Search PubMed⌕ Search

Biomedical subjects

S Sidhu

Publications and source records attributed to S Sidhu.

At least 37 records · Page 2Linked to original sources
PubMed1998

Streptomyces griseus protease B: secretion correlates with the length of the propeptide.

Streptomyces griseus protease B, a member of the chymotrypsin superfamily, is encoded by a gene that express a pre-pro-mature protein. During secretion the precursor protein is processed into a mature, fully folded protease. In this study, we constructed a family of genes which encode deletions at the amino-terminal end of the propeptide. The secretion of active protease B was seen to decrease in an exponential manner according to the length of the deletion. The results underscore the intimate relationship between folding and secretion in bacterial protease expression. They further suggest that the propeptide segment of the zymogen stabilizes the folding of the mature through many small binding interactions over the entire surface of the peptide rather than through a few specific contacts.

Binding Sites↗
PubMed1996

Antigen presentation by T cells inhibits IL-2 production and induces IL-4 release due to altered cognate signals.

Conflicting results of the effects of Ag presentation by MHC class II-expressing T cells have been described. In some studies class II-expressing T cells have been shown to act as effective APCs, while others have reported that the recognition of Ag on the surface of another T cell inactivates IL-2 production. In this study we have investigated the mechanisms involved in Ag presentation by T cells. The results obtained suggest that 1) lack of costimulation is not responsible for the inhibitory effects of T cell Ag presentation on IL-2 production; the provision of costimulation by immobilized anti-CD28 Ab or by the addition of accessory cells failed to reverse the effects of T cell Ag presentation, but restored the response to immobilized anti-CD3; 2) T cell Ag presentation induced a minimal increase in intracellular Ca2+ compared with that induced by antigen-pulsed B cells; this difference in the calcium response is not explained by quantitative differences in ligand density between B cells and T cells; and 3) despite the weak calcium signal, T cell presentation supported IL-4 release in the absence of IL-2 production. Taken together these data suggest that T cell Ag presentation leads to altered TCR/CD3-transduced signals, which biases the T cell towards a Th2 phenotype.

Animals↗
PubMed1996

Is penetrating injury on the increase in south-western Sydney?

BACKGROUND: Few Australian studies describe the epidemiology of penetrating trauma. This study describes the incidence and demographic features of penetrating injuries with emphasis on trends and severity analysis. METHODS: Case analysis was performed utilizing data from the Liverpool Hospital Trauma Registry (1989-94), NSW Department of Health Hospital Separations (1991-93), and the NSW Bureau of Crime Statistics (1991-93) with reference to the Liverpool and Fairfield Local Government Areas (LGA). RESULTS: The Trauma Registry revealed 251 of penetrating trauma. The median age was 26 years (interquartile range 21-33). Ninety-one per cent of the victims were male. Fourteen per cent of patients had an Injury Severity Score (ISS) > 15. Sixty-five per cent of cases were stab injuries and 20% gunshot injuries with the abdomen being the most commonly injured site. Twenty-one per cent of patients underwent laparotomy, 1.6% thoracotomy and 1.2% thoracotomy and laparatomy. There were 10 (4%) deaths. Trends in incidence of penetrating trauma and violent crime involving weapons were analysed. Static trends were observed for the annual incidence of penetrating trauma from the Liverpool Hospital Trauma Registry. Separations for penetrating trauma from Liverpool and Fairfield hospitals showed a slightly increasing trend. Violent crimes involving weapons in the Liverpool and Fairfield LGA showed a static trend. Nevertheless, separations for penetrating trauma and rates of violent crimes involving weapons were higher in south-western Sydney than metropolitan Sydney or NSW. Eight per cent of the LGA population are Vietnamese but this study identified 16% of victims as being Vietnamese. CONCLUSIONS: This study found no significant increase in penetrating trauma or violent crime predisposing to penetrating injury in south-western Sydney.

Adolescent↗
PubMed1996

Chronic pancreatitis: diagnosis and treatment.

Three-dimensional magnetic resonance cholangiopancreatography is currently the most exciting new imaging technique for chronic pancreatitis. Endoscopy-assisted duodenal intubation during the secretin-cholecystokinin test reduces intubation time in difficult cases. The NBT-para-amino benzoic acid test has been refined to enhance its discriminant power. The cholesteryl-[C13]octanoate breath test and the faecal elastase test are newer highly sensitive and specific tubeless tests. Pain in chronic pancreatitis continues to be a vexing therapeutic issue. Enzyme treatment continues despite criticism. Neurotensin is the new suspected mediator of the feedback mechanism, which is downregulated by enzyme therapy. Steroid ganglion block is an exciting therapeutic tool for pain relief. Endoscopic pancreatic sphincterotomy, Dormia basketing and pancreatic stenting in conjunction with extracorporeal shock wave lithotripsy should be performed early in chronic pancreatitis to prevent parenchymal atrophy with ensuing exocrine and endocrine pancreatic dysfunction. The modified Puestow's procedure preserves endocrine and exocrine pancreatic functions besides relieving pain. Closed loop insulin infusion allows superior management of pancreatic diabetes following near total pancreatectomy. The standardised incidence rate of pancreatic cancer is 16.5 in patients with alcoholic chronic pancreatitis and 100 for tropical chronic pancreatitis. Aggressive treatment protocols combining neo-adjuvant chemoradiation and intra-operative radiation with surgery are being used to improve the prognosis in this dismal complication of chronic pancreatitis.

Chronic Disease↗
PubMed1996

Clinical evaluation of tooth-colored materials in cervical lesions.

PURPOSE: To determine the 18-month clinical performance of four tooth-colored restoratives in non-carious cervical lesions. MATERIALS AND METHODS: Buccal abrasion lesions in 83 teeth were restored with each of the following materials: Fuji Cap II, Fuji II LC, APH/Universal Bond 3, Lite Fil II A/Imperva Bond. Baseline and an 18-month recall was carried out using the Ryge (USPHS) method for retention, color match, marginal adaptation, cavosurface marginal discoloration, anatomic form and secondary caries. RESULTS: The USPHS results (% alfa) for the four products were, respectively: color match (9%, 48%, 57%, 55%), marginal discoloration (71%, 76%, 52%, 50%), marginal adaptation (24%, 24%, 33%, 15%), anatomic form (67%, 86%, 95%, 45%) and retention (100%, 95%, 100%, 65%). Results indicated that (1) Fuji Cap II exhibited a poor color match at baseline (2) Color matching of Fuji II LC was comparable to the resin composites and (3) seven Lite Fil II/Imperva Bond restorations (35%) were dislodged after 1 1/2 years.

Aged↗
PubMed1994

Anergic T cells as suppressor cells in vitro.

T cell-mediated suppression is an established phenomenon, but its underlying mechanisms are obscure. An in vitro system was used to test the possibility that anergic T cells can act as specific suppressor cells. Anergic human T cells caused inhibition of antigen-specific and allospecific T cell proliferation. In order for the inhibition to occur, the anergic T cells had to be specific for the same antigen-presenting cells (APCs) as the T cells that were suppressed. The mechanism of this suppression appears to be competition for the APC surface and for locally produced interleukin-2.

Antigen-Presenting Cells↗
PubMed1994

Transfected murine cells expressing HLA class II can be used to generate alloreactive human T cell clones.

Alloreactive human T cells are conventionally generated in vitro using peripheral blood mononuclear cells (PBMCs). The disadvantage of such an approach is that PBMCs express multiple HLA class II molecules and, as a consequence, it is difficult to generate T cells specific for an individual HLA alloantigen. This paper describes a technique in which T cell clones can be generated using stimulators which do express only one alloantigen. This has permitted the generation of HLA-DR-specific T cell clones and will be applied to produce T cell clones specific for other isotypes which cannot easily be obtained using other techniques. Murine DAP.3 cells were transfected with cDNAs encoding human class II molecules and used to stimulate primary alloresponses by purified human CD4+ T cells. The cloning of these T cells provided a good yield of cells allospecific for the class II molecule expressed by the transfected cells. A large percentage of the T cell clones were able to recognise human cells, suggesting that specificity for DR-bound peptides of mouse origin does not limit the applicability of this approach. Despite having been raised against mouse stimulators cells, the responses of the T cell clones to alloantigen-expressing human B cell lines were profoundly inhibited by anti-human LFA-3 monoclonal antibody. The possible mechanisms responsible for these results are discussed.

Animals↗
PubMed1994

Failure of correlation between B7 expression and activation of interleukin-2-secreting T cells.

It is well established that triggering interleukin-2 (IL-2) secretion by helper T cells requires the T cell to receive at least two discrete signals. One signal is transduced by the CD3 complex, usually as the result of T cell receptor (TcR) occupancy, the second, or co-stimulatory, signal involves a non-cognate interaction between cell surface accessory molecules on the antigen-presenting cell (APC) and the T cell. A molecular interaction that has been implicated in the provision of co-stimulatory signals is that between B7/BB1 on the APC and its ligands, CD28 and CTL-A4 on the T cell. We have studied the ability of HLA-class II antigen-positive human T cells and a population of DR1-expressing transfected human fibroblasts to stimulate a proliferative response by human T cell clones, and by freshly isolated peripheral blood T cells. Despite their high levels of B7 expression, the T cell clones, were unable to induce proliferation or IL-2 secretion by DR-restricted, antigen-specific T cells. In contrast, the DR1-expressing transfectants, that were B7 negative, induced a strong proliferative response. When these two populations of DR-expressing cells were used to stimulate a primary alloresponse the results were reversed, in that the T cell clones induced a strong alloresponse but the transfected fibroblasts induced no proliferation. These results suggest that the expression of B7 may be necessary for costimulation of unprimed T cells, but not of established T cell clones. Furthermore the data show that the expression of B7 by an APC does not necessarily lead to IL-2 production or protection from the induction of tolerance. The mechanisms responsible for the inability of these T cells to provide full activation signals when used as APC is currently under investigation.

Antigen-Presenting Cells↗
PubMed1994

The invariant chain inhibits presentation of endogenous antigens by a human fibroblast cell line.

The human fibroblast cell line, M1, expressing the products of transfected DRA and DRB1*0101 genes (M1-DR1) was unable to present intact influenza antigens to a series of DR1-restricted human T cell lines and clones, but was fully able to present synthetic peptides for T cell recognition. In contrast, M1-DR1 cells infected with live influenza virus were recognized by two polyclonal hemagglutinin- or whole virus-specific T cell lines and one of four T cell clones. This difference could not be accounted for simply by the ability of infectious virus to overcome a defect in antigen uptake by the M1-DR1 cells, in that direct studies of endocytosis showed that the M1 cells were more efficient than human B cells in the internalization of exogenous protein. These data suggested that the M1 cells were unable to present exogenous antigens but were capable of loading major histocompatibility complex (MHC) class II molecules with peptides derived from endogenous antigens. To investigate this further, the M1-DR1 cells were super-transfected with a cDNA encoding the p33 and p35 forms of the human invariant chain (Ii). Expression of the Ii chain was detected by intracytoplasmic staining of transfectants, and by metabolic labeling. Equimolar amounts of the p33 and p35 forms were detected, and the high level of p35 Ii was reflected by extensive retention of Ii protein in the endoplasmic reticulum. Addition of the Ii chain led to no recovery of presentation of intact antigens with DR1, but inhibited the presentation of live virus. These data indicate that MHC class II molecules in the M1-DR1 cells can be loaded with peptides derived from endogenous proteins, possibly in the biosynthetic pathway, and that the Ii chain has a role in limiting this route of class II antigen presentation.

Antigen Presentation↗
PubMed1994

Biased TCR gene usage in alloreactive T cells specific for a structurally dissimilar MHC alloantigen.

Two models of allorecognition of MHC molecules have been proposed. One emphasizes specificity for MHC molecule-bound peptides and the other for exposed MHC polymorphisms. We predicted that the latter model would predominate in responder:stimulator combinations whose MHC molecules differed extensively in their TCR-contacting surfaces and that this would be reflected in biased TCR usage. Two panels of anti-DR11 T cell clones were generated, one from a DR17 and the other from a DR15 responder. The TCR-contacting surfaces of DR17 and DR11 have multiple differences, and those of DR15 and DR11 are very similar. TCR analysis by polymerase chain reaction amplification and mAb staining revealed that five out of nine DR17 anti-DR11 clones used the V beta 13 and two the V beta 6, family. In contrast seven different V beta families were used by the eight DR15 anti-DR11 clones. A similar bias in TCR V beta usage was observed in the polyclonal DR17 and DR11 T cell lines from which the clones were derived, and in a second DR17 anti-DR11 line from a different individual. These results support the concept that specificity for the foreign MHC structure itself may play an important role in the alloresponse between responders and stimulators with structurally dissimilar MHC molecules.

Amino Acid Sequence↗
PubMed1994

Myoblasts fail to stimulate T cells but induce tolerance.

Recent interest in myoblast transfer and in the use of myoblasts as vehicles in gene therapy has made it important to understand the potential immunogenicity of allogeneic or neoantigen-expressing myoblasts. Given the problems of producing a pure population of myoblasts, in this study we used a tumour-derived muscle cell line (TE671), with phenotypic features of myoblasts, which we transfected to express HLA-DR1. However, this cell line was unable to stimulate either established HLA-DR1-specific allorective T cell clones or a primary alloresponse. Nor could it present haemagglutinin peptide HA 306-324 to DR1-restricted, HA 306-324-specific T cell clones or lines. Indeed, preincubation with DR1-expressing TE671 and HA 306-324 rendered such T cells tolerant as judged by their subsequent inability to proliferate in response to a DR1+ B cell line plus peptide HA 306-324. These results imply that myoblasts do not provide costimulatory signals, and are therefore unlikely to stimulate allospecific T cells following myoblasts transplantation or to initiate neoantigen-specific immune responses following in vivo transfection.

Antigen-Presenting Cells↗
PubMed1994

Pregnancy wastage in two tribal communities (Gujars and Bazigars) of Punjab, India.

The present report is an attempt to secure adequate data about pregnancy wastage in Gujar and Bazigar females of Punjab. Gujars in general are primarily cattle breeders and shepherds but Gujars of Punjab are farmers, too. In Punjab they mostly occupy the submountainous regions and riverline lowlands. Bazigar is a persian word meaning "he who does Bazi" or any sort of game or play but it is applied only to jugglers and acrobats. Bazigars are a gypsy tribe of vagrant habits. Most of them are now settled in the vicinity of large villages or towns. Analysis of reproductive histories of 250 Gujar females and 360 Bazigar females reveals that in the maternal age group 25-29 years, mothers experienced the least number of abortions and stillbirths. However, beyond this, the risk of pregnancy wastage increases with age. An overall rate of pregnancy wastage is 140.55 and 130.09 per 1000 pregnancies among Gujars and Bazigars of Punjab, respectively.

Abortion, Spontaneous↗