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Biomedical subjects

S Sidhu

Publications and source records attributed to S Sidhu.

At least 19 recordsLinked to original sources
PubMed2002

Fatty acid signalling in a mouse enteroendocrine cell line involves fatty acid aggregates rather than free fatty acids.

Fatty acids induce cholecystokinin (CCK) secretion both in humans and from murine enteroendocrine cell lines. In both cases, only fatty acids above a critical acyl chain length (C(10)) are capable of inducing a response. Using the enteroendocrine cell line STC-1, the aim of this study was to determine whether this acyl chain length dependency is related to the fact that longer chain fatty acids are relatively insoluble in aqueous solutions and, if so, whether it is insoluble aggregates of fatty acids rather than free fatty acids which evoke CCK secretion. Solutions of fatty acids (chain length C(8)-C(14)), which were judged by filtration and Zeta sizer measurement to contain no fatty acid aggregates, never evoked CCK secretion from STC-1 cells. Filtering fatty acid solutions (of chain length C(10), C(12) and C(14)) through polytetrafluoroethylene (PTFE) filters (0.45 microm pore size) revealed a narrow concentration range for each acid over which the amount of fatty acid removed from the solution increased sharply due to the formation of fatty acid aggregates. Filtration experiments, in which suspensions of C(10), C(12) and C(14) fatty acids were passed through pore sizes of 0.2, 0.45 or 1.2 microm, suggested that STC-1 cells did not respond to fatty acid aggregates of greater than 1.2 microm, while at least 50 % of the CCK response was mediated by aggregates which were smaller than 0.45 microm. Fatty acids induce CCK secretion from STC-1 cells by elevating intracellular Ca(2+) concentration ([Ca(2+)](i)). We therefore measured the effects on [Ca(2+)](i) of filtered C(10), C(12) and C(14) fatty acids. In all cases, [Ca(2+)](i) responses were closely correlated with CCK secretion. Interestingly, while filtrates of fatty acid solutions evoked CCK secretion and elevated [Ca(2+)](i), freshly prepared solutions of fatty acids at the same concentration as the filtrates did not. This suggested that fatty acid aggregates were not in equilibrium with the solvent after filtration. The observation that the ability of C(10), C(12) and C(14) filtrates to elevate [Ca(2+)](i) decayed with time was consistent with this hypothesis. Furthermore, sonication of the filtrates abolished their ability to elevate [Ca(2+)](i). These data further suggest that it is a physical property of the fatty acid solution (the presence of insoluble fatty aggregates) which is responsible for the observed cellular responses. We conclude that Ca(2+) mobilisation and CCK secretion in STC-1 cells is driven by a signal transduction mechanism that senses insoluble fatty acid aggregates, rather than free fatty acids in solution.

Animals↗
PubMed2001

Mapping protein-protein interactions with combinatorial biology methods.

Extremely diverse, DNA-encoded libraries of peptides and proteins have been constructed that include a linkage between each polypeptide and the encoding DNA. Library members can be selected by virtue of a particular binding specificity, and their protein sequence can be deduced from the sequence of the cognate DNA. Such combinatorial biology methods have proven invaluable in both identifying natural protein-protein interactions and also in mapping the specificities and energetics of these interactions in fine detail.

Amino Acid Sequence↗
PubMed2001

Initial experience of vocal cord evaluation using grey-scale, real-time, B-mode ultrasound.

BACKGROUND: To evaluate whether grey-scale, real-time, B-mode ultrasound (US) is a reliable alternative to nasopharyngoscopy for assessing vocal cord function post-thyroid and post-parathyroid surgery. METHODS: A prospective validation study was undertaken comparing grey-scale, real-time, B-mode vocal cord US with the standard of nasopharyngoscopy in 100 consecutive patients undergoing thyroid and parathyroid surgery between 1 February 1999 and 31 August 1999, with seven patients with known cord palsy. The sensitivity and specificity of grey-scale, real-time vocal cord US for the detection of vocal cord palsy when compared to the standard of nasopharyngoscopy was analysed. RESULTS: In the postsurgical group, there were six nerves (3.2% of the nerves at risk) transient and no permanent vocal cord palsies. US identified four of six transient palsies and reported two false negatives and three false positives. US identified four of seven cord palsies in the non-surgical group with known cord palsy. Analysis of the 107 combined patients showed US had sensitivity of 62% (8/13), specificity of 97% (91/94), a positive predictive value of 73% (8/11) and a negative predictive value of 95% (91/96) for detecting cord paralysis compared to the standard of nasopharyngoscopy. CONCLUSION: Despite the enthusiasm of earlier reports, our initial experience with grey-scale, real-time, B-mode US suggests it is not a reliable alternative to nasopharyngoscopy for assessing vocal cord function post-thyroid and post-parathyroid surgery. Further recruitment of patients with known vocal cord palsy is required to confirm or refute these initial impressions.

Female↗
PubMed2000

Thyroid pathology associated with primary hyperparathyroidism.

BACKGROUND: Thyroid carcinoma and benign thyroid disease associated with primary hyperparathyroidism (PHPT) have been well described. With the developing trend toward minimally invasive parathyroidectomy without intra-operative thyroid gland palpation, thyroid pathology may be missed. The authors consider it timely to revisit the issue of thyroid pathology found at neck exploration for PHPT. METHODS: A retrospective review of all cases of neck exploration for PHPT between 1993 and 1998 at Liverpool Hospital was undertaken. RESULTS: There were 65 patients in the study group (44 women, 21 men; mean age: 59 years). The most common indication for surgery was asymptomatic hypercalcaemia. The mean pre-operative calcium level was 2.9 mmol/L and the mean parathyroid hormone (PTH) level was 17 pmol/L. There were 26 cases (40%) of coexistent thyroid pathology. Ten cases (15%) were of mild multinodular change, seven cases (11%) were of severe multinodular change requiring thyroidectomy, three cases (4%) were nodules secondary to Hashimoto's thyroiditis and six cases (10%) were suspicious nodules that proved to be either adenomas (n = 3) or carcinomas (n = 3) following excision. There were four papillary carcinomas detected in the present series with a mean metastases, age, completeness of excision, invasion size (MACIS) score of 4.92. CONCLUSION: A 25% association of significant thyroid pathology with PHPT is reported. Despite pre-operative tests there were two cases (4%) of thyroid carcinoma where the decision to resect the thyroid gland was made following intra-operative thyroid gland palpation. One of these two papillary carcinoma patients would have fulfilled criteria for minimally invasive parathyroid surgery. When evaluating results of minimally invasive parathyroid surgery one must be aware of the potential for missed thyroid pathology.

Adult↗
PubMed2000

Prospective evaluation of morphology, function, and quality of life after extracorporeal shockwave lithotripsy and endoscopic treatment of chronic calcific pancreatitis.

OBJECTIVE: Therapeutic endoscopy may be effective in selected patients with chronic calcific pancreatitis (CCP). We prospectively evaluated the early outcome of extracorporeal shockwave lithotripsy (ESWL) in combination with interventional endoscopy, using broad inclusion criteria. METHODS: A total of 48 consecutive patients (35 male, 13 female) were recruited for ESWL and endoscopic therapy of symptomatic CCP. Symptoms, quality of life, pancreatic morphology and function were assessed before and after. RESULTS: Multiple stones (n = 43), strictures (n = 34), and pancreas divisum (n = 11) were found. A median of 13 ESWL sessions (range 2-74) with a median of 22,100 shockwaves (1,700-150,900) were required. Endoscopic pancreatic sphincterotomy (n = 48), stricture dilation (n = 12), and/or stenting (n = 27) were performed. After therapy, drainage of the pancreatic duct system was achieved in 36, complete stone clearance in 21 patients. Follow-up (n = 38) at 7 months (range 5-9) showed a significant decrease in pancreatic duct diameter (p < 0.001) and pain score (p < 0.0001) whereas complete pain relief was observed in 45% of cases. Several quality of life scores improved significantly. Weight gain occurred in 68% of patients. Normalization of fasting blood glucose and HbA1c levels were observed in four patients, without modifying their treatment. Improvement in pain score correlated with weight gain and decrease in pancreatic duct diameter. Nonalcoholic etiology was associated with a better chance for improvement in pain score and decrease in pancreatic duct diameter. The presence of strictures did not deteriorate the clinical outcome. CONCLUSIONS: Besides pain relief, ESWL in combination with interventional endoscopy resulted in pancreatic ductal decompression, weight gain, and improvement in quality of life in a considerable number of patients with advanced CCP.

Calculi↗
PubMed1999

Amoxycillin-induced flexural exanthem.

We describe a 37-year-old man who developed an acute, inflammatory flexural eruption shortly after taking amoxycillin, then erythema multiforme-like lesions on the palms and soles. The eruption resolved with systemic corticosteroids, and positive patch tests with amoxycillin supported a drug-induced aetiology. A few similar cases have been described as the 'baboon syndrome' or intertriginous drug eruptions. We draw attention to this rare, distinctive drug eruption.

Adult↗
PubMed1998

Protection of DNA in HL-60 cells from damage generated by hydroxyl radicals produced by reaction of H2O2 with cell iron by zinc-metallothionein.

Scavenging of hydroxyl radicals (.OH) by the zinc form of metallothionein (ZnMT) was studied in HL-60 cells and in nuclei from such cells previously treated with ZnCl2 (ZnMT cells). Cells were grown for 48 h to label DNA for alkaline elusion experiments. During the last 24 h 0.1 mM ZnMT was included to induce ZnMT. Generation of DNA single-strand breaks (SSBs) by H2O2 in cells (5 x 10(5)/ml) treated at 4 degrees was increased by approximately 70% in Zn-treated cells by comparison with control cells. These cells had grown from an initial concentration of 5 x 10(5)/ml to a concentration at harvest of 16 x 10(5)/ml. Cells started at 6 x 10(5)/ml and growing to a final concentration of 20 x 10(5)/ml did not exhibit a similar increase in SSBs. This elevation in SSBs was traced to an increase in cell Fe content which exhibited a sharp dependence upon concentrations of cells and of ZnCl2 at the time of addition. The diffusion distance (d) from Fe to DNA of ZnMT cells treated with H2O2 was found to be 3.4 nm. This compares with a distance of 6.1 nm in control cells. SSB generation by hydroxyl radicals formed by 137Cs-gamma rays in Zn-treated cells decreased by 12%, accompanied by a decrease in d from 4.8 nm to 2.9 nm. Thus, ZnMT preferentially reacts with OH formed at some distance from DNA. In nuclei isolated from ZnMT cells started at 5 x 10(5)/ml, SSB generation by H2O2 increased by 60%. The d in these nuclei was 4.9 nm, similar to the distance in control nuclei reported previously. These data suggest that, in addition to altering the scavenging environment, treatment of cells with Zn leads to an increase in reactive Fe in cells and in isolated nuclei which can generate DNA damage through reaction with H2O2.

Antioxidants↗
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↗