Search PubMed⌕ Search

Biomedical subjects

A Singh

Publications and source records attributed to A Singh.

At least 379 records · Page 21Linked to original sources
PubMed1995

De novo development of psoriatic plaques in patients receiving interferon alfa for treatment of erythrodermic cutaneous T-cell lymphoma.

Presumably because of its potent immunomodulatory activity, the use of interferon has led to the development of autoimmune disease in susceptible individuals. Because psoriasis is considered to be, in part, an autoimmune phenomenon, it is plausible that interferon may influence disease activity. We describe the development of psoriatic plaques in two patients without a history of this disease while they were receiving interferon alfa and extracorporeal photochemotherapy for erythrodermic cutaneous T-cell lymphoma. Paradoxically, in both patients the erythroderma resolved with subsequent de novo onset of psoriasis. This clinical sequence provides support for disparate immune mechanisms in the pathogenesis of these disorders, both of which are typified by lymphoid infiltrates. A review of the literature reveals that all forms of interferons have been associated with the exacerbation of psoriatic plaques, but that only interferon alfa has induced de novo development of psoriasis.

Adult↗
PubMed1995

Polypeptide profiles and antigenic characterization of cell membrane and flagellar preparations of different stocks of Trypanosoma evansi.

Polypeptides and antigens of cell membrane (CM) and flagellar (Fl) preparations of seven different stocks of Trypanosoma evansi were studied using sodium dodecyl sulphate polyacrylamide gel electrophoresis and by Western blotting. The stocks were collected from Bareilly, Bikaner, Hisar Karnal, Lucknow and Ludhiana localities of northern India and were isolated from either buffalo, equids or camel. Between two and five polypeptides with molecular weights (MW) ranging from 48.4 to 80.2 kDa (except one stock) were detected in the CM preparations and between four and 12 polypeptides ranging from 17.6 to 80.2 kDa were observed in the Fl preparations. The 78.3 kDa polypeptide was common to the CM preparation of all seven stocks. The number of antigens found in the CM of different stocks using homologous and heterologous hyperimmune sera (HIS) varied between three and 11 and were in the MW range of 25-98 kDa. Likewise the number of Fl antigens of different stocks varied between three and 14, predominantly in the MW range 17-98 kDa. Antigenic cross-reactivity among polypeptides of the CM and Fl preparations detected by various HIS was also high, indicating the possibility of less antigenic variability among these seven stocks.

Animals↗
PubMed1995

The role of cytokines and sulphatase inhibitors in regulating oestrogen synthesis in breast tumours.

Synthesis of oestrogens within breast tissues makes an important contribution to the high concentrations of oestradiol which are found in breast tumours. The activities of the enzymes involved in oestrogen synthesis, i.e. the aromatase, oestradiol dehydrogenase (E2DH) and oestrone sulphatase (E1-STS), can be stimulated by several growth factors and cytokines. As it is possible that some of these factors may be derived from cells of the immune system (macrophages and lymphocytes), the effects of basic fibroblast growth factor (bFGF) and interleukin-2 (IL-2), which are produced by these cells, on E2DH activity was examined in MCF-7 cells. Treatment of these cells with bFGF resulted in a dose-dependent increase in E2DH reductive activity whereas IL-2 was inactive at the concentration tested. To obtain further evidence that factors produced by macrophages and lymphocytes can modulate the activities of enzymes involved in oestrogen synthesis, conditioned medium was collected from these cells and found to stimulate both E1-STS and E2DH activities. In addition to understanding the control of oestrogen synthesis in breast tumours an inhibitor to block the synthesis of oestrone via the oestrone sulphatase pathway was developed. Oestrone-3-O-sulphamate (EMATE) is a potent, irreversible, inhibitor of E1-STS. A single dose of EMATE (10 mg/kg) inhibited tissue E1-STS activity in rats by more than 95% for up to 7 days, indicating that this compound may have considerable therapeutic potential for the treatment of breast cancer. Evidence is also reviewed that another steroid sulphatase, dehydroepiandrosterone sulphate sulphatase, may have a crucial role in regulating cytokine production and that this may indirectly control tumour oestrogen synthesis.

Breast Neoplasms↗
PubMed1995

Cell origin and paracrine control of interstitial collagenase in the guinea pig uterine cervix--evidence for a low molecular weight epithelial cell-derived collagenase stimulator.

Dilatation of the uterine cervix at parturition is achieved by degradation of type I collagen, the main structural protein in the cervix, by interstitial collagenase. In order to determine the cell origin of interstitial collagenase in the cervix, separate stromal and epithelial cell cultures were established. Using a highly sensitive and specific assay for collagenase that utilizes [3H]telopeptide-free type I collagen as a substrate, we determined that the cells of origin of collagenase were cervical stromal cells and not cervical epithelial cells. Cells of cervical epithelium produced factors in culture that stimulated stromal cell collagenase production. The addition of epithelial cells or epithelial cell-conditioned culture medium to stromal cells resulted in a dose-dependent stimulation of stromal cell collagenase production with a maximum increase of 3- or 6-fold, respectively. To characterize the collagenase-stimulatory activity produced by epithelial cells, epithelial cell-conditioned culture medium was extracted under conditions that optimized the recovery of peptides and was subjected to ion-exchange batch extraction as well as reverse-phase and size-exclusion HPLC. Collagenase-stimulatory activities were mainly recovered in neutral extracts of epithelial cell-conditioned medium with an apparent molecular mass of 6 kDa. In conclusion, interstitial collagenase is produced by cervical stromal cells and not by cervical epithelial cells. Epithelial cells, however, secrete factors of low molecular size that stimulate stromal cell collagenase production.

Animals↗
PubMed1995

Scintigraphic study of propylthiouracil induced submassive hepatic necrosis.

Drug induced hepatitis is a rare complication of thiourea antithyroid drugs. In some patients, the hepatotoxicity may be severe and lead to submassive hepatic necrosis (SHN). Submassive hepatic necrosis is a potentially fatal complication which is usually recognized on the liver biopsy and histological examination or autopsy. In the case presented here, SHN was identified on Tc-99m SC liver images. Sharply defined intrahepatic photopenic abnormalities without significant colloid shift were noted. SPECT images were most remarkable and exhibited extensive liver necrosis. Resolution of hepatic abnormalities correlated with clinical and biochemical resolution of SHN. In patients with propylthiouracil hepatotoxicity, serial liver SPECT images with Tc-99m SC appear helpful for the diagnosis and follow up of SHN and, in an appropriate clinical context, may obviate the need for liver biopsy.

Adult↗
PubMed1995

Comparison of single-tracer (technetium-99m-sestamibi) and dual-tracer (thallium-201 chloride and technetium-99m-sestamibi) protocols for identification of myocardial ischemia.

BACKGROUND: The objective of this study was to determine if dual-tracer protocol using thallium-201 (201TI) chloride for rest and technetium-99m (99mTc)-sestamibi for stress images (TI-MIBI) detects ischemia better than single-tracer protocol using 99mTc-sestamibi for both rest and stress (MIBI) myocardial perfusion images. METHODS AND RESULTS: A total of 460 patients with suspected or known coronary artery disease (CAD) were included in the study, with 230 (50%) undergoing single-tracer MIBI protocol and 230 (50%) undergoing dual-tracer TI-MIBI protocol. Patient demographics were matched, and the proportion of patients having treadmill stress or dipyridamole stress was similar between the two groups. Stress and rest single photon emission computed tomographic images were recorded in all patients and dual-tracer 201TI and 99mTc-sestamibi (TI-MIBI) perfusion images were acquired separately. The scintigraphic images were analyzed visually, and a semiquantitative method of scoring reversible ischemia was used. Patients' reversibility scores in each group were compiled (ischemia index) and compared to determine the relative ability of each protocol in identifying ischemia. CONCLUSION: The frequency of ischemia and ischemia index was found to be significantly (P < 0.05) higher in the TI-MIBI group compared with the MIBI group. For detecting myocardial ischemia or viability, the dual-tracer TI-MIBI acquisition technique appears superior to the single-tracer MIBI protocol.

Coronary Circulation↗
PubMed1995

Comparison of quantitative methods for brain single photon emission computed tomography analysis in head trauma and stroke.

RATIONALE AND OBJECTIVES: In this study, three semi-automated (SA) methods for brain single photon emission computed tomography (SPECT) analysis were evaluated and compared with a quantitative manual (QM) method that allowed precise demarcation of telencephalic and cerebellar regions of interest. METHODS: Twenty patients with traumatic brain injury or stroke were imaged by SPECT after injection of 30 mCi (1110 MBq) of Tc-99m HMPAO: The SA methods included: 1) SA left-to-right ratio method, which generated uptake ratios in 4 pairs of symmetric brain sectors in each slice; 2) adjusted scale method, which displayed each slice according to a linear 10-color scale; and 3) SA brain-to-cerebellum ratio method, which exhibited a color scale indicating 5% change in the ratio. RESULTS: The concordance with QM method was 85% for the adjusted scale method and 80% for the SA left-to-right ratio method. A combination of the Adjusted Scale Method and SA left-to-right ratio method yielded concordant results with the QM method in 95% of patients. Brain-to-cerebellum ratio method gave inconsistent findings because of variable cerebellar activity. CONCLUSIONS: Semi-automated methods reliably evaluated relative brain perfusion in most patients. Whereas the adjusted scale method had the best correlation with the QM method, a combination of the adjusted scale method and SA left-to-right ratio method ws the most useful for routine analysis of brain perfusion. Semi-automated brain-to-cerebellum ratio method was found to be the least useful because of variability of cerebellum uptake, particularly when the brain uptake was higher than the cerebellum. The QM method allowed precise and most accurate delineation of regions of interest for quantitation of relative brain perfusion but required considerable operator input and knowledge of brain anatomy.

Adolescent↗
PubMed1995

Transesophageal echocardiography for the initial evaluation of the widened mediastinum in trauma patients.

Traumatic disruption of the thoracic aorta is an injury that is rapidly fatal if not recognized and treated early. Increasingly, transesophageal echocardiography (TEE) is being used to evaluate the thoracic aorta after trauma with reported sensitivity and specificity rates of up to 100%. To confirm these results, we instituted a protocol using TEE as the initial diagnostic study for excluding a ruptured thoracic aorta in patients with widened mediastinum. All TEE studies were done by experienced cardiologists; 96% were done in the trauma receiving area. TEE studies were classified as positive, negative, or indeterminant. Indeterminant studies were those in which the diagnosis of aortic injury could not be excluded based solely on TEE findings. Because we were interested in using TEE as a "definitive" diagnostic modality, indeterminant studies were regarded as positive for our analysis. This protocol was used in 114 trauma patients over a 3-year period. TEE identified five thoracic aortic disruptions--three confirmed by aortography and two by thoracotomy. TEE was read as indeterminant in 17 patients and further investigation with aortography showed no aortic injury in these patients. TEE was negative in 89 patients who had no further evaluation and were subsequently discharged or who died from other injuries. TEE failed to reveal significant lesions in three patients who had aortograms that revealed disruptions requiring thoracotomy. The use of TEE for the definitive diagnosis of ruptured aorta in this series yields a sensitivity of 63% and a specificity of 84%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Relative value of femoral and lumbar bone mineral density assessments in patients with ankylosing spondylitis.

The objective of this study was to examine the relative sensitivity of femoral and lumbar bone mineral density (BMD) measurements in patients with ankylosing spondylitis (AS) and to identify the most appropriate test site for detection of osteopenia in these patients. Fourteen patients with ankylosing spondylitis had femoral and lumbar bone mineral density studies using dual energy x-ray absorptiometry. Significant osteopenia was found in 93% of patients when the femoral hip was examined and in 29% of patients when the lumbar region was examined. Moreover, femoral measurements exhibited greater severity of osteopenia than lumbar measurements when average T and Z scores were compared. Bone loss was most marked at Ward's triangle and the neck of the femur. When the lumbar measurements are insensitive and inappropriate, femoral neck and Ward's triangle measurements provide a more reliable indication of the presence and severity of osteopenia in patients with AS. Interpretation of BMD at the trochanter and intertrochanter, as well as total hip BMD, yielded no additional information in the diagnosis of osteopenia.

Absorptiometry, Photon↗
PubMed1995

Pediatric renal transplantation.

Renal transplantation in children is now a well established mode of optimal therapy for children with end-stage renal disease. The cooperative endeavors of the pediatric renal transplant physicians in the USA and Canada have generated a large volume of data that lends itself to rigorous scientific analysis. With changing practice patterns, the percentage 1- and 2-year graft survivals for cadaveric donor pediatric renal transplants have increased to 83 and 78%, respectively, in 1991 compared with 72 and 65% in 1987. Graft failure from acute irreversible rejection continues to take its toll in children under the age of 6 years. With funding from the National Institutes of Health a major cooperative effort has been organized by the North American Pediatric Renal Transplant Cooperative Study to determine the mechanisms that lead to heightened immune response in young children. Surveillance biopsies done in the early post-transplant days will attempt to identify the molecular mediators of acute rejection. Rehabilitation of children will not be satisfactory without accelerated growth after transplantation. Unfortunately, the longitudinal studies of the natural histories of growth after transplantation demonstrates that catch up growth occurs only in a subset of young children and that for the majority of older children, intervention with recombinant growth hormone is necessary. However, concern regarding the potential of recombinant growth hormone to induce chronic rejection necessitates a controlled trial.

Adolescent↗
PubMed1995

Clobazam in long-term epilepsy treatment: sustained responders versus those developing tolerance.

Clobazam (CLB) is a structurally unique benzodiazepine (BZD) that has anticonvulsant activity in all types of refractory seizures. The main drawback to CLB, as to other BZDs, is the occurrence of tolerance. To date, there has been no way to predict which patients will develop tolerance. We compared clinical features and treatment variables between two groups of patients whose seizures were initially well controlled with CLB: patients with a sustained response and patients who developed tolerance. We retrospectively identified a group of 50 very good responders from among 173 consecutive patients with uncontrolled epilepsy treated with CLB. Very good responders were defined as patients with > 75% reduction in seizures after the addition of CLB who continued CLB treatment for at least 1 month. At a mean follow-up of 37.5 +/- 12.8 months, 25 patients continued to respond and 25 developed tolerance (mean follow-up 17.0 +/- 15.7 months). Tolerance was defined as a relapse to a level > or = 50% of pre-CLB seizure frequency after an initial very good response for a minimum period of 1 month, despite constant CLB dose and, when available, serum levels. There was no change in concomitant medication. Significant differences were noted between the two groups. The sustained response group had a shorter duration of epilepsy (mean 16.5 vs. 24.5 years, p = 0.015), a greater proportion of individuals with a known etiology for their epilepsy (48 vs. 16%, p = 0.006), and higher CLB levels (0.50 vs. 0.22 microM, p = 0.017), but no significant difference in N-desmethyl-CLB levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Transesophageal echocardiography as an important tool in the diagnosis of postinfarction papillary muscle rupture.

Papillary muscle complicating acute myocardial infarction is an uncommon but potentially catastrophic event. We present 3 such cases to illustrate the difficulties in early identification of rupture. In each case, transesophageal echocardiography was employed providing rapid and unequivocal identification of the disorder. Prompt surgical intervention led to survival in 2 patients.

Echocardiography, Transesophageal↗
PubMed1995

Aromatase activity and interleukin-6 production by normal and malignant breast tissues.

The aromatase enzyme complex, which regulates the conversion of androstenedione to estrone, may have an important role in regulating estrogen synthesis in breast tissues. In this study the effect of tumor location on aromatase activity in adjacent tissue was examined and related to interleukin-6 (IL-6) production, which has been shown to stimulate aromatase activity in breast cancer cells. Samples of normal and malignant breast tissues were obtained from 11 women undergoing mastectomy. In 7 patients, aromatase activity was highest in the quadrant in which the tumor was located or on which the tumor impinged. Aromatase activity in tumor-bearing quadrants was significantly higher than that in adjacent and opposite quadrants. Aromatase activity and IL-6 production, expressed in terms of tissue weight, were significantly higher for tumor tissue compared with normal breast adipose tissue. A significant correlation was found between aromatase activity and IL-6 production for breast tumor tissue (rs = 0.56; P < 0.05), but not for adipose tissue from the breast quadrants. Aromatase activity and IL-6 production were also measured in tissue obtained from a normal woman undergoing reduction mammoplasty who had previously had breast augmentation by silicone injection, not contained within a capsule. In tissue from this patient there was evidence of chronic inflammation and a marked macrophage response. Aromatase activity in this tissue was considerably higher than that detected in mastectomy adipose tissue samples, and a significant correlation was found between aromatase activity and IL-6 production (rs = 0.77; P < 0.05). A preliminary study to examine the potential role of cells of the immune system in regulating breast tissue aromatase activity revealed that conditioned medium collected from macrophages and lymphocytes could markedly stimulate aromatase activity in tumor-derived fibroblasts. The results of this study confirmed that breast tumor location can influence aromatase activity in adjacent tissues and showed that aromatase activity is increased in tumor-bearing quadrants. The increased production of IL-6 by tumor tissue and its correlation with aromatase activity suggest that tumors may be the major source of IL-6, which is able to influence aromatase activity in adjacent tissues.

Adipose Tissue↗
PubMed1995

IL-6sR: release from MCF-7 breast cancer cells and role in regulating peripheral oestrogen synthesis.

The interleukin-6 soluble receptor (IL-6sR) may regulate the ability of IL-6 to stimulate oestrogen synthesis in breast cancer cells and breast tumours. Significant aromatase activity was detectable in IL-6 stimulated fibroblasts derived from subcutaneous adipose tissue, but the combination of IL-6sR plus IL-6 resulted in a marked 21-fold stimulation of aromatase activity. To examine the control of IL-6sR release, the effects of oestradiol, 4-hydroxytamoxifen (4-OHT), dexamethasone, TPA, TNF alpha or IL-6 on this process was examined using MCF-7 breast cancer cells. Oestradiol, TNF alpha and dexamethasone all markedly increased IL-6sR release. While 4-OHT had a small stimulatory effect on IL-6sR release, it blocked the ability of oestradiol to increase IL-6sR release. Significant concentrations of IL-6sR were also detected in conditioned medium collected from lymphocytes and macrophages and in cytosols prepared from normal and malignant breast tissues. These results indicate that IL-6sR may have an important role in potentiating the effect of IL-6 on oestrogen synthesis in breast cancer cells. The abilities of oestradiol or tamoxifen to potentiate or inhibit the IL-6 stimulation of oestrogen synthesis in breast cancer cells may result from their effects on IL-6sR release.

Antigens, CD↗
PubMed1995

Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis.

Short-term cyclosporine (CsA) has been shown to reduce the proteinuria in refractory nephrotic syndrome, but the effect on disease progression has not been evaluated. This study was undertaken to evaluate whether maintenance CsA therapy in steroid-resistant focal segmental glomerulosclerosis (FSGS) will prevent progression to ESRD. Twenty-one black and Hispanic children (mean age, 8.4 +/- 4.5 yr) with biopsy-proven, steroid/cyclophosphamide-resistant FSGS were treated with CsA (initiated at 6 mg/kg per day and titrated to the serum cholesterol level to achieve a response). The mean CsA dose was 7 (4 to 20) mg/kg per day, the duration of CsA therapy was 27.5 (3 to 97) months, and the duration of follow-up was 8.5 +/- 4.7 yr. At the end of CsA therapy, the mean (+/- SE) proteinuria fell from 6.2 +/- 0.2 to 2.0 +/- 0.1 g/24 h (P < 0.001), the mean albumin rose from 1.95 +/- 0.04 to 3.41 +/- 0.04 g/dL (P < 0.001), the mean cholesterol decreased from 472 +/- 12.7 to 257 +/- 5.3 mg/dL (P < 0.005), and the mean creatinine rose from 0.79 +/- 0.02 to 1.16 +/- 0.03 mg/dL (P < 0.005). Seven children continue to receive maintenance CsA therapy, and 14 patients have had CsA stopped: 6 for an increase in serum creatinine and/or continued proteinuria, 5 for sustained remission, 2 for noncompliance, and 1 for pregnancy. Five (24%) of the 21 patients progressed to ESRD.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗
PubMed1995

An improved method for chemical devitellinization of X-gal stained Drosophila embryos.

In Drosophila developmental biological studies, X-gal staining is commonly employed to study the spatio-temporal expression of the lacZ reporter gene in the transformed flies or their embryos. Study of the lacZ pattern in embryos often suffers from the lack of an efficient and high yielding technique for devitellinization of X-gal stained embryos. Devitellinization techniques employed during antibody staining, in situ hybridization or embryonic cuticular preparations generally do not give satisfactory results when used for similar purpose in X-gal stained embryos. This results in the flaky appearance of the blue stain. We present here an improved chemical devitellinization technique which gives a high yield of devitellinized embryos and a better resolution of the X-gal staining pattern.

Animals↗