Pyrexia, pelvic pain and thrombocytopenia in an Asian man with Paget's disease of bone.
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Bangladesh↗
Biomedical subjects
S Arif
Publications and source records attributed to S Arif.
Abolish C3.
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Ambulatory Care Facilities↗
Promiscuous binding of proinsulin peptides to Type 1 diabetes-permissive and -protective HLA class II molecules.
AIMS/HYPOTHESIS: Presentation of peptide epitopes derived from beta-cell autoantigens, such as insulin and its precursor molecules, by MHC class II molecules to autoreactive T-cells is believed to play a role in the development of Type 1 diabetes. However, little is known about the interaction between peptides of (prepro)insulin and MHC class II molecules permissive and protective for Type 1 diabetes. In this study therefore, peptides spanning the human preproinsulin sequence were assessed for their binding characteristics to Type 1 diabetes-protective and -permissive HLA molecules. METHODS: HLA-DR2, -DQ6.2 (Type 1 diabetes-protective) and HLA-DR4, -DQ8 (Type 1 diabetes permissive) molecule binding affinity for overlapping synthetic 20mer peptides spanning human preproinsulin was measured in a direct competition binding assay against a biotinylated indicator peptide. RESULTS: All HLA molecules tested showed similarity in their binding characteristics across the preproinsulin molecule, with regions of the insulin A-chain showing the highest affinity and C-peptide regions the lowest affinity for all HLA molecules tested. Furthermore, an insulin peptide implicated as a major CD4+ T-cell target in disease pathogenesis (B9-23) had high affinity binding to both protective and permissive HLA molecules but did not represent the highest affinity region of (prepro)insulin identified in either case. CONCLUSION/INTERPRETATION: The results suggest that peptide binding affinity alone is unlikely to be the major determinant of disease susceptibility in relation to interactions between (prepro)insulin epitopes and HLA molecules. The identification of epitopes derived from beta-cell autoantigens that bind promiscuously to diabetes-permissive HLA molecules could be important in the design of peptide-based immunotherapeutic strategies for the prevention of Type 1 diabetes.
Diabetes Mellitus, Type 1↗
Impact of microscopic extranodal tumor deposits on the outcome of patients with rectal cancer.
PURPOSE: Microscopic mesorectal soft tissue extranodal deposits discontinuous with the primary tumor are identified in many rectal adenocarcinomas. Current guidelines consider them to be involved lymph nodes. We studied the impact of these deposits on the outcome of patients with rectal cancer. METHODS: This was a retrospective study, in which histology slides were reviewed from 55 patients whose resection specimens for rectal cancer were staged as Dukes C or Dukes B with extranodal deposits. Twenty-nine patients had extranodal deposits (19 males), and 26 control patients had lymph node involvement only (14 males). Patient outcome was analyzed in terms of local and systemic control and survival. RESULTS: Distant metastases were diagnosed earlier in patients with extranodal deposits (mean, 14 months) compared with controls (mean, 37 months; P = 0.001). On follow-up, 31.03 percent (9/29) from the extranodal deposit group developed liver metastases compared with 11.5 percent (3/26) of the control group (P = 0.08). Local recurrence was seen in 17.2 percent of patients from the extranodal deposit group and 3.8 percent of the control group (P = not significant). Cancer-related mortality was higher in the extranodal deposit group (16 vs. 7 patients; P = 0.09). The three-year actuarial survival was 48.27 percent in patients with extranodal deposits and 65.38 percent in those without. A significant association was noted between the number of extranodal deposits and intramural vascular invasion (P = 0.017), extramural vascular invasion (P = 0.039), perineural invasion (P = 0.039), and lymph node involvement (P = 0.008). CONCLUSION: These data suggest that extranodal deposit is a distinct form of metastatic disease in patients with rectal cancer. The association with vascular invasion and earlier development of metastases probably infers that a significant proportion of extranodal deposits may represent blood-borne spread. These tumor foci should be considered as indicators of poor prognosis.
Adenocarcinoma↗
Hashimoto's thyroiditis shares features with early papillary thyroid carcinoma.
Neoplastic transformation is a multistep process that results in a continuous spectrum from the normal (physiological) state to a fully established neoplasm. The gold standard for diagnosis of papillary thyroid carcinoma is conventional histology, the essential element being the characteristic nuclear features, regardless of whether papillary structures are present or not. However, other criteria are being used increasingly in the diagnosis of neoplasms, including immunohistochemical staining and molecular profile. The RET/PTC gene rearrangement is highly specific for papillary thyroid carcinoma and is associated with the characteristic nuclear features seen in papillary thyroid carcinoma. There is an overlap in the morphological features, immunohistochemical staining pattern, and most importantly, molecular profile between papillary thyroid carcinoma and Hashimoto's thyroiditis. Although considered a 'benign' condition, Hashimoto's thyroiditis almost always harbours a genetic rearrangement that is strongly associated with and is highly specific for papillary thyroid carcinoma. Submicroscopic foci of papillary thyroid carcinoma must be present in Hashimoto's thyroiditis, although the clinical behaviour is still benign. Further studies are required to predict which foci will progress to papillary thyroid carcinoma.
Carcinoma, Papillary↗
3 beta hydroxysteroid dehydrogenase autoantibodies in patients with idiopathic premature ovarian failure target N- and C-terminal epitopes.
The steroid cell enzyme 3 beta hydroxysteroid dehydrogenase (3 beta HSD) has been identified as a target of steroid cell autoantibodies, and autoantibodies to this enzyme are present in patients with premature ovarian failure and patients with autoimmune polyendocrine syndrome 1. The aim of the present study was to develop a radioligand binding assay for 3 beta HSD autoantibodies and to exploit this to examine regions of the molecule targeted by autoantibodies. We generated a construct of 3 beta HSD coupled to a luciferase fusion partner in order to maximize the yield of (35)S-radiolabeled protein. Labeled 3 beta HSD was then immunoprecipitated and the autoantibodies quantified by phosphoimaging. Autoantibodies to 3 beta HSD were detected in 12 of 100 (12%) idiopathic premature ovarian failure patients and 0 of 103 (0%) healthy age-matched controls (P < 0.0001). Three overlapping fragments of 3 beta HSD cDNA were cloned downstream of luciferase to examine autoantibody binding sites. Two of nine sera with 3 beta HSD autoantibodies (22%) displayed reactivity to the N terminus of 3 beta HSD, and seven (77%) showed reactivity to the C terminal; no sera reacted with the middle region. Our study demonstrates a markedly enhanced disease specificity of autoantibodies to 3 beta HSD detected using this novel assay and shows that distinct regions of the molecule are targeted.
3-Hydroxysteroid Dehydrogenases↗
The skin we are in--knowledge and practices regarding skin cancer in pre-clinical medical students.
OBJECTIVE: To assess the level of knowledge about skin cancer in youth and to explore the influence of gender and system of education on their knowledge and practices. MATERIALS AND METHODS: A questionnaire-based study was conducted at The Aga Khan University Medical College (AKUMC), on Year 2 pre-clinical medical students. Descriptive analyses to examine the frequency distribution, chi-square test and factor analysis were applied using SPSS. RESULTS: Seventyone students participated in the study; 90% scored > 55% in the questions regarding knowledge of Malignant melanoma (MM), whereas in the questions assessing practice only 11% of the respondents scored > 52%. They were largely unaware that appearance of a new mole is a risk factor for MM (56% respondents incorrect) and that skin cancer is one of the most common cancers (54% respondents incorrect). 73% reported being sunburned at least once during childhood and 40% suffered sunburns at least once this summer, which points to the inadequacy of sun protection. The risk of MM may double if severe sunburns are experienced during childhood. Education system and gender did not affect the knowledge and practices. The popular sources of learning about skin cancer were magazines (52%) followed by television (42%). CONCLUSION: There is a need for epidemiological studies in Pakistani population regarding skin cancer. For preventing excessive solar exposure which leads to sunburns, we recommend interventions like a Pilot Program for photoprotection education and Sun Awareness Week to improve knowledge and sun protection behavior.
Adolescent↗
T-Cell reactivity to the P2C nonstructural protein of a diabetogenic strain of coxsackievirus B4.
Enteroviruses are proposed as initiating factors in the etiology of Type 1 diabetes mellitus (Type 1 DM). Molecular mimicry between the autoantigen glutamic acid decarboxylase 65 (GAD65) and the coxsackievirus B4 (CVB4) nonstructural protein P2C is frequently cited as a mechanism by which this virus triggers the disease, but little is known about the immunogenicity of this viral protein in humans, mainly due to the problem of obtaining highly pure preparations of P2C. We generated large amounts of highly pure, soluble P2C protein, coupled to the fusion partner maltose binding protein (MBP-P2C) using the PMAL-c2 bacterial expression plasmid and a two-step purification system comprising amylose resin and ion exchange. Using purified viral protein we show that specific T-cell responses against P2C are detected in the blood of healthy donors and Type 1 DM patients. Proliferation responses to P2C were detected only in subjects also demonstrating T-cell proliferation to CVB4 Vero cell lysates. However, in additional cases T-cell responses to P2C were detectable through the release of interferon-gamma or interleukin-4 in individuals who did not make proliferative responses. Taken together, our data show that the P2C nonstructural protein of CVB4 is targeted by T cells during the antiviral immune response and may trigger the production of T helper 1 and T helper 2 cytokines. The availability of pure, immunogenic P2C should allow the putative role of antiviral responses in the development of autoimmune diabetes to be investigated.
Adolescent↗
Prevalence of autoantibodies to autonomic nervous tissue structures in Type 1 diabetes mellitus.
AIMS: The pathogenesis of diabetic autonomic neuropathy is multifactorial, but recent studies have suggested a link between the presence of autoantibodies to nervous tissue structures and severe, symptomatic autonomic neuropathy. The present study was designed to examine the true prevalence of these autoantibodies in a large clinic-based population of Type 1 diabetic patients compared to nondiabetic controls. METHODS: The presence of complement fixing autoantibodies to vagus nerve (CF-VN), sympathetic ganglion (CF-SG) and adrenal medulla (CF-ADM) was assessed by immunofluorescence in a large cohort of patients (n = 394) of varying duration of Type 1 DM (median 28 years, range 6 months to 73 years) and 160 age and sex-matched nondiabetic control subjects. RESULTS: All three autoantibodies were frequently detected in Type 1 DM (CF-VN, 22.1%; CF-SG, 30.7%; CF-ADM, 13.2%) but only rarely in healthy control subjects (4.4%, 4.4% and 3.1%, respectively; P < 0.0005 for all). There was no association between any of the autoantibodies and retinopathy (fundoscopy), peripheral somatic neuropathy (biothesiometry) or nephropathy (urinary albumin-creatinine ratio). CONCLUSIONS: Our results on this large cohort establish the extensive presence of autonomic nervous tissue autoantibodies in Type 1 DM. Their role in reflecting, causing or predicting autonomic neuropathy remains to be determined.
Adolescent↗
Human leukocyte antigen-DQB1* genotypes encoding aspartate at position 57 are associated with 3beta-hydroxysteroid dehydrogenase autoimmunity in premature ovarian failure.
Premature ovarian failure (POF) has an autoimmune pathogenesis in a significant proportion of cases. Autoantibodies to the steroid cell enzyme, 3beta-hydroxysteroid dehydrogenase (3betaHSD) are present in one fifth of patients and may identify an autoimmune subgroup. As autoimmune diseases are associated with alleles of the human leukocyte antigen (HLA) genes, we examined the distribution of HLA-DRB1 and -DQB1 genotypes in 118 women with POF, of whom 21% had 3betaHSD autoantibodies, and 134 racially matched control subjects. Two HLA-DQB1 alleles, 0301 and 0603, were associated with 3betaHSD autoantibody positivity (P = 0.04 and P = 0.006, respectively). As the DQB1*0301 and -0603 genes share an identical codon at position 57 (aspartate, Asp), we analyzed the frequency of DQbeta-Asp57 encoding DQB1 genes in our series. Eighteen of 21 POF patients with 3betaHSD autoantibodies had DQbeta-Asp57-encoding genotypes (haplotype frequency, 27 of 42; 64%) compared with 92 of 134 control subjects (haplotype frequency, 109 of 268; 41%; P = 0.004), and 9 of 21 (43%) cases were homozygous for codon 57 genotypes compared with 17 of 134 (13%) control subjects (P = 0.0006). These probability values were not significant after correction for multiple testing, and these trends will therefore require confirmation in larger cohorts. HLA class II molecules present antigenic peptides to CD4+ T lymphocytes. DQbeta57 occupies a key site at the boundary of the peptide binding groove, with a major impact on peptide binding. Our preliminary demonstration of an association between POF, 3betaHSD autoimmunity, and a distinctive HLA-DQ molecule supports the hypothesis that autoantibodies to this steroid cell enzyme may be markers of autoimmune ovarian failure and suggests that presentation of autoantigenic or external peptides to T lymphocytes by HLA-DQ molecules with Asp57-beta-chains is important in the pathogenesis of this disease.
3-Hydroxysteroid Dehydrogenases↗
Techniques for investigation of an apparent outbreak of infections with Candida glabrata.
A cluster of Candida glabrata isolates recovered from seven patients in an intensive care unit over a 10-week period were compared with a collection of isolates from six epidemiologically distinct outpatients and a reference strain by several DNA typing methods. Restriction enzyme analysis with HinII distinguished 13 strains from the 14 sources and was the method of choice. Pulsed-field gel electrophoresis and random amplification of polymorphic DNA both detected nine types from the 14 sources; however, the results of these two methods did not always correlate. These methods demonstrated that five of the seven patients had distinguishable strains and that cross-infection was unlikely.
Candida↗
Study of neuromyopathy in amyloid kidney transplant patients.
Neuromuscular status of amyloid and control groups of kidney transplant recipients was assessed through complete neurological examination, assay for serum levels of muscle enzymes (CPK and LDH), electromyography and nerve conduction velocity studies. Neuromyopathic findings were detected in both groups but without severe disabling clinical manifestations. These findings were more prominent in the amyloid group, evidenced by a more significant increase in polyphasicity detected by electromyography and longer prolongation of terminal latency measured in the median nerve. From this study, we concluded that amyloid kidney transplant recipients are more prone to neuromyopathy than the general kidney transplant population, which is mostly due to the amyloidosis itself and/or the colchicine therapy.
Amyloidosis↗
Identification of 3 beta-hydroxysteroid dehydrogenase as a novel target of steroid cell autoantibodies: association of autoantibodies with endocrine autoimmune disease.
Autoantibodies directed against steroid hormone-producing cells (SCA) detectable by immunofluorescence are typically found in a small proportion of patients with premature ovarian failure (POF) as well as in other endocrine autoimmune diseases. The SCA pattern stains cells in the outer zones of the adrenal cortex, ovary, and testis. To identify the molecular target of SCA, an adrenal complementary DNA expression library was screened using SCA-positive serum, and the steroid enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was identified. Only 1 of 48 (2%) patients with idiopathic POF, not pre-selected for the presence of other autoimmune diseases, had SCA by immunofluorescence, whereas 10 of 48 (21%) had anti-3 beta HSD autoantibodies detectable by immunoblot using recombinant human enzyme compared with 6 of 115 (5%) control subjects (P = 0.002). Absorption of SCA-positive serum with recombinant human 3 beta HSD abolished the immunofluorescence pattern. We also examined the prevalence of anti-3 beta HSD autoantibodies in other endocrine autoimmune diseases. Two of 112 (2%) diabetic patients, but none of the thyroid or Addisonian patients, had SCA by immunofluorescence. Twenty-six (23%) diabetic subjects (P < 0.001 vs. controls), 3 of 18 thyroid patients (P > 0.05 vs. controls), and none of 4 Addisonian patients had anti-3 beta HSD autoantibodies. 3 beta HSD is the first steroid cell autoantigen defined at the molecular level to be associated with idiopathic POF occurring in the absence of other polyglandular diseases. Autoantibodies to 3 beta HSD in patients with other organ-specific autoimmune diseases indicate that the enzyme behaves as a typical target of polyendocrine autoimmunity. Anti-3 beta HSD autoantibodies in patients with POF may provide a marker of those subjects whose ovarian failure is autoimmune in origin and, as recent studies suggest, may be salvageable with glucocorticoid treatment.
3-Hydroxysteroid Dehydrogenases↗
Peripheral T cell lymphomas: an immunological study of seven unusual cases.
A multiparameter study of malignant lymph node cells and peripheral blood lymphocytes of seven patients with peripheral T cell lymphoma is presented. The results of monoclonal marker studies showed three cases of helper-suppressor T cell lymphoma (OKT4+, OKT8+), one case of suppressor T cell lymphoma (OKT8+), and three cases of helper T cell lymphoma (OKT4+). Immunophenotypic heterogeneity of neoplastic T cells with expression of pan-T antigens, OKT3+, and OKT11+ (erythrocyte rosetting+) was observed in most patients. Six of the seven cases tested showed Ia and DR antigens. No relationship was detected between patterns of reactivity with T cell reagents and histological types. When tested, the in-vitro malignant T cells of five patients proliferated in response to concanavalin A (Con A), but had poor response to phytohaemagglutinin. The interleukin 2 receptors showed maximum expression on Con A-activated T cells of five patients, and phytohaemagglutinin-activated T cells of one patient. The neoplastic T cells (OKT4+, OKT8+) of one patient studied had suppressor activity for IgG and IgA, and helper activity for IgM synthesis on pokeweed mitogen-induced normal B cell differentiations.
Adult↗
Two dimensional NMR studies of chaksine.
Assignments of (1)H and (13)C-nmr signal of chaksine were made with the help of two dimensional (1)H-(1)H homonuclear and (1)H (13)C heteronuclear shift correlation.
Journal Article↗
Avulsion fracture of the index metacarpal.
A case is reported of the avulsion of the insertion of Extensor Carpi Radialis Longus, an injury that has been reported only once before. The anatomy of the region and mechanism of injury are discussed, as is the importance of open reduction with internal fixation.
Adult↗
Ammonia tolerance in dogs with chronic portacaval shunt and arterialization.
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Ammonia↗
Long-term effect of arterialization of the portal vein on the sinusoidal pressure in dogs with portacaval shunt.
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Animals↗