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Biomedical subjects

N Levin

Publications and source records attributed to N Levin.

At least 55 records · Page 3Linked to original sources

Adaptation of the growth hormone and insulin-like growth factor-I axis to chronic and severe calorie or protein malnutrition.

The hierarchy of diet components (e.g., protein, carbohydrate, vitamins, and minerals) influencing growth hormone (GH), insulin-like growth factor-I (IGF-I), and their binding proteins (BP) is not well defined. Young adult rats were fed diets for 1 mo that included low protein or 60% and 40% of carbohydrate calories. We hypothesized that levels of both hormones, their dominant BPs and liver IGF-I mRNA would fall, and that part of the mechanism for decreasing serum IGF-I would be enhanced IGFBP-3 protease activity. By day 30, caloric deprivation to 40% lowered serum GH, GHBP, IGF-I and IGFBP-3, and liver IGF-I mRNA. This was the only condition resulting in body weight loss (-15%) vs 39% gain in controls. Restriction to 60% calories had no impact on BP levels, slightly lowered IGF-I (-12%) in the face of a 95% inhibition of GH levels, while allowing a modest 9% body weight gain. Protein deprivation lowered serum GH, IGF-I and IGFBP-3, and liver IGF-I mRNA, while GHBP levels were normal. The reduced total IGF-I under these dietary conditions could not be explained by an increase in IGFBP-3 protease activity, or a decrease in the association of IGF-I with IGFBP-3 and the acid labile subunit.

Amino Acid Isomerases↗

Human interleukin 1 beta: corticotropin releasing factor and ACTH release and gene expression in the male rat: in vivo and in vitro studies.

Numerous studies have shown that interleukin 1 (IL1), a cytokine secreted by macrophages, is capable of stimulating the hypothalamo-pituitary-adrenal (HPA) axis. Nevertheless, the sites involved in IL1 stimulation of the HPA axis remain, to date, subjects of controversy. In the present study, using in vivo and in vitro approaches, we tried to characterize the route by which IL1 acts on the HPA axis. In vivo, after an i.p. injection of human IL1 beta (1 microgram/rat), we measured plasma ACTH concentration, anterior pituitary (AP) ACTH content, hypothalamic (HT) corticotropin releasing factor (CRF) content, and also AP pro-opiomelanocortin (POMC) and HT CRF gene expression. ACTH and CRF were measured by specific radioimmunoassays (RIAs), and solution hybridization nuclease protection assay was used for quantification of nuclear POMC precursor RNA and nuclear and cytoplasmic POMC and CRF mRNA. Human IL1 beta provoked an increase in ACTH plasma concentration, a decrease in AP ACTH content, and a prolonged increase in AP POMC primary transcript levels (around 100%). A significant increase in AP POMC primary transcript content was evident 30 min after injection of hIL1 beta, while cytoplasmic POMC mRNA levels were increased in the AP only at 4 hr after injection of hIL1 beta. We did not observe an effect of hIL1 beta on either HT CRF content or HT CRF cytoplasmic mRNA levels. In order to characterize a possible direct effect of hIL1 beta at the AP level, we used an AP perifusion system to analyse the effect of hIL1 beta and CRH on ACTH release and on POMC gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Hypothalamic neuropeptide Y and its gene expression: relation to light/dark cycle and circulating corticosterone.

The hypothalamic neuropeptide Y (NPY) system, along with levels of circulating corticosterone (CORT), were examined in rats at different times across the light/dark cycle. Tissue samples were taken from the mediobasal hypothalamus (MBH), which contains the primary hypothalamic NPY cell group of the arcuate nucleus (ARC), and the mediodorsal (MDH) hypothalamus, which contains the paraventricular and dorsomedial nuclei that receive a dense NPY innervation from the ARC. In these dissections, measurements of NPY mRNA and peptide levels were taken using a solution hybridization/nuclease protection assay procedure and radioimmunoassay. The results demonstrate that (i) NPY mRNA levels in the MBH, but not MDH, vary significantly in relation to the light/dark cycle, showing a sharp rise 4-6 h before dark onset, sustained high levels over the next 3-4 h and then, a sharp decline 1 h before dark onset; (ii) this rise in NPY mRNA in the MBH before dark onset, while associated with stable levels of MBH NPY during this time, is followed 2-4 h later, around dark onset, by a rise in NPY peptide levels of the MDH simultaneous to a decrease in NPY levels of the MBH; (iii) levels of circulating CORT shift dramatically across the light-dark cycle, exhibiting an increase from basal levels (< 0.3 microgram/dl) to 5 micrograms/dl approximately 4 h before dark onset, a further rise that peaks at 26 micrograms/dl around dark onset, and then a significant decline to 16 micrograms/dl at 2 h after dark onset; and (iv) there exists a positive relationship between CORT and NPY mRNA or peptide levels in the MBH during the 4-6 h before dark onset, while in the MDH, a positive relationship between this steroid and NPY peptide levels is obtained at dark onset. It is proposed that these rhythms, involving a predark rise in CORT and NPY gene expression leading to a peak in CORT and peptide levels at dark onset, are active in stimulating feeding behavior, particularly carbohydrate ingestion, which predominates at that time.

Adrenocorticotropic Hormone↗

The effect of time of day on levels of hypothalamic proopiomelanocortin primary transcript, processing intermediate and messenger ribonucleic acid in proestrous and estrous rats.

Several lines of evidence from different laboratories suggest that hypothalamic beta-endorphinergic activity decreases around the time of initiation of the LH surge and may increase on estrus to extinguish the expression of the daily neuronal signal for the surge. In several hormone systems, factors that stimulate or suppress hormone release also stimulate or repress transcription of the hormone gene and translation of the messenger RNA encoding the hormone. Therefore, information about neurohormone activity may be inferred from data on changes in the levels of RNA species encoding these neurohormones. We used a solution hybridization/RNase protection assay to test the hypotheses that 1) the abundance of primary transcript of the hypothalamic POMC gene decreases at the time of initiation of the proestrous LH surge and 2) levels of POMC primary transcript (and by inference, levels of beta-endorphin neuronal activity and secretion) increase on estrus. 96 rats exhibiting at least two consecutive 4-day estrous cycles were killed at either 0600 or 1300 h on proestrus and estrus. Dissections of the medial basal hypothalamus were pooled into 4 samples at each time-point (6 rats per sample) and RNA was extracted from nuclear and cytoplasmic fractions separately. We measured levels of POMC primary transcript, processing intermediate and fully spliced mRNA in the nuclear fractions and POMC mRNA in cytoplasmic fractions. Compared to 0600 h, levels of POMC primary transcript decreased significantly during the afternoons of both proestrus and estrus (P < 0.05). Levels of nuclear processing intermediate RNA and cytoplasmic mRNA followed the same trend but the afternoon declines did not reach statistical significance. We conclude from these data that the afternoon decline in POMC gene expression is not unique to the day of proestrus and we speculate that an afternoon decline in beta-endorphinergic neuronal activity may instead be a component of the daily signal for the LH surge.

Animals↗

[Conjunctival epidermoid carcinoma and human immunodeficiency virus].

We describe the clinical and histopathological findings of a conjunctival squamous cell carcinoma occurring in a patient with acquired immunodeficiency syndrome (AIDS). The excisional biopsy specimen disclosed a papillar, well differentiated and mature squamous cell carcinoma with microinvasion. The biopsy was studied for the presence of Human papilloma virus DNA by using in situ hybridization but no signal was demonstrated in any part of the tumour. Although Kaposi's sarcoma and non-Hodgkin's lymphomas are the most common malignancies reported in AIDS, squamous cell carcinomas may be encountered in the disease. Underlying infection with the human immunodeficiency virus should be considered when conjunctival localization of such malignancies is observed.

Acquired Immunodeficiency Syndrome↗

Malnutrition in hemodialysis patients.

Increasing attention has been paid recently to the problem of protein and energy malnutrition and its effects on mortality and morbidity in hemodialysis (HD) patients. Protein deficiency has received more attention than other nutritional problems, largely because its consequences are more easily measured and large population studies have demonstrated the adverse effects of even small decreases in serum albumin on patient's survival. This review discusses these findings and presents other indicators of early malnutrition, which range from static measurements of plasma constituents such as transferrin and insulin-like growth factor 1 (IGF-1), kinetic measurements of protein catabolic rate (PCR) derived from urea kinetic modeling, and noninvasive measurements of body composition. In addition, the predialytic and dialytic factors that influence nutritional status, including the adverse effects of uremia, inadequate dialysis, membrane bioincompatibility, and intercurrent illness requiring hospitalization, as well as socioeconomic factors, are discussed. While some of these are difficult to deal with, the review emphasizes simple interventions that are likely to benefit the patient, including the delivery of optimal dialysis, appropriate choice of medications, and dietary interventions. Once malnutrition is established, parenteral nutrition may reverse the objective evidence of malnutrition, but its effects on survival have not yet been documented. Finally, the review addresses the effects of therapeutic substances such as growth hormone (GH) and erythropoietin (EPO) in combination with nutrients that at present appear to be favorable but are still being evaluated.

Dietary Proteins↗

Behaviour of platelets and beta-thromboglobulin.

Platelet count, platelet aggregation responses, and plasma beta-thromboglobulin were assessed before and at intervals during each study dialysis. As expected, modest thrombocytopenia was observed following treatment with all dialysers, but Filtral showed the least effect. Concordantly, modest increases in plasma beta-thromboglobulin were observed with all devices except Filtral (caveat: the device also seems to adsorb beta-thromboglobulin). Interpatient variability was more striking for platelet aggregation responses, and made it difficult to discern patterns; however, aggregation in response to ADP was augmented during haemodialysis with the Filtral device, and blunted when the G120 M was employed. Differences between hollow-fibre and parallel plate devices with the same membrane material suggest that membrane geometry, manufacturing residues, membrane support, or potting materials may also contribute to platelet activation.

Adenosine Diphosphate↗

Introduction, demography, and general methods.

The International Cooperative Biocompatibility Study was planned to analyse the symptomatic and laboratory response to seven different dialysers studied in five centres in four countries. The dialysers used were the G10-3N, G120 M, CD 4000, T 150, Duo-Flux, F 60, and Filtral (see below for full description). A total of 37 patients in the Veterans Administration Lakeside Medical Center, Chicago; Henry Ford Hospital, Detroit; Osaka City University Hospital, Osaka; Wilhelm Pieck University Hospital, Rostock; and Huddinge University Hospital, Stockholm were studied. All patients had been dialysed for a minimum of 6 months, were non-diabetic, stable, and compliant; and most were middle-aged and male. Patients were treated three times per week for 2 weeks with each new dialyser with random assignment to one of four orders of dialyser use. The same manufacturing lot of each dialyser, blood line sets and needles were used by all centres. Delivery systems were volumetric controlled except for some patients in Osaka treated with negative-pressure equipment. Individual patient prescriptions (Kt/Vs for urea), in use prior to the study, were continued. Kt/Vs for all treatments were derived from reported blood flows and blood water corrected mass transfer coefficients multiplied by dialyser surface area. Clinical data were measure pre-, intra- and postdialysis. Hourly signs, symptoms, drugs, and nursing interventions were recorded using the identical treatment record at all centres. In addition, patients completed a questionnaire form (translated into the appropriate language) at least weekly, relating symptoms experienced with each dialyser. Laboratory investigations were performed during the sixth consecutive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

beta 2-Microglobulin and granulocyte elastase.

Plasma beta 2-M was measured by radioimmunoassay in samples obtained before and after dialysis with seven different dialysers, tested according to the protocol of the International Cooperative Biocompatibility Study (ICBS). Plasma beta 2-M was corrected for contraction of its distribution volume, which was assumed to be equal to the extracellular fluid volume. The uncorrected plasma beta 2-M concentration increased with all conventional dialysers, including the G10-3N, (cuprammonium cellulose plate), G120 M (cuprammonium cellulose hollow fibre), CD 4000 (cellulose acetate) and T 150 (polymethylmethacrylate). However, no significant differences were found between the predialysis and the corrected postdialysis plasma beta 2-M concentrations with these conventional dialysers, and thus no evidence of net generation or release of beta 2-M was found in this study. With high-permeability membranes, the corrected postdialysis beta 2-M values were decreased by 27.1% with the Duo-Flux Artificial Kidney, 53.5% with F 60, and 34.6% with Filtral, indicating that dialysers with these membranes eliminate plasma beta 2-M to a certain extent. The complex of granulocyte elastase with alpha 1-antiproteinase in plasma was also measured in samples from the arterial blood line collected before, and after 30 and 120 min of dialysis with each of the seven dialysers in this study. All dialysers elicited an increase in the mean plasma elastase concentrations which was more than twice as high with cuprammonium cellulose plate than with all of the others. The change of elastase at 120 min of dialysis varied considerably with each dialyser and was statistically significant with all except CD 4000, F 60, and Filtral.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellulose↗

Dialysis-induced hypoxaemia.

A crossover study to compare the effects of seven different dialysers on blood gas conditions during dialysis using acetate-containing dialysate was carried out at five centres in four countries. A significant decrease in pO2 was noted at both 15 and 60 min after the start of dialysis for all dialysers, with the greatest decrease at 60 min. Filtral caused the greatest reduction and F 60 the least change at both 15 and 60 min. These differences were statistically significant according to the ANOVA multiple-range test for variance. pCO2 also declined by 1.0-2.7 mmHg at 15 min and by 0.7-3.8 mmHg at 60 min. The delta pCO2 was comparable across dialysers and no significant differences were found. Although pH showed no change at 15 min, it was slightly but significantly increased at 60 min across all dialysers compared to predialysis values. There were no statistical differences between dialysers. Calculated blood bicarbonate content significantly decreased at 15 min and recovered at 60 min. Along with the greater decrease in pO2, a larger loss of total CO2 was noted for Filtral. On the other hand F 60 caused the least change in total CO2. This difference may be due to membrane characteristics affecting the diffusion coefficient for O2, CO2, and bicarbonate. Multifactorial mechanisms are likely to be involved, but reflex hypoventilation and an increase in O2 consumption also contributed to hypoxaemia in this study.

Acetates↗

Ovine anterior pituitary proopiomelanocortin gene expression is not increased by ACTH secretagogues in vitro.

Recent reports have demonstrated that the secretion of ACTH from sheep anterior pituitary primary cultures is markedly stimulated by arginine vasopressin (AVP) but not by CRF, and that AVP-stimulated ACTH secretion is potentiated by CRF. It has also been reported that AVP increases total ACTH content (secreted plus intracellular ACTH), suggesting that AVP stimulates POMC biosynthesis in the ovine anterior pituitary. These observations differ from the rat, in which CRF is the most potent of the ACTH-releasing factors and the only ACTH secretagogue which stimulates POMC gene expression and biosynthesis. The second messenger pathways which mediate CRF- and AVP-stimulated ACTH release (protein kinase A and protein kinase C, respectively) are the same in sheep and rat corticotrophs. The present studies were undertaken to determine if ovine POMC gene expression, unlike the rat POMC gene, is stimulated by AVP via the protein kinase C pathway. A 295 base pair portion of the ovine POMC gene was isolated using polymerase chain reaction and sequenced. Ovine POMC messenger RNA (mRNA) levels were quantitated using this partial complementary DNA clone in a solution hybridization/nuclease protection assay with cytoplasmic RNA from sheep anterior pituitary primary cultures which had been treated with various combinations of ACTH secretagogues or with glucocorticoids for 18 h. Treatment with AVP, alone or with CRF, greatly increased total and secreted ACTH levels; however, the amount of POMC mRNA in these cells was not significantly increased. Treatments which stimulated secretion to a lesser extent and did not alter total ACTH levels (CRF alone, cAMP alone, or with phorbol ester) were associated with a decrease in POMC mRNA levels relative to untreated cells. Glucocorticoid treatment decreased both total ACTH and POMC mRNA levels. Taken together, the data demonstrate a lack of secretagogue-induced stimulation of POMC mRNA levels concomitant with increased total ACTH levels, an unexpected result given the close association between secretion of POMC-derived peptides and POMC gene expression in other mammalian corticotroph systems.

Adrenocorticotropic Hormone↗

HIV disease in pregnancy.

The years from 1981 to the present have seen a steady increase in the incidence of AIDS in the female population. The corollary increase in the incidence of AIDS in pregnancy increases the responsibility of the obstetrician to become aware of the effect of AIDS on pregnancy and the effect of pregnancy on AIDS.

Acquired Immunodeficiency Syndrome↗

Proopiomelanocortin gene expression in a distinct population of rat spleen and lung leukocytes.

Existence of proopiomelanocortin (POMC) messenger RNA (mRNA) and related peptides in extrapituitary sites has been demonstrated in immune cells, although the particular type of immune cell has been the source of considerable debate. Specifically, double labeling studies have shown that POMC peptide expressing cells in the spleen represent a subpopulation of red pulp macrophages, while splenic lymphocyte areas are POMC negative. In addition, it has also been reported that peripheral blood leukocytes express the POMC gene. Using a sensitive solution hybridization technique with a POMC exon-1 RNA probe, we detected 70 +/- 20 fg and 65 +/- 5 fg POMC mRNA per microgram total RNA in whole spleen and lung, respectively, approximately 20,000-fold lower concentrations than found in the neurointermediate lobe of the pituitary. The presence of nuclease protected full length exon-1 bands, rather than the 5' truncated POMC RNAs seen in many nonpituitary tissues, indicates transcription initiation at the normal pituitary POMC promoter site in lung and spleen. In order to localize POMC gene expression in these tissues we employed an in situ hybridization method. There was an intense signal in a small population of large mononuclear cells scattered throughout the splenic red pulp and lung parenchyma. In the lung, these cells were concentrated in the periarteriolar zone in a manner suggestive of migration from the intravascular lumen. These cells had a histomorphology suggestive of monocyte-macrophages. POMC mRNA was undetectable in the splenic white pulp and bronchus-associated lymphoid tissue, indicating an absence of POMC gene expression in splenic and lung lymphocytes. Immunocytochemical studies suggested that POMC-positive cells made up a subpopulation of cells expressing the rat monocyte-macrophage markers ED1 and ED2. Similarly, the distribution of Jenner-Giemsa stained monocyte-macrophages appeared to overlap with POMC positive cells. Studies with anti-rat beta-endorphin antisera revealed scattered cells in the splenic red pulp and lung parenchyma, suggesting that the POMC mRNA is translated in these cells. In summary, POMC mRNA is expressed in a small population of monocyte-macrophage-like cells in lung and spleen but not in lymphocytes in these tissues.

Animals↗

The dose of hemodialysis according to dialysis prescription in Europe and the United States.

Prior research has shown that, controlling for age and diabetes, patients with end-stage renal disease in Europe generally have better rates of survival than do ESRD patients in the U.S. This analysis compares the dose of hemodialysis prescription in the two regions. Based on the European Dialysis and Transplant Association Registry (EDTA), the U.S. Renal Data System (USRDS), and other sources, European and U.S. ESRD patients were compared by demographic and anthropometric characteristics, dialyzer characteristics, and duration of dialysis treatment times. Average body weight and body mass indices were found to be similar for the ESRD populations of the two societies, suggesting the same overall requirements for dialysis therapy. During 1986 to 1988, dialyzers selected in Europe had a larger surface area by at least 20 percent compared to those selected in the U.S. In addition, duration of hemodialysis treatment times were on average 23.5% longer for EDTA patients. Dialyzer blood flows were not available for EDTA patients, but if EDTA blood flows resemble U.S. practices, total urea clearance per week was at least 29% higher in Europe than in the U.S. Combining similar patient characteristics with substantially greater total urea clearance per week, the hemodialysis prescription in Europe was substantially higher than in the U.S. for the time period of this study.

Europe↗