Search PubMed⌕ Search

Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 217 records · Page 12Linked to original sources

The role of physicians in mammography referral for older Caribbean women in Canada.

BACKGROUND: Despite the fact that the proportion of immigrant and minority women who consult a general practitioner about their health is similar to that of their Canadian-born counterparts, studies suggest that they are less likely to be screened for breast cancer. This study examines physician characteristics associated with mammography referral and perceived barriers to mammography among family physicians serving the Caribbean community of Toronto. METHODS: The study consisted of a mail-back family physician survey. RESULTS: Among the 64 physicians who responded to the survey, over half reported that they were "very likely" to refer women for mammography during a regular preventive check-up. Among physician variables, only the amount of time spent on patient education was significantly associated with the likelihood of referral. Regarding perceived barriers, for male physicians, patient refusal and intervention causing patient discomfort were significantly associated with referral. For female physicians, only forgetting to provide service was identified as a significant barrier to referral. INTERPRETATION: An increased emphasis on patient education may help to increase screening referral among all physicians. Gender differences in perceived barriers to referral suggest that the gender of the physician is of major importance to the Caribbean community.

Aged↗

Evaluation of the diagnostic value of measuring IgG, IgM and IgA antibodies to the recombinant 16-kilodalton antigen of mycobacterium tuberculosis in childhood tuberculosis.

OBJECTIVE: To evaluate the usefulness of the recombinant 16-kDa antigen (re-Ag16) of Mycobacterium tuberculosis in the serodiagnosis of tuberculosis (TB) in children. MATERIALS: Seventy-four children with active TB, 49 apparently healthy contact children and 149 children suffering from non-mycobacterial diseases were evaluated. Detection of anti 16-kDa antigen IgG, IgM and IgA was performed by enzyme-immunoassay. RESULTS: An increased mean antibody response to re-Ag16 was observed in contact children compared with non-mycobacterial disease patients (IgG assay: 89.1 enzymatic units [eu] vs. 40.8 eu; IgM assay: 64.7 eu vs. 38.1 eu; IgA assay: 138.2 eu vs. 78.2 eu for contact children and non-mycobacterial disease patients, respectively), indicating that anti-16-kDa antibodies could be elevated in response to infections even without clinically apparent TB. Setting the specificity as the 95th percentile of the contact group's ELISA units, the sensitivity of the IgG, IgA and IgM assays were 34%, 19% and 3% respectively; combining results of the IgG and IgA assays led to 43% positivity in children with active TB. CONCLUSION: The detection of anti 16-kDa IgG and IgA may be useful as a complementary technique for the diagnosis of childhood TB. Recognition of this antigen seems to be heterogeneous; combining responses against other antigens may be a good strategy to improve the performance of this assay.

Adolescent↗

Effect of change in oxygen tension on release pattern and nature of endothelium-derived substances in isolated rabbit aorta.

AIM: To observe the effect of change in oxygen tension on the release pattern and nature of endothelium-derived substances in isolated rabbit aorta. METHODS: Isometric contractions and relaxations in isolated rabbit strip were observed in response to changes in oxygen tension and effect of various drugs was noted on them. RESULTS: Change in oxygen tension from high [pO2 =(618.9 +/- 0.4) mmHg; 1 mmHg = 133.3 Pa] to low [pO2 = (117.6+/-0.6) mmHg] was observed to convert the relaxant effect of acetylcholine (ACh), in rabbit aorta precontracted with phenylephrine, to a marked contractile response. As the aerating gas was changed from 100 % to 20 % oxygen, the relaxant effect to ACh, recorded every hour, gradually decreased till it gave way to a significant contraction over a period of 3.5 h. On reoxygenation the relaxant effect to ACh was irreversibly inhibited, however, the relaxant effect to SOD (40 kU/L) was not. The per se constrictor effect to ACh was abolished by endothelium removal and by combination of SOD (40 kU/L), catalase (1000 kU/L) and indomethacin (1 x 10(-5 ) mol/L). SQ-030741(1 x 10(-5) mol/L) or GR-32191B (1 x 10(-5) mol/L), both TXA2-PGH2 receptor antagonists but not OKY-046, a TXA2-synthetase inhibitor, also attenuated the ACh-mediated contractions in combination with SOD and catalase. CONCLUSION: The above results implicate that some functional change occurs in the endothelium exposed to low p(O2) such that the stimulated release of endothelium-derived relaxing factor (EDRF) in response to ACh is completely and irreversibly inhibited, whereas, the basally released EDRF in response to SOD is not and marked increase in prostaglandin synthesis is stimulated.

Acetylcholine↗

Dentigerous cyst : a case report.

Presented here is a case report of a 5 year old boy with a dentigerous cyst in the left maxillary canine region associated with cortical expansion and facial asymmetry. Dentigerous cysts are not common at such an early age and are also relatively less common in the maxilla. The management comprised of enucleation and follow up for 6 months.

Child, Preschool↗

A study of plasma alpha-2-macroglobulin levels in type 2 diabetic subjects with microalbuminuria.

BACKGROUND: Alpha-2 macroglobulin (Alpha-2-M) is a major plasma protease inhibitor that also regulates the activity of a variety of bioactive peptides including interleukins and exerts a range of immunomodulatory effects. OBJECTIVE: We conducted the present study with the objective to study the alpha-2-M levels in type 2 diabetic subjects with microalbuminuria in an attempt to establish alpha-2-M as a predictor of microvascular complications in diabetes. MATERIAL AND METHODS: Plasma Alpha-2-M levels were assayed in 100 (53 males and 47 females) randomly selected type 2 diabetic subjects with microalbuminuria. Diabetes was diagnosed according to the expert committee report of 1998. Patients with any acute metabolic complication like hypoglycemia, ketoacidosis, cerebrovascular accident or any acute infection were not included in the study group. RESULTS: Majority of patients belonged to 40-60 years age group. In our study alpha-2-M levels indicated a clear increase in diabetic subjects with the increasing age of subjects confirmed by multiple logistical analysis. Alpha-2-M levels were not found to be significantly different between males and females (55.6 +/- 11.3 vs. 53.7 +/- 10.5). Duration of diabetes was found to be an important confounding variable showing a direct positive correlation with alpha-2-M levels and also a significant correlation was found between alpha-2-M levels with different levels of microalbuminuria on multiple logistical analysis. No significant relation of alpha-2-M levels with either fasting blood sugar or HbA1 was observed. CONCLUSION: The increase in plasma alpha-2 macroglobulin levels in diabetes may be a correlative measure to encounter the potential proteolytic challenge associated with diabetic microangiopathy, even very early in the course of the disease. Alph-2 macroglobulin may yet be one of the most specific markers of microvascular complications in diabetes than any other serum protein.

Aged↗

Pseudomyxoma peritonei of hernial sac--a case report.

A rare presentation of Pseudomyxoma Peritonei of hernial sac is described. The patient was admitted for repair of an inguinal hernia. During herniorraphy large amount of mucinous material was found in hernial sac. Microscopy revealed epithelial glandular cells with bland appearance within mucinous pools. A search for primary remained fruitless.

Diagnosis, Differential↗

Management of acute asthma.

Hospitalization due to acute severe asthma represents a failure in the preventive, long-term as well as home care of asthma. Recognition of danger signs and prompt treatment can prevent the risk of morbidity and mortality of an acute asthma episode. The principle pharmacological management is use of inhaled beta2 sympathomemetrics and systemic steroids given with monitoring of respiratory status with the help of clinical parameters and pulmonary function tests. In patients non responsive to routine management, there is a role of inhaled cholinergic compounds, intravenous magnesium sulphate, and beta2 sympathomemetic infusion. Patients in respiratory failure need intensive care. Carefully managed prognosis of an acute attack of asthma is good.

Acute Disease↗

Prostate specific antigen as tumor marker: relationship with histologic grading.

PSA is emerging as the best marker in oncology and had a profound impact on all aspects of prostate cancer care. From clinically suspected prostate tumor, 395 serum samples were taken out and estimated for serum PSA. Among elevated serum PSA, 98 were correlated with histologic findings. 42(42.8%) cases were BHP among 98 cases and 78.7% had serum PSA level within 10 ng/ml. 5 patients (5.1%) had PIN histologically, 3(60%) of which had PSA level upto 10 ng/ml and 2(40%) had serum PSA upto 20 ng/ml. 51(52%) were adenocarcinoma prostate of different grades and PSA level varies from less than 10 ng/ml to more than 50 ng/ml which almost correlates with the tumor grades.

Adenocarcinoma↗

Evaluation of leprosy lesions by skin smear cytology in comparison to histopathology.

Cytological evaluation of leprosy skin lesion was done to evaluate cytohistological correlation. Twenty five clinically suspected patients of leprosy were evaluated by performing fine needle aspiration (FNA) in nodular lesions and slit skin smear technique in flat lesions to classify across R-J scale. May-Grunwald-Giemsa (MGG) and Ziehl-Neelsen stain were employed on slit skin smears and fine needle aspiration material. Histopathological assessment of slides from same lesion was done. The overall diagnostic accuracy of fine needle aspiration was 76.1% and that of slit skin smear 50%. However, on adequate material diagnostic accuracy of slit skin smear was high, 100% as compared to 81.8% of fine needle aspiration smears. In cases of polar leprosy cytological findings paralleled histopathological diagnosis. Within the constraints of cytological interpretation the cases in borderline unstable spectrum of leprosy can be classified broadly.

Adolescent↗

Structural characterization of the human respiratory syncytial virus fusion protein core.

Human respiratory syncytial virus (HRSV) is a major cause of a number of severe respiratory diseases, including bronchiolitis and pneumonia, in infants and young children. The HRSV F protein, a glycoprotein essential for viral entry, is a primary target for vaccine and drug development. Two heptad-repeat regions within the HRSV F sequence were predicted by the computer program learncoil-vmf. These regions are thought to form trimer-of-hairpins-like structures, similar to those found in the fusion proteins of several enveloped viruses. The hairpin structure likely brings the viral and cellular membranes into close apposition, thereby facilitating membrane fusion and subsequent viral entry. Here, we show that peptides, denoted HR-N and HR-C, corresponding to the heptad-repeat regions from the N-terminal and C-terminal segments of the HRSV F protein, respectively, form a stable alpha-helical trimer of heterodimers. The HRSV N/C complex was crystallized and its x-ray structure was determined at 2.3-A resolution. As anticipated, the complex is a six-helix bundle in which the HR-N peptides form a three-stranded, central coiled coil, and the HR-C peptides pack in an antiparallel manner into hydrophobic grooves on the coiled-coil surface. There is remarkable structural similarity between the HRSV N/C complex and the fusion protein core of other viruses, including HIV-1 gp41. In addition, earlier work has shown that HRSV HR-C peptides, like the HIV-1 gp41 C peptides, inhibit viral infection. Thus, drug discovery and vaccine development strategies aimed at inhibiting viral entry by blocking hairpin formation may be applied to the inhibition of HRSV.

Amino Acid Sequence↗

Possible mechanism of cardioprotective effect of angiotensin preconditioning in isolated rat heart.

The present study is designed to investigate the mechanism of cardioprotective effect of angiotensin II preconditioning. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for lactate dehydrogenase and creatine kinase enzyme release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using triphenyltetrazolium chloride staining. Four episodes of angiotensin II preconditioning markedly reduced lactate dehydrogenase and creatine kinase release in the coronary effluent and decreased myocardial infarct size. Administration of prazosin (alpha(1)-adrenoceptor antagonist) before global ischaemia reduced the extent of ischaemia-reperfusion-induced myocardial injury. Moreover, administration of prazosin during angiotensin II preconditioning or depletion of biogenic amines by reserpinisation (0.5 mg/kg i.p.) did not affect the cardioprotective effect of angiotensin II preconditioning. On the other hand, colchicine (5 mg/kg i.p.) or polymyxin B (50 microM) treatment markedly attenuated the cardioprotective effect of angiotensin II preconditioning. On the basis of these results, it may be concluded that the cardioprotective effects of angiotensin II preconditioning may be mediated through protein kinase C and may not involve release of norepinephrine or activation of alpha(1)-adrenoceptor.

Angiotensin II↗

Fas (CD95/APO-1) plays a role in the pathophysiology of focal cerebral ischemia.

The purpose of this study was to investigate the role of fas antigen, a member of the TNF receptor family, in cell death after focal cerebral ischemia. Focal ischemia was induced in the Sprague-Dawley rat. Evidence for apoptosis was determined by morphology as well as the presence of DNA fragmentation by the end labeling technique (TUNEL). Immunohistochemistry was performed to detect expression of both fas and fas ligand (fasL). In a separate set of experiments, two groups of mice were studied: lpr (that have a loss of function mutation for fas) and wild type. Infarct volume was measured at 24 hr as well as evidence for apoptosis. Twenty-four hours after ischemia, there was evidence for apoptosis based on morphological criteria as well as the TUNEL technique in the rat. Immunohistochemistry demonstrated increased expression of both fas and fasL in the ischemic region, with maximal staining occurring between 24-48 hr for both. Twenty-four hours after ischemia in the mice, there was evidence of apoptosis in both groups, however, the mutant mice (lpr) had significantly smaller infarcts as compared to the wild type. There was no difference in the cerebrovasculature of the two groups of mice. These data support the hypothesis that apoptosis plays a role in the pathophysiology of focal cerebral ischemia. Furthermore, these data suggest that fas-mediated apoptosis contributes to this process.

Animals↗

A multi-antigen print immunoassay for the development of serological diagnosis of infectious diseases.

Serological diagnosis of infectious diseases that generate a highly heterogeneous antibody repertoire, such as tuberculosis, requires tests based on cocktails of antigens. We describe a new method called multi-antigen print immunoassay (MAPIA) for cocktail-based serological diagnosis. The assay entails the application of antigen to nitrocellulose membranes by micro-aerosolization (printing), followed by antibody detection using standard chromogenic immunodevelopment. Cocktails of protein antigens of Mycobacterium tuberculosis tested by MAPIA were found to maintain the serological activity of each of their components. In contrast, the same cocktails tested by enzyme-linked immunosorbent assay (ELISA) had a serological activity that was lower than the sum of the activities of their components. Consequently, cocktail-based MAPIA attained the diagnostic sensitivity expected on the basis of single antigen results, while a significant loss of diagnostic sensitivity was observed with cocktail-based ELISA. Thus, the MAPIA format is superior to conventional ELISA for the serological diagnosis of infectious diseases characterized by heterogeneous antibody responses.

Antibodies, Bacterial↗

Induction of antibody and T-cell responses by immunization with ISCOMS containing the 38-kilodalton protein of Mycobacterium tuberculosis.

In this study, we investigated the influence of different amounts of N-(palmitoyloxy) succinimide (PA-NHS): attachment of lipid tails to the protein and Quil A on the immunogenicity of the 38-kDa mycobacterial protein incorporated into immunostimulating complexes (ISCOMS; 38-kDa ISCOMS). The addition of higher amounts of Quil A during the ISCOMS preparation increased the amount of protein incorporated into ISCOMS, whereas the use of higher amounts of PA did not influence this parameter. Low antibody responses were observed after primary immunization with all 38-kDa ISCOMS preparations which, however, strongly increased after booster injections. IgG2a is the major subclass IgG induced by these ISCOMS preparations. There were only slight differences between the various ISCOMS formulations in their capacity to induce cytotoxic T-lymphocytes (CTLs). Spleen cells primed with ISCOMS prepared with the highest amount of Quil A produced high levels of IFN-gamma after stimulation with T helper cell type one (Th1) peptide of the 38-kDa protein (aa 70-84), 38-kDa protein or purified protein derivate (PPD). Spleen cells primed with ISCOMS prepared with the lowest amount of Quil A only substantial IFN-gamma levels were detected after stimulation with 38-kDa protein. IL-4 secretion was very low or not detectable with all ISCOM preparations. These results therefore demonstrated that all 38 kDa-ISCOMS preparations were: (1) immunogenic by inducing antibodies, Th1 and CTL responses; (2) that the way in which the ISCOMS were prepared, e.g. the amount of Quil A used, modulates the epitope specificity of the Th1 response.

Adjuvants, Immunologic↗

Evaluation of skin sensitization potential of jet fuels by murine local lymph node assay.

Jet A and JP-8 are the major jet fuels used in civilian and military (US Air Force) flights, respectively. JP-8+100 is a new jet fuel recently introduced by the US Air Force. Besides lung exposure, skin is the potential route of exposure to jet fuels. The purpose of the present study was to investigate the skin sensitization potential of jet fuels (Jet A, JP-8 and JP-8+100) using murine Local lymph node assay (LLNA). Female CBA/Ca mice (8-12-weeks-old) were used in the study. Dinitrochlorobenzene (DNCB, 0.25% w/v) and paraaminobenzoic acid (PABA, 2.5% w/v) were used as positive and negative control, respectively and acetone: olive oil (4:1, AOO) was used as the vehicle (control). All three jet fuels caused a proliferative activity significantly greater than the control (P<0.01). Our results demonstrate that JP-8 is a weak skin sensitizer [stimulation index (SI)=3.17]. The SI of Jet A and JP-8+100 were 2.44 and 2.38, respectively, hence are not considered as skin sensitizers. Interestingly, the SI of JP-8 with butylated hydroxytoluene (BHT) was consistently lower than JP-8, though the difference was not statistically significant (P>0.05). BHT, which is an antioxidant additive of JP-8+100, reduced the skin sensitization potential of JP-8. Furthermore, the lower SI of JP-8+100 could be partially attributed to the presence of BHT. The findings reported here suggest that care should be taken to minimize dermal exposure to jet fuels especially JP-8 to avoid skin sensitization.

Animals↗

Cooperative effects of Mycobacterium tuberculosis Ag38 gene transduction and interleukin 12 in vaccination against spontaneous tumor development in proto-neu transgenic mice.

An approach to stimulating an immune response against tumors is to transduce tumor cells with bacterial genes, which represent a "danger signal" and can induce a wide immune response. Mycobacterium tuberculosis genes and their encoded proteins play a pivotal role in linking innate and cell-mediated adaptive immunity and represent ideal candidates as immune adjuvants for tumor vaccines. The efficacy of a cancer vaccine, obtained by transduction of a mammary tumor cell line with the M. tuberculosis Ag38 gene, was investigated in female mice transgenically expressing the rat HER-2/neu proto-oncogene. These mice spontaneously develop stochastic mammary tumors after a long latency period. The onset of spontaneous mammary tumors was significantly delayed in mice vaccinated with Ag38-transduced cells but not in mice vaccinated with nontransduced cells as compared with untreated mice. Protection from spontaneous tumor development was increased when mice were vaccinated with the mycobacterium gene-transduced vaccine plus a systemic administration of interleukin 12 (IL-12) at a low dose. Mice vaccinated with nontransduced cells plus IL-12 developed tumors, with only a slight delay in tumor appearance as compared with the control group. Lymphocytes obtained from lymph nodes of mice vaccinated with transduced cells secreted high levels of IFN-gamma. CD3+CD8+ spleen cells derived from these mice responded to the tumor with IFN-gamma production. These data indicate the efficacy of a short-term protocol of vaccinations exploiting the adjuvant potency of a M. tuberculosis gene and low doses of IL-12 in a model of stochastic development of mammary tumors. This adjuvant approach may represent a promising immunotherapeutic strategy for cancer immunization.

Adjuvants, Immunologic↗