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Biomedical subjects

J George

Publications and source records attributed to J George.

At least 199 records · Page 11Linked to original sources

Immune network and autoimmunity.

The concept of autoimmunity is regarded as the inability of the immune system to distinguish between self and non-self. This oversimplification of the concept is far from explaining the complex and perplexing mechanisms that are postulated to lead to its development. The transition from autoimmune state, in which no corresponding clinical manifestation exist, to an autoimmune disease, is further complicated by the evidence of multiple factors that participate in the evolution of the disease state. This article is written in a stepwise manner, initially reviewing the basic elements of the immune system, which are essential to understanding the fundamental processes underlying the occurrence of autoimmunity. Subsequently, a description of the factors involved in the etiopathogenesis and the presumed triggering events leading to the emergence of autoimmune diseases are described, with special emphasis on the important role of the idiotypic network, either in the maintenance of the normal immune response, or in the breakdown of self-tolerance eventuating in the autoimmune disease.

Animals↗

Radiological parameters of bleeding renal angiomyolipoma.

Angiomyolipomas are rare tumours of the kidney which have a tendency to bleed. We studied the clinical and radiological features of 11 patients from our institution to identify features which may be predictive of a massive haemorrhage. Tumours more than 6 cm in diameter were found to bleed and the demonstration of pseudoaneurysms on contrast CT scanning was associated with massive haemorrhage. We conclude that large angiomyolipomas should be treated to avoid haemorrhage and the detection of pseudoaneurysms should prompt urgent treatment.

Adult↗

Spontaneous rupture of renal angiomyolipoma presenting as acute abdomen.

Five cases of renal angiomyolipoma which underwent spontaneous rupture are described. These patients presented as an "acute abdomen" for which the diagnosis was not initially apparent. A high index of suspicion is required to make the diagnosis even with modern imaging techniques. The treatment of these tumours is discussed.

Abdomen, Acute↗

Comparison of clinical and laboratory parameters for systemic lupus erythematosus activity in Israelis versus Europeans.

The clinical activity of systemic lupus erythematosus (SLE) may be influenced by ethnic and environmental factors. The Consensus group on Activity Criteria for SLE attempted in a multicenter study to determine well-accepted criteria for disease activity. Of the 704 randomly assigned patients, 41 (5.8%) were from Israel. A detailed history including epidemiological, clinical and laboratory data was recorded. Significant differences were found between Israeli and European patients in the occurrence of Raynaud's phenomenon [12 (30%) vs. 358 (51%), respectively (P < 0.05)] and skin vasculitis [6 (15%) vs. 216 (34%), respectively (P < 0.05)]. In addition to those clinical differences, significant differences were also found in the occurrence of VDRL, low complement levels and lupus anticoagulant. Additional differences were found in some laboratory data, indicating differences in the sensitivity of the various laboratories. We conclude that the differences between the Israeli and European groups in the clinical data can be attributed mainly to environmental factors (weather, viruses), and in the laboratory data to ethnic differences (e.g., HLA) and to the different diagnostic methods used.

Adult↗

A high-involvement health care model.

Integrating a traditional approach into a high-involvement culture can result in successful redesign. Examples of successful redesign efforts as well as those that failed are discussed.

Decision Making, Organizational↗

The long-term outcome of ulcerative colitis treated with 6-mercaptopurine.

OBJECTIVES: To determine the long term outcome of ulcerative colitis in patients treated with 6-MP. METHODS: The charts of 105 chronic refractory ulcerative colitis patients treated with 6-MP from 1973-1992 were reviewed. The focus was placed on clinical response, subsequent breakthrough while maintaining 6-MP, and relapse rates when 6-MP was discontinued. RESULTS: Complete clinical remission was achieved in 68 patients (65%), partial remission was achieved in 25 patients (24%), and 12 patients (11%) failed to achieve remission. Of complete responders who continued 6-MP, 35% had a breakthrough, although complete remission was restored in 88% with the majority not requiring systemic steroids. Of complete responders who discontinued 6-MP, 87% subsequently relapsed. There were few major toxicities associated with 6-MP use. CONCLUSION: 6-MP is a reasonably safe and effective treatment for refractory ulcerative colitis. Patients who discontinue 6-MP after successful treatment have high relapse rates, therefore, 6-MP must be maintained long term to sustain remission.

Adult↗

Usefulness of conventional ultrasonography in identifying normal and abnormal gastric antrum.

AIM: This study evaluates the usefulness of measuring gastric antral thickness on conventional ultrasonography as a means of suggesting gastric antral pathology. Normal and abnormal appearances of the gastric antrum are reviewed. METHOD: The control group consisted of 156 patients with a mean age of 43 years (SD 11 years). The control group represented a population with no history or physical findings to suggest possible gastric pathology. The true positives represented six patients with proven gastric antral carcinoma on presentation. RESULTS: The mean value of the greatest thickness of one wall of the gastric antrum in the control group was 5.5 mm (SD 1.9 mm). The 95% confidence interval was 5.2-5.8 mm. The normal range was 1.3-10 mm. This was compared with 6 patients with proven gastric antral carcinoma who presented at the same time-frame of 4 months in which the control study was performed. The mean value of the thickness of the gastric antrum in these patients was 17.7 mm (SD 1.9 mm). The p-value on two-tailed t-test comparison between the two groups was 0.0009 which is statistically significant. This finding is in keeping with the fact that at presentation most gastric antral carcinomas are advanced. CONCLUSION: This study recommends that patients with epigastric pain (gallbladder vs peptic ulcer disease), hypochromic microcytic anaemia, marked weight loss and unknown primary malignancy would benefit from ultrasonography of the gastric antrum at the time of abdominal scan. If the measurement of one wall of the gastric antrum is more than 10 mm and particularly if this is associated with an abnormal echo, the patient should be endoscoped fairly urgently.

Adult↗

Protective effect of curcumin, ellagic acid and bixin on radiation induced toxicity.

Whole body irradiation of rats (10 Gy as five fractions) found to produce lung fibrosis within 2 months as seen from increased lung collagen hydroxyproline and histopathology. Oral administration of antioxidants curcumin, ellagic acid, bixin and alpha-tocopherol at a concentration 200 mumole/kg body weight significantly reduced the lung collagen hydroxyproline in these animals. In serum and liver lipid peroxidation which were found to be increased by irradiation was reduced significantly by antioxidant treatment. The liver superoxide dismutase and glutathione peroxidase activity were also found to be increased and catalase activity decreased in irradiated control. Superoxide dismutase activity reduced significantly by antioxidant treatment while catalase activity was found to be increased with alpha-tocopherol treatment. The increased frequency of micronucleated polychromatic erythrocytes after whole body irradiation of mice was found to be significantly reduced with antioxidants.

Animals↗

Membranous nephropathy in primary antiphospholipid syndrome: description of a case and induction of renal injury in SCID mice.

Primary antiphospholipid syndrome (PAPS) is a recently recognized clinical entity encompassing the combination of thromboembolic phenomena, thrombocytopenia and recurrent abortions in the presence of antiphospholipid antibodies. We present a patient with PAPS accompanied by renal involvement, manifested as membranous nephropathy, as proven by a renal biopsy. To investigate further the possible association between PAPS and the renal lesions we attempted to induce similar renal manifestations by transferring peripheral blood lymphocytes (PBL) from this patient to severe combined immunodeficiency (SCID) mice. The mice transfused with PBL from the affected patient exemplified antiphospholipid antibodies (aPL) following which a renal lesion consistent with the human membranous nephropathy lesion was precipitated. This study substantiates the role of aPL as possible inducers of renal damage.

Adult↗

Clinical and laboratory profile of sixty patients with AIDS: a South Indian study.

Sixty patients who fulfilled the WHO case definition of acquired immunodeficiency syndrome (AIDS) were admitted and treated between January 1993 and June 1995 in JIPMER Hospital, Pondicherry, South India. Their mean age was 30.3 +/- 6.4 years. Male: female ratio was 5 : 1. The heterosexual route was the major mode of transmission (96.7%). Fever was the commonest presentation (98.3%), followed by weight loss (85%) and cough (36.7%). The commonest opportunistic infection seen was tuberculosis (pulmonary, extrapulmonary - single or in combination) followed by esophageal candidiasis. Cryptococcal meningitis, intestinal crytosporidiosis, CNS toxoplasmosis, Pneumocystis pneumonia and group B Salmonella septicemia were the other infections encountered. Ten out of the 38 patients with tuberculosis were followed up on antituberculous treatment for 6 months. Seven out of 18 patients with esophageal candidiasis were treated with ketoconazole.

Acquired Immunodeficiency Syndrome↗

Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival.

Few molecular genetic alterations have been identified in endometrial cancers that are associated with poor clinical outcome. Overexpression of HER-2/neu, transforming growth factor alpha, and p53 proteins have all been associated with poor prognosis in women with endometrial cancer. In this study, the level of HER-2/neu gene amplification and expression was characterized in 92 endometrial cancers. Fluorescence in situ hybridization (FISH) was used to characterize HER-2/neu gene copy number, and immunohistochemistry was used to characterize expression. Forty-seven of the 90 (52%) endometrial cancers were characterized as showing moderate or high immunostaining. HER-2/neu gene amplification was detected in 17 of 81 (21%) cases. Immunohistochemical staining and FISH results were both available for 80 cases. Fourteen of these cases showed both moderate or high immunostaining and gene amplification. Clinical follow-up information was available for 76 women in this study. Women whose endometrial cancer exhibited HER-2/neu gene amplification by FISH had a shorter overall survival than women whose endometrial cancer lacked amplification (P = 0.018). Likewise, tumors with moderate or high HER-2/neu immunostaining were associated with a lower cumulative overall survival than tumors with low immunostaining by log rank analysis (P < 0.0001). Multivariate analysis of survival rates revealed HER-2/neu overexpression to be an independent predictor of overall survival (P = 0.0163). Among those patients with HER-2/neu overexpression, adjuvant chemotherapy or radiation therapy was associated with an improved overall survival (P = 0.039). However, among those women whose tumor lacked overexpression, overall survival was not improved by adjuvant treatment.

Adult↗

Studies on clastogenic and carcinogenic potency of tetramethyl thiuram disulphide.

Tetramethyl thiuram disulphide (Thiram, TMTD), a mutagen, is analysed for its clastogenic property by using micronuclei induction studies in the bone marrow of erythrocytes of male Swiss albino mice. Three concentrations of TMTD, i.e. 100, 150 and 200 mg/kg body wt did not significantly increase the micronuclei in polychromatic erythrocytes or the ratio of poly-to normochromatic erythrocytes. The tumour initiating (10 mg and 1 mg each in 0.2 ml DMSO) and promoting (1 mg in 0.2 ml DMSO) potency of TMTD were tested in female Swiss mice by two stage skin carcinogenic model. There was no significant increase in tumours in the TMTD treated groups, either as initiator or promoter. The results indicated nonclastogenicity and non-carcinogenicity of TMTD under these experimental conditions.

Animals↗

Initiation of the phosphocholine-specific response to Proteus morganii. B cell transfectants expressing unmutated VH/VL can respond to stimulation by P. morganii antigen.

We wished to resolve a paradox of how the response to the phosphocholine (PC) determinant of Proteus morganii could be initiated from a precursor B cell whose receptor, in unmutated form as Ab, appears to be unable to bind Ag. Unmutated VH and unmutated VL constructs were co-transfected into the B cell lymphoma M12.4 to study stimulation via membrane lg (mlg). The same VH construct was expressed in an L+, H- hybridoma line to characterize Ab binding. The unmutated Ab showed no detectable binding in ELISA to the PC-containing Ag from P. morganii PC(PM). By contrast, the unmutated mlg mediated mobilization of calcium in response to the PC(PM) Ag. Single-positive B cell lines of mlgM, mlgD double-positive lines were all capable of responding. The degree of signaling depended greatly on high receptor number, and only a fraction of cells in the population responded. Inhibition of the PC(PM)-induced calcium response by free PC indicated that the response was Ag-specific. A transfectant B cell line expressing moderate levels of a high affinity, mutated mlgM readily responded to PC(PM). These observations indicate that the unmutated lg as a receptor is capable of interacting with PC(PM) and suggest that the immune response to PC(PM) could originate from the precursor B cell expressing the unmutated mlg. The role of mlgD vs mlgM is discussed in terms of the requirement for high receptor number in the signaling process.

Amino Acid Sequence↗