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Depression of elderly outpatients: primary care physicians' attitudes and practice patterns. To determine primary care physicians' attitudes and practice patterns concerning the diagnosis and treatment of depression in elderly outpatients. Survey of primary care physicians' attitudes using a 22-item questionnaire. Current practice patterns were identified from a computerized medical record system. Academic primary care group practice at an urban ambulatory care clinic. Thirty-five faculty general internists and 118 resident internal medicine physicians who had cared for 2,759 patients 65 years of age and older in the previous year. Attitudes: Eighty percent of all physicians considered the diagnosis and treatment of depressed elderly patients to be their responsibility. Fifty-five percent of the internists felt confident in accurately diagnosing depression, and 35% felt confident in prescribing antidepressants for this population. Residents reported more difficulties in dealing with depressed elderly patients than did faculty. Practice patterns: Of patients greater than or equal to 65 years old, 8% were prescribed antidepressants, 5.4% had current diagnoses of depression, and 2% were seen for evaluation by psychiatry professionals. Age was negatively correlated with depression diagnosis, antidepressant drug use, and psychiatry evaluation. Internists in this primary care group practice accept responsibility for the treatment of depressed elderly patients but perceive their clinical skills as inadequate and are frustrated with their practice environment. Interventions aimed at improving the diagnosis and treatment of depressed elderly patients may be more effective if they are able to improve knowledge, attitudes, and the practice environment.

Hypercalcemia with excess serum 1,25 dihydroxyvitamin D in lymphomatoid granulomatosis/angiocentric lymphoma. Hypercalcemia has been described in a variety of granulomatous and lymphoproliferative disorders in association with elevated serum levels of 1,25-dihydroxyvitamin D. In such cases, hypercalcemia appears to be the consequence of excessive production of 1,25(OH)2D by the lymphocyte/macrophage line. The authors report a patient with lymphomatoid granulomatosis/angiocentric lymphoma who developed hypercalcemia with extreme elevation in serum 1,25(OH)2D. Therapy with steroids reduced the serum calcium and 1,25(OH)2D levels to normal. Hypercalcemia has not previously been reported in lymphomatoid granulomatosis/angiocentric lymphoma. The distinctive features of this malignancy, and the derangement in the metabolism of 1,25(OH)2D in lymphoproliferative disorders in general, are discussed.

Isoniazid hepatitis in adolescents. Prophylactic isoniazid therapy is currently recommended for adolescents with positive tuberculin reactions because of the risk of activation of tuberculosis in this age group. Since this drug has been associated with hepatic dysfunction in adults, the present study was undertaken to evaluate its effect on liver function in teen-agers. Accordingly, liver function tests were performed on 178 adolescents prior to and following administration of INH. Abnormalities in SGPT values were encountered in 10% of these patients and occurred in the main within the first 10 weeks of testing, suggesting INH maybe hepatotoxic. However, jaundice was notably absent in the patients with enzyme elevations and prompted a further investigation into the possible effect of INH on bilirubin metabolism. Thus, Sprague-Dawley rats were given four daily injections of INH. These animals manifested increased hepatic bilirubin glucuronyl transferase activity when compared with control rats, supporting the hypothesis that enzymatic induction may be responsible for the absence of jaundice in our adolescent subjects.

Effects of 5-bromodeoxyuridine on development of Mauthner's neuron and neural retina of Xenopus laevis embryos. Bromodeoxyuridine (BrUdR) injected into Xenopus embryos at stages before, during or after the last period of DNA synthesis in Mauthner's neurons had no serious effect on differentiation of Mauthner's neurons. However, the BrUdR caused widespread cell degeneration in the central nervous system. The action of BrUdR on retinal neuronal differentiation depended on dose and stage of infection. At all doses (0.005-0.9 microgram per injection), and all stages (22-29), the main effect was retinal cell degeneration. The drug produced complete absence of differentiated retinal neurons only when given at early stages (22-24) and at the highest doses (0.5-0.9 microgram) that enabled the embryo to survive to stage 44. At stages 22-24 at lower doses (0.005 or 0.05 microgram per injection) and at stages 26-29 at all doses, some retinal neurons differentiated, although retinal cell degeneration was the main effect. In these two systems BrUdR did not selectively inhibit neuronal differentiation.

Angiomyofibroblastoma of the vulva. A benign neoplasm distinct from aggressive angiomyxoma. Aggressive angiomyxoma of pelvic soft parts is a rare lesion with a high risk of recurrence. We report 10 cases of angiomyofibroblastoma, a hitherto uncharacterized benign tumor of the vulva histologically mimicking aggressive angiomyxoma. All patients had a vulval mass, often clinically diagnosed as a Bartholin's cyst. There was no recurrence after excision. The tumors were well circumscribed, measuring 0.5-12 cm in maximum dimension. They were characterized by alternating hypercellular and hypocellular edematous zones in which abundant blood vessels (predominantly of the capillary type) were irregularly distributed. Spindled, plump spindled, and oval stromal cells were aggregated around the blood vessels, sometimes forming solid compact foci, or were loosely dispersed in the hypocellular areas. Their nuclei were bland, but rare ones were enlarged and hyperchromatic in four cases. Some cells had abundant eosinophilic hyaline cytoplasm and eccentrically placed nuclei. Mitotic figures were absent or very sparse. Scattered throughout were thin, wavy strands or thick bundles of collagen. Mast cells were readily seen in eight cases. Immunohistochemically, the stromal cells were reactive for vimentin and desmin, but not cytokeratin, muscle-specific actin, alpha-smooth muscle actin, or S-100 protein. Ultrastructural studies showed well-developed rough endoplasmic reticulum, Golgi apparatus, abundant intermediate filaments, and pinocytotic vesicles in the stromal cells. Angiomyofibroblastoma can be distinguished from aggressive angiomyxoma by its circumscribed borders, much higher cellularity, more numerous blood vessels (which lack prominent hyalinization), frequent presence of plump stromal cells, minimal stromal mucin, and rarity of erythrocyte extravasation.

Estimation of heterogeneous within-herd variance components using empirical Bayes methods: a simulation study. Genetic evaluation using BLUP can accommodate heterogeneous variances if the necessary variance components are known; this may require estimation of variance components within each heterogeneous subclass. Properties of sire and residual variance estimates obtained by an empirical Bayes approach, which combines within-herd and prior estimates, were examined via simulation. Prior estimates were obtained using REML across herds, as if variances were homogeneous. Convergence was improved by incorporation of prior information such that variance component estimates could be obtained in within-herd situations for which a REML algorithm failed to converge. Accuracy of sire variance estimates was greatest when both within-herd and prior information were used, but improvement in accuracy of residual variance estimates associated with incorporation of prior information was minimal. Correlations between sires' standardized true transmitting abilities and PTA that used empirical Bayes variance estimates were larger than those obtained when heterogeneity was ignored. Proportions of sires selected, based on standardized PTA, from environments with differing genetic and residual variances became more uniform as the relative weight placed on within-herd data in variance estimation increased. Thus, useful variance component estimates can be obtained within individual herds by using empirical Bayes methods with across-herd estimates as prior information; this may allow prediction of breeding values that are less influenced by heterogeneous variances.

Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique. The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell--nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell--nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.

Internalization and down-regulation of the human epidermal growth factor receptor are regulated by the carboxyl-terminal tyrosines. The C terminus of the epidermal growth factor receptor (EGF-R) contains three tyrosines (Y1068, Y1148, and Y1173) which correspond to the major autophosphorylation sites. To investigate the role of the tyrosines in internalization and down-regulation of the EGF-R, mutational analysis was performed with receptors in which 1, 2, or all 3 tyrosines were changed to phenylalanines. The triple point mutant EGF-R, expressed in NIH-3T3, exhibited low autophosphorylation in vivo, low biological and reduced kinase activities. Single and double point mutants were down-regulated, as well as wild type EGF-R in response to EGF showing a half-life of about 1 h. Degradation of the triple point mutant, however, was impaired and resulted in a half-life of 4 h in the presence of EGF. EGF-dependent down-regulation of surface receptors was decreased in the triple point mutant EGF-R as was internalization and degradation of EGF. The specific rate of internalization of the triple point mutant was reduced. By contrast, intracellular processing of ligand previously internalized at 20 degrees C was similar between wild type and mutant receptors. Taken together the data indicate that the delay in degradation observed in cells expressing the triple point mutant EGF-R can be attributed mainly to a slower removal from the cell surface. Our results show that in the full-length EGF-R all three C-terminal tyrosines are necessary for rapid internalization, suggesting that autophosphorylation is required for efficient EGF-dependent receptor endocytosis.

The gene for the common alpha subunit of porcine pituitary glycoprotein hormone. The gene for the common alpha subunit of the porcine anterior pituitary glycoprotein hormones was cloned from a genomic library constructed in EMBL3. The nucleotide sequence of the entire coding sequence of the porcine common alpha-subunit gene was determined in addition to one intron and 1059 and 160 bp of the 5'- and 3'-flanking regions respectively. Southern blot analysis of the porcine genomic DNA indicated that the common alpha-subunit gene is present as a single copy. The transcriptional unit of the porcine common alpha subunit spanned about 14 kb and contained four exons interrupted by three introns of about 11.5, 1.2 and 0.4 kb. The short untranslated sequence in the first exon and the location of the exon/intron junctions at amino acid residues +9/+10 and +71/+72 were highly conserved among the rat, human and bovine common alpha-subunit genes. In the proximal portion of the 5'-flanking region, one TATA box and one CCAAT box were present. A steroid-responsive element was not found up to 1059 bases upstream from the transcription start site. The potential AP-1 and AP-2 factor-responsive elements were present at three and one positions respectively in the 5'-flanking region. This feature suggests that hypothalamic gonadotrophin-releasing hormone stimulates the expression of the common alpha-subunit gene predominantly by a signal-transduction system, with the protein kinase C cascade and factors AP-1 and AP-2 as mediators. The cyclic AMP-responsive element was also present at two positions, but a single base substitution was found in each sequence compared with the consensus sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth of cultured human cerebral meningiomas is inhibited by dopaminergic agents. Presence of high affinity dopamine-D1 receptors. We have found that microM concentrations of the dopamine agonist bromocriptine significantly decrease the proliferation rate of human meningioma cells in culture (25-56% inhibition). This effect was also seen with direct application of dopamine, as well as the dopamine-D1 agonist (+)-SKF-38393 (both applied in microM concentrations) to meningioma cell cultures. Receptor studies with the dopamine-D1 ligand (125I)SCH-23982 (dopamine-D1 antagonist) indicated that dopamine-D1 binding sites were present in the membranes of meningioma tissue. The mean dissociation constant (Kd) was 325 ( +/- 74.5 SEM) pM and the receptor density (Bmax) was 25.4 ( +/- 1.5 SEM) fmol/mg pellet protein in 5 human meningiomas. The pharmacological specificity was proven by (+)-SKF-38393, ( +/-SKF-83566 or (+)-butaclamol and their inactive isomers (-)-SKF-38393 and (-)-butaclamol in a 1000 fold excess. These results provide evidence that human meningiomas possess high affinity dopamine-D1 receptors and that dopamine agonists have an antiproliferative effect on these tumors in culture. We conclude that the proliferation of cerebral meningiomas may be under dopaminergic control and that dopamine agonists may have a role in the medical treatment of patients with meningiomas.

Do we need another antihypertensive agent? The factors to be considered in selecting antihypertensive agents have traditionally centered around balancing efficacy against adverse side effects. The former can be achieved by a variety of agents alone or in combination. The latter not only involves safety but is also concerned with whether an otherwise safe agent is tolerated by the patient so compliance with the treatment regimen can be achieved. A relatively new consideration is how antihypertensive agents affect other disease states that may or may not be associated with hypertension. For example, how a drug may affect diabetes, gout, myocardial hypertrophy, atherosclerosis, and coronary events must be evaluated. These concerns taken together answer the question of why yet another antihypertensive agent may be needed in the pharmacologic armamentarium.

Chemotherapy in advanced ovarian cancer. Most patients with epithelial cancer of the ovary are not cured by surgery, since their cancer has spread beyond the ovaries. The majority of these patients are not suitable for postoperative irradiation therapy, since the residual tumors are too large to be effectively treated with irradiation or they have metastasized to areas that cannot be effectively irradiated. Approximately 50% of the patients with advanced ovarian cancer who are treated postoperatively with melphalan will benefit from this chemotherapy. Approximately 40% of the patients who do not respond to chemotherapy with melphalan will benefit from treatment with a combination of actinomycin D, 5-fluorouracil, and cyclophosphamide. A second-look operation after 12 or more cycles of chemotherapy is often helpful in planning future treatment of patients, and it may be curative in a few patients if all the remaining tumor can be excised.

Metabolic investigations after xylitol infusion in human subjects. Evidence has been sought for minor degrees of thiamin and pyridoxine deficiency in patients undergoing surgery who have been infused with xylitol as a parenteral nutrient. Some metabolic changes which are associated with this practice have been studied; the findings are compared with those obtained in similar patients infused with glucose solutions. The thiamin status of all of the subjects was normal. Some of the patients showed slight biochemical evidence of pyridoxine deficiency, but there were no untoward effects of xylitol infusion. The concentration of oxalate in the blood and the excretion of oxalate in the urine did not exceed the normal range in any patient. The plasma and urine orthophosphate and urinary pyrophosphate levels decreased in association with the infusion of both xylitol and glucose. Plasma pyrophosphate and calcium levels, and the urinary calcium level, were essentially unaltered. A detailed quantitative study of the urinary organic acid excretion by means of gas chromatography/mass spectrometry showed that there was an abnormal glycolic aciduria and tetronic aciduria associated with xylitol infusion, but not with glucose infusion. There was no evidence of increased oxalate excretion in any patient by this method. The biochemical and clinical significance of these findings is discussed.

The effect of fat on secretin release. The effect of graded doses of intravenously infused secretin and intestinally perfused sodium oleate and HCl on pancreatic exocrine secretion and plasma secretin was determined in cats and dogs prepared with pancreatic fistulas. The pancreatic dose--response curves for bicarbonate following duodenal perfusion of oleate and HCl in cats were almost identical and paralleled the response to exogenous secretin. Although the bicarbonate response to oleate in dogs was less pronounced than the response to HCl or secretin, the bicarbonate output was observed to increase relative to protein output with increasing doses of the intestinally perfused fat. These observations suggested that secretin or a substance with secretin-like activity may be released from the intestine on contact with fat. The inability to detect changes in secretin immunoreactivity in both cats and dogs with increasing doses of oleate suggests that if secretin is released, it is in amounts undetectable by our radioimmunoassay or that some other unknown substance with secretin-like activity may be released.

Oxytocin augmentation of labor and perinatal outcome in nulliparas. Recent pharmacologic observations in vivo suggest the use of a lower starting dose (0.5-0.1 mU/minute) of oxytocin and a longer interval between dose augmentations (30-60 minutes) than previously advocated. In this study, a high-dose oxytocin protocol was used to augment nonprogressive labor in normal nulliparous women. The rate of oxytocin infusion started at 6 mU/minute and was increased by 6 mU/minute every 15 minutes to a maximum dose of 40 mU/minute. Charts were reviewed of 1080 nulliparous women for whom the principles of active management of labor were followed and delivery occurred between March 1, 1986 and December 31, 1988. Four hundred fifty-six who required oxytocin augmentation in labor were compared with 624 who did not receive oxytocin. There were no statistically significant differences in birth asphyxia or perinatal morbidity.

Rhabdomyolysis: report of eleven cases. This article reports the results of a retrospective study of 11 patients with rhabdomyolysis-induced acute renal failure. All patients had multiple risk factors for rhabdomyolysis, the most common of which were alcoholism, illicit drug abuse, compression, and trauma. Patients with combined alcohol/illicit drug abuse had more severe electrolyte imbalances than patients without alcohol/illicit drug abuse. Myoglobinuria was detected in only half the patients despite rhabdomyolysis and urine "hematest" positivity. The serum creatine phosphokinase level was elevated in all of the patients, which is a good marker for rhabdomyolysis. Rhabdomyolysis is a relatively common disorder in municipal hospitals. Routine serum creatine phosphokinase levels should be checked on patients at risk, especially alcoholics, illicit drug abusers, and older patients.

Maintenance of motility of fowl spermatozoa in vitro is prolonged by a low molecular weight factor derived from cultured chick embryo cells. Gel filtration of a conditioned medium composed of the supernatant fluid removed from a 5-day culture of skeletal muscle cells from 9-day-old chick embryos with Bio-Gel P-2 revealed one peak of motility-prolonging activity (about 0.3 kDa), which was not present in fresh medium. Spermatozoa incubated in this fraction of the conditioned medium maintained their motility for at least 36 h at 37 degrees C. Both the formation of lipid peroxide and the leakage of lactic dehydrogenase of spermatozoa incubated in the conditioned medium fraction were lower than those incubated in the corresponding fresh medium. Initial rate of oxygen consumption of the spermatozoa incubated in the conditioned medium fraction increased compared with that of the fresh medium fraction. These results suggest that a low molecular weight factor(s) supplied by cultured cells effectively prolongs the motility of fowl spermatozoa, and that the effect could result from inhibition of the structural damage to the sperm membrane.

Evaluation of knee joint cartilages and menisci in patients with chronic inflammatory joint diseases. A prospective arthroscopic study before, six and twelve months after open synovectomy. Destruction of joint cartilage is an important feature in chronic inflammatory joint diseases. This article considers the areas of the cartilages of the knee joint prone to destructive changes, pannus growth and marginal erosions, and the changes of pattern after open synovectomy. Twenty-eight patients with chronic inflammatory joint disease which gave indication for synovectomy of the knee joint had arthroscopy immediately before, 6 and 12 months after open synovectomy. A method of grading the changes of the cartilage, pannus growth, menisci and marginal erosions is described. There was an increase in cartilage pathology 12 months after synovectomy (p less than 0.001), particularly on the weight bearing areas of the femur and on the tibial condyles. No significant deterioration in areas with pathology at the time of synovectomy was found in the follow up. Pannus growth was particularly located to areas 2 and 4 on the femoral condyles. We conclude that cartilage destruction after synovectomy is more likely to be a result of osteoarthrosis than arthritic changes.

Structure-activity studies with chiral isomers and with segments of the antimitotic marine peptide dolastatin 10. Eighteen configurational isomers of the antimitotic peptide dolastatin 10 (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990) derived from Dolabella auricularia, together with segments obtained as precursors in its synthesis (Pettit et al., J Am Chem Soc 111: 5463-5465, 1989), were examined as inhibitors of tubulin polymerization and as inhibitors of growth of L1210 murine leukemia cells in culture. Dolastatin 10 consists of four amino acids (in order from the amino terminus: dolavaline, valine, dolaisoleucine, and dolaproine), three unique to D. auricularia, linked to an unusual primary amine (dolaphenine, probably derived from phenylalanine) at what would otherwise be its carboxyl terminus. Dolastatin 10 has nine asymmetric carbon atoms, and available isomers included alternate configurations at five positions (positions 9 and 10 in the dolaproine moiety and positions 18, 19 and 19a in the dolaisoleucine moiety). For tubulin polymerization, only alterations at positions 18 and 19 resulted in loss of inhibitory activity of the isomer. In addition, a tripeptide containing dolavaline, valine and dolaisoleucine with all asymmetric carbons identical configurationally to those in dolastatin 10 was found to be about 30% as effective as dolastatin 10 in inhibiting tubulin polymerization. Cytotoxic effects were much more sensitive to alterations in the dolastatin 10 structure. The only modification which did not lead to reduced cytotoxicity was reversal of configuration at position 19a in the dolaisoleucine moiety. Both this isomer and dolastatin 10 had IC50 values of less than 1 nM. Several other isomers had IC50 values with the L1210 cells in the range of 30-90 nM, but these did not correlate well with their inhibitory effects on tubulin polymerization. The tripeptide effective as an inhibitor of tubulin polymerization had no activity against the L1210 cells.

[Interventional radiologic procedures in complete occlusions of long stretches of the iliac artery]. 15 completely occluded iliac arteries (five cases over 10 cm, 8 cases between 5 and 10 cm and two cases below 5 cm) were reviewed for their interventional management, technical results and complications. The procedure was successful in 14 of 15 cases (93%). In six cases we performed local thrombolysis before PTA. In the patient group with "only PTA" the treatment had to be abandoned in one case because of the risk of embolism. Two patients suffered from a distal embolism of the same side and one patient from an ipsi- and contralateral embolism. A stent implantation was necessary in one patient. In the group of patients with prior local thrombolysis there was no complication nor was there an indication for a stent-implantation. Hence, we conclude that a primary local lysis with a consecutive PTA is an appropriate treatment of complete long occlusions of the iliac artery.

Distinct mechanisms of extrathymic T cell tolerance due to differential expression of self antigen. Self-reactive T lymphocytes escaping thymic tolerance induction can be rendered non-responsive by contact with antigens in the periphery. In order to determine the parameters controlling peripheral tolerance induction we followed the fate of one well-defined self-reactive T cell population in three different mice expressing the self antigen in various nonlymphoid tissues outside the thymus. This was achieved by crossing anti-Kb T cell receptor (TCR) transgenic mice with transgenic animals expressing the Kb antigen exclusively on hepatocytes or keratinocytes or neuroectodermal cells. Due to this differential expression clonotype+, anti-Kb reactive T cells were found to exist at three different levels of tolerance. These levels were distinct with regard to downregulation of TCR and CD8 molecules, and the requirements for reexpression of TCR in vitro. This differential induction of peripheral tolerance suggest that some tissues are more likely to be affected in autoimmune diseases than others.

Mucin-like glycoproteins secreted from cultured hamster tracheal surface epithelial cells: their hydrophobic nature and amino acid composition. Confluent cultures of primary hamster tracheal surface epithelial cells synthesize and secrete high molecular weight mucin-like glycoproteins (HMW MLGP). Secreted HMW MLGP are highly associated with various lipids, indicating that they are extremely hydrophobic. These HMW MLGP are also associated with varying amounts of "small" glycoproteins via hydrophobic interactions and they can be dissociated by heat and detergent treatments. HMW MLGP free of these "small" glycoconjugates have a buoyant density of 1.5 g/ml and can enter 4% but not 7.5% gels during SDS-polyacrylamide gel electrophoresis. Amino acid composition analysis of HMW MLGP free of these "small" glycoproteins shows that they are relatively rich in serine, threonine, and proline, but the total content of these amino acids seems somewhat lower than that of in vivo airway mucins.

Surface markers of porcine lymphocytes and distribution in various lymphoid organs. Three rosette test systems were developed for the classification of subpopulations of porcine lymphocytes and correlated with the presence or the absence of membrane immunoglobulins, as well as agg-P-IgG receptors, by means of various RFC depletion experiments. Among the ED-RFC negative cells, PBL with surface immunoglobulins (SIg), at 4 degrees C, can be subdivided into two about equal populations: (1) One half of these cells have surface stable SIg (B cells) and mu determinants; they possess C3b receptors leading to the formation of rosettes with complement-coated zymosan particles (ZC). (2) The other half have surface labile Ig when the cells are washed at 37 degrees C (L-cells); they possess Fc receptors as detected by EA-RFC, i. e. pig-IgG-coated ox RBC. Receptors for Fc-agg, as detected by agg-P-IgG, were primarily shown on B cells. ZC and EA-RFC are in the highest tissue concentration, in bone marrow and spleen, respectively, and more numerous in adults than in newborns. Moreover, the number of EA-RFC was twofold higher than that of ZC-RFC in spleen, mesenteric lymph node and cisterna chyli. This latter organ was the only one without null cell.

Some problems of alpha-fetoprotein screening. In two years of a routine screening programme for the detection of neural-tube defects over 6000 women had serum-alpha-fetoprotein (A.F.P.) measured. As a result, 80 women carrying live singleton fetuses were offered amniocentesis under ultrasound control. All neural-tube defects detected at birth were recorded and necropsies were done routinely on abortuses, thus permitting evaluation of the screening programme in terms of false negatives and false positives. 16 amniotic-fluid A.F.P.s were abnormal, 1 for an unaffected fetus; and 2 others were normal for fetuses which had closed lesions. At the serum-A.F.P. stage, 3 lesions were missed. The detection-rate compares favourably with those of other series. However, in a pilot study, routine ultrasonic assessment of gestation yielded a substantial proportion of cases where a serum-A.F.P. deemed normal or abnormal when gestation was assessed clinically would have been misleading. Loss of normal fetuses subsequent to amniocentesis (5 in this series) also has to be taken into account.

Reversible hypothyroidism in growth hormone-deficient children treated with human growth hormone. Six children with human growth hormone (hGH) deficiency became hypothyroid during the course of their therapy with hGH. This was accompanied by a decreasing growth rate, clinical symptoms of hypothyroidism and decreased serum T4 concentrations. Three of the 6 patients returned to the euthyroid state, both clinically and biochemically, with cessation of hGH therapy, and reinstitution of hGH precipitated hypothyroidism again in 2 of the three. The patients who remained hypothyroid have evidence of multiple pituitary trophic hormone deficiencies while those who reverted to euthyroidism appear to have isolated hGH deficiency. Evaluation of thyroid function while on hGH showed low T4, free T4 and T3 concentrations. The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent or markedly blunted in 4 of 6 patients while receiving long-term hGH therapy but was normal or exaggerated in all patients when tested before or after only 5 days of hGH therapy. These data indicate that exogenous hGH results in an inhibition of the TSH response to TRH. The mechanism of this inhibition is unclear, but we postulate that it may be mediated by somatostatin secretion in response to pulse doses of hGH.

Prevalence and patterns of drug use among high-school students: a replicated study. A survey of high-school students in Delhi, carried out in 1975, revealed that 34.3 per cent of respondents used psychoactive drugs in the preceding year. The percentage of users of psychoactive substances other than alcohol and tobacco was 15.5 per cent. The percentage prevalence rates by substance ranked as follows: tobacco (35.1), alcohol (26.2), cannabis (12.0), tranquillizers (8.9), amphetamines (5.8), sedatives (4.9) and opium (1.3). The survey was replicated in the same classes of students in 1976. It revealed that the non-response vote was slightly lower, as was also involvement with drugs, though the difference between prevalence rates of drug use in the two years was not statistically significant.

Problem-solving skills, locus of control, and the contraceptive effectiveness of young women. It was proposed that the lack of insight into the risk-taking behavior of many sexually active women who do not want to get pregnant may reflect the lack of an adequate framework from which to investigate the problem. The purpose of this study was to examine the relationships between contraceptive effectiveness and several cognitive factors. The sample consisted of 155 single women, 15.3-25.7 years of age, from a Planned Parenthood clinic and an abortion clinic. Contraceptive effectiveness, operationally defined as the number of unplanned pregnancies in a woman's history, was significantly and negatively related to means-ends problem-solving ability and a belief in internal control and significantly and positively related to a belief in chance control. It was suggested that these results support the utility of a cognitive, problem-solving approach to the study of contraceptive behavior.

Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. Interleukin-3 (IL-3) is a T-cell-derived colony-stimulating factor (CSF) whose primary targets include relatively early, multipotential, hematopoietic progenitor cells. In this trial, we treated 24 patients with recombinant human IL-3 given by a daily 4-hour intravenous infusion for 28 days. The dose levels were 30, 60, 125, 250, 500, 750, and 1,000 micrograms/m2/d. At least three patients were entered at every dose level. Each participant suffered from bone marrow failure, with the underlying diagnosis being myelodysplastic syndrome (13 patients), aplastic anemia (eight patients), or aplasia after prolonged high-dose chemotherapy (three patients) for multiple myeloma, breast cancer, or acute myelogenous leukemia. Most patients tolerated therapy well, with the most frequent side effects being low-grade fever and headaches. Hematopoietic changes included modest increases in neutrophil counts (eight patients), eosinophil counts (six patients), platelet counts (three patients), and reticulocyte counts (two patients). An increase in blasts occurred in one patient who had refractory anemia with excess blasts in transformation and was reversible once IL-3 was discontinued. In addition, one patient with chronic myelomonocytic leukemia showed an increase in monocytes (and granulocytes). Progression to acute leukemia did not occur. Pharmacokinetic analyses showed a rapid clearance with a mean half-life of 18.8 minutes at the 60 micrograms/m2/d dose, and 52.9 minutes at the 250 micrograms/m2/d dose. Serum concentrations of 10 to 20 ng/mL of IL-3 were achievable at the 250 micrograms/m2/d dose. Our observations indicate that recombinant human IL-3 can be given safely at doses of 1,000 micrograms/m2/d or less. In addition, on the basis of preclinical data and the biologic activity observed in this study, further trials of this molecule, alone and in combination with other growth factors, are warranted in patients with pancytopenia.

Biochemical parameters associated with low bone density in healthy men and women. A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women.

[Proceeding: Production rate, metabolic clearance rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)]. The adrenocortical function was studied in 23 patients with hyperthyroidism and compared with a group of 15 normal subjects. Parameters of adrenal function were determined with 1,2(3)H-cortisol. The half-life of cortisol is significantly shortened in hyperthyroidism, as compared to normal subjects (49,5 +/- 6,6 min vs 68,3 +/- 10,5 min) and metabolic clearance rate is increased (418,5 +/- 89,5 L/24 h vs 237,5 +/- 48,5 L/24 h, for normal subjects). The production rate of cortisol, calculated from specific and cumulate activities of THE and THF is increased in hyperthyroidism expressed as mg/24 h or mg/m2/24 h (respectively : 26,7 +/- 7,8 mg/24 h vs 15,7 +/- 3 mg/24 h and 16,9 +/- 4,6 mg/m2/24 h vs 9,5 +/- 1,8 mg/m2/24 h). The mean plasma concentration, calculated as the radio (see article) is not statiscally different in hyperthyroid and normal subjects (6,8 +/- 2,1 microg/100 ml vs 7,3 +/- 1,9 microg/100 ml). 7 patients were reinvestigated after treatment of thyrotoxicosis when they were clinically and biologically in euthyroid state. All the values were normalized, without statistically significant difference from control (T 1/2 = 65,4 +/- 18 min, Metb Cl. Rate : 255 +/- 64,5 L/24 h, production rate : 15,6 +/- 1,8 mg/24 h and 9 +/- 1,4 mg/m2/24 h. mean plasma concentration : 6,8 +/- 2,8 microg/100 ml). Shortened cortisol half life, increased metabolic clearance rate and production rate, and normal mean plasma concentration have been reported in hyperthyroidism (Peterson, Copinschi, Gallagher). These changes, secondary to thyroid hormone excess, are the consequences of increased hepatic catabolism of cortisol. The activity of 11 OH steroid deshydrogenase is increased, as demonstrated by increased ratio (see article) in normal subjects (0,001 less than p less than 0,005). There is a high proportion of 17 kéto metabolites (E, DHE, THE) whose feed-back effect is weak as compared to 17 OH metabolites (F, DHF, THF). The hypothalamo-hypophyso-adrenal system is stimulated to maintain a normal plasma concentration. The fact that the mean plasma concentration is normal despite the increased production rate suggest that changes are rather due to increased catabolism than to central effect of thyroid hormones.

Atrial natriuretic factor-potentiating and antihypertensive activity of SCH 34826. An orally active neutral metalloendopeptidase inhibitor. The effects of SCH 34826, an orally active neutral metalloendopeptidase inhibitor, on responses to atrial natriuretic factor-(103-125) or -(99-126) and on blood pressure were evaluated in rats. SCH 34826 (10, 30, and 90 mg/kg s.c. and 90 mg/kg p.o.) potentiated the antihypertensive action of atrial natriuretic factor (30 micrograms/kg i.v.) in conscious spontaneously hypertensive rats. SCH 34826 (90 mg/kg) also potentiated the diuretic and natriuretic responses to atrial natriuretic factor (30 micrograms/kg i.v.) as well as the plasma levels achieved after peptide injection. SCH 34826 significantly reduced blood pressure in the conscious deoxycorticosterone acetate-salt hypertensive rat, at doses of 90 mg/kg s.c. (-35 +/- 12 mm Hg), 10 mg/kg p.o. (-30 +/- 7 mm Hg), and 90 mg/kg p.o. (-45 +/- 6 mm Hg). SCH 34826 was devoid of acute antihypertensive activity in the spontaneously hypertensive rat but reduced blood pressure by day 3 of a 5-day treatment schedule. SCH 34826 (90 mg/kg s.c.) enhanced urine volume output in the deoxycorticosterone acetate-salt rat (2.78 +/- 0.6 vs. 1.27 +/- 0.3 ml/100 g/3 hr in vehicle-control rats, p less than 0.05). SCH 34826 (90 mg/kg s.c.) increased plasma levels of atrial natriuretic factor at 1 hour (753 +/- 89 vs. 451 +/- 79 pg/ml in vehicle-treated rats, p less than 0.05) but not 3 hours after dosing. The renal excretion of atrial natriuretic factor (3,092 +/- 1,089 vs. 21 +/- 6 pg/100 g/3 hr in vehicle-treated rats, p less than 0.05) and cyclic guanosine monophosphate (2,131 +/- 509 vs. 879 +/- 168 pg/100 g/3 hr in vehicle-treated rats, p less than 0.05) was markedly elevated by SCH 34826 in deoxycorticosterone acetate-salt rats. These studies suggest that neutral endopeptidase inhibition may represent a new approach to treatment of some forms of hypertension.

Laboratory trials with inactivated vaccines against Escherichia coli (O2:K1) infection in fowls. Laboratory trials were carried out with an O2:K1 vaccine prepared with either the Freund's complete or incomplete adjuvant. Both types of vaccine administered subcutaneously were highly effective against a challenge with the vaccine strain within three to four weeks after vaccination at two to three weeks of age. The complete adjuvant vaccine was more effective than the incomplete adjuvant vaccine when administered to chickens of an earlier age, and in the rate of development and duration of immunity. The efficacy of both vaccines was unimpaired by their incorporation with the Newcastle disease oil adjuvant (inactivated) vaccine (Newcadin). The use of an oil adjuvant vaccine was not found to affect the rate of growth adversely or to produce any other reaction prejudicial to its commerical application. The efficacy of the vaccines was unimpaired by their incorporation with Newcastle disease oil adjuvant (inactivated) vaccine (Newcadin) thus demonstrating the possibility of producing a combined Escherichia coli/Newcastle disease virus vaccine.

Effects of brefeldin A on endocytosis, transcytosis and transport to the Golgi complex in polarized MDCK cells. We have studied the effects of brefeldin A (BFA) on endocytosis and intracellular traffic in polarized MDCK cells by using the galactose-binding protein toxin ricin as a membrane marker and HRP as a marker of fluid phase transport. We found that BFA treatment rapidly increased apical endocytosis of both ricin and HRP, whereas basolateral endocytosis was unaffected, as was endocytosis of HRP in the poorly polarized carcinoma cell lines HEp-2 and T47D. Tubular endosomes were induced by BFA both apically and basolaterally in some MDCK cells, comparable with those seen in HEp-2 and T47D cells. In addition, in MDCK cells, BFA induced formation of small (< 300 nm) vesicles, labeled both after apical and basolateral uptake of HRP, as well as some very large (> 700 nm) vacuoles, which were only labeled when HRP was present in the apical medium. In contrast, neither in MDCK nor in HEp-2 or T47D cells, did BFA have any effect on lysosomal morphology. Moreover, transcytosis in the basolateral-apical direction was stimulated both for HRP and ricin. Other vesicular transport routes were less affected or unaffected by BFA treatment. Two closely related structural analogues of BFA (B16 and B21), unable to produce the changes in Golgi and endosomal morphology seen after BFA treatment in a number of different cell lines, were also unable to mimic the effects of BFA on MDCK cells.

[Systolic and diastolic load of right heart and right bundle block]. Analysing the Ecg and VCG of 818 subjects, healthy or with different congenital and acquired cardiopaties, the frequency of right bundle branch block (RBBB) is established to decrease with the increase in age of children, and is observed to be 8.9% in healthy adults. The right bundle block is observed in 82.5% of the patients with atrial septal defect and quite often in patients with right ventricle tension loading, gradually decreasing with the level of the left ventricle loading, as well as with the development of extreme right ventricle hypertrophy. Out of 50 experiments with dogs with acute and chronic right heart tension loading it is evident that the number of certain and marginal (uncertain) cases with RBBB steadily increases. At the same time this increase cannot be connected with the type of loading, in dogs in which dilatation of the right ventricle is presented as well as in others with light or marked hypertrophy. Besides, under the same conditions and durations of loading some hearts exhibit RBBB, while others do not. What has been stated before gives enough grounds to accept that RBBB in healthy subjects, as well as in patients with congenital and acquired cardiopaties manifests the electromotive tension (EMT) of persistent from foetal and children-age more pronounced physiological hypertrophy (as normal variant) of the basal part of the right ventricle. Whether the picture of RBBB is retained, pronounced or disappears is determined by the correlation between the quantity and the time-manifestation of EMT of the left ventricle and of the corps part of the right ventricle.

A technical and biomechanical comparison between two types of microvascular anastomoses. An experimental study in rats. The microvascular sleeve anastomosis, where one vessel is inserted into the other, was compared with the conventional end to end anastomosis. In an experimental study in rat femoral arteries 42 anastomoses of each kind were examined. Operating time, patency rates, flow rates and strength of the anastomoses were recorded at various postoperative time intervals. It is concluded that the sleeve anastomosis is quicker to perform and that the two types of anastomoses in biomechanical respects are similar. Flow rates are slightly decreased immediately postoperatively in the sleeve anastomosis but this is of a temporary nature.

Distinct and overlapping functions of allelic forms of human mannose binding protein. Human mannose binding protein (MBP) is a C-type serum lectin involved in first-line host defense against a variety of bacterial, fungal and viral pathogens. Recently an association was found between low levels of serum MBP and an increased frequency of recurrent infections in infants. A particular genotype, in which glycine is substituted by aspartic acid at codon 54 of MBP in the fifth collagen repeat, shows apparent concordance with the clinical phenotype. We report, however, that this genotype occurs in 5% of the population and encodes a functional protein. Our results indicate that the Gly54Asp allele does not account for a deficiency state, but instead suggest that MBP may have two predominant allelic forms that have overlapping function and differ only in their ability to activate the classical pathway of complement.

Multiple forms of angiotensin II receptors in rat tissues. Angiotensin II (AII) receptors were identified in rat tissue membranes by specific binding of 125I-labelled AII. Using an isoelectric focusing technique, two forms of the high-affinity AII receptor were identified in rat adrenal zona glomerulosa and liver membranes. These migrated to isoelectric points (pI) 6.8 and 6.7. Two low-affinity forms migrated to pI 6.5 and 6.3. The two high-affinity forms were in greatest abundance in the zona glomerulosa, while the low-affinity pI 6.5 isoform was predominant in liver membranes. In uterine membranes both low-affinity isoforms were observed, but there was only one of the high-affinity forms (pI 6.7). Concentrations of AII receptor isoforms were increased in the zona glomerulosa of sodium-deprived rats. Reduction of disulphide bridges with dithiothreitol (DTT) had different effects on the various AII receptor isoforms. Thus 1 mmol DTT/1 caused a twofold increase in 125I-labelled AII binding in zona glomerulosa membranes. DTT produced no appreciable differences in specific AII binding in uterine membranes, whereas there was a 50% reduction of binding in liver membranes. At 20 mmol/l, DTT greatly decreased AII binding in all tissues. The data suggest the existence of multiple forms of AII receptors which may have different functions.

Patients' perceptions of nursing practice. A rationale for a qualitative research approach. The discipline of nursing is, in Sweden, in the early stages of discovering and expanding specific knowledge embedded in nursing practice. This is a challenging as well as a problematic venture. It is important to evaluate nursing practice within the specific cultural context before applying terminology and meaning of concepts used. The purpose of this paper is to present a basis for the study of perceptions of nursing practice as experienced by the patient himself in a specific cultural context. The historical context, the terminology commonly used, and relevant research in this domain of inquiry is critically examined as a means of determining appropriate research methods for further study in the domain of nursing practice.

[Wadding of the axilla in the conservative treatment of cancer of the breast. Prevention of lymphocele]. A randomized prospective study was carried out on 53 consecutive female breast cancer cases hospitalized at the Centre René Gauducheau, In Nantes (France), with the intent of investigating whether surgical wadding of the axillary fossa with the use of proximate muscular tissue can prevent lymphocele from occurring, and avoid placement of suction drains usually required in conservative management of breast cancer. Results have been significant regarding the incidence of lymphocele (p less than 0.001), as well as the mean puncture volume and the total number of punctures needed (p less than 0.001), thus reflecting the efficacy of a simple method, which yields satisfactory cosmetic results. Failures with this method were related to the technical procedure per se, and not to its principle. The lapse of time required before additional treatment was initiated as subject to a factor not related to the method, but depended upon the recovery of normal shoulder mobilization.

Influence of photoinhibition, photostimulation and prolactin on pituitary and hypothalamic nuclear androgen receptors in the male hamster. Testosterone (T) feedback sensitivity is markedly altered in adult male golden hamsters following exposure to short photoperiods (SD). Using a technique which measures total androgen receptors within the cell nucleus, the present study examined pituitary and hypothalamic nuclear androgen receptor levels in animals exposed to (1) long days (LD) or SD in the presence and absence of a constant T level supplied via a Silastic implant, (2) photostimulation following SD-induced testicular regression and (3) short-term prolactin injections following SD-induced testicular regression. Short photoperiods were associated with a drop in nuclear androgen receptor levels which was correlated with a decline in circulating T. When constant T was supplied to gonadectomized hamsters, those exposed to SD possessed higher pituitary and similar hypothalamic nuclear androgen receptor levels than those exposed to LD. As expected, plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were greatly reduced in SD-exposed, castrated, T-treated hamsters as compared to LD-exposed, castrated, T-treated animals. Photostimulation of intact SD-exposed hamsters for 5 or 10 days was associated with a decline in pituitary nuclear androgen receptors. Prolactin treatment caused no noticeable change in pituitary or hypothalamic androgen receptors even though plasma LH and FSH levels were significantly increased. These results support the hypothesis that altered T feedback mechanisms controlling LH and FSH release following chronic exposure to SD may be related to an alteration in the amount of androgen receptors present in the anterior pituitary.

Computer analysis in clinical electromyography. Electromyographic findings are traditionally evaluated in terms of the duration, amplitude and shape of the myoelectric potentials as well as the pattern of discharge. Unfortunately, the evaluation is frequently dependent on the examiner's subjective observations with the result that mild, early cases or variations in the typical symptoms of the disease may be missed. To overcome these deficiencies, various approaches employing either analog or digital computer techniques have been explored. Programs have ranged from recognition and measurement of motor unit potentials to quantification of the interference pattern. Studies have also compared completely automatic analysis with operator-computer interaction and measurements performed manually. It is evident that the general format is still in the developmental stage. The prime need at the present time, however, is not only for quantification of the electromyogram but for innovative approaches which will expand our knowledge and increase diagnostic accuracy.

P2 purinoceptors stimulate inositol phosphate release in the organ of Corti. We examined the effects of purinoceptor agonists on inositol phosphate (IP) release in the guinea-pig organ of Corti. The P2y receptor agonist ATP-gamma-S (200 microM) increased IPs 4-fold; identical concentrations of alpha, beta-methylene ATP, a P2x agonist, and adenosine, a P1 agonist, did not significantly affect IP release. In calcium-free incubations, simulated IP release decreased by 35% indicating partial dependence of ATP-mediated phosphoinositide hydrolysis on calcium influx. ATP-stimulated IP release was not enhanced by the cholinergic agonist carbachol known to increase IPs via muscarinic receptors in the organ of Corti. This is consistent with the notion that ATP and carbachol have a common target, most likely outer hair cells. P2 purinoceptors coupled to the phosphoinositide cascade suggest ATP as an afferent neuromodulator or efferent neurotransmitter in the cochlea.

Humoral responses to type I collagen after surgical curettage procedures employing bovine collagen implants. Freeze-dried bovine type I collagen was implanted into periodontally diseased sites of 11 patients in an effort to repair the affected site. Peripheral blood samples taken at 0, 6 and 12 wk were assayed for antibody to human and bovine collagen using an enzyme-linked immunosorbent assay and compared with samples from 9 control subjects. Antibody levels to both human and bovine collagen, which were present at significantly higher levels in the patients at 0 wk than in the control subjects (P less than 0.01 for human and bovine), were significantly lower at 6 wk than at zero time (P less than 0.05 and P less than 0.01 for human and bovine collagens, respectively). At 12 wk post-implantation, the antibody level to human collagen still remained significantly lower (P less than 0.05) than zero time levels but not in respect of the antibody to bovine collagen.

An inhibitory effect of isoprenaline on stimulation-induced noradrenaline release from rat atria. Isoprenaline (0.1 microM), in the presence of phentolamine (1 microM) to block autoinhibitory alpha-adrenoceptors, significantly increased the efflux of radioactivity produced by field stimulation (2 Hz for 60 s) from rat isolated atria in which the noradrenergic transmitter stores had been labelled with [3H]noradrenaline. This facilitatory effect of isoprenaline on noradrenergic transmission was not affected by the selective beta 1-adrenoceptor antagonist CGP 20712A (0.3 microM). However, the selective beta 2-adrenoceptor antagonist ICI 118551 (0.1 microM) not only abolished the facilitatory effect of isoprenaline but reversed it to an inhibitory effect, indicating that the prejunctional beta-adrenoceptors subserving facilitation of noradrenergic transmission in rat atria are of the beta 2-subtype. The inhibitory effect of isoprenaline that was revealed by blockade of beta 2-adrenoceptors was abolished by atenolol (3 microM) in a concentration which markedly reduced the effect of isoprenaline on the rate of atrial beating. This finding suggests that activation of beta 1-adrenoceptors on atrial myocytes by isoprenaline may have resulted in release of one or more substance(s) which inhibited stimulation-induced release of noradrenaline, presumably by activating prejunctional receptors. The inhibitory effect of isoprenaline on noradrenergic transmission was not affected by the prostaglandin synthesis inhibitor indomethacin (10 microM) suggesting that prostaglandins were not involved.

The effect of acute poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats. The intestinal transport of D-xylose was studied during the acute poisoning of male Wistar rats with orally administered potassium nitrate and sodium nitrite. At the peak of xylose absorption, the metabolic parameters of Na+/K(+)-ATPase, alkaline phosphatase, oxygen uptake, and lactic acid level were determined in the small intestine mucosa. Nitrite in a dose of 80 mg NaNO2/kg b.w. increased the permeability of gastric mucosa for D-xylose and raised the uptake of oxygen by the small intestine mucosa. No changes were observed in the activity of Na+/K(+)-ATPase and alkaline phosphatase. A dose of 10 mg NaNO2/kg b.w. was not followed by increased absorption of this sugar. It was also demonstrated that potassium nitrate had no effect on the process of intestinal absorption of D-xylose and failed to change the determined metabolic parameters of the small intestine mucosa.

Isolation and expression of a cDNA encoding Renilla reniformis luciferase. Renilla reniformis is an anthozoan coelenterate capable of exhibiting bioluminescence. Bioluminescence in Renilla results from the oxidation of coelenterate luciferin (coelenterazine) by luciferase [Renilla-luciferin:oxygen 2-oxidoreductase (decarboxylating), EC 1.13.12.5]. In vivo, the excited state luciferin-luciferase complex undergoes the process of nonradiative energy transfer to an accessory protein, green fluorescent protein, which results in green bioluminescence. In vitro, Renilla luciferase emits blue light in the absence of any green fluorescent protein. A Renilla cDNA library has been constructed in lambda gt11 and screened by plaque hybridization with two oligonucleotide probes. We report here the isolation and characterization of a luciferase cDNA and its gene product. The recombinant luciferase expressed in Escherichia coli is identical to native luciferase as determined by SDS/PAGE, immunoblot analysis, and bioluminescence emission characteristics.

Effects of age on diabetes- and insulin-induced changes in pancreatic levels of alpha-amylase and its mRNA. During aging, protein synthesis undergoes decremental changes in many organs and tissues. In the pancreas, as well as in other exocrine glands, the rate of protein synthesis declines with age. However, it is unknown whether this decline is related to intrinsic aging changes which affect the secretory cell function. In this study, we compared the ability of pancreatic acinar cells to synthesize amylase and its messenger RNA (mRNA) in response to insulin treatment of young and old rats rendered diabetic with streptozotocin (STZ). In STZ-induced diabetic rats, amylase protein and its mRNA levels were reduced drastically in the pancreas of young and old groups. Injections of these diabetic rats with insulin increased pancreatic amylase mRNA contents significantly in both young and old rats. Insulin also increased proportions of amylase protein synthesis in the pancreas of both age groups. These results indicate that the pancreatic cells remain effective during aging in their transcriptional activity for functional amylase mRNA in response to an exogenous stimulus of insulin.

Bisexuality in women. In-depth interviews with women having a history of bisexual behavior and/or a bisexual self-identification revealed only moderate correspondence between behavior and identity. A general description is provided of the sexual relationships of the respondents. The major focus is on the wide diversity of self-identified bisexual women, especially in terms of self-perceived sexual and emotional needs, circumstances precipitating heterosexual and homosexual behavior, and ideological supports for a bisexual life style. Heterosexual behavior among homosexual women is discussed in terms of economic necessity, experimentation, and the response of the lesbian community. Homosexual behavior among heterosexual women is discussed in terms of responses to different kinds of situational exigencies and the rationalizations used to deal with the experience while insulating the heterosexual self-identification.

[Neurochemical mechanisms of the action of tricyclic antidepressants of the imipramine group]. The main role in determination of the pharmacologic effects of the imipramine groups antidepressants is given to their influence on neurotransmitters metabolism in synapses, the activity of enzymic systems regulating the transport of ions, as well as on the system of cyclic AMP metabolism. Interaction of tricyclic antidepressants with membrane and, as the result, distrubance in reuptake of transmitters (epinephrine and 5-hydroxytryptamine) in neurons is supposed to be one of the mechanisms of synaptic transmission regulation. The possible role in inhibition of biological amines deamination, in particular of phenylethylamine, in antidepressive effect of tricyclic antidepressants is discussed. It is supposed that the thymoanaleptic effects of the imipramine group antidepressants are due to activation of central serotoninergic processes, and their psychoanaleptic effect due to activation of the adrenergic system. Inhibition of the Na+, K+-ATPase activity quilizing effect of tricyclic antidepressants.

Kinin metabolism in the perfused ventilated rat lung. I: Bradykinin metabolism in a system modeling the normal, uninjured lung. Bradykinin (BK) in an asanguinous salt solution was perfused through intact rat lung. BK concentration varied from 0.0015 to 89 microM. Below 17 microM, the amount degraded was greater than or equal to 90% of the dose. The BK fragment distributions expressed as a percentage of the BK dose degraded were constant. The BK fragments formed and percentage yields were Pro-Pro (2-3) 49%, Arg-Pro-Pro-Gly-Phe (1-5) 32%, Pro-Pro-Gly-Phe-Ser-Pro (2-7) 6%, Arg-Pro-Pro-Gly-Phe-Ser-Pro (1-7) 6%, Arg-Pro-Pro (1-3) 3% and residual BK 4%. Above 17 microM, the amount of BK degraded was not proportional to the dose. Captopril and enalaprilat inhibited BK degradation, and their maximum inhibitions were about 50% and 30%, respectively. The percentage yield of the 1-5 fragment was greatly reduced by both inhibitors, but the percentage yields of the 2-3 and 1-8 fragments were moderately increased. It was concluded that (1) the intact rat lung itself has a very large capacity to degrade BK in the range of 2 mumoles/min/kg body weight; (2) two major and several minor enzyme pathways exist to degrade BK; (3) the relative contributions of these pathways to overall BK degradation remain essentially constant over a bradykinin concentration range from 0.0015 to 17 microM; (4) ACE/kininase-II catalyzed hydrolysis is one of the major pathways but is not the single major route for BK degradation; and (5) the other major BK degradation pathway involves enzymes cleaving the Arg1-Pro2 and Pro3-Gly4 bonds of BK.

Antifungal susceptibility testing of Candida spp. by relative growth measurement at single concentrations of antifungal agents. The relative growth (percentage of growth relative to control growth) of 496 isolates representing six Candida species was assessed as a means of determining in vitro susceptibilities of the isolates in microdilution plate wells containing single concentrations of each of seven antifungal agents. The relative growth data were highly reproducible. With flucytosine and amorolfine they correlated well with MICs, but for an azole antifungal agent, terconazole, they did not correlate with MICs. Distributions of relative growth percentages for different Candida spp. showed significant differences in species susceptibility to individual agents. For example, C. albicans was less susceptible than the other species to amorolfine; C. parapsilosis isolates were particularly susceptible to terbinafine; and C. glabrata, C. guilliermondii, and C. krusei isolates were less susceptible than C. albicans to fluconazole and ketoconazole but equally susceptible as or more susceptible than C. albicans to itraconazole. Differential patterns of susceptibility to individual azole antifungal agents were noted for some individual strains as well as for Candida spp.

Direct in vivo gene introduction into rat kidney. We established a simple and highly efficient method for in vivo gene transfer using HVJ (Sendai virus) and liposomes. Plasmid DNA and high mobility group 1 (HMG1) protein were co-encapsulated in liposomes by agitation and sonication and were co-introduced into cells by HVJ-mediated membrane fusion. pACT SVT DNA, as a reporter gene, was introduced into the kidney of intact rats through a cannula in the renal artery, and SV40 large T antigen was detected by enzyme immunohistochemistry in glomerular cells 4 days after its introduction. This newly developed kidney-directed gene transfer method should be useful not only in basic research but also in potential gene therapeutics of renal diseases.

Metabolic deviation of mouse liver by RhIL1-alpha or RhTNF/cachectin. In this work deviation of liver metabolism by cytokines, especially recombinant human interleukin 1-alpha (rhIL1-alpha), was investigated. Administration of rhIL1-alpha or recombinant human tumor necrosis factor (rhTNF/cachectin) to normal mice resulted in rapid, dose-dependent induction of high liver ornithine decarboxylase (ODC) activity. The effects of these cytokines on liver ODC were not indirect effects mediated by eicosanoids. The induction of liver ODC by rhIL1-alpha was at least partly a direct effect on hepatocytes, and was due to increase in de novo synthesis of the enzyme protein after increase in ODC mRNA. No specific protein was required for increase in the level of ODC-mRNA. On IL1 treatment, actinomycin D caused superinduction of liver ODC, which was at least partly due to increased stability of the ODC enzyme, because actinomycin D doubled the apparent half-life (from 50 to 95 min). Daily administration of 2 x 10(3) U of rhIL1-alpha to mice for 3 days also caused decrease in the level of the differentiated type of pyruvate kinase isozyme (PK-L) and marked increase in that of the prototype isozyme (PK-M2) in the liver, but did not cause significant change in the isozyme patterns of the kidney, thymus, and spleen. RhIL1-alpha also induced hypertrophy of the spleen. These results indicate that rhIL1-alpha causes metabolic deviation of the liver similar to that in tumor-bearing hosts.

The ultrastructure of pulmonary arteries and arterioles in emphysema. The lungs from three cases of pulmonary emphysema obtained at heart-lung transplantation were examined by electron microscopy to determine the origin of intimal longitudinal muscle and the formation of muscular tubes in small pulmonary arteries and arterioles. The earliest change consisted of migration of mature smooth muscle cells from the media of small pulmonary arteries, through gaps in the internal elastic lamina, into the subendothelial space. Most of these cells then adopted a longitudinal orientation, maintained a muscular phenotype, and became enmeshed in a web of elastic fibres. A small minority, immediately subjacent to the endothelium, were orientated circularly and, in some vessels, were enclosed by rudimentary internal and external elastic laminae to form early muscular tubes. Pulmonary arterioles, which are normally devoid of a media, contained several layers of circularly orientated smooth muscle cells, some of which also formed muscular tubes. It is postulated that the limited migration of mature smooth muscle cells seen in states of chronic hypoxia is mediated by a different stimulus from that causing the florid invasion of the intima by immature smooth muscle, with subsequent transformation into myofibroblasts, which characterize plexogenic pulmonary arteriopathy.

[Latentiation of naphthylazoderivatives by polymerarization]. Five naphthylazoderivatives (of sulfadiazine, sulfamethazine, sulfathiazole, sulfamethoxazole, and sulfamonomethoxine) -- the first four displaying schistosomicidal activity -- were latentiated, in the form of polyamides of acrylic and methacrylic acids, by reacting those compounds with these polymers. In biological tests in mice experimentally infected by Schistosoma mansoni, the new nine compounds were found to be inactive. However, the original method of latentiation described in this paper has possibilities of wide application, owing to its favourable features: versatility of the reactive group of the polymer, lability of the bond (easily hydrolyzable) formed between drug and polymer, greater viability of reaction between the polyanhydride and the drug, and solubility in water of the polymers thus formed.

Transcriptional regulation of hepatic angiotensinogen gene expression by the acute-phase response. The acute-phase response is a protective physiological reaction to tissue injury manifested by the immediate increase in production and secretion of liver proteins the function of which is to re-establish the homeostasis altered by injury. Such proteins include blood coagulation factors, opsonins, protease-inhibitors and angiotensinogen, a precursor of the potent vasopressor peptide angiotensin II. The angiotensinogen gene is typical of genes regulated during the acute-phase response inasmuch as the promoter regulating its transcription rate is acutely responsive to three known mediators of the acute-phase response: glucocorticoids, and the cytokines interleukin-1 and tumor necrosis factor. We present a model, based on experimental evidence, for the mechanism by which angiotensinogen gene transcription is regulated in a graded fashion by the interplay of several hormonally-inducible transcription factors that bind a hormonally-inducible enhancer unit of the angiotensinogen promoter. These factors include the glucocorticoid receptor, nuclear factor kappa B and members of the CAAT/viral enhancer (C/EBP) family of DNA-binding proteins.

Rationality and cost-effectiveness of diagnosis and treatment of group A streptococci in primary care patients with pharyngitis. Rationality and cost-effectiveness of several strategies for diagnosing and treating sore throat patients were evaluated in primary care. In an empirical material of 2016 patients, 3 different bacteriological methods (traditional culture, slide culture, and latex agglutination test) for the detection of group A beta-hemolytic streptococci (GAS) were compared. Sensitivity analyses were done for several variables, including GAS test performance, testing frequencies, medication rates, and accuracy of clinical evaluation. The amounts of unnecessary medication varied from 19 to 33%, and there were 2.2-8.9% of untreated GAS infections. Strategies based on bacteriology achieved more rational and economic results than treating no one, treating all patients, or using clinical evaluation without bacteriology. The cost-effectiveness of the latex agglutination test depended on the sensitivity of the test. The results were further sensitive to sick leave lengths, cost of antibacterials, and clinical accuracy, but not to GAS test cost. Rapid tests for GAS detection can be recommended, if the sensitivity of the test in the actual working conditions is acceptable.

Socio-economic differentials in mothers at risk based on pre-pregnancy weights & heights. Data on heights and weights of women measured as part of a longitudinal study on maternal and child health in Tamil Nadu state, south India are presented and discussed in relation to various socioeconomic and demographic factors. The mean (+/- SD) heights in rural and urban women were 151.2 +/- 5.4 cm and 150.8 +/- 6.6 cm respectively. The mean weights were 42.6 +/- 5.4 kg; and 44.0 +/- 7.9 kg respectively. The mean BMI were 18.6 +/- 2.2 and 19.4 +/- 3.5 respectively. The differences were statistically significant. Forty two per cent of rural and 48 per cent of urban women were less than either 145 cm in height or 40 kg in weight. The need to identify and care for such women as part of the "Risk Approach" in maternal and child health programmes is emphasized.

Cyclic nucleotides attenuate thrombin-evoked alterations in parameters of platelet Na/H antiport. The role of cytosolic Ca. In this work, we explored the role of cyclic nucleotides in modulating parameters of the Na/H antiport in human platelets. Sodium nitroprusside and iloprost, as well as cyclic nucleotide analogues, were used to raise cellular levels of cAMP and cGMP. Cyclic nucleotides reversed the thrombin-evoked alkaline shift in cytosolic pH set point and the activity of the Na/H antiport, concurrently with attenuation of thrombin-induced rise in cytosolic free Ca. No effect of cyclic nucleotides was observed in platelets not treated with thrombin, or platelets subjected to phorbol 12-myristate 13-acetate. cAMP did not reverse ionomycin-induced changes in the parameters of the Na/H antiport. Collectively, these observations indicate that cyclic nucleotides modulate the Na/H antiporter in human platelets through their effect on thrombin-evoked changes in cytosolic free Ca. Presumably, this effect holds for other agonists which stimulate phospholipase C, raise cytosolic-free Ca, and activate the Na/H antiport through protein kinase C dependent and protein kinase C-independent mechanisms.

Development of a sensitive enzyme immunoassay for OPC-7251, a novel antimicrobial agent for percutaneous application. A sensitive enzyme immunoassay for OPC-7251, a novel pyridone carboxylic acid antimicrobial agent, was developed and applied for the determination of human plasma levels. OPC-7251 was coupled to bovine serum albumin through a formation of N-hydroxysuccinimide ester. By immunization of rabbits, highly specific antiserum was raised. Using the antiserum and beta-D-galactosidase-labeled hapten, the homologous assay system allowed the detection of 2 pg of this compound. Plasma samples were precisely analyzed down to the minimum value of 200 pg/ml after heat treatment. The system was further validated by the recovery test and correlation with the HPLC analyses. Percutaneous application of 10 g of 1% OPC-7251 cream to healthy volunteers resulted in the peak plasma value of 1.6 ng/ml about 8 hours after dosing, indicating extremely low absorption efficiency through a transdermal system.

CA-549 serum levels in breast cancer monitoring. CA-549 serum levels were assessed in 288 patients, 156 with early breast cancer (after surgery) and 132 with advanced breast cancer. CA-549 was abnormal (> 12 U/ml) in 25/156 patients (16%) without clinical signs of disease after surgery (median 9 U/ml), in 49/60 patients (82%) with disease in progression (P) (median 50 U/ml), in 19/27 patients (70%) with stationary disease (NC) (median 14 U/ml), in 25/33 patients (76%) with partial remission (PR) (median 18 U/ml) and in 4/12 patients (33%) with complete remission (CR) (median 9 U/ml). CA-549 serum levels correlated mainly with the extent of disease and secondarily with the prevalent metastatic site, higher values being observed in patients with visceral involvement (median 32.5 U/ml). CA-549 serum levels were also assessed in 51 patients at the start of treatment and at the time of objective evaluation: the results underline the concordance of CA-549 behavior with the clinical outcome in 71% of the cases. We conclude that CA-549 is a useful marker for monitoring breast cancer patients during the advanced stages of the disease.

[On the circadian changes of concentration of free amino acids in pregnancy (author's transl)]. Concentrations of 17 free amino acids were measured in the serum of 15 healthy pregnant women at the end of pregnancy in intervals of 4--5 h. A circadian rhythm with its concentration peak at 5 p.m. could be observed for Ser, Val, Met, Ile, Leu, His, Lys and Arg. Exogenic and endogenic synchronizators are being discussed as possible causes for these fluctuations during the day. The rhythm of the free amino acids makes it necessary that only fasting blood is examined and that the time of day is always registered when the blood specimen is taken.

Is a man, a man, a man? (or: is an EEG, an EEG, an EEG?) some remarks on the homogeneity of "normal subjects". Many studies involving computerized EEG analyses are based on the assumption that normal subjects constitute a homogeneous population, so that under specified conditions across-subject averaging is justified. Quite often EEG signals are processed with little or no concern for the state of the particular person from whom they are obtained. It is the purpose of this discussion to draw attention to the fact that only can normals have different EEG's one from another, but also that the same ones can display markedly different EEGs from recording session to recording session. A consequence of this situation is that there is always a large between-subject variability, and that the source of the signals needs to be carefully documented before generalizations can be made.

Gastric evacuation and propulsive intestinal motility in acute afferent loop syndrome in the rat. The acute afferent loop syndrome, i.e. occlusion of the afferent loop after partial gastrectomy by the Billroth II method, was produced in the rat. In a primary session a gastrojejunostomy with division of the pylorus was performed. 2-3 months later the afferent loop was ligated. The gastric evacuation and the propulsive motility of the intestine were studied quantitatively, using an inert radioisotope. Both the gastric evacuation and the propulsive intestinal motility were considerably delayed in ALS, both in relation to the laparotomized controls and in relation to previous findings in mechanical intestinal obstruction and paralytic ileus due to retroperitoneal irritation or bacterial peritonitis.

Interactions between phospholipase C-coupled and N-methyl-D-aspartate receptors in cultured cerebellar granule cells: protein kinase C mediated inhibition of N-methyl-D-aspartate responses. The N-methyl-D-aspartate (NMDA) receptor of rat cerebellar granule cells in primary culture is inhibited by phospholipase C-coupled receptor activation. In the absence of ionotropic agonist, cells modulate their cytoplasmic free Ca2+, [Ca2+]c, in response to stimulation of M3 muscarinic receptors, metabotropic glutamate receptors, and endothelin receptors by the respective agonists carbachol, trans-1-amino-1,3-cyclopentanedicarboxylic acid, and endothelin-1. The response is consistent with the ability of phospholipase C-coupled receptors to release a pool of intracellular Ca2+ and induce a subsequent Ca2+ entry into the cell; both of these responses can be abolished by discharge of internal Ca2+ stores with low concentrations of ionomycin or thapsigargin. In the case of cells stimulated with NMDA, the [Ca2+]c response to the phospholipase C-coupled agonists is complex and agonist dependent; however, in the presence of ionomycin each agonist produces a partial inhibition of the NMDA component of the [Ca2+]c signal. This inhibition can be mimicked by the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate. It is concluded that NMDA receptors on cerebellar granule cells are inhibited by phospholipase C-coupled muscarinic M3, glutamatergic, and endothelin receptors via activation of protein kinase C.

Penetrating missile injuries in the Gulf war 1991. During the recent Gulf war 63 patients with penetrating missile injuries (including 29 Iraqi prisoners of war) underwent operation in a British Army Field Hospital. Their injuries and initial operative management are reported. Fifty-one casualties (81 per cent) suffered an average of nine wounds (range 1-45) due to fragmentation weapons, and 12 casualties sustained bullet wounds. All wounds were explored following the established principles of war surgery. The extremities were involved in 48 patients (76 per cent). Eight compound long bone fractures were managed with external skeletal fixators applied at the time of initial operation. Laparotomy was performed on seven patients, one of whom died. The average duration of operation was 77 min for shrapnel wounds and 85 min for bullet wounds.

The role of the laterodorsal tegmental nucleus of the rat in experimental seizures. This study determined the effects of discrete microinjections of GABA agonists in the cholinergic nuclei of the pontomesencephalic tegmentum on spontaneous behavior and seizures induced by intravenous pentylenetetrazol, bicuculline or strychnine, in the rat. Injections of both the GABAA agonist piperidine-4-sulfonic acid and the GABAB agonist (-)baclofen in the laterodorsal tegmental nucleus produced a dose-dependent suppression of behavioral arousal and a reduction in the threshold of myoclonic and clonic but not tonic seizures induced by bicuculline and pentylenetetrazol. There were no significant effects on any type of strychnine seizure. Injections in the surrounding brainstem structures, including the pedunculopontine tegmental nucleus, had little effect on spontaneous behavior and did not significantly alter the thresholds of pentylenetetrazol-induced seizures. We have previously demonstrated that injections of GABA agonists in the central medial intralaminar nucleus of the thalamus have similar effects on behavior and seizures. Since the central medial nucleus receives important direct cholinergic projections from the laterodorsal tegmental nucleus, these two nuclei form a discrete ascending system which regulates seizure threshold.

Structural specificity in the lethal and mutagenic activity of furocoumarins in yeast cells. Using monofunctional (Angelicin) and bifunctional furocoumarins (Psoralen and 8 Methoxypsoralen) plus 365 nm light it is shown that both damages, the induced monoadducts and/or crosslinks in DNA, provoke lethal and mutgenic effects in haploid and diploid cells of Saccharomyces cerevisiae. Bifunctional furocoumarins are about 20 times more effective in cell killing than Angelicin. Diploid cells are always more resistant than haploid cells. Dark repair (agar haolding) increases survival. This effect can be at least in part correlated to the release of bound material from DNA in dark repair conditions. Bifunctional psoralens (10 mug/ml) are at least 10-fold more effective in inducing nuclear gene black mutations (his- to HIS+) than Angelicin (10 mug/ml) plus 365 nm light or 254 nm ultraviolet light. In contrast cytoplasmic "petite" (delta-) mutations are about as frequently induced by Angelicin plus 365 nm light as by 254 nm UV light. Bifunctional furocoumarins are less effective. The frequency of cytoplasmic "petite" mutations per survivors decreases during dark repair conditions more efficiently after Angelicin than after Psoralen plus 365 nm light treatment.

The incidence of cone epiphyses and ivory epiphyses of the hand in Nigerian children. Radiographs of the left hand of 594 children from Ibadan, Nigeria were inspected for skeletal anomalies to determine differences in the incidence of cone and ivory epiphyses for the rich and poor children and differences in incidence for four hemoglobin types. Ivory epiphyses ovvurred more often in children in the lower socio-economic class and children with hemoglobin AA. The cone epiphyses observed in Hb SS children were primarily a result of bone infarcts, while cones in children of other hemoglobin types appeared to be normal variants. The incidence of ivory epiphyses was higher in the Nigerian children than in American black children in the Ten-State Nutrition Survey. The incidence of cone epiphyses was much lower than those reported for other normal populations.

Premature escape beats induced by overdrive pacing in canine Purkinje fibers. Evidence for the role of normal automaticity as an underlying cellular mechanism. Premature escape beats induced in conscious dogs with chronic complete atrioventricular block have been defined as escape beats occurring on cessation of overdrive pacing and having a coupling interval to the last paced beat shorter than the coupling interval between the premature escape beat and the second postpacing beat. Triggered activity has been proposed as the primary underlying mechanism. We used standard microelectrode techniques to study the effects of overdrive pacing on normal automatic canine Purkinje fibers to determine if premature escape beats could be induced and if so, to define the underlying cellular mechanism(s). For this purpose, we overdrive-paced Purkinje fibers for 10 and 50 seconds and for 10 and 50 beats at a pacing cycle length (PCL) of 1,000-200 msec. In addition, to help distinguish among major arrhythmogenic mechanisms, we used a matrix of drugs consisting of propranolol, nadolol, lidocaine, ethmozin, and doxorubicin. Fifty-second stimulation trains induced "classic" overdrive suppression of the first three postpacing impulses, whereas 10-second overdrive pacing induced significant overdrive suppression only at a PCL of 200 msec. With 50-beat overdrive pacing and a PCL of 1,000-600 msec, there was overdrive suppression of postpacing impulses, whereas reduced overdrive suppression was observed at a PCL of 400-200 msec. Ten-beat stimulation trains induced a "flat response" of postpacing impulses. Ten- and 50-beat overdrive pacing provoked premature escape beats in 66% of the fibers, with the higher incidence at a PCL of 200 msec for 50-beat stimulation trains. No shortening of the coupling interval of premature escape beats was observed at faster pacing rates. Only lidocaine (which suppresses normal automaticity) abolished premature escape beats. We conclude that normal automaticity is the most likely mechanism underlying premature escape beats in Purkinje fibers with high levels of membrane potential.

Polymorphism and reproductive mode in the rotifer, Asplanchna sieboldi: relationship between meiotic oogenesis and shape of body-wall outgrowths. Sexuality and polymorphism are closely coupled in the rotifer Asplanchna sieboldi. In a graded response to dietary tocopherol, embryos develop body-wall outgrowths of various sizes and shapes. Also in a graded response to this compound, some of the affected females produce eggs undergoing meiotic instead of mitotic oogenesis. The haploid eggs of such mictic females develop parthenogenetically into males instead of females. The incidence of mictic females among animals with different shapes was studied among cohorts from mothers subjected to different inducing conditions. The hypothesis that external tocopherol concentrations absolutely fix the probability of meiotic oogenesis was rejected. The other extreme hypothesis, that the probability of meiotic oogenesis is fixed by morphotype, was rejected for animals at the low end of the morphotypic scale but accepted for the more strongly-affected individuals. The probability of meiotic oogenesis is thus constant for the higher morphotypes. The ascertainment of morphotype frequencies in natural or laboratory populations may suffice for estimating the incidence of sexual forms; furthermore studies of factors affecting the body-wall-outgrowth response may also bear directly upon regulation of sexual reproduction in this species.

Heart in thyroid diseases. The paper examines the basic pathophysiologic mechanisms playing a role in the development of cardiovascular changes on thyroid hyper- and hypofunction. The haemodynamic changes typically associated with increased and decreased secretion of thyroid hormones are described and compared. Using echocardiography, the haemodynamics changes are documented in 12 patients with hyperthyroidism and 19 patients with myxoedema prior to thyrostatic and substitution therapy. Characteristic findings in florid hyperthyroidism include a significant rise in left ventricular end-diastolic volume as well as increases in stroke volume (SV) and cardiac index (CI). Mean velocity of circumferential fibre shortening (mVCF) is also significantly increased. Left ventricular myocardial weight shows a tendency towards an increase. Hypothyreosis is primarily associated with decreases in SV and CI; mVCF also declines. The paper underlines the importance of causative therapy as the above haemodynamics changes are fully reversible on attaining normal thyroid function.

Metaplastic cartilage in nondysplastic kidneys. Four hundred ninety-seven patients representing the 525 total or polar nephrectomies performed at the Children's Memorial Hospital from 1938 to 1973 (excluding 1947), were reviewed retrospectively to determine the incidence and characteristics of renal dysplasia. The 46 specimens with this histologic diagnosis all exhibited typical primitive ducts with 13 being also associated with cartilage formation. In five patients, kidney showed focal chondrous metaplasis of the interstitium in association with chronic inflammation but without primitive ducts. The findings strongly suggest that the renal interstitium occasionally may react to injury by chondrous metaplasia and that, in the absence of primitive, ducts, cartilage in the kidney is not pathognomonic of renal dysplasia.

A prospective evaluation of glucose reagent teststrips in the prehospital setting. Reagent teststrip determination of blood glucose has been shown to be accurate for hospital and home testing and is commonly used in prehospital care despite the lack of studies in this arena. This prospective, multicenter study examines the ability of glucose reagent teststrips to detect hypoglycemia when used under field conditions compared with simultaneously drawn control samples for laboratory glucose determination. Also examined was the accuracy of the teststrips in the laboratory glucose range less than or equal to 200 mg/dL. One hundred eighty-one pairs of data were analyzed. Hypoglycemia was defined as laboratory glucose less than or equal to 60 mg/dL. The teststrips correctly identified 31 of 33 patients in this range (sensitivity = 94%), and 125 of 148 patients without hypoglycemia (specificity = 85%). The two false negative readings were 70 and 90 mg/dL. Reagent teststrips were within +/- 40 mg/dL of the laboratory value in 70% of cases. The correlation coefficient (Spearman r) between teststrip and laboratory glucose in the range less than or equal to 200 mg/dL was .80. Using teststrip readings of 90 mg/dL or less as a measure of hypoglycemia yields 100% sensitivity with a specificity of 57%. We conclude glucose reagent teststrips are a useful adjunct for use in the prehospital setting and may be valuable for the detection of hypoglycemia.

Mechanisms of baclofen action on spasticity. This investigation estimated the mechanisms of baclofen action on spasticity using a battery of electromyographic methods. Thirty patients with old post-stroke spastic hemiparesis took part in the investigation. They were treated with baclofen-mean daily dose 54.3 alpha 11.6 mg for a mean of 26.3 alpha 4.9 days. A questionnaire for assessment of subjective improvement after treatment used a 5-point scale. For standardization of the neurological examination 5-point scales were used to assess muscle tone, muscle force and tendon reflexes. A battery of electromyographic methods was used to analyse different mechanisms of spasticity: for alpha motoneurone activity--the F wave parameters; for gamma motoneurone activity--the T/H reflex amplitude ratio; for presynaptic inhibition--the ratio of H reflex amplitudes before and after vibration on the achilles tendon (Hvibr./Hmax); for common interneurone activity--the flexor reflex parameters. Our results revealed that baclofen reduces spastically increased muscle tone and Babinski sign. It has no influence on muscle force, tendon reflexes and ankle clonus. Baclofen acts by normalizing the altered interneurone activity and decreasing of alpha motoneurone activity. When spasticity has altered interneurone activity and increased motoneurone activity, it is better to treat with baclofen.

Dengue virus-specific, human CD4+ CD8- cytotoxic T-cell clones: multiple patterns of virus cross-reactivity recognized by NS3-specific T-cell clones. Thirteen dengue virus-specific, cytotoxic CD4+ CD8- T-cell clones were established from a donor who was infected with dengue virus type 3. These clones were examined for virus specificity and human leukocyte antigen (HLA) restriction in cytotoxic assays. Six patterns of virus specificities were determined. Two serotype-specific clones recognized only dengue virus type 3. Two dengue virus subcomplex-specific clones recognized dengue virus types 2, 3, and 4, and one subcomplex-specific clone recognized dengue virus types 1, 2, and 3. Four dengue virus serotype-cross-reactive clones recognized dengue virus types 1, 2, 3, and 4. One flavivirus-cross-reactive clone recognized dengue virus types 1, 2, 3, and 4 and West Nile virus (WNV), but did not recognize yellow fever virus (YFV), whereas three flavivirus-cross-reactive clones recognized dengue virus types 1, 2, 3, and 4, WNV, and YFV. HLA restriction in the lysis by these T-cell clones was also heterogeneous. HLA-DP, HLA-DQ, and HLA-DR were used as restriction elements by various T-cell clones. We also examined the recognition of viral nonstructural protein NS3, purified from cells infected with dengue virus type 3 or WNV, by these T-cell clones. One serotype-specific clone, two dengue virus subcomplex-specific clones, and three dengue virus serotype-cross-reactive clones recognized NS3 of dengue virus type 3. One flavivirus-cross-reactive clone recognized NS3 of dengue virus type 3 and WNV. These results indicate that heterogeneous dengue virus-specific CD4+ cytotoxic T cells are stimulated in response to infection with a dengue virus and that a nonstructural protein, NS3, contains multiple dominant T-cell epitopes.

[Suicide attempts in the Fribourg Canton. II. Suicide attempts in patients of the Marsens psychiatric hospital in the period from August 1st 1977 till July 31st 1978]. Subject of these two papers are the suicidal attempts in the Canton of Fribourg: - The first considers their admissions to the Cantonal Hospital at Fribourg. - The second, to the Psychiatric Clinic at Marsens This is a relatively restricted choice because may patients do not come to these hospitals. They are examined by a general practitioner or admitted to a private or a district hospital. The first paper analyzes the personaltiy types and emphasizes the rapidity of medical intervention and the cooperation between psychiatrists and other physicians and health personnel. The second paper is a statistical attempts, their numbers and their repetition, according also to the sex of the patients. Some considerations are made on preventive measures.

The e antigen and vertical transmission of hepatitis B surface antigen. The relationship of e antigen (eAg) and its antibody (anti-e) to vertical transmission of hepatitis B surface antigen (HBsAg) from chronic asymptomatic HBsAg carrier women to their children was investigated in Taiwan. Sera from 20 of the 62 women studied were positive for eAg (32%); serum from only one woman was positive for anti-e (2%). A total of 85% of the babies born to eAg positive mothers became HBsAg carriers, while only 31% of the babies became carriers when the mother was eAg negative. Maternal e antigenemia correlated with a high HBsAg titer, and both parameters were equally good predictors of vertical transmission.

Serial reconstruction of beta-protein amyloid plaques: relationship to microvessels and size distribution. The suggestion that the amyloid plaques in Alzheimer disease are formed by abnormal leakage from microvessels is mainly based on the finding that many plaques are topographically associated with microvessels. However, because the microvessel network is dense and amyloid plaques are numerous, the frequently observed association may result from chance contact, especially for larger plaques. Therefore, we determined the frequency of this association as a variable of plaque size. If all the amyloid plaques are associated with microvessels, a constant and high rate of association would be expected for all plaque sizes. On the other hand, if the association is a chance contact, larger plaques would show more frequent contact than smaller ones. Sections were double-immunostained for amyloid plaques and microvessels with antibodies raised against beta-protein and collagen type IV, respectively. Amyloid plaques were reconstructed using 12 serial sections (7 microns thick) from the entorhinal cortex of two Alzheimer patients. With reconstruction we determined the size distribution of amyloid plaques as well as the influence of size on vascular association. All the amyloid plaques larger than 42 microns were associated with microvessels, however, the smaller the amyloid plaques, the less frequently they were associated with microvessels. Interestingly, although diffuse amyloid plaques occur in all size classes, core-containing amyloid plaques have a more discrete size. We conclude that the topographical relationship between amyloid deposition and capillaries does not support the leakage theory for amyloid plaque formation.

Microneme secretion in Coccidia: confocal laser scanning and electron microscope study of Sarcocystis muris in cell culture. A monoclonal antibody (mcab) raised against a subcellular fraction of Sarcocystis muris cystozoites was used to localize microneme antigens before, during and after invasion of cultured cells. The mcab recognized a 20 and 22 kDa protein under reducing and non-reducing conditions on Western blots and localized an antigen in cystozoites in the apical part of the parasites. Confocal laser scanning microscopy of invading cystozoites revealed the secretion of a microneme antigen at the apical tip of the parasite. The secreted microneme antigen was attached to the host cell surface at the invasion site and spread along the surface of the infected cells. Electron microscopy using immunogold labeling showed that the microneme antigen was distributed in patches on the surface of infected cells and present on infected cells more than 60 min post-infection. The function of microneme antigens during parasite-host cell interactions is discussed.

Influence of histidine on lipid peroxidation in sarcoplasmic reticulum. The free amino acid, histidine, which exists at high concentrations in some muscle systems, has previously been demonstrated to both inhibit and activate lipid peroxidation in membrane model systems. This study sought to characterize the specificity of histidine's effect on iron-catalyzed enzymatic and nonenzymatic lipid peroxidation. Under conditions of activation (histidine added to the reaction mixture after ADP and ferric ion), alpha-amino, carboxylate, and pyrrole nitrogen were demonstrated to be involved by kinetic techniques in the activation of the enzymatic system. It is hypothesized that a mixed ligand complex (iron, ADP, and histidine) formed may allow rapid redox cycling of iron. While increasing concentrations of histidine led to increasing levels of stimulation in the enzymatic system, the maximum stimulation of a nonenzymatic lipid peroxidation system of ascorbate and ferric ion occurred at histidine concentrations near 2.5 mM. Inhibition of a nonenzymatic system (ferrous ion), on the other hand, occurred at all concentrations of histidine when the ferrous ion was exposed to ADP prior to histidine. In enzymatic systems, under conditions when the ferric ion was exposed to histidine prior to ADP, inhibition of lipid peroxidation by histidine also occurred. The inhibitory effect of histidine was ascribed to the imidazole group and may arise from the formation of a different iron complex or the acceleration of polymerization, dehydration, and insolubilization of the ferric ion by the imidazole nitrogen. The demonstrated ability of histidine to affect in vitro lipid peroxidation systems raises the possibility that this free amino acid may modulate lipid peroxidation in vivo.

Initial experience with a multiplane transoesophageal echo-transducer: assessment of diagnostic potential. the prototype of a transoesophageal echocardiographic transducer with a rotatable cross-sectional scanning plane underwent initial evaluation. the 5 MHz, phased array, 64 element transducer is incorporated into a 16 by 11 by 40 mm echoscope tip. The instrument also has pulsed wave and colour flow Doppler capabilities. Exterior controls allow continuous mechanical rotation of the scanning plane from 0 degree, corresponding to the conventional transverse plane, through 180 degrees, thereby encompassing all possible planes. 103 patients underwent examination without complications; two additional patients were excluded because of difficulty in swallowing the probe. Advantages include precise alignment of aortic valve long- and short-axis views, long-axis views of the ascending aorta (mean visualized length: 6 cm), and full scanning of the entire circumference of the mitral valve and the left ventricle. Separation of paravalvular and transvalvular leakage in prosthetic valves is distinctly improved. multiplanar transoesophageal imaging is feasible and increases the diagnostic yield, especially in mitral and aortic pathology and in the assessment of left ventricular wall motion. Three-dimensional reconstruction is an attractive potential application.

Effect of acute distension on cholinergic innervation of the rat urinary bladder. The effect of short-term urinary bladder distension on its cholinergic innervation was studied in Sprague-Dawley rats. Distension was induced for 3 h by forced diuresis and balloon outlet obstruction, and whole thick biopsy specimens were taken from the dome and lateral side of the anterior body 2, 7 and 21 days afterwards. The acetylcholinesterase (AChE) method was used to demonstrate the cholinergic nerves in the distended bladder wall. Cholinergic hypoinnervation was observed 7 days after the distension, persisting up to 21 days, although AChE-reactive nerves were then observed to be more numerous. The distribution of hypoinnervation was uneven, being more marked in the lateral side of the anterior body than in the dome. The distribution of AChE-reactive nerves varied even in the same biopsies, with areas of total hypoinnervation occurring next to areas of slightly diminished innervation. This was especially true 21 days after distension. The findings indicate transient damage to the cholinergic innervation, which may in turn explain the prolonged voiding difficulties often seen after catheterization of an overdistended bladder in a patient with urinary retention. The short-lasting effect of bladder dilatation therapy used to treat detrusor instability or interstitial cystitis may be due to the fairly rapid regeneration of cholinergic innervation.

Effects of dobutamine on coronary circulation and cardiac metabolism of the dog. Effects of (+/-)-4-[2-(3-p-hydroxyphenyl-1-methyl-amino)ethyl]pyrocatechol (dobutamine) on coronary circulation and cardiac metabolism were investigated using the heart in vivo and the isolated perfused heart of dogs. In the heart in vivo dobutamine 1--30 microgram/kg i.v. and 1--100 microgram i.c. produced dose-dependent increases in coronary perfusion pressure, coronary blood flow, heart rate and left intraventricular pressure. In the perfused heart dobutamine 10 microgram i.c. increased coronary flow, heart rate, cardiac contractility and myocardial oxygen consumption. Delta redox potentials decreased but did not show negative values. Propranolol 0.1 mg/kg i.v. and 0.1 mg i.c. inhibited these effects of dobutamine. Dobutamine shows basically the same actions as isoproterenol, but does not reduce the coronary perfusion pressure by the relatively high dose applied. The results suggest that dobutamine may have a selective adrenergic beta 1 receptor stimulating action on the heart and have a merit in maintaining the coronary perfusion pressure.

Do the benefits outweigh the costs of PACS? The results of an International Workshop on Technology Assessment of PACS. On May 26-27, 1991, an International Workshop on the Technology Assessment of PACS was held at Enkhuizen, The Netherlands. During this workshop 35 experts in the field, from 13 different countries, discussed amongst others the required functionality of PACS, diagnostic aspects and the quality of care and organizational aspects. The key question was whether, when and how PACS is feasible, both from a financial and a clinical point of view. Data which were collected with the aid of the software tool CAPACITY formed the starting point of this meeting. This paper gives an outline of the discussions during this workshop. The main conclusion is that more clinical research is needed, to get a better insight into the costs and the clinical benefits of PACS. Because of the high costs of the PACS technology, international cooperation in this field is requested. It is recommended that the CAPACITY project, which is set up to stimulate the international dialogue and data exchange on PACS, is continued.

Metabolism of cholecalciferol in land snails. 1. Radioactively labelled cholecalciferol was injected into the land snails Levantina hiersolyma and Theba pisana. Three metabolites (C, D and E), more polar than cholecalciferol, were found. 2. Metabolite C was found to be identical with 25-hydroxycholecalciferol. On injection of 25-hydroxy[26,27-3H]cholecalciferol, metabolite E was predominantly formed. Metabolite D was predominantly formed from cholecalciferol. Metabolites D and E differ from any known cholecalciferol metabolites. 3. The intestine was found to be the tissue capable of carrying out the transformation of 25-hydroxycholecalciferol into metabolite E. 4. 25-Hydroxycholecalciferol and metabolite E were localized in the digestive gland of the snail, the tissue responsible for the absorption of Ca2+ and its storage. Metabolite D was not localized in any specific tissue.

[Giardiasis in dog and cat owners]. In subjects with positive giardiasis tests examinations of contacts were made not only in all members of the family but also in dogs and cats living with them in the same household. Attention was paid to the possible transmission of giardias. A total of 174 families were examined, i.e. 1140 subjects incl. 156 positive ones. Of 123 examined dogs 9 were positive and of 56 cats 8 were positive. Forty-three dog keepers were negative, of their 222 dogs 60 were positive. Although no association was proved between the infection of domestic animals and humans in the examined group, it is recommended to treat not only humans but also domestic animals.

[Interference of platelet-activating factor antagonist, BN50739 with the releasing of inflammatory mediators from anaphylactic lung of guinea pig]. BN50739 is a new and potent PAF antagonist. In this experiment, we have further confirmed that it is a selective PAF antagonist by means of rabbit platelet aggregating test. And also, when BN50739 was applied, in the concentration of 10 uM, to the isolated lung of guinea pig sensitized by ovalbumin, we observed that the amount of histamine and thromboxane A2 released was a little less (about 19.0% and 19.2%, respectively) than that of controls (P < 0.05). Whereas, the ratio of PGI2/TxA2 was increased by 17.6% comparing to that in control group (P < 0.05). But the level of LTC4 remained unchanged regardless of the presence of BN50739. We conclude that PAF may play a role in allergic reaction.

The sebotrophic effect of pregnancy. The sebum excretion rate (SER) in forehead skin was measured in late pregnancy and 8-20 weeks after delivery in 43 women. There was considerable individual variation but the mean SER during pregnancy was significantly higher than in a control group of non-pregnant women and it showed a large and significant decrease to the control level after delivery. This suggests that a powerful sebotrophic hormone is secreted during pregnancy. The mean SER during pregnancy in women with twins or triplets was no greater than the SER in women with a single foetus. This suggests that the sebotrophic factor of pregnancy is unlikely to be of placental origin, and is in keeping with the idea that the sebotrophic factor may come from the pituitary.

[A study for womanhood and caring]. This study is to explore the womanhood and caring. To explore the meaning of caring for nursing, it is necessary to identify the terms of the relationship between caring and womanhood as these bonds have been formed over the last century. Historically, nurses were expected to act out of on obligation to care, taking on Caring more as an identity than as work, and expressing altruism without, thought of autonomy either at the bedside of in their profession. Not only did the role of nursing evolve from the mother's role in the family, but the family itself served as a modal for care in the hospital. Thus, Nurses, like others who perform what is defined as "womens'work" in own society, have had to content with what appears as a dichotomy between the duty to Care for others and the right to control their own activities in the name of caring. Nursing was to be, therefore, a woman's duty, not the job. Obligations and love, not the need of work, were to bind the Nurses bo her patient. Caring was to be an unpaid labour of Love Gender studies suggests a basis for caring the stresses individual discretion and values, acknowledging that the Nurses'right to Care should be given equal consideration with the physician's right to Cure. Nursing continues to struggle with the basis, and the value of caring. But the dilemma of nursing is too tied to society's broader problems of gender and class. Nurses will have both to create a new political understanding for the basis of caring and to find ways to gain the power to implement it.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased reticuloendothelial phagocytic function following prolonged in vivo blood pumping - preliminary observations. The composite findings described above suggest that the relatively mild blood trauma (and possibly altered arterial pulse waveforms), which were produced during the prolonged pump perfusions, sufficed to produce a modest but distinct measure of compromise in the phagocytic function of the RES in the majority of animals. Among possible factors contributing to the observed decreases in the RES phagocytic function of perfused animals are 1) pump-induced alteration of blood flow pattern RES elements (particularly decreased hepatic perfusion), 2) impaired opsonization, and 3) depressed phagocytic capability of RES cellular elements (due possibly to partial RES blockade by blood breakdown products. The specific role of these and possibly other factors requires furher clarification. The findings thus suggest that fixed tissue elements, as well as circulating blood cells, may be vulnerable to the hematological, and possibly the hemodynamic derangements which accompany prolonged perfusion with mechanical circulatory devices.

Bacteriophage T5-induced endonucleases that introduce site-specific single-chain interruptions in duplex DNA. Four site-specific endodeoxyribonucleases have been partially purified from extracts of bacteriophage T5-infected Escherichia coli by gel filtration and affinity chromatography on single- and double-stranded DNA. The enzymes were detected and characterized by agarose gel electrophoresis of alkali-denatured digestion products. None of the four is found in uninfected cells. In the presence of a divalent cation, all four endonucleases make ligase-repairable, single-chain interruptions at specific sites in the duplex DNA of several bacteriophages (lambda, T7, and T5) and a mammalian virus (adenovirus 2). These activities are not stimulated by ATP. None of the four is active on single-stranded DNA. The fragments produced by each enzyme from ligase-repaired T5 DNA do not correspond to those derived from mature T5 DNA. Each of the enzymes is able to cleave the intact strand of T5 DNA.

[Electroencephalographic curves in diseases of the basomedian cerebral structures]. In twenty-two patients bilaterosymmetric, slow frequencies occurring in groups frontoprecentrally and frontoparietally, respectively, were found for a total of thirty-four spaceoccupying processes of basomedian structures. Such alterations should not be considered to be characteristic of tumors located adjacent to the median line, but may be regarded as an important indication. The changes themselves are due to the diffuse thalamocortical system as well as the reticular activating system. The overlapping of functions of these systems and the different responses of equal structures to different intensities of stimulation make it impossible for clinicians to assign them to individual basomedian structural levels even if necropsy records and reports on surgical operations are taken into consideration.

Incidence of ABO(H) blood group variants among the Bulgarian population. The result of a screening of ABO (Hh) variants after investigating the blood group of 106,980 persons are presented. The Ax variant is registered most frequently among the Bulgarian population. As a whole the frequencies of ABO blood group variants Ax, Ael, A3, Aend and Am among the Bulgarian population are similar to that established by other authors among the French population and nearly twice as high as among the population of Bombay. The group of H-deficient phenotypes includes AA1Xh, AHm, OHm variants. Their frequency is significantly lower when compared with the frequency of AHm and OHm variants among the population of Thailand. Variants A1 and Aint with unusually high H-content are classified as A1H, A1Hint, Aint H and integrated as a category of H-excess phenotypes. Their incidence among the Bulgarian population is significantly lower than that registered among Maharastrian, South African Bantu and Indian.

Automated determination of total plasma cholesterol: a serum calibration technique. The automated (AutoAnalyzer II) determination of cholesterol in nine serum pools in the concentration range 3.465-8.871 mmol/l, gave results that were approximately 10% higher than reference values when the analyses were based on unesterified cholesterol standards containing the same amount of water as the sample extracts (1963 analyses in 12 laboratories during a 12 month period; automated value = 0.032 + 1.10 X (Reference value)). A serum calibration procedure was successful ilues, and was equally effective in correcting the values observed for aliquots of 368 fresh-frozen plasma samples analyzed in each of the 12 laboratories during a 38 month period.

Selection of U937 histiocytic lymphoma cells highly responsive to phorbol ester-induced differentiation using monoclonal antibody to the eosinophil cytotoxicity-enhancing factor. Monoclonal antibodies (MoAbs) to the eosinophil cytotoxicity-enhancing factor (ECEF) were used to detect ECEF in U937 cells before and after phorbol ester (PMA)-induced differentiation into ECEF-secreting macrophages. Membrane-associated ECEF (mECEF), apparently an integral membrane component, is found in U937 cells and in 70% of monocytes and, at lower levels, on blood T lymphocytes. Expression of mECEF in U937 cells is heterogeneous, as is responsiveness to PMA. In PMA-treated cultures, the strongest mECEF expression is on adherent, differentiated macrophages, rather than on activated, nonadherent cells. To study the relationship of mECEF to PMA responsiveness, we positively selected by "panning" a cell line (U937 P+) with significantly higher mECEF expression than that of U937. U937 P+ cells respond to PMA as a differentiation stimulus more effectively than do U937 cells, with a fourfold increase in the number of differentiated macrophages (P less than .001) and a faster rate of differentiation (a fourfold increase at t = 12 hours, P less than .001). U937 P+ cells also show a 7.4-fold increase in response to suboptimal doses of PMA (P less than .001). These findings suggest that mECEF expression correlates with responsiveness to a differentiation stimulus in a histiocytic lymphoma cell line that is widely used as a model of monocyte maturation.

Are we ready for PL 99-457? Public Law 99-457 has renewed interest in providing preschool education for hearing-impaired children. It is not clear, however, whether we're ready for this mandate to expand services to an ever-younger population and its families. This study presents a "snapshot" of the trends in preschool programs and of the availability of programming to students in various parts of the country. We obtained lists of programs from a sample of state level special education offices, and then sent the programs detailed questionnaires. The returned surveys provided a snapshot of the instructional approaches used in many preschool programs and indicated that there may still be some problems in the availability of preschool programming and in the ability of programs to uniformly provide the sorts of quality comprehensive services mandated by the law.

Charge shift electrophoresis: simple method for distinguishing between amphiphilic and hydrophilic proteins in detergent solution. Seventeen hydrophilic proteins and five amphiphilic membrane proteins were subjected to agarose gel electrophoresis in the presence of a nonionic detergent (Triton X-100), a mixture of anonionic and an anionic detergent (Triton X-100 and sodium deoxycholate), and a mixture of a nonionic and a cationic detergent (Triton X-100 and cetyltrimethylammonium bromide). The electrophoretic mobility of the hydrophilic proteins was unaffected in the three detergent mixtures. However, the mobility of the amphiphilic proteins shifted anodally in the Triton X-100-deoxycholate system and cathodally in the Triton X-100-cetyltrimethylammonium bromide system when compared to the mobility in Triton X-100 alone. The detergent-induced shift in mobility provides a simple, rapid, and sensitive method for distinguishing between hydrophilic and amphiphilic proteins.

[The correlation of IgA-class antigliadin and antiendomysial antibodies (AGA-IgA--EmA-IgA) with the intestinal histology in celiac disease (CD)]. The aim of this work was to establish the diagnostic and follow up value of IgA-class antiendomysium (IgA-EmA) and IgA-class antigliadin (IgA-AGA) antibodies in celiac disease. Correlation with the intestinal histology at the different stages of the disease was evaluated, as well as its therapeutic monitoring ability. Fifty six children, twenty seven girls and twenty nine boys, aged six months to twelve years old, were studied. Thirty nine celiac children were all different diagnostic stages of the disease. Seventeen children with malabsorption symptoms and with normal intestinal histology were used as controls. Sixty blood samples were obtained simultaneously with the small intestinal biopsy. IgA-AGA (ELISA method) and IgA-EmA (immunofluorescent test performed over lower third Rhesus monkey esophagus) were determined in every blood sample. In 34 serum samples from patients with total or subtotal villous atrophy, two were negative for IgA-AGA and only one was negative for IgA-EmA. In 26 samples from patients with normal intestinal histology, two were positive for IgA-AGA and four were positive for IgA-EmA. The results for IgA-EmA had sensitivity 97%, specificity 84.6%, positive predictive value 89.2% and negative predictive value 95%. In the case of IgA-AGA were: sensitivity 94.1% specificity 92.3%, positive predictive value 94.1%, negative predictive value 92.3%. IgA-AGA and IgA-EmA showed a high correlation with intestinal histology and are in combination powerful tools for the diagnosis and follow up of celiac patients. Besides, they provide a useful aid in the indication of a jejunal biopsy and in close monitoring of the dietary treatment compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of parathyroid hormone on cyclic AMP-formation and cytoplasmic free Ca2+ in the osteosarcoma cell line UMR 106-01. The effects of parathyroid hormone (PTH) on cytoplasmic free Ca2+ (Cai2+) and cAMP-formation were investigated in the rat osteosarcoma cell line UMR 106-01. In fura-2 loaded adherent single cells bPTH 1-34 (10 nM - 1 microM) induced a rapid transient increase in Cai2+ in 11% of the studied cells. In fura-2 tracings from UMR 106-01 cells in suspension, bPTH 1-34 (0.1 microM) induced a transient increase in Cai2+ in 20% of the experiments. The transient increase in Cai2+ seen in suspensions of cells was not abolished by addition of EGTA (2.5 mM) prior to challenge with PTH, suggesting that the increase in Cai2+ was derived from intracellular stores. A marked rapid increase in cAMP-formation was observed in all experiments with cells in suspension, also in the experiments where PTH did not affect Cai2+. These data show that PTH causes a release of Ca2+ from intracellular stores in a small percentage of osteosarcoma UMR 106-01 cells, and that PTH is capable of inducing an increase in cAMP-formation without affecting Cai2+ in osteoblasts.