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Biomedical subjects

R Schwartz

Publications and source records attributed to R Schwartz.

At least 199 records · Page 11Linked to original sources
PubMed1988

Preparation of islets of Langerhans from the hamster pancreas.

We describe a method for the preparation of viable islets from the pancreas of normal 8-week-old female Syrian golden hamster, based on the injection of the pancreatic duct with collagenase and on mechanical dissociation which liberates islets that maintain their normal morphological appearance and physiologic function. In a series of 11 animals, we examined the dose response of intraductal collagenase on islet yield. The mean number of isolated islets was 423 with a range from 130 to 873 per pancreas. Islet yield was most dependent on the concentration of collagenase solution used to inject the duct. The optimal concentration was determined to be 3.5 mg/ml when a total volume of 3.0 ml was injected. Islets responded to glucose stimulus in a normal biphasic pattern. Mesh filtration, rather than Ficoll, can be performed rapidly and results in a high yield of functional islets with minimal contamination by acinar tissue.

Animals↗
PubMed1988

The use of deep duplex scanning to predict hemodynamically significant aortoiliac stenoses.

Hemodynamic assessment of aortoiliac occlusive disease is necessary for successful arterial reconstruction of the aorta and legs. Various methods have been proposed and "pull-through" intra-arterial pressures are the "gold standard." Deep Doppler duplex imaging was supplemented with real-time spectral analysis and velocity measurements in 29 cases. Twenty-three of these patients needed arteriography. One hundred sixty-six (166) arterial segments extending from the proximal aorta to the common femoral arteries were independently graded on duplex scans and arteriograms. For severe occlusive disease, duplex scanning is highly accurate (sensitivity 82%, specificity 93%). Velocity measurements were useful in determining the hemodynamic significance of stenoses. Peak systolic velocities in stenoses were measured with a duplex scanner. The pressure gradient calculated with the modified Bernoulli equation (delta P = 4Vmax2) correlated well with the gradients measured during arteriography (r = 0.9, n = 11). These noninvasive velocity measurements and Bernoulli calculations alert arteriographers to obtain special views of suspected areas and suggest the need for "pull-through" pressures and possible balloon angioplasty. In addition, these noninvasive measurements are useful to follow up patients who have mild to moderate aortoiliac disease and after angioplasty.

Aged↗
PubMed1988

Lower extremity edema from bladder compression of the iliac veins.

Two elderly men were referred to our vascular clinic for the management of bilateral lower extremity edema of 2 to 3 months' duration. Their evaluation included phlebograms, which demonstrated external compression of their iliac veins. CT scans of the pelvis suggested that large bladders caused the compression. Each patient had mild symptoms of prostatism. Transurethral resection of the prostate was recommended to and accepted by each patient. Decompression of the bladder was accompanied by complete relief of the lower extremity venostasis in both patients. Review of the literature yielded only eight similar cases of this unusual cause of lower extremity edema.

Aged↗
PubMed1988

Effect of tricarballylic acid, a nonmetabolizable rumen fermentation product of trans-aconitic acid, on Mg, Ca and Zn utilization of rats.

trans-Aconitic acid has been implicated in magnesium deficiency of ruminants since the 1960s, but recent experiments indicated that much of it can be converted by rumen bacteria to tricarballylic acid (TCBA). Rats were used as experimental models in the studies described here because analogous experiments in ruminants would have been very expensive. When TCBA was fed to young male Sprague-Dawley rats as 2% of an AIN-76A diet with marginal (200 mg/kg) or adequate (500 mg/kg) Mg, virtually all of the dietary acid was recovered in the urine. Mg and Ca absorptions were unaffected by TCBA but urinary losses of Mg, Ca and Zn were higher than in pair-fed controls. TCBA was highly correlated (r = 0.93) with titratable acid excretion, and Mg, Ca and Zn retentions were reduced by 90, 35 and 56%, respectively. Rats fed 2% citric acid, a structurally similar but metabolizable acid, excreted more Zn than controls but did not excrete excess Mg or Ca. Since TCBA led to a depletion of Mg and other cations, it could be a contributing factor in the etiology of the Mg deficiency known as grass tetany in ruminants. Additional work in ruminants now seems warranted.

Administration, Oral↗
PubMed1988

Glutathione formation in Penicillium chrysogenum: stimulatory effect of ammonium.

Penicillium chrysogenum produced glutathione after growth in a defined medium containing 10 mM-NH4Cl as the sole source of nitrogen. The use of higher ammonium concentrations (100 mM) resulted in stimulation of growth and glutathione formation. In addition, increases in the intracellular pools of glutamate, alanine and glutamine, proportional to the amount of ammonium present in the medium were observed. Resting cell systems, prepared from cells previously grown with ammonium, were able to produce glutathione when incubated with ammonium or the amino acids glutamate, alanine and glutamine. A mutant lacking NADP-dependent glutamate dehydrogenase activity (which has a leaky phenotype on ammonium as sole nitrogen source) required glutamate to synthesize glutathione. Resting cell systems of this mutant, prepared from cells previously grown with ammonium, did not produce glutathione even when incubated with glutamate or glutamine. On the other hand, resting cell systems of this mutant produced glutathione if prepared from cells previously grown with glutamate. The addition of glutamate to resting cell systems of the wild-type strain stimulated the synthesis of gamma-glutamylcysteine synthetase, the first enzyme of glutathione biosynthesis.

Ammonium Chloride↗
PubMed1988

Binding of proinsulin and proinsulin conversion intermediates to human placental insulin-like growth factor I receptors.

Insulin-like growth factor I (IGF-I) and proinsulin share similarities in both primary and tertiary structure. Proinsulin, endogenously secreted or exogenously administered, would, therefore, be expected to interact with IGF-I receptors. We determined the relative activities of IGF-I, insulin, proinsulin, and the proinsulin conversion intermediates in IGF-I radioreceptor assays using term human placental membranes. Insulin was approximately 0.5% as potent as IGF-I, and proinsulin was only 2% as potent as insulin. The six major proinsulin conversion intermediates were studied; all had activities intermediate between those of insulin and proinsulin. We conclude that the binding of proinsulin and the proinsulin conversion intermediates to IGF-I receptors is not of physiological significance at the concentrations occurring endogenously or after exogenous administration of proinsulin.

Binding, Competitive↗
PubMed1987

Cerebral glucose consumption following verbal auditory stimulation.

We studied the effect of auditory stimulation upon cerebral glucose metabolism in young normals. The stimulus consisted of a non-English discourse which was presented monaurally to 10 normal blindfolded subjects (5 left ear, 5 right); the opposite ear was plugged. Six subjects studied blindfolded and with ears plugged served as controls. Sixteen discrete homologous cortical and subcortical regions of interest were examined. Regional glucose consumption and side-to-side differences in glucose metabolism were analyzed. Monaural stimulation produced significant increases in temporal metabolism contralateral to the side of stimulation. Significant asymmetries in metabolism were found at the temporoparietal junction, inferior parietal region, insula and corpus collosum. The left frontal speech areas remained unaffected. These findings demonstrate that in man the primary auditory pathways retain a contralateral organization. Further, cerebral activation induced by non-meaningful verbal stimulation is widespread within the left temporal and parietal regions but does not impact upon the frontal speech cortices.

Adult↗
PubMed1987

The cognitive orientation of expressive communicability in schizophrenics and normals.

The study dealt with expressive communicability (EC), i.e., the amount, fluency, elaboration, clarity, and veracity of the voluntarily transmitted information about oneself. Low EC is considered as a schizophrenic symptom and as a cause of interpersonal difficulties in normals. For investigating the motivational antecedents of EC we applied the cognitive orientation (CO) theory that deals with explaining, predicting, and manipulating behaviors by means of cognitive contents and processes. The hypotheses were that schizophrenics would have fewer positive and more negative EC manifestations than normals, and that beliefs of four types would predict EC in both groups. Subjects were 30 hospitalized schizophrenics and 30 matched normals of both genders. They were administered individually the CO questionnaire and role-playing situations providing EC scores. Hospital personnel and close acquaintances answered a 13-item questionnaire about the subjects' EC. The findings confirmed the hypotheses: schizophrenics differed from normals on all EC measures, and the beliefs predicted 81%-100% EC measures in each group and the whole sample. The discussion focused on theoretical implications for cognitive motivation, the similarity of the motivational processes in schizophrenics and normals, and therapeutic implications for changing EC by changing the relevant beliefs.

Adult↗
PubMed1987

Effect of chronically elevated androgen or estrogen on the glucose tolerance test and insulin response in female rhesus monkeys.

Insulin concentrations, in response to an intravenous glucose bolus after a 24-hour fast, have been studied in female rhesus monkeys in which the circulating levels of androstenedione and testosterone or estrone and estradiol have been increased for as long as 4 1/2 years. No significant differences were observed in the basal insulin or C-peptide concentrations in the androgen or estrogen-treated animals compared with each other or with normal cycling, nontreated control animals. The insulin and C-peptide responses to intravenous glucose were similar in control and androgen-treated monkeys. Compared with both the control and androgen-treated monkeys, the responses of the estrogen-treated monkeys tended to be lower but were not significantly different. The glucose disappearance rate after the intravenous glucose bolus was not significantly different in androgen and control monkeys but was significantly slower during the initial 30 minutes in the estrogen-treated monkeys compared with both the control and androgen-treated monkeys. These studies suggest that chronically elevated androgen levels in the mature female subhuman primate do not lead to insulin resistance or overt glucose intolerance.

Androstenedione↗
PubMed1987

Epithelium-specific surface glycoprotein of Mr 34,000 is a widely distributed human carcinoma marker.

An epithelial cell surface antigen is described which is defined by monoclonal antibody HEA125 (IgG1). The antibody was raised against the colon carcinoma cell line HT-29. Under reducing conditions HEA125 immunoprecipitates a surface glycoprotein of Mr 34,000 which was designated Egp34. The antigen does not contain disulfide-linked subunits. A slightly different migration behavior under non-reducing conditions (Mr 39,000) may be due to intrachain disulfide bonds. After enzymatic cleavage of N-linked carbohydrate residues the apparent molecular weight of the antigen was 29,000. Egp34 is a major cell surface component of HT-29 cells (10(6) molecules per cell). No antigen could be detected in the sera of colorectal cancer patients. A panel of malignant cell lines and normal cells was studied for surface expression of the antigen. 17/17 carcinoma lines of 6 different origins expressed the antigen, whereas 16/16 melanoma, neuroblastoma, sarcoma and lymphoma/leukaemia were unreactive as it was the case for normal fibroblasts and blood cells. Immunoperoxidase staining of frozen tissue sections with HEA125 demonstrated the presence of Egp34 in almost all normal epithelia and tumours derived therefrom. No reactivity with non-epithelial tissues was observed. Undifferentiated carcinomas of various origins homogeneously expressed Egp34. Therefore, HEA125 may become a valuable tool for the immunohistochemical diagnosis of carcinoma.

Animals↗
PubMed1987

A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia.

Gruppuso et al. [Gruppuso, P.A., Gordon, P., Kahn, C. R., Cornblath, M., Zeller, W. P. & Schwartz, R. (1984) N. Engl. J. Med. 311, 629-634] have recently described a family in which hyperproinsulinemia is inherited in an autosomal dominant pattern, suggesting a structural abnormality in the proinsulin molecule as the basis for this disorder. However, unlike two previous kindreds with a similar syndrome, the serum proinsulin-like material in this family did not appear to be an intermediate conversion product but instead behaved like normal human proinsulin by several criteria. To further characterize this disorder we isolated and sequenced the insulin gene of the propositus. Leukocyte DNA was cloned into lambda-WES and recombinants containing the two insulin alleles, lambda MD41 and lambda MD51, were isolated by plaque hybridization. DNA sequencing of lambda MD51 showed that it contained the normal coding sequence for human preproinsulin. Sequence analysis of lambda MD41, however, revealed a single nucleotide substitution in the codon for residue 10 of proinsulin (CAC----GAC) that predicts the exchange of aspartic acid for histidine in the insulin B chain region. This mutation was also found in an insulin allele cloned from a second affected family member (propositus's father). These results, along with the linkage analysis of Elbein et al. [Elbein, S.C., Gruppuso, P., Schwartz, R., Skolnick, M. & Permutt, M.A. (1985) Diabetes 34, 821-824], strongly implicate this mutation as the cause of the hyperproinsulinemia in this family. Inhibition of the conversion of proinsulin to insulin may be related to altered folding and/or self-association properties of the [Asp10]proinsulin.

Cloning, Molecular↗
PubMed1987

Effects of the antituberculous drug ethambutol on zinc absorption, turnover and distribution in rats fed diet marginal and adequate in zinc.

Ethambutol, [CH3CH2-CH(CH2OH)-NH-CH2]2 (EMB), is an oral antituberculous agent that is administered therapeutically over extended time periods. It has chelating properties and may affect mineral metabolism. Male weanling Sprague-Dawley rats received 0, 400 or 600 mg EMB per kilogram body weight daily by gavage for 30 d. They were fed a casein-based diet with either adequate (49 ppm) or marginal (11 ppm) zinc. Both adequate-Zn (AZn) and marginal-Zn (MZn) rats receiving EMB showed alopecia and dose-dependent reductions in feed intake, weight gain and feed efficiency. None of these changes was seen in rats fed the MZn diet without EMB. Serum and tissue zinc levels were similar in rats not receiving EMB, regardless of the dietary zinc level. Serum zinc was consistently lower in AZn and MZn rats receiving EMB than in rats without EMB. Apparent zinc absorption, measured by 65Zn balance, was higher in AZn rats receiving EMB than in AZn rats without EMB. Thus changes in absorption could not account for lower serum zinc levels in EMB-treated rats. However, 65Zn turnover was also higher in EMB groups. This suggests that EMB may have increased urinary zinc losses resulting in reduced circulating zinc and a consequent increase in zinc absorption.

Animals↗
PubMed1987

Metabolism and placental transfer of 125I-proinsulin and 125I-tyrosylated C-peptide in the pregnant rhesus monkey.

125I-Proinsulin or 125I-tyrosylated-C-peptide (125I-tyr-CP) was administered to pregnant Rhesus monkeys by bolus followed by constant infusion to examine placental transfer of these peptides. At the end of each infusion, fetuses were exsanguinated in situ via the umbilical vein. The bolus-constant infusion technique produced a steady state in maternal plasma of immunoprecipitable label, measured using excess insulin or C-peptide antiserum. In animals infused with 125I-proinsulin, analysis of umbilical venous plasma revealed no apparent transfer to the fetus of immunoprecipitable label. In animals infused with 125I-tyr-CP, 3-13% of the umbilical venous plasma radioactivity was immunoprecipitable, representing 1.4-5.8% of the immunoprecipitable radioactivity in maternal plasma at delivery. Gel filtration chromatography of umbilical venous plasma revealed that the immunoprecipitated moiety was a fragment of 125I-tyr-CP. Analysis of maternal plasma showed that the predominant peak of radioactivity represented intact C-peptide. A peak corresponding to the fetal immunoprecipitable peak was also present. Analysis of simultaneous maternal arterial and uterine vein plasma samples showed that degradation of 125I-tyr-CP occurred across the uterus. Studies in one nonpregnant and three postpartum animals indicated that pregnancy increased the rate of metabolism of 125I-tyr-CP. When 125I-tyr-CP was incubated with trophoblastic cells in culture, degradation to a species corresponding on gel filtration to the immunoprecipitable fetal metabolite was found. We conclude that proinsulin, like insulin, does not traverse the placenta. Immunoreactive fragments of C-peptide do cross, however, and pregnancy alters the metabolism of 125I-tyr-CP, probably owing to placental degradation.

Animals↗