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Biomedical subjects

S Bloom

Publications and source records attributed to S Bloom.

At least 19 recordsLinked to original sources
PubMed1998

The NPY Y1 receptor antagonist BIBP 3226 blocks NPY induced feeding via a non-specific mechanism.

We have previously shown that intracerebroventricular BIBP 3226 inhibits NPY induced feeding in rats. However, this was associated with abnormal behaviour, likely to be due to interaction with Y1 receptors involved in mechanisms other than the control of food intake. In order to minimise such interactions we investigated the effects of paraventricular nucleus (PVN) injections of BIBP 3226 and its inactive enantiomer BIBP 3435. Intra-PVN injection of NPY (0.1-2.5 nmol/animal) increased food intake, with an EC50 of approximately 0.15 nmol/animal. Injections of BIBP 3226 and BIBP 3435 (0.25-25 nmol) reduced NPY-induced food intake in a dose responsive manner, with BIBP 3226 reducing food intake by 95%, and BIBP 3435 by 65% at the highest dose tested. The reversibility of the effect of BIBP 3226 was investigated by measuring the feeding response to NPY (0.5 nmol) in animals 1 week after BIBP 3226 injection. The response to NPY was less in animals which had received high doses of BIBP 3226. Animals previously injected with saline vehicle alone showed a normal NPY feeding response. These results suggest that BIBP 3226 may be inhibiting NPY-induced food intake in a non-specific manner, not secondary to inhibition of the Y1 receptor. This does not, however rule out a role for the Y1 receptor in the control of food intake by NPY.

Animals↗
PubMed1998

Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk.

In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore considered that alterations in plasma leptin concentrations could constitute an additional component of a metabolic syndrome of cardiovascular risk. To explore this hypothesis, we employed factor analysis, a multivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meaningful factors. Seventy-four men [age, 48.4+/-1.3 years (mean+/-SEM); body mass index (BMI), 25.6+/-0.3 kg/m2] who were free of coronary heart disease and diabetes underwent anthropometric measurements (subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness ratios, measurement of fasting plasma leptin, and an intravenous glucose tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin concentrations were correlated with BMI (r=0.57, P<0.001), S:T (r=0.34, P=0.003), S:B (r=0.37, P<0.001), systolic and diastolic blood pressures (both r=0.24, P=0.044), fasting triglycerides (r=0.31, P=0.007), serum uric acid (r=0.35, P=0.003), fasting glucose (r=0.32, P=0.003) and insulin (r=0.33, P=0.004), and IVGTT insulin (r=0.63, P<0.001). A negative correlation was observed between leptin and insulin sensitivity (r=-0.32, P=0.006). No significant correlations emerged between plasma leptin concentrations and age, high density lipoprotein cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI (standardized coefficient [SC]=0.40, P=0.001), fasting insulin (SC=0.23, P=0.036), and IVGTT insulin (SC=0.51, P<0.001) emerged as independent predictors of plasma leptin concentrations (R2=0.56, P<0.001). After adjustment for BMI, only IVGTT insulin emerged as a significant predictor of plasma leptin concentrations (SC=0.56, P<0.001, R2=0.45, P<0.001). Factor analysis of plasma leptin concentrations and the variables that are considered relevant to the insulin resistance syndrome revealed a clustering of plasma leptin concentrations with a factor dominated by insulin resistance and high IVGTT insulin, separate from a high IVGTT glucose/central obesity factor and a high triglyceride/low high density lipoprotein cholesterol factor. Together, these factors accounted for 55.9% of the total variance in the dataset. In conclusion, interindividual variations in plasma leptin concentrations are strongly related to the principal components of the insulin resistance syndrome. Further studies are needed to determine whether the insulin-leptin axis plays a coordinating role in this syndrome and whether plasma leptin concentrations could provide an additional measure of cardiovascular risk.

Blood Pressure↗
PubMed1997

Evaluation of two simplified methods for genotyping hepatitis C virus.

A number of different approaches have been used for genotyping hepatitis C virus (HCV). Two simplified methods were evaluated, both of which used polymerase chain reaction (PCR) to amplify products from the 5' non-coding region of HCV: non-isotopic restriction fragment length polymorphism (RFLP) analysis and type-specific PCR. Sixty-four viraemic patients suffering from chronic HCV infection were studied using these two techniques; 25/64 samples were further tested with a commercial serotyping ELISA based on synthetic NS4 antigen (Murex, U.K.). The results of the three typing methods were generally in agreement with each other. When only the predominant genotype identified by each method was analysed, the 3 methods had 100% agreement. RFLP did not detect any mixed infections and it was unsuccessful in 16/64 (25%) samples. Both type-specific PCR and serotyping ELISA detected mixed infections. However, serotyping ELISA did not give typeable results in 7/25 (28%) samples, whereas type-specific PCR gave typeable results in all 64 samples. Type-specific PCR detected more mixed infections than serotyping ELISA. Direct sequencing of four PCR products with indeterminate RFLP confirmed changes in restriction enzyme recognition sites. The sequences also confirmed the validity of the predominant genotype in cases of apparent mixed infections. It is possible that some of these cases were artefacts as a result of quasispecies.

Base Sequence↗
PubMed1997

Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue.

Lymphocyte homing to normal tissues and recruitment to inflammatory tissue sites are controlled, in part, by the selective expression of chemokines, pro-inflammatory cytokines and mediators, and various adhesion proteins and molecules. In the mouse, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is selectively expressed on endothelium of high endothelial venules in gut and gut-associated lymphoid tissue. By interaction with its integrin ligand, alpha 4 beta 7, lymphocytes presumed to be involved in mucosal immunity are selectively recruited to these intestinal sites. After generating monoclonal antibodies against a murine cell line expressing recombinant human MAdCAM-1, we qualitatively and semiquantitatively assessed MAdCAM-1 expression in human tissue sections from various normal and inflammatory disorders. We found that human MAdCAM-1, as in the mouse, is expressed in a tissue-selective manner. In normal tissues, MAdCAM-1 is constitutively expressed to endothelium of venules of intestinal lamina propria. Interestingly, using computer-assisted morphometric analysis, the proportion of venular endothelium within lamina propria that expresses MAdCAM-1 is increased, compared with normal tissues, at inflammatory foci associated with ulcerative colitis and Crohn's disease. Moreover, for the most part, MAdCAM-1 is not detected in the majority of normal or inflamed extra-intestinal tissues, including those with mucosal surfaces. These results are consistent with a role, as originally defined in the mouse, for human MAdCAM-1 in the localization of alpha 4 beta 7+ lymphocytes in the gastrointestinal tract and associated lymphoid tissue. As such, the pathway defined by MAdCAM-1/alpha 4 beta 7 may be a relevant tissue-specific therapeutic target for the modulation of inflammatory bowel disease activity.

Animals↗
PubMed1996

A role for central glucagon-like peptide-1 in temperature regulation.

We have already established that central glucagon-like peptide-1 (GLP-1) has a role in the central control of food intake. In this study, experiments were conducted to establish the effect of acute intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of GLP-1 on temperature. Injection of 10 micrograms GLP-1 i.c.v. caused a significant reduction in temperature over the subsequent 2 h and reduced food intake as expected. Both effects were blocked by prior i.c.v. administration of the GLP-1 antagonist exendin 9-39 at a ratio of 30:1. Administration of 300 micrograms GLP-1 i.p. also reduced temperature over the 2 h following injection but had no effect on food intake. Administration of exendin 9-39 alone by the i.c.v. route had no effect on temperature. These results indicate that GLP-1 is a neuropeptide involved in the regulation of temperature. Furthermore, the mechanisms that mediate the effect on temperature may be different from those regulating food intake given the effect on temperature but not food intake of i.p. GLP-1.

Animals↗
PubMed1996

Intermediate filament-mediated stretch-induced changes in chromatin: a hypothesis for growth initiation in cardiac myocytes.

Excessive stretching of the myocardium leads to hypertrophy, but how the stretch message is communicated to hypertrophy-initiating genes is unknown. Candidates hypothesized as couplers of physical stretch to growth initiation include neural and hormonal factors, stretch-activated and stretch-inactivated ion channels, microtubules, microfilaments, and contractile activity. Upon investigation, however, all were ruled out. We provide evidence here that it is the intermediate filaments in the mechanically stressed myocyte that transmit the stretch message to the chromatin. Using rat myocytes and an immunogold desmin-lamin-labeling technique, we found that when cardiac myocytes are stretched there are changes in the spatial arrangement of both the desmin-lamin intermediate filament network and the nuclear-envelope-associated chromatin. We hypothesize that (a) by physically linking the sarcomere to chromatin, the desmin-lamin intermediate filament network couples sarcomere length to chromatin distribution, and (b) stretch-induced changes in chromatin (mediated by the intermediate filament network) activate hypertrophy-associated genes. Further investigation is needed to test this hypothesis.

Animals↗
PubMed1996

Recombinant human erythropoietin: effect on the functional performance of anemic orthopedic patients.

OBJECTIVE: To determine whether rapid correction of anemia improves the functional and cognitive performance of postoperative orthopedic patients. DESIGN: A randomized, double-blind, placebo-controlled clinical trial. SETTING: A rehabilitation institute. PATIENTS: Persons having orthopedic surgery at least 2 weeks previously, and a hemoglobin concentration < 10g/dL. INTERVENTIONS: Recombinant human erythropoietin (rH-EPO) or the EPO vehicle for up to 8 weeks. All patients received ferrous sulfate. MEASUREMENTS: Blood counts were performed at weekly intervals, and functional and cognitive tests at baseline and weeks 4 and 8. RESULTS: In patients receiving vehicle only, hemoglobin levels increased from a mean of 9.0 at baseline to 11.0 at 4 weeks and 11.7 at 8 weeks; corresponding values for rH-EPO were 8.8 (p = NS), 12.6 (p = .02), and 13.5 (p = .01). However, functional improvement in dressing, toileting, and mobility was similar between groups, and the results of neuropsychological tests showed no trends favoring rH-EPO. CONCLUSIONS: Although hemoglobin increases more rapidly in anemic orthopedic patients treated with rH-EPO, equally rapid functional improvement occurs in those who receive only iron therapy.

Activities of Daily Living↗
PubMed1996

Surgical treatment of penile veno-occlusive dysfunction: is it justified?

OBJECTIVES: Veno-occlusive dysfunction is a commonly diagnosed cause of impotence. Surgical removal of the intermediate (deep dorsal vein and its tributaries) venous system of the penis has been advocated as an effective treatment but recurrence of the dysfunction is common after a few months. We studied prospectively the first 100 cases of veno-occlusive dysfunction undergoing surgical treatment at our institutions. METHODS: One hundred consecutive patients undergoing penile venous ligation surgery were evaluated. All patients had a comprehensive workup prior to therapy. Surgery involved excision of the intermediate venous drainage. Short-term results were investigated by personal interview, and long-term outcome was determined by separate telephone interview of patients and their partners when available. RESULTS: Short-term success (3 months) was 62%, and long-term success (45 months) was 31%. Historical factors, preoperative testing results, and histologic assessment of the surgical specimens were not found to be helpful in predicting outcome. CONCLUSIONS: Despite the mediocre long-term results of the surgical procedure and lack of preoperative predictive factors, we believe that venous leak surgery could be offered to well-selected patients in whom the only other available alternative would be a prosthetic device.

Adult↗
PubMed1995

Adhesion molecules intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and B7 are not expressed by epithelium in normal or inflamed colon.

Adhesion molecules are involved in facilitating cell-mediated immune events. Because lymphocyte-epithelial cell interaction has been implicated in the pathogenesis of colonic inflammation, we analysed expression of a range of adhesion molecules on colonic epithelium in vitro and in vivo using flow cytometry, immunohistochemistry and in situ hybridization. Expression of ICAM-1 by cell lines HT29 and int407 was increased by proinflammatory cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-1 but not by IL-6. Vascular cell adhesion molecule (VCAM) and E-selectin were not expressed. Immunohistochemistry using sections of inflamed colon from 16 patients with ulcerative colitis (UC), five patients with Crohn's disease (CD) and seven patients with normal colonoscopic biopsies, showed no expression of ICAM-1 on colonic epithelium. VCAM was seen in isolated lymphoid aggregates and E-selectin was expressed on endothelium. In situ hybridization showed no ICAM-1 or ICAM-3 mRNA in colonic epithelium. B7, the ligand for CD28, was not found on normal or inflamed colonic epithelium. The adhesion molecules ICAM-1, ICAM-3 and B7 are not involved in lymphocyte-epithelial cell interaction in the normal or inflamed colon. This may have implications for the development of T cell tolerance to intestinal luminal antigens.

Antigen-Presenting Cells↗
PubMed1995

Adhesion molecule expression in primary sclerosing cholangitis and primary biliary cirrhosis.

There are conflicting reports regarding intercellular adhesion molecule-1 (ICAM-1) expression in primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Expression of adhesion molecules ICAM-1, lymphocyte adhesion molecule-1 (LFA-1), vascular cell adhesion molecule (VCAM), and E-selectin was examined together with HLA-DR in 16 liver biopsy specimens showing PSC and 12 specimens showing PBC. These were compared with biopsy specimens showing large duct obstruction (n = 7), chronic active hepatitis (n = 4), alcoholic liver disease (n = 4), and normal liver histological results (n = 5). ICAM-1 was detected on biliary epithelium in five of seven PSC specimens of histological stage 3 or 4, but not in nine early PSC specimens or in specimens from disease controls. In PBC, ICAM-1 was positive on three of 12 cases, two stage 2, and one stage 3. Nine of 16 PSC specimens (three of nine early, six of seven late disease) and six of 10 PBC specimens (three early, three late disease) were positive for HLA-DR. LFA-1 stained infiltrating inflammatory cells in PSC, PBC, and disease controls. In conclusion, ICAM-1 expression on biliary epithelium in PSC occurs mainly in late stage disease and therefore may be secondary to previous events inducing inflammation rather than of primary pathogenic importance. ICAM-1 expression in PBC is less common and not clearly associated with a particular disorder. Previous reports of ICAM-1 prevalence may have been biased towards end stage, pre-transplantation biopsy specimens.

Cell Adhesion Molecules↗
PubMed1995

Effect of peptide YY on human renal function.

Peptide YY (PYY) is released from the intestine into the circulation in response to ingestion of food. As PYY/neuropeptide Y (NPY) receptors have recently been identified in the human kidney, we examined the effect of PYY on human renal function. Male subjects (6 per group) received control infusate or PYY at 0.4 or 1.2 pmol.kg-1.min-1 intravenously for 90 min with control periods before and after. Infusion of PYY at the lower dose reproduced normal postprandial plasma concentrations and caused significant decreases in glomerular filtration rate (10% reduction), plasma renin activity (30% reduction), and aldosterone levels while increasing sodium excretion by approximately 30% (all P < 0.01). Infusion of PYY at the higher dose, which reproduced plasma levels seen during a diarrheal illness, resulted in similar changes in renal function and also reduced renal plasma flow by approximately 10% (P < 0.05). Therefore, PYY may be an important mediator of the normal postprandial natriuretic response, and PYY agonists could provide a novel approach to the treatment of patients with sodium overload.

Adult↗
PubMed1995

Adhesion molecule expression on vascular endothelium and nitroblue tetrazolium reducing activity in human colonic mucosa.

BACKGROUND: Expression of adhesion molecules is increased in inflamed colonic mucosa, but little is known about their functional activity in vascular endothelium. METHODS: We studied in situ nitroblue tetrazolium reducing activity and expression of E-selectin, ICAM-1, CD31, and VCAM-1 by immunohistochemistry in the same biopsy specimen in controls and patients with ulcerative colitis (UC). RESULTS: VCAM-1 expression was negative in mucosal vessels. E-selectin-positive vessels were significantly increased in endoscopically active colitis compared with normal mucosa. ICAM-1-positive vessels were consistently found in normal, quiescent UC and active UC. CD31-positive vessels were not significantly increased in quiescent UC and active UC compared with control. Only E-selectin significantly correlated with the histologic grade of inflammation. Nitroblue tetrazolium reducing vessels were increased in inflamed mucosa, and these vessels expressed ICAM-1 and CD31. E-selectin positivity in association with nitroblue tetrazolium reduction was mainly seen in the large mucosal vessels, but capillaries showing nitroblue tetrazolium reduction were rarely positive for E-selectin. CONCLUSIONS: Phenotypic and functional activation of vascular endothelium might be involved in the recruitment of leukocytes and tissue destruction of inflamed colonic mucosa.

Adult↗
PubMed1994

The prevalence of eating disorders in thyroid disease: a pilot study.

The aim of this study was to determine the prevalence of eating disorders and partial syndromes in women with thyroid disease. Female patients between the ages of 18 and 45 who attended a specialist thyroid clinic, in 1990, were asked to complete two self-report questionnaires (Bulimic Investigatory Test, Edinburgh, BITE and General Health Questionnaire, GHQ). High scoring patients were invited to attend for a research interview. The case notes of non-responders were examined. Seventy-three patients were entered into the study and 50 subjects returned their questionnaires (69%). Eleven patients scored highly on the BITE, nine of these patients also scoring highly on the GHQ, as did a further 12 patients. Ten patients were interviewed; of these, three patients (4%) met DSM111R criteria for bulimia nervosa and three patients met criteria for an eating disorder not otherwise specified. These results suggest that there is an increased prevalence of eating disorders in women thyroid patients.

Adolescent↗
PubMed1994

Inappropriate expression of blood group antigens in hepatic allografts.

We examined the expression of blood group antigens of the ABO, Lewis and Kell antigen systems using monoclonal antibodies and immunohistochemical study on 42 liver allograft specimens from 33 patients who underwent liver transplantation between 1986 and 1991 to learn whether altered blood group antigen expression might have a bearing on the immunopathogenesis of transplant rejection. Specimens were obtained at intervals of 0 days to 3 yr after transplant; they yielded the following histological diagnoses; time zero (n = 4), acute rejection (n = 4), pure cholestasis (n = 4), biliary obstruction (n = 4), early chronic rejection (n = 4), end-stage chronic rejection (n = 15) and miscellaneous late posttransplant biopsies (n = 7). Aberrant expression of blood group antigens was observed in 5 of 15 patients with chronic rejection. Two transplants into the same group O patient showed aberrant expression of AB antigens on hepatocytes, with a canalicular pattern, in group O-transplanted livers. In all three cases in which a group O liver was transplanted into a group A recipient and histological signs of chronic rejection were present, antibody staining showed acquisition of recipient blood phenotype by the donor liver bile ducts, endothelium or both. Aberrant expression of ABO antigens was seen only in chronic rejection. In seven cases we noted canalicular staining of periportal hepatocytes with the Lewis antibodies, normally confined to ducts and ductules. This was associated with severe cholestasis in six of the seven cases and may have represented early ductular metaplasia. These changes in carbohydrate cell surface phenotype may play a role in regulation of hepatic allograft susceptibility to immune-mediated damage.

Adolescent↗
PubMed1993

Trans-cellular desmin-lamin B intermediate filament network in cardiac myocytes.

Excessive stretch of heart muscle is thought to be a determinant of myocardial hypertrophy. Because cell shape and nuclear shape are closely coupled in cardiac myocytes, we hypothesize that excessive stretch causes physical deformation of the nucleus which might be responsible for some molecular events leading to hypertrophy. Cell shape and nuclear shape are most likely to be coupled by cytoskeletal elements. With this in mind, we have used immunogold labeling to examine the topological associations of desmin cytoskeletal and lamin B nucleoskeletal intermediate filaments with various intracellular structures in mammalian cardiac myocytes. We found that desmin filaments form a sarcoplasmic network radiating from the sarcolemma to the nuclear surface. Perpendicular to the long axis of the cell, strands of desmin filaments traverse the interfibrillary space in a co-linear arrangement with Z-discs. The desmin filament strands extend between peripheral regions of adjacent Z-discs. Desmin filaments traversing the interfibrillary space closely associate with the surface of mitochondria. At the cell surface, desmin filaments extend from Z-discs to terminate immediately beneath the sarcolemma. Close to the nucleus, desmin filaments extend from Z-discs towards nuclear pores. At the same time, lamin B filaments, which co-localize with heterochromatin immediately beneath the inner nuclear membrane, encircle the inner aspect of each nuclear pore. We hypothesize that desmin and lamin B are functionally anchored to each other at the nuclear pore, either directly or through anchorage proteins within the pore complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Inappropriate expression of blood group antigens on biliary and colonic epithelia in primary sclerosing cholangitis.

The distribution of carbohydrate antigens of the ABO, Lewis, and Kell systems was examined in biliary and colonic epithelial of 11 patients with primary sclerosing cholangitis (PSC) using a panel of 11 monoclonal antibodies. Controls consisted of 27 liver biopsy specimens (11 normal, six alcoholic liver disease, five extrahepatic obstruction, and five primary biliary cirrhosis) and 24 colonic biopsy specimens (six normal, four Crohn's disease, and 14 ulcerative colitis). There was inappropriate staining with anti-A (four of six, 66%) and anti-B (nine of 11, 81%) in biliary epithelium of PSC patients compared with normal and disease controls. Expression of Lewis antigens was increased in patients with cholestatic liver disease. Ninety one per cent of PSC patients showed a similar pattern of inappropriate staining by anti-A and anti-B antibodies in colonic epithelium compared with 33% of normal and 42% of inflammatory bowel disease controls. There is inappropriate expression of A and B carbohydrate antigens in biliary and colonic epithelium in PSC. Whether these oncofetal antigens are implicated in the pathogenesis of this condition is discussed.

Adult↗
PubMed1993

Many peptides that are present in the external zone of the median eminence are not secreted into the hypophysial portal blood of sheep.

Apart from the well recognized factors that are produced by the hypothalamus and secreted into hypophysial portal blood to regulate pituitary function, there is a range of neuropeptides that are present in the median eminence and could be secreted to serve a modulatory function. In this study we have collected hypophysial portal blood and jugular venous blood from sheep in an attempt to identify which of these putative modulatory peptides might be secreted from the median eminence. We have measured neuropeptide Y (NPY), substance P (SP), galanin (GAL), neurokinin A (NKA), peptide histidine isoleucine (PHI), vasoactive intestinal peptide (VIP), neurotensin (NT) and cholecystokinin (CCK). We also examined the sheep median eminence using immunohistochemistry for NPY, SP and GAL and determined degradation profiles of NPY, SP, GAL and NKA in portal and jugular plasma. In no instance did we find that levels of the above peptides were consistently higher in portal blood than in peripheral blood. In some cases levels of peptide were lower in portal plasma e.g. for NPY (6/10 sheep). In one experimental series SP levels in portal plasma were significantly (p < 0.05) lower than levels in jugular plasma but this was not found in another experimental series. Galanin levels were significantly (p < 0.01) lower in portal plasma compared to levels in jugular plasma. We conducted in vitro studies to determine whether or not the above peptides are selectively degraded in portal blood but were unable to show any differences between the rates of degradation in portal and jugular plasma. Immunohistochemistry revealed projections into the external zone of the median eminence for NPY, GAL and SP. This study shows that none of the above peptides are secreted into the hypophysial portal blood of sheep. For some peptides e.g. GAL, enzymes from the endothelial cells of the portal vessels may enhance degradation. Projections into the external zone of the median eminence of neuronal systems containing these peptides may serve to modulate the secretion of the well recognized release and inhibiting factors by acting on the neurosecretory terminals.

Animals↗