MMSE), at approximately annual intervals. An initial plateau phase, during which language and cognitive functions did not change for periods of 9 to 35 months, was observed in 5 patients who initially had an isolated memory impairment without significant impairment of nonmemory language or visuospatial function. Once nonmemory functions began to decline, the rate of decline was remarkably steady in most individual patients but varied markedly among patients. The initial rate of decline after the plateau phase, as measured with the WAIS and DRS, was a significant predictor of subsequent rate in individual patients (r = .66, p less than .01, and r = .67, p less than .01, for the WAIS and DRS, respectively). The MMSE was a less reliable measure of longitudinal change in dementia severity and did not predict future rates of decline (r = .29). These results demonstrate a biphasic trajectory of decline in patients with DAT. Stable interindividual differences in rate of decline may provide a basis for designing more sensitive studies of treatments intended to slow or halt the progress of DAT.

Missed opportunities for measles immunisation in selected western Cape hospitals. Measles is still a major cause of childhood mortality and morbidity in South Africa. The World Health Organisation (WHO) has recently recommended that greater attention be paid to opportunities for immunisation in the curative sector. This study quantified the extent of missed opportunities for measles immunisation in children attending primary, secondary and tertiary level curative hospitals in the western Cape. Exit interviews of 1,068 carers of children aged between 6 and 59 months inclusive showed that 2.4-40.7% of carers had been requested to produce a Road-to-Health card, and that 4.8-43.1% of carers had a card available. The proportion of children with documented evidence of measles immunisation available ranged from 4.8% to 40.0% between facilities. The study demonstrated that a considerable number of potential opportunities to immunise children against measles are currently being missed in children attending hospitals and day hospitals in the western Cape. The study documents the effect of a fragmented approach to health care, and indicates a need for rapid integration of preventive and curative components of health care into a metropolitan-based primary health care service.

[Physiotherapy and mask treatment of chronic bronchitis and chronic obstructive lung disease]. The literature concerning traditional chest physiotherapy (postural drainage, percussion, vibration, breathing exercises), treatments with masks (CPAP, IPPB, RMT, PEP, PEEP) and general physical training in the treatment of chronic bronchitis is reviewed. The mucociliary clearance is increased after postural drainage, cough, forced expiratory manoeuvres and general physical training, but the influence of this upon the course of the disease is unknown. Chest physiotherapy in the treatment of patients admitted due to acute exacerbation of chronic bronchitis seems of no help. The use of face masks in this population has only been subject to limited investigation, but results from controlled trials do not indicate any favourable effect. In contrast general physical training seems to increase physical endurance and decrease dyspnoea. Specific rehabilitation programmes comprising psychological assistance, cessation of smoking and general physical training seem promising.

Mutations in Neurospora crassa which affect multiple amino acid transport systems. Characterization of a double mutant, his-6: hgu-4, which is unable to utilize L-histidyl-glycine as a source of histidine has revealed a new locus on linkage group V. The hgu-4 genotype results in a generalized reduced transport activity for amino acids, with a concomitant increased resistance to amino acid analogs. Transport rates and analog resistance for amino acids by this mutant are compared to the previously reported transport deficient mutants fpr-1, nap and un-3. Transport of L-aspartate as a function of temperature is examined in a variety of transport deficient strains in an attempt to explain the mode of action of mutation which pleiotropically affect several genetically and biochemically distinct amino acid transport systems.

Inhibition of aldosterone biosynthesis by 18-ethynyl-deoxycorticosterone. The inhibiting effects of 18-ethynyl-deoxycorticosterone (18-E-DOC) as a mechanism-based inhibitor on the late steps of aldosterone biosynthetic pathway were examined in calf adrenal zona glomerulosa cells placed in the primary culture. Baseline and ACTH (10(-9) M)-, angiotensin-II (10(-8) M)-, and potassium (12 mM)-stimulated production of aldosterone and 18-hydroxycorticosterone were inhibited in a dose- and time-dependent manner. At 1 microM, 18-E-DOC produced a 73% inhibition, and at 10 microM, it produced a 94.6% inhibition of aldosterone secretion. Preincubation with 10 microM 18-E-DOC for 5 min followed by washing resulted in 75% inhibition of aldosterone secretion. The maximal degree of inhibition was reached after 60 min of preincubation. The degree of the inhibition of 18-hydroxycorticosterone production was almost same as that of aldosterone. Preincubation with 10 microM 18-E-DOC for 60 min, followed by extensive washing and reincubation with medium for 24 h, resulted in recovery to more than half the production of the control cells. Minimal changes occurred in the production of corticosterone (slight increase), 18-hydroxydeoxycorticosterone (slight increase) in zona glomerulosa cells, and cortisol (no changes) in zona fasciculata cells. These studies show that 18-E-DOC is a specific inhibitor of the late pathway of aldosterone biosynthesis. 18-E-DOC could be valuable as a therapeutic agent in those conditions associated with increased aldosterone production where a specific inhibitor would be useful.

Turnover rates of hexokinase I, phosphofructokinase, pyruvate kinase and creatine kinase in slow-twitch soleus muscle and heart of the rabbit. Hexokinase I was purified from rabbit heart to a specific activity of 70 U/mg protein. The purified enzyme was electrophoretically homogeneous with an apparent molecular weight of 102,000. Purified immunoglobulins from sheep were used to titrate the percentage of hexokinase I in various tissues of the rabbit. Precipitating antibodies from sheep were also prepared against rabbit muscle MM-creatine kinase, phosphofructokinase and pyruvate kinase. Apparent turnover rates of these phosphotransferases and of hexokinase I were determined in rabbit heart and soleus muscle by means of the immunoprecipitation technique after single pulse labelling with [U-14Cl]leucine in vivo. Apparent half-lives of phosphofructokinase, pyruvate kinase and hexokinase I were 0.56 d, 0.73 d and 0.93 d in rabbit heart. In slow-twitch soleus muscle half-lives of phosphofructokinase, pyruvate kinase, hexokinase II and creatine kinase were 0.63 d, 0.72 d, 0.85 d and 0.82 d. The similarity of the rate constants of degradation of these enzymes is interpreted as an indication that different tissue concentrations result primarily from different rates of synthesis.

[Treatment of chronic uveitis with long-term administration of penicillin]. The authors followed up a group of 20 patients with chronic uveitis (10 men and 10 women), mean age 36.5 years. Despite treatment of the foci, they suffered on average from seven relapses of the disease, frequently several times in the course of one year. From the anamnestic aspect there was a significantly high number of spells of tonsillitis, respiratory infections and arthralgia. Half the cases of uveitis, mainly anterior, were bilateral. The patients suffered from dysimmunoglobulinaemia with low values of FW, ASLO, Latex. HLA B 27 was positive in five subjects. After one-year of Pendepon or Penclen administration (in half the patients with NORG) 18 patients did not develop a relapse for a period of 2-3 years. The method is simple, cheap, easy to use in field practice, in particular in junior patients. The clinical effect of treatment justifies the use of this method as an alternative of intermittent immunosuppression.

[Comparative study of biological effect of purified gonadotropins of sturgeon (Acepenser stellatus) and carp (Cyprinus carpio)]. A comparison was made of the biological effect of purified gonadotropins of the sevryuga and the carp on the activation of adenyl cyclase in the homogenate of the goldfish ovary, the reaction of spermiation in two species of frogs, and the in vitro maturation of oocytes of two amphibian species and sevryuga. The ratio of specific activities of the preparations under study was shown to vary markedly with respect to test-subject and test-reaction. The data obtained suggest, thus, qualitative differences in the effect of the gonadotropins under study and the response of organs-targets. It is proposed to use the system of in vitro maturation of amphibian oocytes for studying the phenomenon of species specificity of gonadotropins of lower vertebrates.

Antisperm antibodies in split ejaculates. The split ejaculation technique concentrates the most motile and viable spermatozoa in the first part of the ejaculate. Several clinicians use this fraction for insemination and in vitro fertilization. Eleven vasovasostomized men with antisperm antibodies participated in this study. The mixed antiglobulin reaction (MAR) for IgG, IgA, and secretory component was carried out on the whole ejaculate and the fractions of the split ejaculate. The isotype and concentration of free antisperm antibodies were determined in serum, the whole ejaculate and the fractions of the split ejaculate by the indirect MAR and the tray agglutination test. The detection of bound antisperm antibodies revealed almost identical reactions in fractions one and two and in the whole ejaculate. The results suggested that the majority of antisperm antibodies in the ejaculate from vasovasostomized men are transuded from serum not only at the epididymal and/or the prostatic level but also in the seminal vesicles.

Cytochemical studies on sarcolemma: Na+, K+-adenosine triphosphatase and adenylate cyclase. Two highly lead-sensitive ATPases, Na+,K+-ATPase and adenylate cyclase, can be demonstrated cytochemically by the lead precipitation technique in briefly prefixed tissue, provided that the free Pb2+ concentration in the incubation medium is kept below 0.1 mM by a heavy metal chelator. Under conditions suitable for Na+,K+-ATPase activity precipitation of final reaction product (lead phosphate) at the sarcolemma of cardiac muscle is abolished by 0.1-1mM ouabain. In contrast, reaction product deposition at the intramuscular part of the plasma membrane and at intracellular sites is not noticeably affected by the glycoside. These findings indicate either that the sarcolemma is the exclusive location of Na+,K+-ATPase in cardiac muscle or that the presence of the enzyme at other loci is masked by active Na+,K+-independent, ouabain resistant ATPases. Under conditions favoring adenylate cyclase activity, precipitation by Pb2+ of orthophosphate derived, with the help of added cyclic nucleotide phosphodiesterase and 5'-nucleotidase, from cyclic AMP formed from adenylyl imidodiphosphate (AMP-PNP) is seen after prolonged incubation in myocardial cells along the entire course of the plasma membrane and also at the transverse tubules and is particularly intense at the tight junction regions of the intercalated disks. Ouabain has no effect on these reactions. Reaction product deposition is also observed at the sarcolemma in red skeletal muscle and at the terminal cisternae of the sarcoplasmic reticulum in white skeletal muscle, where the reaction is intensified by adrenaline. Sarcoplasmic reticulum of cardiac and of red skeletal muscle exhibits only relatively weak staining attributable to cyclic AMP formation. These observations are in agreement with the results of tissue fractionation studies according to which the plasma membrane is the chief site of adenylate cyclase in heart and in red, but not white skeletal muscle.

Functional analysis of mononuclear cells infiltrating into tumors. VI. The effect of lymphocyte chemotactic factors on lymphocyte adhesion to endothelial cells. We have analyzed mechanisms controlling infiltration of T lymphocytes into tumor tissues. A lymphocyte chemotactic factor-b (LMF-b) produced by tumor infiltrating CD4+ T lymphocytes was purified. LMB-b was specifically chemotactic for CD8+ T lymphocyte. Furthermore, LMF-b augmented lymphocyte adhesion to high endothelial venule (HEV) cells. The binding of CD8+ T cells to HEV cells was specifically augmented by LMF-b. The LMF-b primarily acted on T lymphocytes, whereas tumor necrosis factor as well as IFN-gamma acted on HEV cells or fibroblast cells. The binding of lymphocytes to fibroblast cell line was not augmented by LMF-b. The augmentation of lymphocyte adhesion to endothelial cells by LMF-b was mediated by the lymphocyte function associated antigen-1/intercellular adhesion molecule (LFA-1/ICAM) pathway, the CD2/LFA-3 pathway, and the very late antigen-4/culture supernatant-1 (VLA-4/CS-1) pathway.

[Sudden unexpected nocturnal death: report of a case and review of the literature]. Sudden death usually affects individuals with severe heart disease. A more dramatic phenomenon is the sudden unexpected death of individuals with no evidence of heart disease. It has been described mainly in young healthy males under severe stress. We present a 32 year old man who presented ventricular fibrillation during sleep and was resuscitated by his wife. Recurrent episodes of VF occurred in the following hours. The study, including coronary angiography, revealed a normal heart. Endomyocardial biopsy showed minimal alterations with scarce areas of atrophy and fibrosis. Electrophysiologic evaluation showed an extremely short refractory period of the right ventricle, but the arrhythmia could not be induced by electrical stimulation. An internal cardioverter defibrillator was implanted since the risk of recurrent VF was high. A review of the literature concerning this unusual entity is offered.

[Colonic and rectal villous tumors. Comparative study of treatment by surgery or radiotherapy. Report of 104 cases]. The authors report and analyse two series of observations of colonic and rectal villous tumours. 47 treated initially by surgical removal, 57 treated by radiotherapy, (contact radiotherapy or interstitial radium therapy). After recalling the basic pathology, they expose the results of each group of treatment and draw practical conclusions. The treatment should first be surgical, the method depending on the site and volume of the tumour; radiotherapy may be a beneficial complement when the tumour is malignant and non-invasive or when a recurrence occurs. It may exceptionally be used as a cure when the tumour has a small diameter (less than 3 cm) and is situated less than 12 cm from the anus.

Some characteristics of blood shed into the Solcotrans postoperative orthopaedic drainage/reinfusion system. To assess the suitability of blood shed into the Solcotrans orthopaedic autotransfusion system as a source of autologous blood for transfusion. Blood samples were taken from patients after surgery and from shed blood within the Solcotrans units. Surgery was performed at a public hospital. All six patients underwent total knee replacements. Measurements were made of haemoglobin, haematocrit, platelets, pH, potassium, plasma haemoglobin, fibrinogen, D-dimer, plasminogen activator, thromboplastin and fibrinopeptide A. The non-activated partial thromboplastin time was estimated. Shed blood was compared with homologous whole blood to assess the thrombogenic potential of shed blood in vitro. The haemoglobin and haematocrit levels of the shed blood were significantly lower than venous blood (P = 0.008). Levels of potassium in shed blood were normal although there was significant haemolysis. Shed blood was depleted of clotting factors, with increased levels of D-dimer (16-128 g/L). Activation of the coagulation pathway within the shed blood was shown by a shortened non-activated partial thromboplastin time (90-120 s), and detectable levels of thromboplastin. Propionibacterium acnes was isolated from one of the units. Reinfusion of large volumes of shed blood should probably be avoided, but use of the Solcotrans orthopaedic transfusion system in conjunction with other autologous transfusion practices can reduce the patient's requirement for homologous blood.

Plasma erythropoietin in polycythemia. Erythropoietin titers of plasma cannot be used to differentiate polycythemia vera from secondary polycythemia since the limit of sensitivity of our current bioassay technics is 50 mU, considerably higher than levels found in normal subjects and in patients with polycythemia. However, erythropoietin is relatively heat stable, and since abundant plasma is available from therapeutic phlebotomies it is possible to prepare and assay highly concentrated, erythropoietin-containing extracts. In 35 normal subjects, erythropoietin levels ranged from less than 5 mU/ml (the limit of sensitivity) to 18 mU/ml with a mean of 7.8 mU/ml. In 21 patients with proved polycythemia vera, the levels were less than 5 mU/ml in all. In 41 patients with suspected secondary polycythemia or polycythemia of unknown origin, the levels ranged from less than 5 to 3,000 mU/ml. Three of the 11 patients with levels less than 5mU/ml were subsequently shown to have polycythemia vera. These results suggest that this refinement of the routine bioassay for erythropoietin may be of clinical importance in the differential diagnosis of polycythemia.

Massive occurrence of rickettsiae of the spotted fever group in fowl tampan, Argas persicus, in the Armenian S.S.R. Fowl tampans (Argas persicus) collected in Oktemberyan in the Armenian S.S.R. in 1974 were found to be massively infected with rickettsiae of the spotted fever (SF) group. One isolated rickettsial strain, designated Armenia 9, is antigenically related to, and probably identical with, strain Armenia 11 and strain B of Rickettsia slovaca, isolated from Dermacentor marginatus ticks. Strain Armenia 9 grows readily in chick embryo yolk sacs and in chick embryo cell (CEC) and L-cell cultures. It causes generalized infection in both soft and hard ticks. A fatal disease was produced in Clethrionomys glareolus after subcutaneous inoculation. Similar inoculation of other small wild rodents (Mus musculus, Microtus arvalis, Apodemus flavicollis), hens and laboratory animals (guinea pigs, white mice and hamsters) resulted only in an antibody response.

Structural characterization of mating pheromone precursors of the ciliate protozoan Euplotes raikovi. High conservation of pre and pro regions versus high variability of secreted regions. The precursors of Euplotes raikovi pheromones Er-2 and Er-10 have been structurally characterized from the sequences of their coding regions that were amplified and cloned using the polymerase chain reaction and oligonucleotide primers corresponding to conserved sequences of the gene for pheromone Er-1. The predicted amino acid sequences contain 75 residues distributed through three domains: signal peptide, pro segment and mature pheromone. Despite the conservation of the overall length, there is variation in the size of the pro segments and of the mature pheromones. The comparison of the sequences shows a gradient of identity from the amino to the carboxyl terminus; the signal sequences are identical (with greater than or equal to 95% identity in the nucleotide sequences), the pro segments more variable and the mature pheromones quite diverse. The processing site of the pro pheromones, to produce the mature forms, is apparently characterized by the unusual Xaa-Asp sequence.

Ability of spirometry, flow-volume curves and the nitrogen closing volume test to detect smokers. A population study. Vital capacity, FEV1 and various measurements of forced expiratory flows as well as closing volume (CV), closing capacity (CC), the mean slope of the alveolar plateau (phase III), the maximal amplitude of the cardiogenic oscillations (N2-osc), and other variables obtained from the nitrogen CV-test were measured in random samples of 50- (n = 221) and 60-year-old (n - 410) men in Gothenburg. All the variables were significantly different in smokers consuming 15 g or more tobacco daily compared with asymptomatic non-smokers. Reference values were established from measurements in the non-smokers without respiratory symptoms, and the sensitivities of the measured variables to tobacco smoking were assessed. Phase III revealed the highest sensitivity, being abnormal in about 40-60 % of subjects smoking 15 g or more tobacco daily and in about 30-35 % of subjects smoking less. CV and FEV1 were approximately equally sensitive, being abnormal in about 10-30 % of subjects smoking 15 g or more daily and in about 5-20 % in subjects smoking less. Other measurements of maximal expiratory flow rates gave values below minus two standard deviations for the appropriate reference group in less than 15 % of the smokers. However, when we took the skewed distribution of reference values into account we found a two- to sixfold increase of the sensitivities of these variables in the 50-year-old smokers, in which abnormal values were obtained in about 30-40 % of subjects smoking 15 g or more daily and in about 10-15 % in subjects smoking less. Taking all variables obtained from the CV-test in conjunction, one or more abnormal valves were obtained in 60-70 % of the subjects smoking 15 g or more daily. To the extent that sensitivity to smoking reflects sensitivity to abnormalities in small airways, phase III appeared to be the most efficient single measurement for detection of this condition in the present age groups.

Brucella abortus stimulates human T cells from uninfected and HIV-infected individuals to secrete IFN gamma: implications for use of Brucella abortus as a carrier in development of human vaccines. Brucella abortus has been characterized as a T-independent type 1 antigen/carrier in human and murine antibody responses. In this report it is shown that BA can activate human CD3+ T cells to secrete interferon-gamma (IFN gamma). Unlike mitogens, such as phytohemagglutinin, this stimulation was associated with minimal T-cell proliferation or upregulation of interleukin-2 (IL-2) receptor. Monocytes inhibited BA-mediated IFN gamma secretion since their removal resulted in increased responses, whereas adding monocytes back to cultures caused inhibition. BA elicited IFN gamma from CD4+ and CD8+ T cells, although CD4+ T cells secrete significantly more (p less than 0.05) IFN gamma than CD8+ T cells. The ability of BA to elicit IFN gamma from human T cells was inhibited in the presence of anti-Tac, suggesting that BA also induces IL-2 secretion and that IL-2 is involved in BA-mediated IFN gamma secretion. Detectable IL-2 secretion was induced by BA in the presence of anti-Tac. Exogenous IL-2 acted synergistically with BA to enhance IFN gamma secretion, suggesting that the amount of IL-2 released by BA alone was insufficient for optimal IFN gamma release. Furthermore, addition of IL-2 to T cells from individuals with poor or absent responses to BA, including individuals infected with HIV-1, restored their ability to secrete IFN gamma in response to BA. These data indicate that BA is capable not only of activating human B cells but can also induce T cells, probably of the TH1 phenotype, to secrete IFN gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anatomical and functional evaluation before and after the operative treatment of mitral stenosis via echocardiography]. A confrontation was made of the echocardiographic data and the operation findings in 33 patients with "pure" mitral stenosis confirmed by catheterization and intraoperation. A significant correlation was found between the decelerated movement rate of the diastolic part of the anterior mitral cusp (E--F) and the mitral stenosis degree. The not negligible diagnostic value upon the position of the posterior mitral cusp during diastole is stressed--forward of the horizontal, passing through point C of the mitral closing, as well as upon the size of the left ventricle. The correlation between the valvular calcinosis, established by the echocardiogram and that, established at the operation proved to be poor.

[Immune function and abdominal surgery in blood stasis syndrome in patients with gastrointestinal diseases]. 52 Patients with Blood Stasis Syndrome (BSS) in abdominal surgical diseases were divided into 3 types according to their symptoms, signs and natures of diseases. Peripheral blood T lymphocyte subsets of these BSS patients and 12 healthy persons were studied with Flow Cytometry and monoclonal antibodies. The immunoglobulins and complements of these cases were also studied. There were no difference in T cell subsets, immunoglobulins and complements between Qizhi-BSS group and normal control. The Shire-BSS group showed that CD8 cell, IgG, IgM, and C1, C3c were increased. These results showed that the immune response increased in this type of BSS patients. In the Qixu-BSS group, the CD3 was nearly normal, and the CD4+, CD4+/CD8+ ratio, and CD16+ were statistically decreased. However, the CD8+ cells markedly increased, the IgG, IgM and IgD were also lowered significantly in this type. The marked morphologic abnormal changes in ultrastructures of T lymphocyte were found in 6 patients with Qixu-BSS group. These results showed that the Qixu type of Blood Stasis Syndrome patients were in the immuno-suppressive status.

Decreased adrenergic sensitivity in patients with hypothyroidism. Cardiovascular sensitivity to catecholamines was assessed in 15 patients with hypothyroidism (mean [+/- SEM] thyroxine [T4] index 2.7 +/- 0.5 micrograms/100 ml, thyroid stimulating hormone [TSH] 136.9 +/- 48.3 microU/ml), aged 45 +/- 4 years and in 8 healthy control subjects. The study was repeated in 10 patients with hypothyroidism 4.0 +/- 0.5 months after thyroid replacement therapy (T4 index 9.9 +/- 2.1 micrograms/100 ml, TSH 3.5 +/- 1.3 microU/ml). In addition, basal, average and maximal heart rates were measured using 24 h ambulatory electrocardiographic (ECG) monitoring, and plasma levels of epinephrine and norepinephrine were determined before and after thyroid replacement. Heart rate increased less after bolus injection of 0.8, 1.6 and 3.2 micrograms of isoproterenol in the hypothyroid (10 +/- 2, 15 +/- 2 and 21 +/- 4 beats/min, respectively) than in the euthyroid (16 +/- 3, 22 +/- 3 and 30 +/- 4 beats/min, respectively) state (p less than 0.05). Control subjects reacted similarly to patients receiving thyroid replacement. Basal heart rate (64 +/- 3 versus 68 +/- 3 beats/min, p less than 0.05) and maximal heart rate (116 +/- 5 versus 133 +/- 5 beats/min, p less than 0.05) were lower on 24 h ambulatory ECG monitoring in the hypothyroid than euthyroid state despite higher basal plasma norepinephrine levels (394 +/- 45 versus 315 +/- 45 pg/ml, p less than 0.05). Thus, patients with hypothyroidism display a decreased cardiac chronotropic response to beta-adrenergic stimulation. This may contribute in part to the decreased basal and maximal daily heart rates seen in patients with hypothyroidism, which occurs despite elevated plasma norepinephrine levels.

[Peripheral nerve injuries during carotid endarterectomy]. Our experience with patients undergoing carotid endoarteriectomy over a 10 year period has been retrospectively reviewed. Nerve injuries were detected by reviewing postoperative progress and clinical notes. One hundred thirty-four procedures were performed on 120 patients, to 15 of whom (9%) occurred major nerve injuries. These included seven vagal nerve injuries causing ipsilateral vocal cord paralysis and hoarseness, five injuries of the marginal mandibular nerve and three injuries of the hypoglossal nerve. None of the patients with nerve injury had a stroke as a result of carotid operation. Vocal cord paralysis was documented by laryngoscopy. The incidence of cranial nerve injury during carotid endoarteriectomy appears to be higher than expected, particularly if asymptomatic patients are controlled.

A novel enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to HIV-1 envelope glycoproteins based on immobilization of viral glycoproteins in microtiter wells coated with concanavalin A. We have developed a novel method that greatly simplifies the preparation of solid-phase HIV-1 envelope glycoproteins for use in an ELISA that detects serum antibodies to HIV envelope antigens. This method utilizes concanavalin A absorbed to wells of microtiter plates to affinity immobilize detergent-solubilized viral glycoproteins released in culture fluids of HIV-1 infected cell lines grown in serum free medium. Antibodies binding to ConA-immobilized viral antigens are detected by peroxidase-conjugated antibodies and appropriate enzyme substrates. Unlike most commercial HIV ELISAs, which utilize gp120 depleted-purified virus as the source of antigens and thus favor detection of antibodies to core antigens, the ConA envELISA is highly sensitive for detecting antibodies to native gp120, as evidenced by the strong reactivity of gp120-specific human monoclonal antibodies. Our results also suggest that representation of gp41 in the assay varies and depends on which virus infected cell lines are used for antigen production. Since this assay accurately identified 14 HIV-1 antibody positive patient sera and no false positives were detected among 16 HIV-1 negative sera, the ConA envELISA shows promise as an inexpensive assay for the serologic diagnosis of HIV infections.

Sensitivity of toad rods: Dependence on wave-length and background illumination. 1. There are five morphological types of photoreceptors in the retina of the toad, Bufo marinus: red and green rods, single cones, and the principal and accessory members of double cones. The largest and most abundant of these is the red rod. 2. Intracellular recordings were used to investigate the dependence of the sensitivity of red rod responses on wave-length and background light. 3. The spectral sensitivity of dark-adapted and moderately light-adapted red rods can be satisfactorily fitted with the absorbance spectrum of the red rod photopigment. There are no significant contributions to red rod responses from cones or green rods. 4. In contrast, L-type horizontal cells, whose responses are dominated by input from the red rods near threshold, can be shown also to receive input from cones. 5. Steady background light produces a response in the red rods consisting of an initial hyperpolarization, followed by a decay of potential to a steady-state plateau level. The slow decay of response amplitude is accompanied by an increase in sensitivity to increment test flashes. 6. The increment sensitivity at steady-state decreases with increasing background intensity according to a modified Weber-Fechner relation. The dependence of increment sensitivity on the wave-length of the background light can be predicted by the red rod spectral sensitivity, showing that cones do not influence the light adaptation of rods. 7. At a background [corrected] intensity of 11-5 log equivalent quanta cm-2sec-1, sensitivity begins to deviate from the Weber-Fechner relation. In background light one log unit brighter, the rods are completely saturated. 8. Small responses having the spectral sensitivity of cones can be recorded from saturated rods. These potentials have a prominent off response whose wave form resembles the d-wave of the e.r.g. 9. A comparison of the increment--sensitivity curves of single receptors shows that rods are light-adapted by backgrounds one thousand times dimmer than those which affect cones. The increment--sensitivity curves of rods and cones cross, so that single cones become more sensitive than single rods even before the rods begin to saturate.

Antimicrobial activity of subinhibitory concentrations of aminoglycosides against Pseudomonas aeruginosa as determined by the killing-curve method and the postantibiotic effect. This investigation used the postantibiotic effect (PAE) and killing curves to provide data on the antimicrobial activity of subinhibitory (1/8x, 1/4x and 1/2x minimum inhibitory concentration; MIC) and inhibitory (1x MIC) concentrations of amikacin, gentamicin and tobramycin against Pseudomonas aeruginosa. Subinhibitory concentrations (1/4x and 1/2x MIC) of aminoglycosides demonstrated a reproducible PAE. At 1/4x MIC, the order of duration of the PAE was approximately 15 min for all aminoglycosides, while at 1/2x MIC all three aminoglycosides displayed a similar PAE of approximately 40 min. Killing-curve studies demonstrated that subinhibitory concentrations of aminoglycosides either decrease bacterial growth for several hours (1/4x and 1/2x MIC) or produce stasis of growth for several hours (1/8x MIC). Only inhibitory aminoglycoside concentrations (1x MIC) proved to be bactericidal. Subinhibitory concentrations of aminoglycosides decrease bacterial growth and produce a PAE against P. aeruginosa.

[Dietary fiber in the dietetic therapy of diabetes mellitus. Experimental data with purified glucomannans]. In the last years the use of alimentary fibres in dietetic management of diabetic patients increased. The aim of this work was to evaluate, in type 2 diabetic subjects, the glycaemic and insulinemic increments after a standard breakfast with glucomannanos enriched biscuits and with common slices of toast containing the same amounts of carbohydrates and calories. The basal serum values of glucose and C-peptide were similar in the two days of the test. The mean increments of glucose and C-peptide were significantly higher (p < 0.001) after slices of toast than after glucomannanos enriched biscuits. In conclusion our results show a reduction in glycaemic increments after breakfast with glucomannanos-biscuits. The decreased insulin secretion and the reduction of insulin need can longer preserve the functional reserve of beta-cells.

Stable three-stranded DNA made by RecA protein. When RecA protein, in the form of a nucleoprotein filament containing circular single-stranded DNA (plus strand only), reacts with homologous linear duplex DNA, a directional transfer ensues of a strand from the duplex DNA to the nucleoprotein filament, resulting in the displacement of the linear plus strand in the 5' to 3' direction. The initial homologous synapsis, however, can occur at either end of the duplex DNA, or anywhere in between, and when homology is restricted to different regions of the duplex DNA, the joint molecules that form in each region show striking differences in stability upon deproteinization: distal joints greater than proximal joints much greater than medial joints. In the deproteinized distal joints, which are thermostable, 2000 nucleotide residues of the circular plus strand are resistant to P1 nuclease; both strands of the original duplex DNA remain resistant to P1 nuclease, and the potentially displaceable linear plus strand, which has a 3' homologous end, remains resistant to Escherichia coli exonuclease I. These observations suggest that RecA protein promotes homologous pairing and strand exchange via long three-stranded DNA intermediates and, moreover, that, once formed, such triplex structures in natural DNA are stable even when RecA protein has been removed.

[Segmentary topography and ventilation gradients in human lungs]. Segmentary topography of the air volume was studied by regional electroplethysmography of the lungs. A distinct apical-basal gradient was shown to be present in men tested in supine position, along with the dorsal-ventral gradient; the origin of the apical-basal gradient could not be explained from the point of view of the gravitational mechanism. A possibility of recalculation of the electroplethysmographic index of the percentage of the air content in the lobe of the lung to the regional air volume index in the lungs, and the principal possibility of calculation of the regional total lung capacity index with the help of electroplethysmography was shown.

[Regulation of glutamine metabolism in Chlorella pyrenoidosa. Regulation of glutamine synthetase activity by adenylic system components]. A decrease of glutamine synthetase (E. C. 6.3.1.2.) activity was observed under the assimilation of ammonium nitrogen in Chlorella. At the same time a decrease of ATP content in Chlorella cells took place. The ATP content was 7-fold decreased, while ADP and AMP contents were 4-fold and 3-fold increased respectively, after 15 min. of Chlorella incubation on "ammonium" medium. Further incubation for 45 min, resulted in gradual increase of ATP content and in decrease of ADP and AMP contents. The value of energy charge in ammonium assimilating Chlorella cells sharply decreased for first 15 min. of incubation and then it normalized gradually. The experiments with glutamine synthetase preparation, isolated from ammonium assimilating cells, have shown that ADP and AMP are strong inhibitors of the enzyme in the presence of Mg2+, and only ADP produces the inhibitory effect in the presence of Mn2+. No enzyme reactivation was observed after the transfer of ammonium assimilating cells into nitrogen-free medium or nitrate medium, the enzyme activity increasing at the expense of enzyme protein synthesis denovo.

Tyrosine- and phenylalanine-restricted formula diet augments immunocompetence in healthy humans. Previous studies indicate that limiting tyrosine and phenylalanine intake in the diet decreases tumor growth and metastasis. General health status, immune status, and platelet function were studied in nine healthy human subjects consuming low-protein foods supplemented with formula diets free of tyrosine and phenylalanine to maintain total daily intake of tyrosine at 2.4 mg/kg body wt and phenylalanine at 3.5 mg/kg body wt. This regimen decreased plasma tyrosine (p less than 0.05) but not phenylalanine. Blood indicators of protein status were not changed. Platelet aggregation decreased in response to adenosine diphosphate and platelet activating factor in seven of nine subjects. Natural killer, T-helper, and T-cytotoxic/suppressor lymphocyte numbers proportionally increased relative to neutrophils (p less than 0.05). Natural killer cell activity increased in six of nine subjects. Increased natural killer cell activity and decreased platelet aggregation are two indices associated with decreased tumor growth and metastasis.

Balance studies and polymeric glucose solution to optimize therapy after massive intestinal resection. The aim of this study was to determine whether fluid homeostasis could be maintained by using a hypo-osmolar (200 to 221 mosmol/kg), relatively low-sodium (50 to 52 mmol/liter) solution that contained a glucose polymer in a 54-year-old patient with high ileostomy output attributed to short-gut syndrome and resultant prerenal azotemia. Sequential balance studies were performed to assess stool and urinary output, stool fat, and urinary electrolytes initially during intravenous rehydration and subsequently during administration of the necessary fluids and nutrients exclusively by oral supplementation. The additional effects of high-fat and low-fat diet, loperamide hydrochloride, and octreotide acetate were evaluated. When the patient sipped a hypo-osmolar oral rehydration solution while she was awake during the day and received a high dose of loperamide and a 40-g fat, disaccharide-free diet, salt and water homeostasis was maintained. The addition of octreotide did not substantially enhance fluid balance; rather, it increased fecal fat and fluid losses from the small bowel. Thus, hypo-osmolar polymeric glucose solutions maintain fluid homeostasis in patients with the short-gut syndrome. In such patients, simple balance studies are useful for assessing the absorptive capacity of the residual intestine, for developing an optimal individualized treatment, and for eliminating the need for costly, long-term home parenteral nutrition.

Analysis of the cuticular collagens of Ascaris suum. The nematode cuticle is an extracellular structure composed mainly of collagens, with an insoluble epicuticle on the surface. The extracted collagens from adult Ascaris suum can be separated by SDS-PAGE into three major groups of polypeptides with apparent molecular masses of 34, 60-70 and 120-140 kDa. Densitometric evaluation of the polypeptide bands indicated that the three groups are present in the ratio of 1:2:6. Rotary shadowing of reduced, extracted molecules showed fibers 45 nm in length. This length is in excellent agreement with the calculated total length of amino acids in (Gly-X-Y) regions deduced from the collagen gene sequence of Caenorhabditis elegans and A. suum. It is proposed that the three groups of collagen polypeptides found in SDS-PAGE correspond to collagen monomers, dimers and trimers, and that the molecules in the dimeric and trimeric forms are cross-linked via non-reducible bonds.

[Toxicological effect of a fatty acid mixture in rats]. The effects of a fatty acids mixture containing nearly 50% odd numbered fatty acids (PC-Säure) were studied in a subchronic toxicity test in male and female rats. The animals received PC-Säure in their diet at levels of 0, 1.25, 2.5 and 5% for 13 weeks. Food intake was increased at 5% PC-Säure level in males. Food efficiency was initially decreased in males and females of this group. Ingestion of PC-Säure resulted in increases of the urine volume and the urinary lactate dehydrogenase activity in both sexes. Male and female rats fed PC-Säure showed elevated serum activities of alkaline phosphatase and leucine aminopeptidase and decreases in serum cholesterol and triglycerides. Dietary PC-Säure elevated the serum creatinine content in males at the two highest levels. A transitory increase in the activity of the serum alanine aminotransferase was observed in females fed 5% PC-Säure. Increased liver and kidney weights were found in both sexes.

The response of the dog colon mucosa one hour's ischaemia. Segments of dog colon were subjected to one hour's ischaemia, and their morphology and function were studied either immediately after the ischaemia or 24 hours later. As functional tests, net sodium transport across the mucosa in vitro, the transport capacity in vitro for sugars and amino-acids, tissue respiration, lactate production, and the liberation of acid phosphatase were applied. Immediately after the ischaemia, all parameters differed significantly from the control mucosa: net sodium transport was abolished; amino-acid and sugar uptake, oxygen consumption and lactate production were reduced; and lysosomal enzyme release was increased. All parameters, except sugar uptake, had normalised 24 hours after the trauma. Histological examinations revealed much variation in the lesions occurring after the ischaemia, varying from slight epithelial desquamation to considerable mucosal destruction. In most cases, the mucosa had almost normalised 24 hours later. Morphometric analysis revealed decreased mean mucosal thickness immediately after the trauma, though 24 hours later, there was again no significant difference with the control group.

Herpes esophagitis: clinical syndrome, endoscopic appearance, and diagnosis in 23 patients. The unexpected diagnosis of herpetic esophagitis in a patient with nausea led us to review our experience with this disease. Review of our records from 1979 to 1989 produced 23 cases proven by endoscopic culture or microscopic examination (Cowdry-type A inclusions), the largest such series reported to date. Twenty-two of the 23 patients were immunocompromised. Odynophagia and chest pain were each present in half of the cases, but 26% of patients had neither. Gastrointestinal bleeding was attributable to herpetic esophagitis in 30%. Thirty percent of patients had disseminated herpes simplex infection and 70% had simultaneous infections with other organisms. Endoscopic findings included nonspecific inflammation, discrete ulcers, coalescent ulcers, and pseudomembranous esophagitis. Herpes virus was not suspected endoscopically as the cause of esophagitis in 30% of cases. Culture was slightly more sensitive than microscopic examination for diagnosis (89% vs. 76%), but both methods should be employed in any immunocompromised patient with esophagitis.

Warfarin: stereochemical aspects of its metabolism in vivo in the rat. The biotransformation of the R and S isomers of warfarin was investigated in the rat. The formation of 7-hydroxywarfarin was stereoselective for the R enantiomer, while the formation of 4'-hydroxywarfarin was stereoselective for the S enantiomer. The 6-, 8-, and benzylic hydroxylation of both isomers was approximately the same. The reduction of the side chain ketone function of warfarin to the corresponding diastereomeric warfarin alcohols was stereoselective for the S isomer. The reduction also displayed a degree of stereospecificity with S reduction occurring predominantly. The results of the in vivo study agree in many cases with a previous in vitro investigation. However, differences between the in vitro and in vivo studies do exist and suggest that secondary stereoselective biotransformation routes occur in vivo and that the microsomal and soluble enzymes employed in the in vitro study may have been disrupted during isolation. Large amounts of polar labile conjugates of R and S warfarin, and metabolites were found in the urine. The 4-hydroxyl group of the coumarin ring appears to be the position of conjugation and this process appears to be regio and stereoselective.

Fibrodysplasia ossificans progressiva in the cat. A case report. Clinical, radiographic, electromyographic, and pathologic findings in a cat with fibrodysplasia ossificans progressiva are described. The features of five previously reported cases of this feline disorder are also presented. This disorder affects young adult to middle-aged cats of both sexes. Characteristic clinical features include progressive stiffness of gait, with enlargement of proximal limb musculature. Radiography reveals multiple mineralized densities within the affected musculature. The clinical course is rapid, with development of severe disability within 2 weeks to several months. Electromyographic and pathologic findings suggest that this is a disorder of connective tissue, affecting primarily the epimysium, tendons, and fasciae, and results in marked proliferation of fibrovascular connective tissue, with associated chondroid and osseous metaplasia.

[Biopathology of fibrosing alveolitis]. Fibrosis is a condition where the functional tissue of an organ has been replaced by mesenchymal cells and their extracellular matrix. The process is frequent and may be regarded as univocal and independent of aetiology. An initial tissue damage is responsible for an inflammatory reaction which modulates and controls tissue repair with accumulation of mesenchymal cells, an accumulation which results from their migration and replication under the influence of chemotactic and/or mitogenic mediators (cytokines). Fibrosis occurs as an accentuation of this physiological process and may be understood as a healing process that has succeeded beyond normal expectation. Studies of idiopathic pulmonary fibrosis have improved our understanding of the physiopathology of pulmonary fibrosis. Alveolitis sets in response to an initial injury of undetermined nature, and from then on lymphocytes, neutrophils and macrophages intervene in the pathological process: (1) lymphocytes contribute to the perpetuation of the process by local production of immune complexes and coactivation of other inflammatory cells; (2) neutrophils and, to a lesser extent, eosinophils worsen the initial tissue injury by producing proteases and oxydants; (3) finally, macrophages control the local accumulation of mesenchymal cells by producing chemotactic and growth factors and by modulating the secretion by these cells of extracellular matrix.

Influence of anti-rheumatic drugs on human lymphocytes in vitro. Influence of anti-rheumatic drugs on human lymphocytes, especially T and B cell membranes, was studies with D-penicillamine, aurothiomalate, dexamethasone, cyclophosphamide, mitomycin C and aspirin. Peripheral blood obtained from five healthy individuals and lymphocytes were separated by centrifugation with Lymphoprep. The separated lymphocytes were adjusted to 5 X 10(6)/ml in PBS. The suspension of lymphocytes was mixed with equal volume of each concentration of the above drugs. After suspensions, we investigated the percentages of T -and B-cells, compared to control. The results are as follows: 1. Drugs which act only on the T cell membrane: D-penicillamine, aurothiomalate. 2. Drug which acts only on B cell membrane: dexamethasone. 3. Drugs which act on both T- and B-cell membrane: mitomycin C, cyclophosphamide and aspirin.

The management of mid-face fractures with intracranial injury. Recent advances have radically changed the management of facial fractures. CT scanning, extensive exposure, and rigid plate fixation in the setting of the trauma center have permitted early operation with improved results. A subset of patients with facial fractures will also have intracranial injuries (ICI). We sought to identify parameters associated with an increased risk for ICI. We also sought to examine the safety and limits of early craniofacial repair in patients with intracranial injuries. Of 114 mid-face fractures treated over a 1-year period, 43 (38%) had a concomitant ICI. The majority, 36 (84%), were from motor vehicle accidents (MVA). Frontal sinus and orbitoethmoid fractures were at the highest risk for ICI, although orbitozygomatic fractures caused by MVAs also had a surprisingly high incidence of ICI. Our results show that early craniofacial repair can be performed safely with appropriate general surgical and neurosurgical support.

Structure and replication of echovirus type 12. 2. Viral polypeptides synthesized in the infected cell. A technique has been devised which allows us to label predominantly echovirus-12-specific proteins: upon infection in the presence of D-(--)-2-(alpha-hydroxybenzyl)benzimidazole plus actinomycin D the shut-off of host-cell protein synthesis takes place as in infected, untreated cells, but the bulk of viral protein synthesis is inhibited. Upon removal of 2-(alpha-hydroxybenzyl)benzimidazole a peak of viral protein synthesis is visible 3 h later. The time course of appearance of viral proteins is followed by dodecyl sulfate/polyacrylamide gel electrophoresis of the proteins which had been pulse-labeled at different times post-infection. The protein patterns induced in the infected cells by echovirus 12 and poliovirus 2 are compared; though they are different, some analogies are observed. The molecular weights of the polypeptides are determined. In the presence of amino acid analogs cleavage of viral proteins is impaired. A group of large proteins up to Mr 220,000 is detectable in the infected cell which ordinarily is not observed. The 220,000-Mr protein may represent the translation product of the total viral RNA. The hierarchy of the virus-specific proteins originating from post-translational cleavage is discussed.