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Biomedical subjects

S Islam

Publications and source records attributed to S Islam.

At least 37 records · Page 2Linked to original sources

Parathyroid hormone-related peptide: expression in prostate cancer bone metastases.

Parathyroid hormone-related peptide (PTHrP) is a regulatory protein associated with cell growth in non-osseous tissues and with osteoclast stimulation in bone. It has been implicated in the pathogenesis of bone metastases, particularly in breast carcinoma. PTHrP is widely expressed in primary prostate cancers, but there are few reports of its expression in prostatic metastases. The aim of this study was to examine the expression of PTHrP in bone metastases from patients with untreated adenocarcinoma of the prostate. Ten bone biopsies containing metastatic deposits of untreated prostatic cancer were identified. These were immunohistochemically stained for PTHrP using a murine monoclonal antibody (PTHLP[Ab1]) and the streptavidin-biotin complex technique. Intensity of staining for PTHrP was graded by two observers. In total, PTHrP expression was positive in 5/10 specimens. This was graded as moderate in four and weak in one. In those specimens with positive staining, the expression varied between cells. There was no obvious association between expression of PTHrP and tumour differentiation. PTHrP is expressed in prostatic bone metastases and may have a role in their pathogenesis and pathophysiology. However, expression is not universal.

Adenocarcinoma↗

Socio-economic aspects of areca nut use.

The socio-economic aspects of areca nut consumption have been overlooked. A narrative review was conducted to establish some of these features of areca nut consumption. Medline, Pubmed and the World Wide Web were searched using the terms: areca nut, betel nut, areca catechu and pan masala. Further analysis was conducted of datasets describing aspects of United Kingdom areca nut sales and consumption. South Asian economies at different stages of development have varying areca nut cultivation practices, employment opportunities and marketing strategies. Attempts at regulation of areca nut import and sales are described. Retail practice among the South Asian communities of the United Kingdom was found to reflect the diverse consumer practices current in their countries of origin. A study of areca nut consumption patterns and motivations among Bangladeshi women resident in East London identified differences between those chewing areca nut in paan with and without tobacco. Further research into the socio-economic aspects of areca nut consumption is needed which should be multidisciplinary in focus, of sound scientific quality and incorporating the opinions of consumers.

Adolescent↗

Suspected testicular torsion: a survey of clinical practice in North West England.

Several aspects of the management of suspected testicular torsion are controversial. A questionnaire was mailed to all 33 consultant urologists in the North West region of England to elicit their policies for routine clinical management. 29 of 33 questionnaires were returned (2 incomplete). As regards radiological investigation, 4 consultants always request ultrasound examination; the others do not favour routine imaging. When the diagnosis of testicular torsion is confirmed at operation, all consultants would perform bilateral testicular fixation, although with considerable variations in technique; most use Vicryl sutures (66%) and three-point fixation (57%). One-third would do an ipsilateral orchidopexy if there was no clear evidence of testicular torsion at operation. The variation revealed by this survey prompted an attempt to formulate a protocol for management. A review of the published work indicates that, in cases of proven testicular torsion, treatment should include bilateral fixation with delayed-absorption or non-absorbable sutures; fixation should be at three points. When torsion is not found at operation, there is no evidence of benefit from orchidopexy.

England↗

Expression profile of protein tyrosine kinase genes in human osteoarthritis chondrocytes.

OBJECTIVE: To determine the expression profile of protein kinase (PK) and protein tyrosine kinase (PTK) genes in human primary osteoarthritis (OA) chondrocytes and to compare it with that of immortalized human chondrocytes T/C 28a4 with a view to learning whether T/C 28a4 cells can be used for elucidating signal transduction pathways in human chondrocytes. DESIGN: We used the Atlas Human cDNA Array and a method based on PCR with degenerate primers to analyse the expression profile of protein kinase genes in primary human OA chondrocytes and compared it with that of immortalized human chondrocyte cell line T/C 28a4 using RT-PCR and Western blotting. RESULTS: A total of 21 PTK genes were identified and several of these have never been shown to be expressed in human OA chondrocytes. Comparative expression analysis of some selected kinase genes showed that the mRNA expression pattern of many protein kinase genes in OA chondrocytes was identical to that of T/C 28a4 cells. However, there were differences in the level of protein expression of selected protein kinases in these cells. For example, mRNA expression of the novel kinase HCK was detected in OA chondrocytes and in the cell lines analysed but by Western blotting HCK protein was not detected in OA chondrocytes. In these studies, we also identified a novel mutant form of the discoidin domain receptor 2 (DDR2) transcript from chondrocyte-like cell line HTB-94. CONCLUSIONS: Our results provide novel information about protein kinase gene expression in OA chondrocytes and indicate that the transformed chondrocyte cell line T/C 28a4 may be suitable for elucidating signal transduction pathways in chondrocytes and to investigate how they regulate chondrocyte function in inflammatory and degenerative joint diseases.

Blotting, Western↗

Nonfixation of an atretic colon predicts Hirschsprung's disease.

PURPOSE: After noting the colon to be nonfixed and coiled in the pelvis of a patient with colonic atresia and total colonic Hirschsprung's disease, the authors sought to determine whether this colonic position might be predictive of aganglionosis in the atretic colon. METHODS: The authors reviewed all cases of colonic atresia treated in their institution over the past 2 decades with regard to colonic orientation and the presence of aganglionosis. RESULTS: We identified 9 patients with colonic atresia. Two of these patients, as well as one patient with ileal atresia, also had long-segment Hirschsprung's disease. All 3 of these patients had foreshortened nonfixed colons located predominantly in the pelvis. None of the other 6 patients with colonic atresia had this configuration. Reviewing 12 reported cases from other institutions of total colonic aganglionosis associated with atresia, 7 appear to have had a pelvic nonfixed colon; colonic orientation could not be determined from the remaining reports. The diagnosis of Hirschsprung's disease was not established in any case before repair of the atresia, and each patient required a secondary enterostomy. CONCLUSIONS: An early gestational atresia, occurring before secondary retroperitoneal fixation of the colon at approximately 11 weeks may result in interruption of caudal migration of enteric nerves manifesting as Hirschsprung's disease distal to the atresia. Moreover, the aganglionosis may be predicted by a foreshortened, nonfixed colon coiled in the pelvis. Thus, biopsy of the colon should be performed at initial exploration in all cases of atresia in which the colon is not properly fixated to avoid immediate or delayed anastomosis to an aganglionic colon.

Colon↗

Tracheal resection and reanastomosis in the neonatal period.

BACKGROUND/PURPOSE: Severe congenital tracheal stenosis is rare. Most of these can be managed conservatively before elective repair. Focal tracheal stenosis has been treated with resection of the involved trachea and primary reanastomosis in older infants. The authors found no reports of repair of this lesion in neonates. Two patients are presented with severe respiratory failure on the first day of life that required extracorporeal life support (ECLS) who underwent successful tracheal resection and reanastomosis (TRR) during the first week of life. METHODS: A retrospective review was conducted. RESULTS: Both babies had severe pulmonary hypertension and carbon dioxide retention despite maximal therapy and were placed on ECLS shortly after transfer. One had an isolated stenosis of the upper trachea, and the other had agenesis of the right lung, esophageal atresia with tracheoesophageal fistula, and a tracheal stenosis at the end of a short trachea with a long, narrow left bronchus. Both underwent diagnostic studies and had surgical repair while on ECLS at day 3 and 7 of life without bleeding complications. They were weaned off ECLS 1 and 8 days after surgery. One patient was extubated and did well. The other was extubated transiently, but required a tracheostomy because of left mainstem bronchomalacia. Both are alive and well at 18 and 38 months of age, with no narrowing of the repairs. CONCLUSION: In the setting of severe respiratory failure requiring ECLS support, TRR can be performed safely and successfully in the neonate with focal tracheal stenosis.

Anastomosis, Surgical↗

Decreased mitogen activated protein kinase activities in congenital diaphragmatic hernia-associated pulmonary hypoplasia.

BACKGROUND/PURPOSE: The mechanisms that cause pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) currently are unknown. The authors proposed that the reduced size and immaturity of these lungs may be associated with differences in the levels of mitogen activated protein (MAP) kinase phosphorylation (extracellular signal regulated protein kinases, ERK-1 and -2). METHODS: ERK-1 activities were measured using immune-complex kinase assays on fetal whole-lung lysates obtained from both nitrofen and olive oil-treated (control) pregnant rats. In addition, ERK-1 and ERK-2 functional activities were estimated by semiquantitative Western blot analysis, using an antibody specific for the diphosphorylated (dp-ERK, activated) forms of the enzymes. RESULTS: ERK-1 activities, measured using immune-complex kinase assays, were reduced in CDH lungs compared with olive oil-treated controls (P <.02). In addition, dp-ERK-1 and dp-ERK-2 levels were found to be reduced in CDH lungs compared with controls (dp-ERK-1, P =.003; dp-ERK-2, P =.04), whereas ERK-1 and ERK-2 protein levels were unchanged. CONCLUSIONS: The lower values of ERK-1 activity and reduced amounts of dp-ERK-1 and dp-ERK-2 in lung tissue from CDH animals, suggests that ERK-1 and ERK-2 activities are reduced in pulmonary hypoplasia associated with CDH. The observed reduction in ERK-1 and ERK-2 activities implicates attenuated cell signaling upstream of the ERK-1 and -2 enzymes.

Animals↗

A sustainable community-based arsenic mitigation pilot project in Bangladesh.

A sustainable community-based arsenic mitigation pilot project has been successfully operating for 22 months in the Chapainawabganj arsenic hot spot (Bangladesh) where safe treated drinking and cooking water derived from tubewells is being supplied below the Bangladesh maximum permissible limit (0.05 ppm total arsenic). There has been close community involvement in all stages and the arsenic removal mechanism used adapted from the simple process of adsorption by natural ferric oxyhydroxide. Supplemented ferric oxyhydroxide produces daily de-contaminated water batches until replaced at the end of the cycle. A regional renewal/recycling centre supplies new, and safely stores used, ferric oxyhydroxide. Recycling is beginning where adsorbed arsenic can be separated prior to ferric oxyhydroxide reuse. The mechanism is flexible regarding water volumes, cycle lengths, pre and post-treatment arsenic concentrations, tubewell chemistries and is cost-effective. Pilot project parameters were set at 60 l per day ( < 0.05 ppm total arsenic) and 16 day cycles per tank for each of the four selected families with pretreatment concentrations up to 1.1 ppm. A maximum of ~ 24 g of arsenic is produced from the approximately 900 g (dry) of ferric oxyhydroxide used per tank per year. Anecdotal evidence possibly suggests positive health effects within a few months and villagers report an improved water taste. The project should contribute to coping with such arsenicosis crises and expansion is planned.

Arsenic↗

Increased nitrite and nitrate concentrations in sera and urine of patients with cholera or shigellosis.

OBJECTIVES: Nitric oxide (NO) is an important regulator of cell function. In the intestine, NO regulates blood flow, peristalsis, secretion, and is associated with inflammation and tissue injury. The objectives of this study were to assess and compare the role of NO in cholera, a noninflammatory enteric infection, and in shigellosis, a bacterial inflammation of the colon. METHODS: We determined serum and urinary concentrations of nitrite and nitrate during acute illness and early convalescence in 45 hospitalized children: 24 with cholera and 21 with shigellosis; 18 healthy children served as controls. Nitrite and nitrate concentrations were determined spectrophotometrically using Greiss reaction-dependent enzyme assay. RESULTS: Serum nitrite and nitrate concentrations were significantly (p < 0.05) increased during acute illness compared to the early convalescence in both cholera and shigellosis. Urinary nitrite and nitrate excretions were significantly (p < 0.01) increased during acute disease in shigellosis, but not in cholera. Nitrite concentrations correlated with stool volume (r2 = 0.851) in cholera and with leukocytosis (r2 = 0.923) in shigellosis. CONCLUSIONS: Both cholera and shigellosis are associated with increased production of NO, suggesting its pathophysiologic roles in these diseases.

Acute Disease↗

N-Cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility.

E- and N-cadherin are members of the classical cadherin family of proteins. E-cadherin plays an important role in maintaining the normal phenotype of epithelial cells. Previous studies from our laboratory and other laboratories have shown that inappropriate expression of N-cadherin by tumor cells derived from epithelial tissue results in conversion of the cell to a more fibroblast-like cell, with increased motility and invasion. Our present study was designed to determine which domains of N-cadherin make it different from E-cadherin, with respect to altering cellular behavior, such as which domains are responsible for the epithelial to mesenchymal transition and increased cell motility and invasion. To address this question, we constructed chimeric cadherins comprised of selected domains of E- and N-cadherin. The chimeras were transfected into epithelial cells to determine their effect on cell morphology and cellular behavior. We found that a 69-amino acid portion of EC-4 of N-cadherin was necessary and sufficient to promote both an epithelial to mesenchymal transition in squamous epithelial cells and increased cell motility. Here, we show that different cadherin family members promote different cellular behaviors. In addition, we identify a novel activity that can be ascribed to the extracellular domain of N-cadherin.

Breast Neoplasms↗

Involvement of caspase-3 in epigallocatechin-3-gallate-mediated apoptosis of human chondrosarcoma cells.

Green tea polyphenol-(-)epigallocatechin-3-gallate (EGCG)-is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis. In this study we describe a novel observation that EGCG displayed strong inhibitory effects on the proliferation and viability of HTB-94 human chondrosarcoma cells in a dose-dependent manner and induced apoptosis. Investigation of the mechanism of EGCG-induced apoptosis revealed that treatment with EGCG resulted in DNA fragmentation, induction of caspase-3/CPP32 activity, and cleavage of the death substrate poly(ADP-ribose)polymerase (PARP). Pretreatment of cells with a synthetic pan-caspase inhibitor (Z-VAD-FMK) and a caspase-3-specific inhibitor (DEVD-CHO) prevented EGCG-induced PARP cleavage. The induction of apoptosis by EGCG via activation of caspase-3/CPP32-like proteases may provide a mechanistic explanation for its antitumor effects.

Antineoplastic Agents↗

Vimentin expression in human squamous carcinoma cells: relationship with phenotypic changes and cadherin-based cell adhesion.

Phenotypic changes resembling an epithelial-to-mesenchymal transition often occur as epithelial cells become tumorigenic. Two proteins that have been implicated in this process are vimentin and N-cadherin. In this study, we sought to establish a link between expression of vimentin and N-cadherin as oral squamous epithelial cells undergo a morphologic change resembling an epithelial-to-mesenchymal transition. We found that N-cadherin and vimentin did not influence the expression of one another.

Animals↗

Tumour necrosis factor alpha enhances the expression of hydroxyl lyase, cytoplasmic antiproteinase-2 and a dual specificity kinase TTK in human chondrocyte-like cells.

Tumour necrosis factor alpha (TNF-alpha) is a cytokine with pleiotropic effects on cells ranging from proliferation to apoptosis. These biological effects of TNF-alpha are believed to be elicited by the induction or enhancement of the expression of TNF-alpha responsive genes in the target cells. TNF-alpha is pro-inflammatory and a principal mediator in the pathogenesis of arthritis. The activation of an inflammatory cascade by TNF-alpha in arthritis results in the degradation of cartilage, joint destruction and loss of function. Because TNF-alpha is an important mediator in the pathogenesis of arthritis, the present study addresses the identification of novel TNF-alpha responsive genes in HTB-94 cell line which is of human origin and maintains a chondrocytic phenotype. The three identified cDNAs were previously not known to be induced or upregulated by TNF-alpha in chondrocytes or cells of chondrocytic lineage. One of the identified cDNAs had sequence similarity to human hydroxyl lyase mRNA (PLOD), an enzyme involved in collagen biosynthesis and its metabolism; the second cDNA had sequence similarity to the human cytoplasmic anti-proteinase-2 mRNA (CAP-2), a member of a group of proteins shown to be associated with protecting cells from TNF-alpha-induced apoptosis; and the third cDNA had sequence similarity to a dual specificity kinase, TTK, which is associated with cell proliferation. Relative gene expression level analysis by PCR and by Northern blotting revealed that treatment with TNF-alpha enhanced the expression of PLOD, CAP2 and TTK transcripts which confirmed the results obtained with display gels. Furthermore, TTK mRNA expression was also induced in human articular chondrocytes treated with TNF-alpha but not in untreated chondrocytes. Our results suggest that these genes may play a role in chondrocytic responses to TNF-alpha-mediated stimuli affecting the cartilage homeostasis.

Base Sequence↗

Sensory neuropathy in the prodromal phase of hepatitis A and review of the literature.

We report an unrecognized clinical presentation of hepatitis A with unilateral peripheral acute sensory loss in the prodromal phase of the illness. Although rare, focal neurological signs are known to occur in hepatitis A before, during and after the icteric phase; a pure peripheral sensory neuropathy is distinctly uncommon. Possible lesions could include radiculopathy of the lower thoraco-lumbo-sacral dorsal nerve roots or a partial transverse myelitis of Brown-Séquad like distribution. The signs and symptoms lasted only a few days and the patient had an uneventful recovery.

Adult↗

Insufficient penetration of systemic vancomycin into the PermCath lumen.

BACKGROUND: Catheter infection is a major cause of morbidity and catheter loss in chronic haemodialysis patients. There has been a large discrepancy in the catheter salvage rate, after an episode of documented bacteraemia, whether the patients receive systemic antibiotic alone or systemic antibiotics concomitant with 'antibiotic-lock technique' (20-30% vs 100%, respectively). To test the hypothesis that vancomycin may not adequately penetrate into the lumen of the catheter, despite therapeutic plasma levels, a series of in-vivo, ex-vivo, and in-vitro experiments were performed. METHODS: We compared serum and intralumenal (0.3-0.5 ml aspirate from venous port of the catheter) vancomycin concentrations in 24 chronic haemodialysis patients, with documented bacteraemia, who had received prior systemic vancomycin therapy with 14 similar patients who had additionally received 'vancomycin-lock technique' (100 microg/ml of vancomycin in heparin solution) after each haemodialysis session. RESULTS: Despite serum vancomycin concentration of approximately 17 microg/ml in each group, the vancomycin concentration in the venous hub of the catheter was only 0.2+/-0.6 microg/ml in the former group, in sharp contrast to 125. 6+/-13 microg/ml in the latter group. In the ex-vivo experiment, four uninfected PermCaths which had been removed were immediately fixed and studied with scanning electron microscopy. No cellular or fibrin barrier could be found at the terminal pore of the catheter interfering with the diffusion of vancomycin from plasma into the catheter lumen. In the in-vitro experiments, three PermCaths filled with standard heparin solution were incubated for 48 h in 100 ml of plasma containing 20 microg/ml of vancomycin. Vancomycin concentration was measured in 0.3-0.5 ml solution aspirated from each port of the catheters. Vancomycin concentration was 0.2+/-0.1 microg/ml in the aspirated samples. Finally, two PermCaths filled with the standard heparin solution were incubated for 48 h in 100 ml of plasma containing 20 microg/ml of vancomycin, after which the catheters were sectioned at 4-cm intervals. Only the distal 4 cm of the catheters had vancomycin concentrations of 2 and 5 microg/ml, the remaining segments had levels </=0.5 microg/ml. CONCLUSION.: Our results indicate that diffusion of vancomycin from plasma into the haemodialysis catheter is negligible. Thus, haemodialysis patients with central venous catheter who have to be treated for bacteraemia with systemic antibiotic therapy must always receive 'antibiotic-lock technique' of the catheter after each haemodialysis session.

Anti-Bacterial Agents↗

Do obese inner-city children with asthma have more symptoms than nonobese children with asthma?

OBJECTIVE: To test whether obesity is associated with decreased peak expiratory flow rates (PEFR), increased asthma symptoms, and increased health service use. DESIGN/METHODS: Secondary analysis of data from a cross-sectional convenience sample. SETTING: Emergency departments (EDs) and primary care clinics in 8 inner-city areas in 7 cities. PARTICIPANTS: One thousand three hundred twenty-two children aged 4 to 9 years with asthma. MEASURES: Obesity was defined as a body mass index (BMI, weight/height(2)) >95th percentile. Nonobese children were those with a BMI between the 5th and 95th percentile. Underweight children with a BMI <5th percentile were eliminated from the study. Demographic and anthropometric data were obtained during a baseline interview with the primary caretaker and the child. Symptoms, health service use data and measurements of PEFR were obtained by parental report during the baseline interview and at 3-month intervals by telephone interview over the following 9-month period. RESULTS: Obese (n = 249) and nonobese (n = 1073) children did not differ in terms of age, gender, family income, passive smoke exposure, caretaker's mental health, and skin test reactivity to indoor allergens. Obese children were more often Latino (28% vs 17%) and, in the 3 months before the baseline interview, were more likely to have used oral steroids (30% vs 24%). There were no differences between groups in terms of baseline PEFR scores. During the 9 months after baseline assessment, the obese group had a higher mean number of days of wheeze per 2-week period (4.0 vs 3.4), and a greater proportion of obese individuals had unscheduled ED visits (39% vs 31%). There were no differences between the groups in terms of frequency of hospitalization, or in nocturnal awakening. CONCLUSIONS: In our sample of inner-city children with asthma, obese children used more medicine, wheezed more, and a greater proportion had unscheduled ED visits than the nonobese children.

Asthma↗