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Biomedical subjects

B Singh

Publications and source records attributed to B Singh.

At least 145 records · Page 8Linked to original sources
PubMed2001

Matriptase and HAI-1 are expressed by normal and malignant epithelial cells in vitro and in vivo.

Matriptase and its cognate, Kunitz-type serine protease inhibitor, HAI-1, comprise a newly characterized extracellular matrix-degrading protease system that may function as an epithelial membrane activator for other proteases and latent growth factors. Both enzyme and inhibitor have been detected in breast cancer cells, immortalized mammary epithelial cells, and human milk, but not in cultured fibroblasts nor in fibrosarcoma cells. To test the hypothesis that this system is expressed by normal breast epithelium, invasive breast cancers, and other cancers of an epithelial origin (carcinomas) but not in cancers of a mesenchymal origin, we have expanded our expression analysis of matriptase and HAI-1 in vitro and in vivo. Matriptase and HAI-1 were detected at the protein and mRNA levels both in hormone-dependent and hormone-independent cultured breast cancer cells, and this expression correlated with the expression of the epithelial markers E-cadherin or ZO-1. However, none of the breast cancer cell lines tested that express the mesenchymal marker vimentin express matriptase or HAI-1, consistent with an epithelial-selective expression of this system. Expression of matriptase, as determined by Western blot analysis, was observed in primary human breast, gynecological, and colon carcinomas, but not in stromal-derived ovarian tumors and human sarcomas of various origins and histological grades. The epithelial-selective expression of matriptase and HAI-1 was further confirmed in human breast cancers by immunohistochemistry and in situ hybridization, where the expression of the protease and the inhibitor were found in the carcinoma cells and in surrounding normal breast epithelia. The expression of the matriptase/HAI-1 system by malignant epithelial cells in vivo suggests a possible role for this protease in multiple aspects of the pathophysiology of epithelial malignancy, including invasion and metastasis.

Biomarkers↗
PubMed2001

The impact of sucrose-derived unconditioned and conditioned negative feedback on the microstructure of ingestive behavior.

We describe at the microstructural level the impact of unconditioned and conditioned negative feedback on the licking behavior of the rat. Seven groups of rats were trained to ingest one of seven different concentrations of sucrose (0.025, 0.05, 0.1, 0.2, 0.4, 0.6, and 0.8 M sucrose) under real-feeding conditions until intake was stable. They were then given three sham-feeding tests with the same solution. We compared the size of the clusters (SC) and number of clusters (NC) during the 17-min period when intake rate was declining in the real-feeding test with SC and NC during the corresponding 17-min period in the following sham-feeding test. Intake increased significantly over the three sham-feeding tests with the three highest concentrations, indicating the extinction of conditioned negative feedback. With these three solutions, we compared the microstructure of licking behavior in the first with that in the third sham-feeding test to determine if conditioned negative feedback affected SC or NC or both. The effect of both unconditioned and conditioned negative feedback on licking behavior was to decrease the NC without significantly affecting their size. We conclude that negative feedback derived from the accumulation of sucrose in the gastrointestinal tract decreases the probability of initiating a bout of licking during a pause. It has no effect on the ability to continue a bout of licking once it has begun.

Animals↗
PubMed2001

Extreme geographical fixation of variation in the Plasmodium falciparum gamete surface protein gene Pfs48/45 compared with microsatellite loci.

Comparing patterns of genetic variation at multiple loci in the genome of a species can potentially identify loci which are under selection. The large number of polymorphic microsatellites in the malaria parasite Plasmodium falciparum are available markers to screen for selectively important loci. The Pfs48/45 gene on Chromosome 13 encodes an antigenic protein located on the surface of parasite gametes, which is a candidate for a transmission blocking vaccine. Here, genotypic data from 255 P. falciparum isolates are presented, which show that alleles and haplotypes of five single nucleotide polymorphisms (SNPs) in the Pfs48/45 gene are exceptionally skewed in frequency among different P. falciparum populations, compared with alleles at 11 microsatellite loci sampled widely from the parasite genome. Fixation indices measuring inter-population variance in allele frequencies (F(ST)) were in the order of four to seven times higher for Pfs48/45 than for the microsatellites, whether considered (i) among populations within Africa, or (ii) among different continents. Differing mutational processes at microsatellite and SNP loci could generally affect the population structure at these different types of loci, to an unknown extent which deserves further investigation. The highly contrasting population structure may also suggest divergent selection on the amino acid sequence of Pfs48/45 in different populations, which plausibly indicates a role for the protein in determining gamete recognition and compatibility.

Africa↗
PubMed2001

The ICH guidance in practice: stress degradation studies on ornidazole and development of a validated stability-indicating assay.

The present study describes degradation of ornidazole under different ICH prescribed stress conditions (hydrolysis, oxidation and photolysis), and establishment of a stability-indicating reversed-phase HPLC assay. Degradation was found to occur in alkaline medium, under high acidic conditions, under oxidative stress, and also in the presence of light in acid conditions. Previously the drug is only known to decompose under alkaline conditions. Separation of drug and the degradation products under various conditions was successfully achieved on a C-18 column utilising water-acetonitrile in the ratio of 86:14. The detection wavelength was 310 nm. The method was validated with respect to linearity, precision, accuracy, selectivity, specificity and ruggedness. The response was linear in the drug concentration range of 5-500 microg ml(-1). The mean values (+/-RSD) of slope, intercept and correlation coefficient were 45251 (+/-1.59), 104418 (+/-2.49) and 0.9996 (+/-0.03), respectively. The RSD values for intra- and inter-day precision studies were <1 and <2.6%, respectively. The recovery of the drug ranged between 100-103% from a mixture of degradation products. The method was specific to drug and also selective to degradation products.

Chromatography, High Pressure Liquid↗
PubMed2001

Parasites that cause problems in Malaysia: soil-transmitted helminths and malaria parasites.

Malaysia is a developing country with a range of parasitic infections. Indeed, soil-transmitted helminths and malaria parasites continue to have a significant impact on public health in Malaysia. In this article, the prevalence and distribution of these parasites, the problems associated with parasitic infections, the control measures taken to deal with these parasites and implications for the future will be discussed.

Helminthiasis↗
PubMed2001

Expression of the nuclear coactivator AIB1 in normal and malignant breast tissue.

The gene of the nuclear receptor coactivator AIB1 (amplified in breast cancer 1) is amplified in breast cancer cell lines as well as in breast tumor tissues. AIB1 mRNA is often highly expressed (>60%) in primary breast tumors and it has been shown that AIB1 enhances estrogen and progesterone dependent transcription in vitro. Therefore, it has been postulated that AIB1 contributes to the development of breast cancer. However, to date, it has not been shown that AIB1 amplification and overexpression correlates with elevated protein levels in breast cancer tissues. In this study we analyzed protein levels of AIB1 in normal and breast tumor tissues by immunohistochemistry. We compared 41 human breast tumor tissues with 24 normal breast tissue samples and found that AIB1 stained in the nuclei of approximately 46% of the tumors and 30% of the normal tissues. Overall, AIB1 protein levels were significantly higher in tumor tissue than in normal tissue and the highest levels of nuclear staining were found exclusively in breast tumor tissues in 9.8% of the cases. These data suggest that increased AIB1 mRNA expression does not always translate into elevated protein levels and that AIB1 most likely will be relevant to the etiology of a subset of about 10% of breast carcinomas.

Adult↗
PubMed2001

Control of intestinal inflammation by regulatory T cells.

Transfer of CD4+ T cells to immune-deficient mice in the absence of the CD25+ subset leads to the development of colitis, indicating that regulatory cells capable of controlling a bacteria-driven inflammatory response are present in normal mice. Cells with this function are present in the thymus as well as in the periphery of germ-free mice, suggesting they may be reactive with self-antigen. These cells resemble CD4+CD25+ cells that inhibit organ-specific autoimmunity, suggesting that a similar subset of regulatory T cells may control responses to self and foreign antigens. Development of colitis is dependent on accumulation of activated CD134L+ dendritic cells (DC) in the mesenteric lymph nodes, which is inhibited by CD4+CD25+ cells, indicating that regulatory T cells may control DC activation in vivo. Whilst inhibition of T-cell activation in vitro by CD4+CD25+ cells does not involve interleukin-10 and transforming growth factor-beta, these cytokines are required for the suppression of colitis. It may be that control of responses that activate the innate immune system requires multiple mechanisms of immune suppression. Recently, we identified CD4+CD25+ cells with immune suppressive activity in the thymus and peripheral blood of humans, raising the possibility that dysfunction in this mechanism of immune regulation may be involved in the development of autoimmune and inflammatory diseases.

ADP-ribosyl Cyclase↗
PubMed2001

Non-operative management of haemobilia.

BACKGROUND: The aim was to evaluate a non-operative approach to the management of haemobilia. METHODS: This was a retrospective analysis of patients presenting over 10 years with haemobilia. All patients had upper gastrointestinal endoscopy, abdominal ultrasonography and digital subtraction angiography. Superselective coil and/or Gelfoam embolization was done as close as possible to the bleeding site. Completion angiography was performed routinely to confirm adequate embolization. RESULTS: There were 23 patients with liver trauma and six with inflammatory conditions. All patients required resuscitation with fluids and blood transfusion, and had the haemobilia controlled successfully by angiographic embolization. There was one death from fulminant hepatic sepsis. CONCLUSION: This series attests to the efficacy of a non-operative approach to haemobilia using radiological diagnosis and intervention.

Adolescent↗
PubMed2001

Immune therapy in inflammatory bowel disease and models of colitis.

BACKGROUND: A proliferation of animal models has not only improved our understanding of inflammatory bowel disease, it has also formed the basis of new treatment strategies. METHODS: A search was conducted using the National Library of Medicine for articles discussing immune therapies for inflammatory bowel disease. This was supplemented by findings from the authors' own laboratory. RESULTS: An overview of the different animal models is presented. These models are used to highlight the recent human trials of immune therapies. Potential future therapies are also discussed. CONCLUSION: Immune therapies have altered the management of patients with inflammatory bowel disease. In future they will influence not only the indications for surgery but also its timing and outcome.

Animals↗
PubMed2001

The role of economic evaluation in mental health care.

OBJECTIVE: A consequence of the integration of psychiatry into acute and public health medicine is that psychiatrists are being asked to evaluate their services. There is pressure on mental health-care systems because it is recognized that funds should be directed where they can provide the best health outcomes, and also because there are resource constraints which limit our capacity to meet all demands for health care. This pressure can be responded to by evaluation which demonstrates the effectiveness and efficiency of psychiatric treatment. This paper seeks to remind psychiatrists of the fundamental principles of economic evaluation in the hope that these will enable psychiatrists to understand the methods used in evaluation and to work comfortably with evaluators. METHOD: The paper reviews the basic principles behind economic evaluation, illustrating these with reference to case studies. It describes: (i) the cost of the burden of illness and treatment, and how these costs are measured; (ii) the measurement of treatment outcomes, both as changes in health status and as resources saved; and (iii) the various types of economic evaluation, including cost-minimization, cost-effectiveness, cost-utility and cost-benefit analysis. RESULTS: The advice in the paper provides psychiatrists with the necessary background to work closely with evaluators. A checklist of the critical questions to be addressed is provided as a guide for those undertaking economic evaluations. CONCLUSIONS: If psychiatrists are willing to learn the basic principles of economic evaluation and to apply these, they can respond to the challenges of evaluation.

Australia↗
PubMed2001

A comparison of the Composite International Diagnostic Interview (CIDI-Auto) with clinical assessment in diagnosing mood and anxiety disorders.

OBJECTIVE: Increasingly, epidemiological studies are employing computerized and highly standardized interviews, such as the Composite International Diagnostic Interview (CIDI-Auto), to assess the prevalence of psychiatric illness. Recent studies conducted in specialist units have reported poor agreement between experienced clinicians' and CIDI-Auto diagnoses. In this study we investigated the concordance rate between clinicians and the CIDI-Auto for the diagnosis of six anxiety disorders and two mood disorders, whereby the CIDI-Auto was treated as the 'gold standard'. METHOD: Subjects were 262 patients who were assessed by a clinical psychologist or psychiatrist and completed the CIDI-Auto at a tertiary referral unit for anxiety and mood disorders. Agreement between the clinicians' diagnoses and the diagnoses generated by the CIDI-Auto according to both DSM-IV and ICD-10 codes, were examined by kappa statistics. Sensitivity and specificity values were also calculated. RESULTS: Agreement between clinicians and the CIDI-Auto (DSM-IV) ranged from poor for social phobia and posttraumatic stress disorder (kappa < 0.30) to moderate for obsessive- compulsive disorder (OCD; kappa = 0.52). Agreement between clinicians and the CIDI-Auto (ICD-10) ranged from poor for major depressive episode (kappa = 0.25) to moderate for OCD (kappa = 0.57). With the CIDI diagnosis treated as the gold standard, clinicians' diagnoses showed low sensitivity (kappa < 0.70) for all the disorders except for OCD (for ICD-10), but high specificity (kappa > 0.70) for all the disorders. CONCLUSION: Poor agreements between experienced clinicians and the CIDI-Auto were reported for anxiety and mood disorders in the current study. A major implication is that if diagnosis alone directed treatment, then patients could receive different treatments, depending on whether the computer, or a clinician, made the diagnosis.

Adult↗
PubMed2001

Radioisotope scintigraphy in the diagnosis of hepatic hydrothorax.

BACKGROUND: Pleural effusion in cirrhotic patients (hepatic hydrothorax) may result from migration of ascitic fluid across defects in the diaphragm. Biochemical analysis of ascitic and pleural fluid provides only indirect information about the nature and origin of the effusion. The present study was performed in order to demonstrate the presence/absence of peritoneo-pleural communication by radioisotope imaging. METHODS: Ten patients with cirrhotic ascites and pleural effusion were studied with 99mTc sulfur colloid scintigraphy to look for movement of the radiotracer from the peritoneal to the pleural cavity. Serum-ascitic albumin gradient (SAAG) and serum-pleural fluid albumin gradient (SPAG) values were determined in eight patients to examine the nature of the ascitic and pleural fluids. RESULTS: Transdiaphragmatic movement of ascitic fluid into the pleural space was demonstrated (generally within 2 h of intraperitoneal injection of the radiotracer) in eight of 10 patients; six on the right side, one on the left and one bilaterally. Two patients in whom pleural fluid was transudative on SPAG values were negative for peritoneo-pleural communications. CONCLUSIONS: Radionuclide scintigraphy is a simple, safe and relatively non-invasive method to confirm passage of ascitic fluid across the diaphragm.

Adult↗
PubMed2001

Thoracic splanchnic nerves: implications for splanchnic denervation.

Splanchnic neurectomy is of value in the management of chronic abdominal pain. It is postulated that the inconsistent results of splanchnicectomies may be due to anatomical variations in the pattern of splanchnic nerves. The advent of minimally invasive and video-assisted surgery has rekindled interest in the frequency of variations of the splanchnic nerves. The aims of this study were to investigate the incidence, origin and pattern of the splanchnic nerves in order to establish a predictable pattern of splanchnic neural anatomy that may be of surgical relevance. Six adult and 14 fetal cadavers were dissected (n = 38). The origin of the splanchnic nerve was bilaterally asymmetrical in all cases. The greater splanchnic nerve (GSN) was always present, whereas the lesser splanchnic nerve (LSN) and least splanchnic nerve (ISN) were inconsistent (LSN, 35 of 38 sides (92%); LSN, 21 of 38 sides (55%). The splanchnic nerves were observed most frequently over the following ranges: GSN, T6-9: 28 of 38 sides (73%); LSN, when present, T10-11: (10 of 35 sides (29%); and ISN, T11-12: 3 of 21 sides (14%). The number of ganglionic roots of the GSN varied between 3 and 10 (widest T4-11; narrowest, T5-7). Intermediate splanchnic ganglia, when present, were observed only on the GSN main trunk with an incidence of 6 of 10 sides (60%) in the adult and 11 of 28 sides (39%) in the fetus. The higher incidence of the origin of GSN above T5 has clinical implications, given the widely discussed technique of undertaking splanchnicectomy from the T5 ganglion distally. This approach overlooks important nerve contributions and thereby may compromise clinical outcome. In the light of these variations, a reappraisal of current surgical techniques used in thoracoscopic splanchnicectomy is warranted.

Abdominal Pain↗
PubMed2001

Thoracic origin of a sympathetic supply to the upper limb: the 'nerve of Kuntz' revisited.

An understanding of the origin of the sympathetic innervation of the upper limb is important in surgical sympathectomy procedures. An inconstant intrathoracic ramus which joined the 2nd intercostal nerve to the ventral ramus of the 1st thoracic nerve, proximal to the point where the latter gave a large branch to the brachial plexus, has become known as the 'nerve of Kuntz' (Kuntz, 1927). Subsequently a variety of sympathetic interneuronal connections down to the 5th intercostal space were reported and also described as the nerve of Kuntz. The aim of this study was to determine: (1) the incidence, location and course of the nerve of Kuntz; (2) the relationship of the nerve of Kuntz to the 2nd thoracic ganglion; (3) the variations of the nerve of Kuntz in the absence of a stellate ganglion; (4) to compare the original intrathoracic ramus with sympathetic variations at other intercostal levels; and (5) to devise an appropriate anatomical classification of the nerves of Kuntz. Bilateral microdissection of the sympathetic chain and somatic nerves of the upper 5 intercostal spaces was undertaken in 32 fetuses (gestational age, 18 wk to full term) and 18 adult cadavers. The total sample size comprised 99 sides. Sympathetic contributions to the first thoracic nerve were found in 60 of 99 sides (left 32, right 28). Of these, 46 were confined to the 1st intercostal space only. The nerve of Kuntz (the original intrathoracic ramus) of the 1st intercostal space had a demonstrable sympathetic connection in 34 cases, and an absence of macroscopic sympathetic connections in 12. In the remaining intercostal spaces, intrathoracic rami uniting intercostal nerves were not observed. Additional sympathetic contributions (exclusive of rami communicantes) were noted between ganglia, interganglionic segments and intercostal nerves as additional rami communicantes. The eponym nerve of Kuntz should be restricted to descriptions of the intrathoracic ramus of the 1st intercostal space. Any of these variant sympathetic pathways may be responsible for the recurrence of symptoms after sympathectomy surgery.

Adult↗
PubMed2001

Inhibitors of caspase homologues suppress an apoptotic phenotype in cultured rabbit corpora lutea.

Apoptosis is a morphologically defined type of cell death initiated by various stimuli that results in the activation of caspases (cysteine-containing aspartate-specific proteases). In the present study, it was determined that caspases are present during, and play a role in, corpus luteum (CL) apoptosis in vitro. Pseudopregnancy was induced in rabbits with 100 IU human chorionic gonadotrophin. On Day 11 of pseudopregnancy, CL were isolated and cultured for 0, 2, 4, 6, and 8 h in the absence of trophic support to induce spontaneous apoptosis. Total RNA was extracted and analysed for caspase-I expression by Northern blot analysis. The results demonstrated caspase-I expression from 4 h. In the second part of the study, CL were incubated without trophic support for 4 h with increasing concentrations of three general caspase inhibitors, sodium aurothiomalate (SAM), iodoacetic acid (IAA) and N-tosyl-L-phenylalanylchloromethylketone (TPCK), and two specific caspase inhibitors, N-acetyl (Ac)-Tyr-Val-Ala-Asp (YVAD)-chloromethylketone (CMK) (Ac-YVAD-CMK) and Ac-Asp-Glu-Val-Asp (DEVD)-aldehyde (CHO) (Ac-DEVD-CHO). At completion, DNA was isolated and integrity assessed. Treatment of CL with SAM, IAA or Ac-DEVD-CHO effectively suppressed apoptotic DNA fragmentation. The final component of the study was to examine caspase-3 protein expression. Western blot analysis revealed a significant increase in caspase-3 expression over the experimental time-course. The results of the present study clearly demonstrate a time-dependent link between the caspases, specifically caspase-3 and spontaneous apoptosis in the rabbit CL.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Adaptogenic activity of a glyco-peptido-lipid fraction from the alcoholic extract of Trichopus zeylanicus Gaertn.

A glyco-peptido lipid fraction ("AF") from the alcoholic extract of Trichopus zeylanicus Gaertn. was evaluated for putative antistress activity in a battery of tests. "AF" exhibited significant antistress activity in dose dependent manner in all the parameters studied, against the different stresses use to induce non-specific stress. Ashwagandha, the commercial extract of Withania somnifera roots was used as control: A preliminary acute toxicity study in mice showed a good margin of safety, as the ALD50 value was more than 3000 mg/kg body wt. p.o. with no signs of abnormalities.

Adaptation, Psychological↗