In vitro response of human small-cell lung-cancer cell lines to chemotherapeutic drugs; no correlation with clinical data. Three cell lines derived from small-cell lung carcinoma (SCLC) tumors of patients who had no clinical response after treatment with a multi-drug regimen were compared to 3 cell lines derived from tumors of patients who, upon treatment, showed a complete clinical response. These 2 groups of cell lines were considered to represent the in vitro counterparts of the 2 extremes of the clinical spectrum of sensitivity for chemotherapeutic drugs in small-cell lung cancer. To assess whether the in vivo (in)sensitivity of a tumor to a certain drug regimen is retained in vitro, the cell lines were tested for drug sensitivity using the microtiter-well tetrazolium assay and the results were compared with the in vivo data. No correlation was found. Since in vitro models using cell lines are based on the assumption that a cell line reflects the properties of the tumor from which it is derived, several additional parameters such as MAb staining against different SCLC-associated antigens and DNA content were analyzed in the biopsies and the cell lines. The results showed that selection of discrete tumor-cell populations in vitro occurs. Results of in vitro chemosensitivity testing for individual SCLC patients should be interpreted with caution.


Heterologous regulation of inositol lipid hydrolysis in human breast cancer cells by oestradiol 17 beta, bombesin and fluoroaluminate. Inositol lipid turnover has been implicated in the action of oestradiol 17 beta and bombesin-related peptides on the human breast cancer cell line MCF-7. In the present study, in addition to measuring inositol lipid turnover as indicated by inositol monophosphate (IP) accumulation, we have also monitored the effect of oestradiol on the incorporation of both 3H-inositol and 14C-glycerol into MCF-7 cell phospholipids. Pre-treatment of MCF-7 cells with oestradiol (10 nM) for 48 hr stimulated a 4.3-fold increase in IP production. This was similarly accompanied by a 3.4-fold increase in the incorporation of 3H-inositol into total phosphoinositides and a 40% increase in cell growth. The oestrogen antagonist LYI 17018 completely attenuated these effects. Oestradiol also stimulated 14C-glycerol incorporation into phosphatidyl inositol, -choline and -ethanolamine by 97%, 82% and 99%, respectively. IP production in response to bombesin was potentiated by oestradiol in a dose-dependent fashion. Fluoroaluminate (AlF4-) stimulated a dose-dependent increase in IP production and oestradiol pre-treatment increased the sensitivity of this IP response to AlF4-. Medroxyprogesterone acetate inhibited bombesin-stimulated IP production but had no effect on the response to AlF4-. Our data suggest that the oestrogenic action on basal IP production in MCF-7 cells may reflect an effect on inositol lipid synthesis rather than turnover. However, the potentiation by oestradiol of both bombesin- and AlF4(-)-stimulated inositol lipid hydrolysis suggests the operation of a post-receptor regulatory mechanism(s) which is independent of the inositol lipid pool size.


Tibial osteomyelitis due to Aspergillus flavus in a heart transplant patient. Aspergillus flavus was identified as the causative organism of a case of osteomyelitis involving the proximal epiphysis of the left tibia in a heart transplant patient. History revealed a previous pretibial wound due to a fall in the street as the consequence of a sudden cardiac arrest. Surgical debridement combined with fungostatic treatment including amphotericin B and itraconazole was followed by clinical improvement, although the fungus could still be recovered by culture on subsequent samples.


Incidence of bulimia in substance misusing women in residential treatment. The incidence of bulimia in 100 consecutive adult women entering a residential substance misuse treatment program was examined utilizing DSM-III-R self-report data. Fourteen percent of the clients were diagnosed as having a concurrent eating disorder, seven times the community prevalence rate. The demographic variable of race was an important distinguishing characteristic, while age was not. Cocaine addicts had the highest rate of bulimia, while opioid addicts had the lowest. The clinical significance of these data for treatment and future research is discussed.


Oncogenesis of squamous carcinoma of the uterine cervix. Carcinoma of the uterine cervix is the most frequent neoplasm among women in India, accounting for up to 85% of all female gynecological malignancies. In the United States, it accounts for about 48% of all female tumors and 4% of all cancer deaths of females. Epidemiological evidence suggests involvement of numerous risk factors in the etiology of cervical cancer, including sexual behavior, number of pregnancies, cigarette smoking, and venereal disease. Recent studies, however, tend to emphasize viral involvement in the development of cervical cancer along with concomitant cytogenetic and immunological changes. This review focuses on the roles of human papillomavirus infection, chromosomal abnormalities, and immune function changes in the pathogenesis of cervical carcinoma.


Synchronous papillary mucinous adenocarcinoma of the endocervix and fallopian tubes. A unique case of synchronous, trifocal mucinous papillary adenocarcinoma involving the uterine cervix and both fallopian tubes is presented. Unequivocal carcinoma in situ changes are demonstrated in all three primary sites. A discussion of synchronous development of malignancies of the female genital tract and differentiation from contiguous or metastatic spread of a single primary focus follows.


Relationship between questionnaire data and medical records of height, weight and body mass index. Although some studies have analysed the accuracy of self-reported weight and height data in survey studies, no attention has been paid to the accuracy of the body mass index (BMI, kg/m2), derived from these data and often considered as a reliable indirect estimate of relative body weight. Based on data from about 3400 participants in a study, questionnaire self-reports of these anthropometric data were compared to measured weight and height. A flat slope syndrome (under-reporting of high values, over-reporting of low ones) was found for weight and BMI for both sexes. A low sensitivity of BMI based on self-reported values were found, especially for the obese sub-population. Reliance upon questionnaire-derived self-reports will lead to considerable underestimation of the prevalence of obesity. Only 55 per cent of obese women and 60 per cent of obese men according to measured values were correctly classified as such. Correction of self-reported data according to regression models describing the relationship between questionnaire self-reports and medical records of body size parameters should be considered for some types of epidemiologic studies such as those using BMI as a categorized variable. The statistical rationale for the models used here is discussed.


Resting metabolic rate in obese children before, during and after weight loss. Resting metabolic rate (RMR) and body composition were measured by indirect calorimetry and body impedance analysis in 14 obese children before weight loss, during weight reduction for 3 weeks with a conventional hypocaloric diet (730 kcal/3050 kJ) and 12 months after weight loss. The initial weight reduction (5.8 +/- 1.2 kg) resulted in a decrease in RMR and fat free mass (FFM) of 17 +/- 10 per cent (P less than 0.001) and 3.1 +/- 2.3 kg (P less than 0.001), respectively. Prior to weight loss (r2 = 0.89, P less than 0.001) and after 12 months follow up (r2 = 0.88, P less than 0.001) RMR correlated positively with FFM. Changes in RMR after 3 weeks weight loss and throughout the follow-up were positively correlated with changes in FFM (r2 = 0.29, P less than 0.05 and r2 = 0.90, P less than 0.001). Our data indicate that RMR in obese children considerably decreased during a 3 weeks weight reduction, but no sustained depression of the metabolic rate after 12 months was found.


Fat distribution in European men: a comparison of anthropometric measurements in relation to cardiovascular risk factors. It has been proposed that subcutaneous fat patterning assessed by skinfolds is measuring different aspects of fat distribution compared to circumferences and circumference ratios. In this study in 510 men born in 1950 selected from six European towns we compared the associations between five skinfolds, eight circumferences and several skinfold and circumference ratios and metabolic risk factors after adjustment for body mass index (BMI). All skinfolds were independently of BMI positively related to diastolic blood pressure. Waist circumferences at most levels were independently of BMI positively related to blood pressure and triglycerides and negatively to HDL-cholesterol. Circumferences at the levels of chest, hips, thigh and arm were not related to any of the risk factors studied. Waist/thigh ratios were generally more strongly and more consistently related to risk factors than waist/hip ratios. The partial correlations of anthropometric variables with risk factors were relatively weak and never exceeded r = 0.20. The results give an indication, however, that subcutaneous fat patterning is related to different risk factors compared to waist/hip ratios. Moreover, waist/thigh and waist circumference alone (measured either as the minimal circumference or midway between the lower rib margin and the iliac crest) were stronger correlates of cardiovascular risk factors compared to waist/hip ratio.


Stability over time of adrenergic sensitivity in isolated human fat cells. The stability over time for lipolysis in isolated human subcutaneous fat cells was investigated in 13 non-obese volunteers who underwent two gluteal fat biopsies under local anaesthesia at random intervals (mean 18 months). Glycerol release to the incubation medium was measured in the absence or the presence of lipolytic or antilipolytic adrenergic agents. The half-maximum effects (ED50) of norepinephrine, the non-selective beta-agonist isoprenaline and the selective alpha 2 agonist clonidine were determined and each had an intraindividual coefficient of variation of 7 per cent. The precision of the lipolysis assay, performed in duplicate, was 10 per cent. The coefficient of variation for lipolysis at the maximum effective concentrations of the agonists was between 20 per cent and 30 per cent. The addition of adenosine deaminase does not reduce the variability. In conclusion, the isolated human fat cell lipolysis assay shows some variability for maximum action of adrenergic agonists on lipolysis. However, there is a small variability in ED50 for such agents which indicates that the assay is well suited for determining drug sensitivity.


Abnormal incisor teeth and body weight in the obese mouse (genotype ob/ob). Inherently obese mice (genotype ob/ob) developed abnormal incisor teeth at 26 weeks of age. Up to that age, their teeth were indistinguishable by visual criteria, from those of lean (wild-type) litter-mate mice. Radiography and preliminary histology suggested impaction of the tooth in its alveolus (socket) due to the disorganized production of enamel and dentine. Incidence was high (92 per cent) in obese and zero in lean mice. Upper incisor teeth were more severely affected than lower. The severity of teeth lesions could not be correlated with age or body weight. Both sexes were equally affected. The onset of teeth lesions marked the end to the rapid rise in body weight characteristic of the obese mouse. An irregular fall in body weight ensued which could be alleviated by powdering the pelleted food. This indicated the fall to be a consequence of impaired function of the incisor teeth. Abnormality of the teeth was entirely prevented by feeding obese mice from weaning, a similar amount of food to that eaten by lean mice. The high circulating levels of adrenocorticosteroids in the obese mouse are suggested as a cause of the incisor tooth abnormality.


Dexfenfluramine as adjuvant to a low-calorie formula diet in the treatment of obesity: a randomized clinical trial. Dexfenfluramine (dF) was compared to placebo as adjuvant to a very energy-restricted diet (1.6-4.2 MJ/24 h). The diet was continued as long as possible or until a satisfactory weight loss had been achieved, and dietary efforts were continued throughout the study. Of the 37 females and five males included, 71 per cent could be followed up for 12 months. Initial BMI ranged from 28 to 54 kg/m2. The lowest body weight was reached 1 month earlier in the dF group (P = 0.037). Throughout the study, the reduction of excess weight (REW) was greater in dF patients (P less than 0.05 only at 4 and 6 months). At 6 months, excess weight had declined by 15 per cent more in the dF group than in the placebo group (95 per cent confidence limits of the median being 1-31 per cent). Between 6 and 12 months, both groups regained weight significantly, the rates of regain differing only insignificantly. At 12 months, excess weight showed a net decrease of only 8 per cent more in the dF group than in the placebo group (95 per cent confidence limits being -7 to +24 per cent). Therefore, REW showed no significant group difference after 12 months. Type of obesity (android or gynoid) as determined by waist to hip ratio had no significant impact on either weight loss, REW, reductions of waist and hip circumferences, or on waist to hip ratio changes. S-alkaline phosphatases and s-uric acid declined significantly in the dF group only. Side-effects were all mild and their prevalence showed no group difference.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of weight loss on resting energy expenditure in obese prepubertal children. To assess the effect of weight loss on resting metabolic rate (RMR), the energy expenditure of eight obese prepubertal children (age 9 +/- 1 years; weight 48.7 +/- 9.1 kg; BMI 25.3 +/- 3.9) and of 14 age-matched children of normal body weight (age 9 +/- 1 years; weight 28.8 +/- 5.6 kg; BMI 16.5 +/- 1.7) was measured by indirect calorimetry. The obese children were reinvestigated after a mean weight loss of 5.4 +/- 1.2 kg induced by a six-months mixed hypocaloric diet. Before slimming, the obese group showed a higher daily energy intake than the control group (10.40 +/- 3.45 MJ/day vs 7.97 +/- 2.02 MJ/day respectively; P less than 0.05) but a similar value was observed per unit fat-free mass (FFM) (0.315 +/- 0.032 MJ/kgFFM/day vs 0.329 +/- 0.041 MJ/kgFFM/day respectively). The average RMR of the obese children was greater than that of the control group (5217 +/- 531 kJ/day vs 4477 +/- 506 kJ/day) but similar after adjusting for FFM (4728 +/- 3102 kJ/day vs 4899 +/- 3102 kJ/day). Weight loss resulted in a reduction in RMR (5217 +/- 531 kJ/day vs 4874 +/- 820 kJ/day), each kg of weight loss being accompanied by a decrease of RMR of 64 kJ (15.3 kcal) per day. The changes in RMR induced by weight loss paralleled the changes in FFM. No difference was found in average RQ in obese children vs controls (0.85 +/- 0.03 vs 0.87 +/- 0.03 respectively) and in the obese children before and after weight loss (0.87 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


Serum cholesterol profiles during treatment of obese outpatients with a very low calorie diet. Effect of initial cholesterol levels. We studied relative changes of serum cholesterol in obese patients during and after weight loss to determine if they depend on initial cholesterol levels as classified by the National Cholesterol Education Program. Three groups of obese free-living outpatients with desirable (normal) (less than 5.17 mmol/l, n = 26), borderline-high (5.17-6.18 mmol/l, n = 29), and high (greater than 6.21 mmol/l, n = 32) initial total cholesterol completed a 26-week program employing a very low calorie diet. The program involved 12 weeks of supplemented fasting, followed by 6 weeks of refeeding and then 7 weeks consumption of step 1 diet that maintained the new reduced weight. The groups were similar in initial clinical characteristics and they also lost comparable percentages of initial weights. Relative reduction in total cholesterol throughout the study was significantly larger in both borderline-high and high cholesterol groups compared to normal. In patients of borderline-high and high cholesterol groups favourable and significant reduction of total cholesterol, LDL cholesterol, total cholesterol/HDL cholesterol, and LDL cholesterol/HDL cholesterol ratios were maintained at the end of the study. The percent decrease in total serum cholesterol at the end of the study positively correlated with the percent of weight loss in patients of the high cholesterol group. We conclude that obese hypercholesterolemic patients have favorable changes in cholesterol profile following weight loss, and that relative reduction of cholesterol levels depend on initial levels. However, specific roles of weight loss, change in diet and/or increased physical activity in observed changes in lipid profiles cannot be determined by this study.


The effect of weight loss on change in waist-to-hip ratio in patients with type II diabetes. This study sought to determine whether weight loss would alter body fat distribution in obese men and women with type II diabetes. Subjects were 60 women and 33 men who participated in a year-long weight loss program. Weight losses of women and men, respectively, averaged 13.4 kg and 16.8 kg at six months and 11.2 kg and 13.1 kg at one year. WHR decreased significantly in both genders: for women, WHR decreased from 0.95 at baseline to 0.93 at six months and 0.94 at one year; for men WHR decreased from 0.99 at baseline to 0.96 at six months and 0.96 at one year. Subjects with greater upper body obesity at baseline did not lose more weight than subjects with less upper body obesity, but they did have greater reductions in WHR at six months in both genders and at one year in men. The magnitude of WHR reduction was strongly related to the amount of weight lost in men, but was not related to weight loss in women. Improvements in fasting glucose, fasting insulin, and HbA1 were significantly related to weight loss, but not to reductions in WHR. Thus, participation in a weight loss program had beneficial effects on body fat distribution in patients with type II diabetes, but these changes in WHR were not independently associated with improvements in glycemic control.


Does lipid oxidation differ in gynoid and android obese women? This study was performed to investigate whether body fat distribution influences resting metabolic rate and lipid oxidation in obese individuals. Eighty-nine obese women were divided in two groups (android obese, n = 36, BMI = 31.1 +/- 4.5 kg/m2 (mean +/- s.d.); gynoid obese, n = 53, BMI = 29.9 +/- 4.5 kg/m2 on the basis of their waist/hip ratio (0.86 +/- 0.05 vs 0.75 +/- 0.04 respectively). Body weight, per cent body fat and fat-free mass were similar in the two groups. Moreover, resting metabolic rate and respiratory quotient were also identical in android and gynoid obese women, indicating that there was no intergroup difference in the absolute level of lipid oxidation. If, like most other android obese women, they had higher rates of lipolysis and plasma FFA concentrations, the failure of android obese individuals to exhibit a higher lipid oxidation than gynoid obese women may partly explain their increased risk to develop metabolic complications.


Studies on phosphoribosylpyrophosphate synthetase from Giardia intestinalis. A substantial degree of purification, up to 3200-fold, with recoveries of 8-11% of phosphoribosylpyrophosphate (P-Rib-PP) synthetase from Giardia intestinalis extracts was achieved by the high resolution techniques of anion exchange chromatography and chromatofocusing columns on a fast protein liquid chromatography system. A Mono P chromatofocusing column gave rise to an enzyme peak eluting from the column at pH 4.5, indicating that the enzyme has an isoelectric point (pI) at approximately this value. The molecular weight of the enzyme was found to be 150,000 from a Sephacryl S-200 column. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the purified enzyme gave a single protein band with a subunit molecular weight of 38,000, indicating that the enzyme existed as a tetramer. The properties of G. intestinalis P-Rib-PP synthetase in terms of pH optimum, isoelectric point, subunit structure, phosphate requirement, metal and nucleotide specificity, appear to be very similar to those of the enzyme from other sources.


Ultrastructural and cytochemical analysis of Na+, K+, ATPase and H+, K+, ATPase in parietal cells of gastric mucosa in the rabbit. Rabbit gastric secretion has the physiological peculiarity of being continuous and uninfluenced by food intake. In this respect, ultrastructural analysis of rabbit parietal cells has revealed morphofunctional features situated between states of rest and very active acid secretion. Our cytochemical study shows that Mg2+ ATPase and ADPase activities vary from cell to cell and can even be totally absent. These activities concern either microcanaliculi or laterobasal folds or both, but never tubulovesicles. Application of the technique of Mayahara to K+ pNPP, associated or not with inhibitors (ouabain, vanadate, N-ethyl-maleimide, sodium fluoride), enabled us to confirm the coexistence of H+, K+, ATPase and Na+, K+, ATPase activities in the rabbit and to determine that these activities concern basolateral folds, microcanaliculi, hyaloplasm and tubulovesicles. The global activity of K+, pNPPase varied considerably in intensity. The results of using inhibitors suggest that proton transport ceases completely in certain cells. The signs of functional alternation found in this study are in agreement with physiological data relative to this animal.


Nuclear location of phosphoglycerate mutase BB isozyme in rat tissues. We have previously reported (Ureña et al. Eur. J. Cell Biol. 1990) that in skeletal muscle, type MM phosphoglycerate mutase isozyme is present in the nucleus as well as in the cytosol. To determine whether type BB phosphoglycerate mutase isozyme is also present in nucleus, the subcellular location of this isozyme was studied in different rat tissues by cell fractionation and immunogold techniques. With the aid of high affinity-purified anti-phosphoglycerate mutase BB isozyme antibodies, the isozyme was located in the nucleus of neuronal, astroglial and liver cells but not in the nucleus of oligodendroglial and endothelial cells. Biochemical studies on purified nuclear fractions also demonstrated the presence of phosphoglycerate mutase activity in the nucleus. Both immunocytochemical and biochemical techniques showed that nuclear phosphoglycerate mutase-specific activity depended on the type of cell.


Beta-adrenergic receptor binding in crude porcine adipose tissue plasma membranes. Methods have been detailed to prepare a crude membrane fraction from isolated porcine adipose tissue cells. Adipocytes were obtained after incubation of 5 g of adipose tissue slices with 4,500 units of a selected lot of collagenase in a total volume of 15 mL at 37 degrees C for 90 min. There was no bovine serum albumin present during cell isolation because albumin did not enhance cell yield or yield of lipolytic activity. Isolated cells were lysed by exposure to hypotonic conditions in the presence of 7.5 mM ethylene glycol tetraacetic acid (EGTA) and .8 mM phenylmethylsulfonyl fluoride (PMSF). A 30,000 x g centrifugal pellet was used as the crude membrane preparation. Binding of tritiated dihydroalprenolol (DHA), a beta-adrenergic antagonist, was measured in the presence of 7.5 mM EGTA and .2 mM PMSF, because these protease inhibitors improved specific binding by approximately 50% to greater than 150 fmol/mg of protein and decreased non-specific binding to less than 10% at 2.5 nM DHA.


Effect of extrusion on the ileal and fecal digestibilities of lysine, nitrogen, and energy in diets for young pigs. Forty crossbred barrows (initial average BW of 20 kg) were fitted with T-cannulas in the distal ileum to determine the effects of extrusion of soybean meal on the apparent ileal and fecal digestibilities of lysine, N, and GE. A basal corn-soybean meal diet was formulated to contain .525% lysine. Nonextruded soybean meal (SM), extruded soybean meal (ESM), and L-lysine.HCl (LLH) replaced cornstarch in the basal diet to make diets containing .60, .675, and .75% total dietary lysine for each lysine source. Treatments were arranged as a 3 x 3 factorial with the basal diet as an additional treatment. Ileal and fecal digestibilities of lysine were not affected (P greater than .05) by source of lysine. However, linear increases (P less than .05) occurred in ileal lysine digestibilities with increasing concentrations of dietary lysine provided as LLH, but not when lysine was provided as SM or ESM. Apparent ileal and fecal retention of N as percentages of N absorbed or consumed were greater (P less than .05) for diets containing LLH than for diets containing SM, and diets containing ESM were intermediate. Linear increases (P less than .05) occurred in ileal and fecal N retained as percentages of N absorbed or consumed with increasing concentration of dietary lysine provided as LLH or ESM, but not when provided as SM. Fecal DE and ME (kilocalories per gram of diet) for diets containing LLH and ESM were similar and greater (P less than .05) than the values obtained for diets containing SM.(ABSTRACT TRUNCATED AT 250 WORDS)


Source and feeding level of nitrogen on growth and carcass characteristics of beef steers fed grass as hay or silage. Sixty medium-framed Hereford steers averaging 243 kg were used in an experiment including a growing period (28 wk) and a finishing period ending when the animals had approximately 4 to 10 mm of fat thickness (Canadian grade A1). Steers were assigned randomly to a 2 x 3 factorial arrangement of treatments for 28 wk (growing period). From the end of the growing period until slaughter, all steers received the same diet to study the residual effect of treatments fed during growth. Treatments during the growing phase consisted of two types of forage conservation (silage or hay) and three levels of protein supplement (0, 200 g of fish meal plus 43 g of urea, or 400 g of fish meal). There was an interaction (P less than .05) between forage conservation and protein supplementation for BW gain during the growing phase; the greatest gain was by steers fed silage and 400 g of fish meal (.87 kg/d). There was no difference in BW gain among animals fed the hay diets, which averaged .75 kg/d. Body weight gain during the finishing phase, and for the overall experiment, was affected only by forage conservation; greater gains were made by steers fed silage during the growth phase. Protein supplementation did not affect performance in either the finishing phase or overall. Carcass composition did not differ among treatments, and time spent on the finishing phase tended to be less (P less than .08) for steers fed silage plus 400 g of fish meal during the growth phase.


Feed utilization of beef steers fed grass as hay or silage with or without nitrogen supplementation. Six Hereford steers averaging 256 kg were used in a 2 x 3 factorial arrangement within a 6 x 6 Latin square design to study the effect of forage conservation (silage vs hay) and N supplementation (0, 200 g of fish meal plus 43 g of urea, or 400 g of fish meal) on ruminal characteristics, digestibility, blood urea, and in situ degradability of DM, N, and ADF. Dry matter intake of forage and total DMI did not differ among treatments (P greater than .05) and averaged 5.3 and 5.5 kg, respectively. Steers fed silage had greater (P less than .05) pH and concentrations of ammonia N, isobutyrate, isovalerate, and valerate in the rumen than in the rumen of those fed hay. Nitrogen supplementation increased (P less than .05) concentrations of total VFA and valerate in the rumen. Digestibility of N and ADF was greater (P less than .05) for silage than for hay, and N supplementation increased digestibility of N. Plasma urea concentrations were greater (P less than .05) for steers fed silage than for those fed hay. These data suggest that feed utilization is better with silage than with hay and is increased by N supplementation.


Effects of source and level of dietary neutral detergent fiber on feed intake, ruminal fermentation, ruminal digestion in situ, and total tract digestion in beef cattle fed pelleted concentrates with or without supplemental roughage. The effects of source and level of dietary NDF on intake, ruminal digestion in situ, ruminal fermentation, and total tract digestion were evaluated in Hereford steers using a replicated 5 x 5 Latin square design. Diets contained 62 to 64% TDN and included 1) 80% control concentrate (contained pelleted ground grains) and 20% timothy hay (traditional diet), 2) 80% control concentrate and 20% alfalfa cubes, 3) 90% control concentrate and 10% cubes, 4) a completely pelleted diet using corn cobs as the primary NDF source, and 5) 80% textured (rolled instead of ground grains) concentrate and 20% hay. Dry matter intake differed (P less than .05) between the traditional and cube diets due to limited acceptance of alfalfa cubes. Increased (P less than .05) ruminal osmolality, total VFA, and NH3 N and lower (P less than .01) ruminal pH in steers fed corn cob and cube diets relative to steers fed the traditional diet were due to preferential consumption of concentrate over supplemental roughage and the resultant rapid fermentation of concentrates. Potentially degradable DM in the traditional diet exceeded (P less than .06) all other diets, resulting in the increased (P less than .10) extent of DM disappearance despite a slower (P less than .05) rate of DM disappearance. Rate of NDF disappearance and all in situ starch disappearance parameters were similar between the traditional, corn cob, and cube diets. All ruminal digestion parameters involving NDF disappearance were similar between hay diets and between cube diets, whereas rate and extent of starch disappearance differed (P less than .05) between hay diets. Although formulation of diets with different sources of dietary NDF did not affect total tract digestion of nutrients, nutrient availability and ruminal fermentation were altered due to dietary differences in sources of dietary NDF and preferential selection of feedstuffs by steers.


Effects of source of dietary neutral detergent fiber on chewing behavior in beef cattle fed pelleted concentrates with or without supplemental roughage. Ten 394-kg, ruminally fistulated Hereford steers were used in a replicated 5 x 5 Latin square design to evaluate the effects of source and level of dietary NDF on chewing activities during eating and rumination. Diets contained 62 to 64% TDN and included 1) 80% pelleted concentrate (control; contained ground grains, fibrous byproducts, molasses, and protein, vitamin, and mineral supplements; 36% NDF, 16% CP) and 20% long timothy hay (67% NDF, 8% CP), 2) 80% control concentrate and 20% alfalfa cubes (56% NDF, 15% CP), 3) 90% control concentrate and 10% alfalfa cubes, 4) a completely pelleted diet using corn cobs as the primary NDF source (40% NDF, 17% CP), and 5) 80% textured (coarse instead of ground grains; 42% NDF, 15% CP) concentrate and 20% hay. Diets were formulated to be similar in NDF content, and dietary protein satisfied NRC recommendations. Chewing during eating did not differ (P greater than .10) between diets containing supplemental roughage but decreased (P less than .001) with the corn cob diet. Rumination chewing decreased (P less than .001) with the corn cob and cube diets. The number of chews per day during eating corrected for NDF intake/BW.75 decreased (P less than .05) in the corn cob diet. Rumination periods and duration increased and latency before rumination decreased in hay diets. Steers fed the corn cob diet tended to be more (P less than .10) consistent in time spent eating across 4-h intervals than steers fed the traditional diet. Replacement of long hay with the completely pelleted corn cob diet decreased rumination activity.


Platelet imipramine binding in depressed children and adolescents. Kinetic constants of platelet imipramine binding were determined in youths with major depression, and a contrast group. Subjects actively depressed (N = 10) had significantly fewer imipramine binding sites (Bmax) (877 +/- 148 fmol/mg protein) than recovering depressives (N = 12) (1220 +/- 428 fmol/mg protein) and contrasts (N = 10) (1270 +/- 230 fmol/mg protein). Affinity constants (Kd) (1.14 +/- 0.36 nM, 0.97 +/- 0.31 nM, and 1.17 +/- 0.39 nM, respectively) were similar among the groups. Actively depressed males but not females had fewer imipramine binding sites than both their sex-matched comparison groups. Although actively depressed females' Bmax was significantly lower than recovering depressed and nondepressed males, neither age, Tannner stage, nor circannual rhythms influenced Bmax, but suicidality may be associated with low Bmax. A decrease in Bmax may be a state-specific marker of major depression in boys or associated with a depressive disorder with a suicidal history.


Desipramine facilitation of cocaine abstinence in an adolescent. An adolescent who was simultaneously dependent on cocaine and treated for attention-deficit hyperactivity disorder (ADHD) with dexedrine developed symptoms of severe depression followed by suicidal behavior. The patient was treated for cocaine craving, depression, and ADHD with desipramine on an inpatient adolescent unit for substance abusers with comorbid psychiatric disorder. The Minnesota Cocaine Craving Scale was used to monitor the cocaine craving. Issues about the strategies for the treatment of cocaine craving and the stimulant treatment/abuse dilemma are discussed with a special emphasis on comorbidity in adolescent substance abusers. Suicidal behavior related to cocaine abuse and craving and the application of the cocaine abstinence three phase model to an inpatient setting are illuminated.


High-performance liquid chromatography and preliminary pharmacokinetics of rufloxacin and its metabolites, N-desmethylrufloxacin and rufloxacinsulfoxide, in urine of rhesus monkey Macaca mulatta. A gradient high-performance liquid chromatographic method for the quantification of rufloxacin and two of its metabolites in urine, N-desmethylrufloxacin and rufloxacinsulfoxide, has been developed and validated. Monkey urine samples were diluted ten times with distilled water and 20 microliters were injected onto a Cp Spher 5-ODS column, 5 microns particle size. The mobile phase was a mixture of 4% acetonitrile and 96% buffer at time 0, which changed linearly over 37 min to 26% acetonitrile and 74% buffer. Detection was achieved at 246 nm. The limit of detection of the three compounds was 0.50 microgram/ml. An example of a pharmacokinetic study of rufloxacin and its metabolites in monkeys is shown.


Measurement of femoral torsion with ultrasound: evaluation of a new technique using reference lines on the posterior surface of the femur. A technique of measuring femoral torsion employing reference lines on the posterior surface of the femur has been described. This technique was evaluated on 27 dry adult femora and then on 40 adult patients. The technique was found to be reliable and reproducible. The values of femoral torsion obtained by this technique is lower than that obtained when anterior reference lines are used.


Flow velocity analysis of umbilical and uterine artery flow in pre-eclampsia treated with propranolol or pindolol. In a double blind study, 20 gravidas with pre-eclampsia were randomly allocated to treatment with either propranolol 120 mg/day or pindolol 15 mg/day for 7 days. Flow velocimetry was performed before and after treatment to assess the influence of these two regimens of beta blocker on the feto-placental circulation. A continuous wave Doppler unit was used to measure umbilical and uterine artery flow velocity waveforms. The systolic/diastolic (A/B) ratio and the systolic minus diastolic divided by systolic (A-B)/A ratio (resistance index) were used as indexes of blood flow resistance in the umbilical and uterine arteries, respectively. A resistance to flow in the uteroplacental circulation was significantly less in patients treated with pindolol compared to those treated with propranolol (P less than 0.01). The same pattern was also found in umbilical velocimetry, although the statistical significance was borderline (P = 0.06). Although both drugs were equally effective in reducing blood pressure at rest, their effect on the peripheral resistance was different. Pindolol appears to act in part through a peripheral vascular mechanism. Our data support this assumption because the flow in the uteroplacental bed, as reflected by a decrease in resistance index, improved when patients were treated with the drug pindolol.


Sonographic detection of stones in poorly opacified left intrahepatic ducts. Intrahepatic duct (IHD) stone is a common disease in Taiwan. In some cases, left IHD stones cannot be demonstrated by endoscopic retrograde cholangiography (ERC) or even by percutaneous cholangiography (PTC). This study was designed to evaluate the efficacy of sonography in demonstrating left IHD stones in poorly opacified left IHD by either ERC or PTC. Of 109 patients with hyperechoic nodular lesions in either the dilated left IHD or atrophic left lobe of the liver, with or without acoustic shadows, 49 patients were excluded because they refused further study. Among the remainder (60 patients), 33 patients had good opacification of left IHD in ERC or PTC. Stones were seen in 31 patients, and tumor obstruction in 2 patients. Twenty-seven patients had complete or partial absence of the left IHD in cholangiograms. Stones were found at surgery in 23 patients and by CT scan in 3 patients. Mucin-producing cholangiocarcinoma was found in 1 patient. The positive predictive value of the demonstration of stones in left IHD by ultrasound was 95% (57/60). Only 15% of patients with atrophy of the left hepatic lobe and stones were demonstrated by sonogram in this series. We conclude that the detection of left IHD stones by ultrasound in patients with poor opacification of the left IHD in cholangiograms is reliable procedure.


Intrahepatic venous and portal venous aneurysms examined by color Doppler flow imaging. Thirteen cases with liver cystic lesions, which were suspected to communicate with intrahepatic vessels on the basis of ordinary sonography, were examined by color Doppler flow imaging. By this method, blood flow within the cystic lesion was detected in 5 of these cases, and the communication to the intrahepatic vessel confirmed. Information about the hemodynamics of aneurysms was obtained. Two of these lesions were diagnosed as an aneurysmal porta-hepatic venous fistula, another 2 as a portal venous aneurysm, and the remaining 1 as a hepatic venous aneurysm.


Sjogren syndrome: comparison of sialography and ultrasonography. Ultrasonography and sialography of parotid glands were prospectively performed on 30 patients with Sjogren syndrome and follow-up ultrasonography was done on 12 patients. Ultrasonography revealed multiple hypoechoic areas (MHA) 2 mm to 5 mm in diameter within the glands in 43% of the patients with intermediate severity of the disease, either homogeneous or slightly nonhomogeneous parotid glands in patients with early stage of the disease, and marked nonhomogeneous glands in patients with advanced diseases. Follow-up ultrasonography showed MHA in one patient, reduction in nonhomogeneity in another three, and no interval changes in the remaining cases. Pathologic studies suggested that MHA represent enlarged parotid lobules replaced by lymphocytic infiltration. We suggest that MHA are characteristic of Sjogren syndrome and that ultrasonography is useful in following the course of the disease and response to treatment.


Effect of hyperthyroidism of short duration on cardiac sensitivity to beta-adrenergic stimulation. The effect of hyperthyroidism on cardiac sensitivity to beta-adrenergic stimulation in humans is controversial. To determine whether heart rate and left ventricular contractile sensitivity to beta-adrenergic stimulation are altered by hyperthyroidism in human subjects, the frequency, velocity and extent of left ventricular shortening at rest and during a 4-stage graded dose isoproterenol infusion were characterized in eight young healthy subjects before and after 2 weeks of daily administration of 100 micrograms of triiodothyronine (T3). The rate and extent of left ventricular shortening were determined by Doppler and two-dimensionally guided M-mode echocardiography. In the hyperthyroid state, heart rate at rest was faster (57 +/- 3 vs. 68 +/- 4 beats/min; p less than 0.001) and the slope of the relation of heart rate to the rate of isoproterenol infusion was 36% steeper (1,538 +/- 126 vs. 1,131 +/- 95; p less than 0.05). The left ventricular ejection time was shorter and the mean velocity of left ventricular circumferential fiber shortening (mVcf) was greater during all stages of isoproterenol infusion in the hyperthyroid versus the euthyroid state (p less than 0.01). After adjustment for the faster heart rate after T3 administration, left ventricular ejection time and mVcf were similar in the euthyroid and hyperthyroid states at baseline and during maximal beta-adrenergic stimulation but shortened and enhanced, respectively, during stages 1 and 2 of isoproterenol infusion (p less than 0.05). There was no effect of T3 administration on left ventricular mass, dimensions, end-systolic wall stress or stroke volume at rest or during any stage of isoproterenol infusion. These results indicate that in human subjects hyperthyroidism of short duration increases the sensitivity of heart rate and left ventricular shortening velocity to beta-adrenergic stimulation in the absence of changes in left ventricular mass, loading conditions or extent of shortening.


Basic fibroblast growth factor in cells derived from Dupuytren's contracture: synthesis, presence, and implications for treatment of the disease. Dupuytren's contracture (DC) is associated with fibroblast and endothelial cell proliferation. We have identified a fibroblast and endothelial cell mitogen, basic fibroblast growth factor (FGF), in cells derived from this tissue and characterized the effects of this growth factor on DC cells. Northern blot analysis of DC cells reveals the presence of basic FGF mRNA species, and the DC cells coexpress multiple forms of basic FGF. Radioreceptor assays establish that the DC cells have high-affinity binding sites for basic FGF and proliferate in response to exogenous recombinant basic FGF. Furthermore, a conjugate between saporin (a ribosome-inactivating protein) and basic FGF, which is cytotoxic to cells possessing the basic FGF receptor, is also cytotoxic to DC cells. The possibility that basic FGF-saporin could be a potential therapeutic agent for prevention of recurrence of the disease after surgery is discussed.


A simple and rapid radioimmunoassay for human interleukin-6. Studies were undertaken to develop a sensitive radioimmunoassay for human IL-6 using commercially available reagents. The assay utilized a polyclonal rabbit anti-IL-6 binding to iodinated IL-6; the reaction was carried out in solution and the immune complexes were precipitated using anti-rabbit IgG coupled to magnetic particles. Using a format where sample IL-6 was added in advance of the radiolabelled IL-6, the working range of the assay was found to fall between 0.1 and 10 ng/ml (IC50 around 1 ng/ml) for a 50 microliters sample volume, and was run overnight. However, the assay could be completed in 2 h, using a direct competitive format when less sensitivity is required (working range 1.5-25 ng/ml, IC50 12 ng/ml). The RIA correlated directly with a standard functional assay for IL-6 (proliferation of the mouse hybridoma B9.9) for both recombinant IL-6 and natural IL-6 from human monocytes. The total assay variance was less than 12% and no reactivity with interleukins-1-5 was found. Using the RIA, IL-6 produced in culture by human monocytes in response to various stimuli (LPS, IL-1, dibutyryl cAMP) was measured.


[A case of subclavian paraganglioma in the superior mediastinum extending to the neck]. A 52-year-old female was admitted to our hospital with left anterior chest pain. On physical examination, an elastic hard mass sized in 3.0 x 2.5 cm was palpable at the left suprasternal area. Chest X-ray film showed a large mass shadow in the cervico-thoracic region, and CT films revealed a well-defined mass in the superior mediastinum which was heterogeneously enhanced by contrast medium. Operation was performed under the preoperative diagnosis of thymic tumor extending upwards. At operation, the tumor was located between the trachea and the left subclavian artery in the superior mediastinum displacing these structures and extending to the neck. Resected specimen which was 5.5 x 3.5 x 3.0 cm in size and 42 gm in weight was well encapsulated and highly vascularized. On microscopic findings, the tumor was finally diagnosed as paraganglioma. According to the classification of Glenner and Grimley, it was thought that the tumor originated from subclavian paraganglion in the superior mediastinum. Subclavian paraganglioma had rarely been reported in the literatures. As subclavian paraganglioma, our patient was the first reported case in Japan.


Malignant head and neck germ cell tumours. Malignant germ cell tumours of the head and neck are extremely rare. Their behaviour, despite aggressive surgical and adjuvant therapy, is relentless with most cases resulting in a fatal outcome. In this paper we present a case of a cervical embryonal carcinoma and review the presentation, clinical course and treatment of malignant germ cell tumours.


View from beneath: pathology in focus. Synovial sarcoma of hypopharynx. Synovial sarcoma of the hypopharynx is a rare neoplasm. To date only 23 cases of synovial sarcoma of the hypopharynx have been reported in the literature. An additional case in an 18-year-old male is presented. This is the first case of synovial sarcoma in the hypopharynx to be reported in Singapore. The presentation was that of a mass in the hypopharynx; progressive dysphagia, intermittent hoarseness and gradual airway compromise. A CT scan was valuable in determining the site of origin and extent of the lesion. Histopathology was diagnostic. Treatment comprised of wide surgical excision of the tumour and post-operative radiotherapy.


In vitro modulation of the toxicity associated with the use of zidovudine on normal murine, human, and murine retrovirus-infected hematopoietic progenitor stem cells with basic fibroblast growth factor and synergistic activity with interleukin-1. The antiviral drug used in the treatment of acquired immunodeficiency syndrome, zidovudine, has proved effective in ameliorating the morbidity and mortality associated with human immunodeficiency virus infection. However, associated with zidovudine is the development of severe bone marrow toxicity manifested by anemia, neutropenia, and occasionally thrombocytopenia. We report the results of studies that demonstrate the ability of basic fibroblast growth factor (B-FGF) to reduce zidovudine toxicity to several classes of hematopoietic progenitors (granulocyte-macrophage, CFU-GM; megakaryocyte. CFU-Meg; and erythroid, BFU-E) from normal murine, human, and murine retrovirus-infected bone marrow cells when cocultured with zidovudine in vitro. Optimal response to B-FGF was observed at a dose concentration of 10 ng/ml. The specificity of B-FGF was demonstrated in the presence of protamine sulfate, an effective inhibitor of B-FGF mitogenic activity. In addition, synergistic activity of B-FGF on zidovudine-induced hematopoietic stem cell toxicity was observed in the presence of interleukin 1 (IL-1) (30 ng/ml). These studies demonstrate that B-FGF is capable of reducing the hematopoietic toxicity associated with zidovudine and that such an effect can be amplified in the presence of IL-1.


Regulation of pinocytosis in murine macrophages by colony-stimulating factors and other agents. Lucifer yellow (LY) accumulation was used to measure macrophage pinocytosis. The hematopoietic growth factors, macrophage colony-stimulating factor (CSF-1), granulocyte-macrophage CSF (GM-CSF), and interleukin 3, and the macrophage activators, lipopolysaccharide and zymosan, all stimulated LY uptake in both murine bone marrow-derived macrophages (BMMs) and resident peritoneal macrophages (RPMs) without affecting LY efflux. The stimulation of pinocytosis in the poorly cycling RPMs and in BMMs by nonmitogens dissociates stimulation of pinocytosis from subsequent DNA synthesis. Regulation of pinocytosis in BMMs appears to be independent of that of urokinase-type plasminogen activator expression. The increases in CSF-mediated BMM pinocytosis were not inhibited by pertussis toxin, by elevations in intracellular cAMP, or by glucocorticoids and were only partially inhibited by inhibitors of Na+/H+ antiport and Na+/K(+)-ATPase activities. Protein kinase C activation could be involved in regulating BMM pinocytosis because phorbol myristate acetate, oleoylacyglycerol, and exogenously added phospholipase C can all stimulate it. Ca2+ ionophores were inactive, whereas the Na+/H+ ionophore monensin potently inhibited BMM pinocytosis.


A monoclonal antibody specific for immunoglobulin A receptor triggers polymorphonuclear neutrophil superoxide release. An immunoglobulin M (IgM) monoclonal antibody, My43, specific for IgA Fc receptor (Fc alpha R) on human monocytes, bound to human polymorphonuclear neutrophils (PMNs) and inhibited their ability to bind IgA but not IgG. It was observed that the PMN oxidative burst was induced by both polymeric IgA and aggregated IgG, whereas IgM was without effect. The IgG-mediated oxidative burst was inhibited by anti-Fc gamma RII Fab and anti-Fc gamma RIII F(ab')2 but not by My43. Conversely, the IgA-mediated oxidative burst was inhibited by My43 but not by anti-Fc gamma RII or anti-Fc gamma RIII. When anti-Fc receptor monoclonal antibodies (mAbs) were used directly as ligands, it was observed that both anti-Fc gamma RII Fab and anti-Fc gamma RII F(ab')2 promoted the oxidative burst when cross-linked. Moreover, My43, when cross-linked with F(ab')2 antimouse IgM, also triggered the oxidative burst, whereas an IgM anti-CD15 mAb, PM81, did not stimulate function. This demonstrates that IgA receptors on PMNs are function-triggering molecules and that an anti-IgA receptor mAb may be substituted as a ligand.


Human recombinant activin-A modulates the steroidogenesis of cultured bovine adrenocortical cells. The effect of human recombinant activin-A on adrenal steroidogenesis was studied in cultured bovine adrenocortical cells. Activin-A significantly reduced cortisol output from ACTH (10nmol/l)-stimulated adrenocortical cells incubated for 24 hours in a dose-dependent manner (10, 100 and 500ng activin-A/ml suppressed cortisol secretion by 19, 33 and 40%), although no significant effect was observed in the case of 3 h incubation. Dehydroepiandrosterone (DHEA) secretion from ACTH-stimulated adrenocortical cells incubated for 24 h was also decreased by the addition of activin-A in a dose-dependent manner. (10, 100 and 500ng activin-A/ml suppressed DHEA secretion by 22, 56 and 58%). These inhibitory effects of activin-A (100ng/ml) on cortisol and DHEA secretion were partially blocked by the addition of follistatin/FSH-Suppressing Protein (200ng/ml). In contrast, activin-A treatment resulted in no significant decrease in aldosterone secretion. There were no significant effects of activin-A on basal secretions of cortisol, DHEA or aldosterone from adrenocortical cells. These results suggest that activin-A has a direct inhibitory effect on ACTH-stimulated bovine adrenocortical steroidogenesis.


Herpes simplex virus infection of cultured human term trophoblast. Mononuclear trophoblast cells were isolated from term placentas of uncomplicated pregnancies, purified to homogeneity by negative immunomagnetic separation using monoclonal antibodies to the major histocompatibility complex, and challenged with herpes simplex virus (HSV). The cultures were highly susceptible to virus-induced cytopathic effect as evidenced by cytopathic alteration and inhibition of human chorionic gonadotropin (hCG) secretion. Both HSV I and II underwent a full replicative cycle in the trophoblast, although the production of progeny virus was 10-100 times less than that obtained with placental fibroblasts or choriocarcinoma cells. The permissiveness was independent of in vitro syncytial differentiation of the trophoblast. The results suggest that the trophoblast layer may be involved in intrauterine HSV infection.


Hepatitis C virus in the etiology of chronic hepatitis and liver cirrhosis: possibility of mixed viral infections due to parenteral transmission. Sera obtained from 381 patients with chronic liver disease from four cities within the USSR were studied for HBV, HDV, and HCV markers of infection. Anti-HCV activity was detected in 41.2% of non-A, non-B cases. The etiological distribution of chronic hepatitis in Moscow and Dushanbe was similar with an approximate 20% prevalence for HBV, HDV, and HCV infections, whereas in Yakutsk 40% of cases were caused by HDV infections. The etiology of disease remained unrecognized in approximately 40% of patients with chronic liver disease in Moscow and Dushanbe and in 15% in Yakutsk. Anti-HCV activity was detected in 18.8% of patients with chronic HBV infections and in 8.3% of patients with chronic HDV infections. Anti-HCV activity was detected in 41% of patients without markers of HBV or HDV infections. The reasons for the observed differences in HCV prevalence among patients chronically infected with HDV are discussed.


Persistent rubella-specific IgM reactivity in the absence of recent primary rubella and rubella reinfection. Between two and seven sera from cases of persistent detection of rubella-specific IgM for periods in excess of 2.5 months, but in the absence of recent primary rubella or rubella reinfection, were examined for rheumatoid factor, heterophile antibody, and IgM reactivity against toxoplasma and a number of viruses. The relative avidity of the rubella-specific IgG1 has been assessed in all the sera by two methods. None of the sera contained rheumatoid factor or heterophile antibody, nor did any contain detectable concentrations of IgM specific for any of the panel of antigens apart from five sera which contained low concentrations of IgM specific for some coxsackieviruses B. No sera were positive for low avidity specific IgG1 although three did give equivocal results with one avidity test and one gave equivocal results with the second avidity test.


Early diagnosis of enteroviral meningitis by detection of specific IgM antibodies with a solid-phase reverse immunosorbent test (SPRIST) and mu-capture EIA. A solid-phase reverse immunosorbent test (SPRIST) and a mu-capture enzyme immunosorbent assay (EIA) for detection of enterovirus-specific IgM antibodies were evaluated for enterovirus diagnosis of aseptic meningitis in 160 consecutive patients from whom enterovirus (11 different serotypes) were isolated in 64. In patients with an enterovirus isolate and/or four-fold titre rise in the complement fixation test (CFT) for enterovirus, specific enterovirus IgM antibodies were detected on the day of admission to hospital in 48% by SPRIST and in 50% by EIA and 4-6 days after onset of symptoms in 71% by SPRIST and 79% by EIA. A significant increase in titre was observed between serum sampled on the day of admission and 2 days later in 38% by SPRIST and in 41% by EIA. These results indicate that the IgM antibody response appears early in the course of aseptic meningitis. Since both SPRIST and EIA provide rapid results the tests may be of differential diagnostic value and the IgM antibody kinetics may be utilized for diagnosis during the acute phase of aseptic meningitis. With optimized serum sampling the positive outcome was 76% in SPRIST and 82% in EIA among patients with positive virus isolation and/or CFT for enterovirus. In 67 patients virus isolation and CFT for enterovirus yielded negative results as well as all non-enteroviral diagnostic tests. Thirty-eight of these patients were positive by SPRIST and/or EIA and in half of these 38 a significant titre rise and/or fall in SPRIST and/or EIA was recorded. The majority of these IgM-positive patients became ill in the late summer or autumn, i.e., the "enterovirus season."(ABSTRACT TRUNCATED AT 250 WORDS)


Virus safety of human immunoglobulins: efficient inactivation of hepatitis C and other human pathogenic viruses by the manufacturing procedure. Human immunoglobulins are plasma derivatives with a low risk of transmitting viral infections. To the present, no proven case of human immunoglobulins transmitting human immunodeficiency viruses has been reported. However, there have been a few reports on the transmission of hepatitis C virus by these plasma proteins. To improve further the safety of both 5s iv human immunoglobulins and 7s im immunoglobulins, we introduced a 10-hour heat treatment of the aqueous solutions at 60 degrees C (i.e., pasteurization) into the manufacturing procedure. This treatment was not added to the manufacturing procedure of 7s iv immunoglobulin that already contained the S-sulfonation as a virus inactivating method. We now report on experimental data that show that the whole manufacturing procedures of the above immunoglobulins inactivate efficiently hepatitis C virus and that the specific virus inactivation methods alone, namely, pasteurization or S-sulfonation, also inactivate completely viruses of the flavivirus family, to which the hepatitis C virus belongs. The inactivation of the Flaviviridae bovine viral diarrhea virus, tick-borne encephalitis virus, and yellow fever virus by pasteurization or S-sulfonation was at least 10(5). The clearance of HCV achieved by the entire manufacturing process of each of these immunoglobulins was also at least 10(5). The experiments therefore show that pasteurization or S-sulfonation provides a high margin of safety to human immunoglobulins regarding the transmission of hepatitis C virus.


Salivary antibody titers in adults challenged with a human rotavirus. To determine whether salivary antibody is a reliable indicator of rotavirus infection and mucosal rotavirus antibody concentrations, salivary rotavirus antibody titers were determined as a function of time following inoculation of 24 adult volunteers with a virulent strain of human rotavirus (CJN). Twenty of the subjects became infected and all produced detectable amounts of salivary rotavirus IgA. These antibody concentrations remained undetectable in the four uninfected subjects. Rises of greater than or equal to fourfold in either salivary rotavirus IgA or neutralizing antibody to the challenge virus were detected in all but two subjects. The titers of both antibodies were maximal at 13 days after inoculation and decreased significantly (p less than .02) by 27 days, a result very similar to that previously found with stool rotavirus IgA in CJN-infected subjects. These results suggest that salivary rotavirus antibody titers are an accurate reflection of mucosal rotavirus antibody and a possible surrogate for intestinal rotavirus antibody.


Mechanical failure of hydroxyapatite- and polysulfone-coated titanium rods in a weight-bearing canine model. Three types of material that have shown potential as coatings for orthopaedic implants were studied. Using a weight-bearing canine model, Ti-6A1-4V femoral intramedullary rods coated with (1) sintered titanium beads, (2) plasma-sprayed hydroxyapatite, and (3) silyl coupled polysulfone beads were evaluated for mechanical strength and bone ingrowth. The model was designed to secure optimal prosthetic stability by obtaining maximal bony ingrowth during an initial non-weight-bearing phase, then stressing the implant during a full-weight-bearing phase. None of the rods coated with titanium beads failed. All 17 polysulfone-coated rods failed, 13 of them at the interface between the polysulfone coating and the titanium core. Of 18 rods coated with hydroxyapatite, 15 suffered implant breakdown at the interface between the hydroxyapatite coating and the titanium core. This may be due to dissolution of the plasma-sprayed hydroxyapatite in vivo. Testing of retrieved specimens from both hydroxyapatite- and polysulfone-coated implants showed that the shear strength at the coating-rod interface had decreased to less than 40% of the shear strength at manufacture. Despite mechanical failure, histologic study showed extensive bone ingrowth or apposition onto both the polysulfone and hydroxyapatite coatings.


The accessory deep peroneal nerve: a pitfall for the electromyographer. The presence of an accessory deep peroneal nerve may alter the usual clinical and electrophysiological characteristics of peroneal nerve lesions. Three cases of such an anomalous innervation and a peroneal nerve lesion are presented.


Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. In 8 brains of patients with various combinations of striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome, inclusion bodies were demonstrated in the cytoplasm and nucleus of both neuronal and oligodendroglial cells and in neuronal processes by means of silver staining, immunocytochemistry and electron microscopy. Differing from oligodendroglial cytoplasmic inclusions recognized by anti-ubiquitin, anti-alpha- and anti-beta-tubulin, and anti-tau antibodies, neuronal cytoplasmic inclusions were stained only by anti-ubiquitin antibody but not with those raised against cytoskeletal proteins. Tubular structures forming the inclusion bodies irrespective of their glial or neuronal location, have fuzzy cover and side extensions which make them similar to the linear structures described in motor neuron diseases. Our study proves that the accumulation of abnormal tubular structures in both oligodendrocytes and neurons is the basic pathological alteration in multiple system atrophy and defines multiple system atrophy as a group of diseases with similar cellular pathology or as a nosological entity.


The effect of chronic subarachnoid hemorrhage on basal endothelium-derived relaxing factor activity in intrathecal cerebral arteries. The authors have investigated the hypothesis that loss of endothelium-derived relaxing factor (EDRF) activity contributes to cerebral vasospasm after subarachnoid hemorrhage. Adventitial exposure to hemoglobin was studied angiographically by injecting purified hemoglobin solution or autologous whole blood into the cisterna magna of anesthetized pigs. Both interventions induced intra- but not extracerebral vasoconstriction, which persisted for 2 and 7 days, respectively. Cyclic guanosine monophosphate (cGMP) levels were measured in isolated buffer-perfused pig intrathecal arteries to quantify inhibition of basal EDRF activity by hemoglobin. Adventitial exposure was less effective than intimal exposure, 10 microM hemoglobin applied adventitially for 30 minutes having an effect equivalent to that of 1 microM applied intraluminally for 5 minutes. The depression of cGMP levels by hemoglobin was reversible and equivalent to the effect of endothelial denudation or incubation with NG-nitro-L-arginine methyl ester, so that the effects of hemoglobin can be attributed to a specific action on EDRF rather than interaction with a nitric oxide-like substance produced by vascular smooth muscle or adventitial nerves. Cyclic GMP levels in isolated arteries were unchanged after in vivo exposure to hemoglobin for either 2 or 7 days or to whole blood for 2 days, and were reduced by intraluminal perfusion with 1 microM hemoglobin. In contrast, after 7 days of in vivo exposure to whole blood, cGMP levels were already depressed, and not further reduced by intraluminal perfusion with 1 microM hemoglobin. The findings support the view that adventitially applied hemoglobin can inhibit basal EDRF activity and that in vivo adventitial exposure to whole blood leads to a reduction in basal cGMP levels in association with vasoconstriction of intrathecal arteries. Both mechanisms could contribute to the clinical syndrome of cerebral vasospasm after subarachnoid hemorrhage.


In vitro efficacy of transferrin-toxin conjugates against glioblastoma multiforme. The cytotoxic activity of immunotoxins constructed with human diferric transferrin (Tfn) as the carrier ligand and an abrin variant Pseudomonas exotoxin A (PE) and the diphtheria toxin mutant cross-reacting material (CRM) 107 as the toxin moieties were studied in vitro. Three malignant human cell lines, the glioblastomas multiforme SNB19 and SF295 and the LOX melanoma, and a nonhuman control murine melanoma cell line B16 were assessed. The presence of transferrin receptors on the cell lines was confirmed by direct 125I-Tfn binding assays. The 50% protein synthesis inhibitory concentration (IC50) values for all cell lines demonstrated that Tfn-abrin variant and Tfn-PE had comparable potency and were both more effective than Tfn-CRM 107. Monensin, a carboxylic ionophore, potentiated the effect of Tfn-abrin variant against glioma cells approximately 35-fold with IC50 values of 4.0 x 10(-13) M and 4.7 x 10(-12) M for SNB19 and SF295, respectively. Cytotoxic activity of Tfn-abrin variant (with or without monensin) and Tfn-PE was correlated with the degree of Tfn receptor expression measured on the cell lines. The exquisite in vitro cytotoxicity of Tfn-abrin variant and Tfn-PE immunotoxins against glioma and melanoma cells warrants further in vivo evaluation and future consideration of these agents for potential clinical application against glioblastoma multiforme and leptomeningeal neoplasia.


Predictors of success on NCLEX-RN and within the nursing curriculum: implications for early intervention. A retrospective prediction study was conducted to identify predictors of success on the NCLEX-RN and within the nursing curriculum. Records of 192 graduates of an upper-division, single-purpose baccalaureate nursing program were examined using multiple regression techniques. NCLEX-RN success could be predicted by GPA at end of Level 1 in nursing program, ACT composite and social science subscale scores, Anatomy and Physiology I grade, and percent correct on Mosby Assesstest. These findings have implication for entering a nursing student into an early intervention program designed to enhance success within the nursing program and on the NCLEX-RN.


Nursing students rank high in autonomy at the exit level. Professional status based on the criterion of autonomy continues to elude nursing. It is important to determine if this condition is due to the denial of professional status by employing organizations or to the lack of individual autonomy possessed by nurses. Female nursing school students were compared to women students from the schools of education, business, technology, and arts and sciences just prior to graduation. Nursing students scored as high on autonomy and masculinity as other female students, and higher on autonomy-related attitudes and behaviors specific to women. These findings conflict with earlier studies and with the position that nursing's denial of professional status is due to a lack of individual autonomy in nurses.


Honors program participation and performance postgraduation. Four groups of students were surveyed four to six years postgraduation regarding enrollment in graduate studies, research involvement, and occupancy of leadership positions in professional organizations. Group 1 (n = 20) consisted of honors graduates, Group 2 (n = 52) were high GPA non-honors graduates, Group 3 (n = 39) were low GPA graduates, and Group 4 (n = 16) were RN-to-BSN graduates with high GPAs but not in the honors program. Enrollment in graduate studies was the strongest outcome indicator of participation in the honors program. Honors graduates also held leadership roles in professional organizations significantly more than Groups 2 and 3, but were quite comparable to Group 4. Follow-up at 10 years postgraduation and replication of the study in other settings are recommended.


A study to determine the difference in clinical judgment abilities between BSN and non-BSN graduates. The purpose of this retrospective study is to determine the difference in clinical judgment abilities of recent baccalaureate nurses (BSN) seeking employment in a large metropolitan hospital and of nurses without a baccalaureate degree. Using an ex post facto design, the orientation records of 116 newly hired nurses were analyzed to determine the clinical judgment abilities using video vignettes produced by Medcom, Inc. Findings indicated that there was no difference in clinical judgment in newly hired BSN and non-BSN graduates. These findings indicate a need for more research studies to determine how clinical judgment is developed and to evaluate teaching strategies that facilitate clinical judgment.


Effect of writing across the curriculum techniques on students' affective and cognitive learning about nursing research. A descriptive design evaluated the effect of writing across the curriculum techniques on students' attitudes toward, and critical understanding of, nursing research. Using a semantic differential, students' (n = 17) attitudes were measured prior to a research theory course, immediately after the course, and at the end of the following term in which they were required to write a partial research proposal. This writing assignment was supported by a writing laboratory. Data analysis included paired t tests to measure differences after the course and after completion of the writing assignment and to measure differences in quality of papers submitted by those who attended the writing lab and those who did not. Results demonstrated significant positive changes in students' feelings about doing research and their beliefs about the desirability of research. No significant differences in quality of papers were found.


Comparison of role conception and role deprivation in LPN-transition students and traditional ADN students in a specially designed associate program. This study compared differences in role orientation and role deprivation between 41 LPN-transition students and 123 basic traditional associate degree nursing (ADN) students upon entry and exit to a specially designed ADN program. The Corwin Role Conception Scale was used to assess role conception and deprivation. Statistically significant differences were noted upon entry between LPN-transition students and traditional ADN students in professional and service role conceptions and in role deprivation, upon exit in professional role conception and role deprivation between LPN-transition and traditional ADN students, and in professional role conception within the LPN-transition students. No differences were found within traditional ADN students from entry to exit of the program.


Barley diets with different fat sources have hypocholesterolemic effects in chicks. Saturated fat is known to elevate serum cholesterol, whereas soluble dietary fiber has a hypocholesterolemic effect. The objective of this study was to compare the effects of barley and wheat diets supplemented with five fat sources on lipid metabolism in chicks. In two separate experiments, broiler chicks were fed isonitrogenous diets containing 23% protein, 11.4% dietary fiber and 10% dietary fat for 17 d. Diets contained 60% either hull-less barley or red spring wheat, with either palm oil, dehydrated egg yolk, butter, tallow or corn oil. Growth, feed efficiency, plasma lipids, liver cholesterol, and fecal fat and dry matter were measured. All chicks fed wheat grew faster and had greater food efficiency than those fed barley. All barley-fed chicks had lower (P less than 0.0001) total plasma cholesterol concentration (3.1 to 4.0 mmol/L) than those fed wheat (6.0 to 11.3 mmol/L). Chicks fed palm oil with wheat had the highest total cholesterol, 11.3 mmol/L. Liver cholesterol concentration was higher (P less than 0.0001) for all wheat-fed chicks (22.8-86.4 mmol/g) compared with those fed barley (6.7 to 12.2 mmol/g). Fecal crude fat was higher (P less than 0.05) for chicks fed barley, and excreta dry matter was lower for barley-fed chicks. Results indicate that the high soluble fiber content of this barley exerts a hypocholesterolemic effect in chicks regardless of dietary fat source, possibly mediated through lowered fat absorption.


Hepaticopancreaticogastroduodenectomy with transplantation for metastatic islet cell carcinoma in childhood. Symptomatic islet cell carcinoma of the pancreas with liver metastasis, a rare tumor cured only by complete resection, was unresponsive to chemotherapy and was treated with hepaticopancreaticogastroduodenectomy en bloc resection with transplantation in an 11-year-old girl. This radical surgery in conjunction with adjuvant chemotherapy and interstitial and external beam irradiation has resulted in symptomatic relief and no evidence of disease at 15 months posttransplant.


A prospective study of nonrhabdomyosarcoma soft tissue sarcomas in the pediatric age group. Nonrhabdomyosarcoma soft tissue sarcomas in infants and children are rare malignancies with most of the clinical data gained by retrospective analysis. In 1986, a prospective multicentered study was initiated by the Pediatric Oncology Group (POG) with a total of 75 cases now entered for epidemiologic examination. Median age of presentation was 12 years (range, newborn to 20 years). The male to female ratio was 2.3 to 1. The most common soft tissue tumor was synovial cell sarcoma (32/75, 42%), followed by fibrosarcoma (10/75, 13%), malignant fibrous histiocytoma (9/75, 12%), and malignant neurogenic tumors (8/75, 10%). Sixty-five percent of all tumors presented on the extremities (44% lower extremity, 21% upper extremity). Tumors of the trunk accounted for 28% (abdomen 15%, thorax 13%), whereas head and neck tumors were 7%. By TNMG classification, 16% presented as stage I, 21% as stage II, 33% as stage III, and 30% as stage IV. Age at presentation did not affect clinical site or stage. All upper extremity tumors presented with localized disease, whereas lower extremity tumors presented with regional nodal disease in 7% and metastatic disease (pulmonary) in 23% of the cases. Seventy-eight percent of the abdominal tumors were metastatic at diagnosis; the other 22% had extensive regional disease. In the thorax 78% had localized lesions with 22% having extensive regional disease. Ninety percent of synovial cell sarcomas were on the extremities: 84% localized disease and 12% metastatic spread at presentation. Sixty percent of the fibrosarcomas presented on the extremities with 80% having localized disease and 20% metastatic spread. Only 25% of the neurogenic tumors presented with localized disease, whereas 50% had metastases at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Specific insulin-like growth factor-I receptors on circulating bovine mononuclear cells. We have examined the presence and properties of specific receptors for IGF-I on bovine mononuclear cells. Competitive binding studies showed that binding of [125I]IGF-I to mononuclear cells was inhibited by unlabelled peptides with the rank of IGF-I greater than IGF-II greater than insulin. The binding of [125I]IGF-I was a function of the cell concentration. Equilibrium dissociation constant and receptor concentration values for the average of 9 adult cows were 1.13 +/- 0.11 nM and 108.9 +/- 24.1 fMol/10(7) cells, respectively. Moreover, IGF-I stimulated thymidine incorporation into bovine mononuclear cells in the absence of serum and phytohemagglutinin (PHA). The existence of specific and functional IGF-I receptors on circulating bovine mononuclear cells would provide an easily accessible source for studying IGF-I receptor changes in the bovine, both in physiologic and pathologic states.


Characterization of opioid binding sites in rat spinal cord. Binding sites were characterized in rat whole spinal cord crude membrane preparations using selective labelling techniques with multiple methods of mathematical analysis of experimental curves. Mathematical analysis of single [3H]-[D-Ala2,MePhe4,Gly-ol5] enkephalin (DAGO) saturation curves suggested binding of the [3H]-ligand at one site, while displacement curves of low concentrations of [3H]-DAGO with selective mu-ligands indicated the presence of high- and low-affinity sites. All the [3H]-DAGO curves processed simultaneously by LIGAND analysis showed the presence of high (27%) and low (73%) affinity components, with a total Bmax of 3.19 pmol/g tissue. Eighty percent of [3H]-[D-Ala2,D-Leu5] enkephalin (DADLE) binding was displaced by DAGO with high affinity, indicating that a high percentage of [3H]-DADLE binding was at mu-sites. Saturation curves of [3H]-DADLE after inhibition of mu-sites by unlabelled DAGO (delta-sites) were monophasic with non-linear fitting analysis and the Bmax was 0.90 pmol/g tissue. Most mathematical analysis of single saturation curves of [3H]-(-)-bremazocine indicated binding at more than one site. DAGO, DADLE, U-69,593 and PD 117302 displaced 0.15 nM of [3H]-(-)-bremazocine biphasically: the percentages of displacement calculated with the non-linear fitting program were respectively 50 (mu-sites), 64 ((mu + delta)-sites), 18 and 25 (kappa-sites). Haloperidol displaced [3H]-(-)-bremazocine only at microM concentrations. suggesting no binding at sigma-sites. In the presence of 225 nM of DAGO, DADLE displaced only 21% of [3H]-(-)-bremazocine 0.15 nM binding (delta-sites). Most mathematical analysis of saturation curves of [3H]-(-)-bremazocine, after inhibition of binding at mu- and delta-sites by DAGO and DADLE, still indicated binding at more than one site and the selective kappa-ligands U-69,593 and PD 117302 displaced [3H]-(-)-bremazocine in these experimental conditions. LIGAND analysis of saturation and inhibition curves of [3H]-(-)-bremazocine by U-69,593 and PD 117302 showed the presence of high (43%) and low (57%) affinity components, with a total Bmax of 2,73 pmol/g tissue. Thus in rat spinal cord there are at least two mu-sites bound by [3H]-DAGO which amount together to approximately 47% of total opioid sites, delta-sites bound by [3H]-DADLE amounting to approximately 13%, kappa-sites and other unknown sites (possibly a kappa-subtype) bound by [3H]-(-)-bremazocine, which together are approximately 40% of total opioid sites.


Changes in intracellular Na+ during Na,K pump inhibition in sheep cardiac tissues. The differences in inotropic and toxic sensitivities of cardiac ventricular tissue to cardiac glycosides were investigated in order to determine whether or not the reportedly greater sensitivity of Purkinje fibers compared to myocardium is the result of a fundamentally different response to Na,K pump inhibition. I measured the changes in intracellular Na+ activity (aiNa) in the two tissue types simultaneously during exposure to actodigin (4.0 microM) and ouabain (0.5 microM) under quiescent conditions. A sheep papillary muscle and a Purkinje fiber from the same heart were placed in an experimental chamber and measurements of aiNa from both were obtained with Na+ -sensitive microelectrodes. In five experiments in which all electrode impalements were successfully maintained, actodigin caused similar changes in aiNa in the two tissues (from 7.2 +/- 1.0 mM in control to 12.9 +/- 1.9 mM in the presence of drug in papillary muscles compared to 7.3 +/- 0.3 mM in control and 13.2 +/- 1.0 mM in Purkinje fibers; means +/- S.E.M.). After washout, exposure to ouabain increased aiNa in both papillary muscles and in Purkinje fibers (from 7.2 +/- 0.7 mM in control and 16.2 +/- 1.4 mM during exposure to drug in papillary muscles compared to 7.4 +/- 0.3 mM and 14.9 +/- 0.8 mM in Purkinje fibers). In fact, ouabain caused a greater increase of aiNa in papillary muscles than in Purkinje fibers (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Acute respiratory failure secondary to a complete tracheal ring. This is a case presentation of a neonate with McKusick-Kaufman Syndrome (hydrometrocolpos, polydactyly and congenital heart disease) accompanied by a complete tracheal ring in the distal trachea. This undiagnosed anomaly caused acute respiratory failure after another surgical procedure. Emergent bronchoscopy revealed the diagnosis and the ring was successfully dilated. This is the only known survivor of a complete tracheal ring associated with this syndrome.


[Small cell carcinoma of urinary bladder. A case report]. A 57-year-old male patient was admitted because of a severe lumbar pain and gross hematuria. The rectal examination revealed a fist-sized soft tissue mass in the small pelvic space. A huge non-papillary tumor, which occupied the intravesical space, was found on cystoscopic examination. CEA IAP, TPA, CA19-9 and NSE were abnormally elevated in the serum. The pelvic CT scan shown an enormous polypoid tumor arising from the anterior vesical wall, while no abnormal lesion was found in the head, neck, chest and abdominal CT scans. The bone scintigraphy revealed multiple abnormal accumulations. The transurethral biopsy of the tumor was carried out. The pathological examination revealed homogeneous and small tumor cells arranged in sheet and solid patterns, which were positive for the anti-NSE stain and anti-NF stain, but negative for Grimelius stain. The final diagnosis was small cell undifferentiated carcinoma of the urinary bladder. The patient died of cancer five months after diagnosis.


The anti-leukaemic effects and the mechanism of sodium selenite. The anti-proliferative effects of selenium were studied both in vivo and in vitro. At a selenium concentration of 0.6 micrograms/ml, cells from patients with ALL-L1, L2 and AML-M1, M3 and M5 were more sensitive than cells from patients with CML. Cells from patients with AML-M2, CLL and leukaemic lymphoma were least sensitive. Normal bone marrow or peripheral blood cells were not sensitive to selenium at this concentration. In the mouse leukaemia models (L797, L615, L7712), the sensitivity of leukaemic cells were: L797 (93% cytotoxicity) greater than L615 (49.7% cytotoxicity) greater than L7712 (4.4% cytotoxicity). Sodium selenite injected i.p. increased the longevity of L797-inoculated mice. Administration of 40 micrograms selenium daily for 7 days resulted in a significant increase in the longevity of mice inoculated with 10(5) L797 cells. However, no remarkable increase of the longevity was observed in either L615- or L7712-inoculated mice after treatment with sodium selenite for 7 days. Treatment of the HL-60 leukaemic cell line with selenium caused a dose- and time-related decrease in DNA, RNA and protein syntheses as measured by [3H]-thymidine, [3H]-uridine and [3H]-leucine uptake respectively. The inhibitory effect of selenium on DNA synthesis was reversed when selenium was removed from the medium, demonstrating that selenium-induced inhibition of DNA synthesis was due to interference with DNA biosynthesis rather than DNA template damage. These results suggest that the anti-leukaemic effect of sodium selenite is associated with inhibition of DNA replication, transcription and translation.


Myeloid differentiation of HL-60 cells induced by anti-tumor drug 3-nitrobenzothiazolo[3,2-a]quinolinium. Drugs which elicit cell differentiation might have an important role in the treatment of leukemias and other neoplasias. Various chemotherapeutic agents promote leukemic cell differentiation. The HL-60 cell line is a useful model to study in vitro myeloid differentiation. Sublethal concentrations of 3-nitrobenzothiazolo[3,2-a]quinolinium (NBQ), an antitopoisomerase II drug, were given to HL-60 cells from one to five days to evaluate its capacity to induce differentiation. NBQ-induced HL-60 cells reduced nitroblue tetrazolium (NBT), increased MY-4 receptors, increased phagocytic activity and displayed the granulocytic morphology. Flow cytometric DNA analysis of NBQ-induced cells revealed an arrest in the G1 phase a reduction in the relative percentage of cells in S and G2+M phases. Our results suggest that NBQ induces an S-phase specific differentiation of HL-60 cells comparable to that previously described with dimethyl sulfoxide and retinoic acid. NBQ and its analogs, as differentiation inducers, may have potential utility as a novel therapeutic modality for leukemias.


Induction of the fms proto-oncogene product in HL-60 cells by vitamin D: a flow cytometric analysis. Agents which induce monocytic characteristics in HL-60 human acute promyelocytic leukemia cells induce mRNA for the fms proto-oncogene, which encodes the receptor for M-CSF. Previous studies of fms expression in HL-60 cells have characterized chiefly induction by phorbol esters of fms mRNA. Our studies of fms expression in HI-60 cells have characterized induction by vitamin D3 of the fms protein. We have used flow cytometry to correlate fms antigen with a monocyte-specific differentiation antigen recognized by antibody MO2 (CD14), with DNA content, and with the nuclear antigen Ki-67, a marker of cell cycling. HL-60 cells were cultured with or without 1 microM vitamin D for 7 days. fms antigen was found on 42 +/- 5.8% of the cells cultured without vitamin D, but on 63 +/- 4.3% of the cells cultured with vitamin D. MO2 binding was detected on only 2 +/- 0.5% of the cells without vitamin D, but on 59 +/- 9% with vitamin D. Cells cultured with vitamin D that were fms-positive were also predominantly (83%) MO2-positive. Analysis of DNA content, measured by propidium iodide staining, showed that 57 +/- 1.5% of cells cultured without vitamin D, but 93 +/- 0.5% of cells cultured with vitamin D, were in the G0/G1 cell cycle phase. Analysis of nuclear antigen Ki-67 revealed that, of the vitamin D-treated cells that were fms-positive, a significant proportion (37%) were still cycling. We conclude that (1) fms is demonstrable on some uninduced HL-60 cells, (2) when HL-60 cells are induced to develop monocytic characteristics by vitamin D, fms induction is part of the program for monocytic differentiation that includes MO2 expression, yet (3) some induced cells expressing fms are still cycling.


Reversed-phase liquid chromatographic purification and isolation of a radio-iodinated selective probe for mu opioid receptors in the brain. A Guard-PAK precolumn system was used for the reversed-phase liquid chromatography purification of a small, synthetic radiolabeled opioid peptide, FK 33-824 (D-Ala2, methyl-phe4, Met (O)ol5 enkephalin) (FK). This procedure involves trace enrichment of iodinated peptide onto the precolumn while iodination reagents are not retained. Radioactive contamination of high-performance liquid chromatography columns and injectors is thus avoided. Precolumn chromatography has sufficient resolving power to separate not only labeled from unlabeled peptide but also mono- from di-iodinated peptide. Purified 125I-labeled FK (estimated specific activity 85.9-153.7 Ci/mmol) showed high specific binding to mouse corpus striatum, neocortex, cingulate cortex, nucleus accumbens septi, diagonal band of Broca, nucleus medialis septi, area preopticus magnocellularis, and the nucleus of the caudate/putamen. Radioligand binding was inhibited by both antagonists (naloxone and naltrexone); and agonists D-Ala2, N-methyl-phe4, gly-ol5-enkephalin [DAGO]; FK; and beta-endorphin at all concentrations tested (1 x 10(-8) to 1 x 10(-4) M). Adrenocorticotropin hormone (ACTH) did not block ligand binding at any concentration tested. Distribution of mu opioid receptors was analyzed by light microscopic autoradiography. Sections incubated with 125I-labeled FK in the presence of agonists and antagonists demonstrated decreasing ligand binding with increasing doses of competitor. ACTH did not block ligand binding at any concentration tested. HPLC analyses of ligand which had been iodinated 1.5 half lives before the date of the experiment demonstrated a single peak similar to that of freshly iodinated ligand. Similar binding kinetics and autoradiographic labeling patterns were observed as compared to those obtained with freshly iodinated peptide.(ABSTRACT TRUNCATED AT 250 WORDS)


Hepatocellular carcinoma in a case of Wilson's disease. Hepatocellular carcinoma has rarely been reported in Wilson's disease, particularly in women. We describe the case of a female patient who was diagnosed with Wilson's disease at the age of 39 years, after presenting with severe neurological symptoms. She had significant neurological improvement following penicillamine therapy and succumbed to hepatocellular carcinoma at the age of 72 years, following 33 years of penicillamine therapy. The patient described here was the oldest and only the third female patient with hepatocellular carcinoma complicating Wilson's disease to be reported in the literature.


Prevention and control of tuberculosis in U.S. communities with at-risk minority populations. Recommendations of the Advisory Council for the Elimination of Tuberculosis. Tuberculosis (TB) is an increasing public health problem in the United States, particularly among racial/ethnic minorities. In 1990, the number of reported TB cases increased 9.4% compared with 1989 and 15.5% compared with 1984. In 1990, almost 70% of all TB cases and 86% of those among children ages less than 15 years occurred among racial/ethnic minorities. Compared with non-Hispanic whites, the 1990 TB case rate was notably higher for racial/ethnic minorities. Adverse social and economic factors, the human immunodeficiency virus epidemic, and immigration of persons with tuberculous infection are contributing factors to the increase in TB cases. Other contributing factors include physician nonadherence in prescribing recommended treatment regimens and patient nonadherence in following prescribed recommended treatment regimens. To eliminate TB in U.S. communities with at-risk racial/ethnic minorities, the Advisory Council for the Elimination of Tuberculosis recommends a) initiating public awareness campaigns to alert these communities about the increasing TB problems; b) training and educating public and private health-care providers in the skills needed to relate effectively to the at-risk communities being served, and empowering at-risk populations with knowledge and other resources needed to influence the TB programs directed toward their communities; c) building coalitions to help design and implement intensified community TB prevention and control efforts; d) intensifying the screening of at-risk populations for TB and tuberculous infection and providing appropriate treatment and preventive therapy; e) increasing the speed and completeness with which all health-care providers report confirmed and suspected TB cases to appropriate health departments; and f) improving the availability and quality of TB health-care services in socioeconomically disadvantaged areas.


Prevention and control of tuberculosis among homeless persons. Recommendations of the Advisory Council for the Elimination of Tuberculosis. Because tuberculosis (TB) is a major problem among homeless persons, the Advisory Council for the Elimination of Tuberculosis has developed recommendations to assist health-care providers, health departments, shelter operators and workers, social service agencies, and homeless persons prevent and control TB in this population. TB should be suspected in any homeless person with a fever and a productive cough of more than 1-3 weeks' duration, and appropriate diagnostic studies should be undertaken. Confirmed or suspected TB in a homeless person should be immediately reported to the health department so that a treatment plan can be decided upon and potentially exposed persons located and examined. Patients with TB should be counseled and voluntarily tested for human immunodeficiency virus (HIV) infection because TB treatment recommendations are different for HIV-seropositive and HIV-seronegative persons (1). TB therapy should be directly observed whenever possible. This may require the establishment of special shelters or other long-term-care arrangements for homeless persons with TB. For each person with an infectious case, an investigation should be conducted to identify exposed persons, and those found to be infected should be considered for preventive therapy. Shelter staff should receive a tuberculin skin test when they start work and every 6-12 months thereafter. Those with positive skin test results should be considered for preventive therapy according to current guidelines. Shelters for the homeless should be adequately ventilated. The installation of ultraviolet lamps also may be useful to further reduce the risk of TB transmission.


Implementation of the Lead Contamination Control Act of 1988. The U.S. Department of Health and Human Services has set as an objective the elimination of elevated blood lead levels (BLLs) in children in the United States by the year 2010 (1); an interim goal, specified as a national health objective for the year 2000, is to reduce BLLs greater than 15 micrograms/dL and greater than 25 micrograms/dL among children aged 6 months-5 years to no more than 500,000 and zero, respectively (objective 11.4) (2). The Lead Contamination Control Act of 1988 authorized CDC to make grants to state and local agencies for comprehensive programs designed to 1) screen infants and children for elevated BLLs, 2) ensure referral for medical and environmental intervention for lead-poisoned infants and children, and 3) provide education about childhood lead poisoning. This report summarizes efforts to implement the Lead Contamination Control Act.


Properties of monoclonal antibodies to thyroliberin (TRH) induced by different immunogens: comparison with pituitary TRH receptor. Thyroliberin E-H-P-NH2 (TRH) is a small neuropeptide pGlu-His-Pro-NH2 widely distributed in neural sites. The aim of this work was to obtain an antibody molecule with the nearest properties to that of TRH-receptor in GH3 cells. Different TRH-protein conjugates were prepared and utilized to induce monoclonal antibodies in mice. Several monoclonal antibodies were obtained using E-H-P-NH2 (TRH) coupled either to the histidyl residue (immunogen I) or to the prolyl residue (immunogen II). Antibodies generated using immunogen I and immunogen II were characterized in a radioimmunoassay system and an enzyme immunoassay system respectively. Their selectivities regarding a series of TRH related peptides were compared to those of rabbit polyclonal antibodies using three differently labelled TRH (tritiated-TRH, mono-iodinated-TRH and TRH-OH-acetyl-cholinesterase) as tracers and to prolactin secreting cells TRH receptors using 3H-TRH. Whatever the immunogen, the stereospecificity of monoclonal antibodies tested were found more different from TRH receptor characteristics than rabbit polyclonal antibodies.


Jitter of the stimulated motor axon.

Jitter of the stimulated motor axon. Electrical microstimulation of motor axons in conjunction with single fiber EMG (SFEMG) is increasingly used to measure the jitter of the motor endplates. This study examines the jitter of the stimulation site on the axon when stimulus strength is at threshold. In the absence of spurious blocking, this was found to be 5 microseconds on the average. With intermittent blocking, however, a mean additional jitter of 40 microseconds was obtained. The latter is considered to result from changing propagation velocity in the muscle fiber due to irregularity of activation rate. In clinical jitter studies, inadvertent threshold stimulation can result in significant error when associated with intermittent blocking.


A unique case of reducing body myopathy. The clinical, electromyographic, and histologic characteristics of a 17-year-old girl with reducing body myopathy are described. She is, to our knowledge, the oldest reported case and the only patient described with severe mitral valve prolapse and scoliosis. Electromyography demonstrated spontaneous positive sharp waves and fibrillation potentials with many low-amplitude, short, polyphasic motor unit potentials. The right deltoid muscle was characterized by focal areas with large fibers associated with increased endomysial connective tissue and "split" fibers. Purple-gray sarcoplasmic masses stained with trichrome were PAS-negative, appeared as "empty" spaces with both ATPase and NADH-TR, and stained darkly with menadione NBT. The features described expand the clinical presentation of this myopathy, and may lead to a better understanding of its etiology.


Reversible conduction block in human ischemic neuropathy after ergotamine abuse. Conduction block [a significant reduction in compound muscle action potential (CMAP) amplitude after proximal compared to distal stimulation] is often found in demyelinating neuropathies, including inflammatory neuropathies and degenerative neuropathies, such as "liability to pressure neuropathy." There is experimental evidence that a transient conduction block can occur in rats after ischemic lesions of peripheral nerves are induced either by ligation of arterial vessels supplying nerve trunks, or by injection of arachidonic acid into peripheral arterial vessels. Conduction block has also recently been described in cases with necrotizing vasculitis. To date, however, no example of a reversible conduction block has been reported in human ischemic neuropathy.