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Biomedical subjects

S Jain

Publications and source records attributed to S Jain.

At least 307 records · Page 17Linked to original sources
PubMed1999

Neural tissue transplant in the lateral hypothalamic lesioned rats: functional recovery pattern.

Transplantation has come of age as an important investigative tool for studying normal growth and development of the brain tissue. The present study reports the effect of lateral hypothalamic (LHA) lesion and foetal hypothalamic tissue transplantation on the feeding behaviour. In a group of rats, LHA was lesioned bilaterally by passing direct current. Subsequently, in a separate group of rats, foetal hypothalamic tissue was transplanted at the lesioned site. Following LHA lesion, all the rats died of aphagia and adipsia within 7 days, whereas, the rats in whom foetal hypothalamus was transplanted, started taking food and water in small quantities from the first day of transplantation itself. Later, they were able to attain their preoperative values. This recovery of the feeding behaviour following foetal tissue transplantation may be due to the formation of synaptic connections or due to the release of neurotrophic factors.

Animals↗
PubMed1998

Characterization of the Ah receptor-associated protein, ARA9.

The unliganded aryl hydrocarbon receptor (AHR) is found in a complex with other proteins including the 90-kDa heat shock protein (Hsp90) and a 37-kDa protein we refer to as ARA9. We found that the three tetratricopeptide repeats found in the COOH terminus of ARA9 are necessary and sufficient for interaction with the AHR complex. Conversely, the AHR's "repressor"/Hsp90 binding domain is required for interaction with ARA9. Because ARA9 closely resembles the 52-kDa FK506-binding protein (FKBP52), found in the unliganded glucocorticoid receptor (GR) complex, we compared the binding specificities of ARA9 and FKBP52 for AHR and GR. In co-immunoprecipitation experiments, ARA9 specifically associated with AHR-Hsp90 complex but not with GR-Hsp90 complexes. In addition, ARA9 showed a greater capacity than FKBP52 to associate with AHR-Hsp90 complexes. The biological importance of this interaction was suggested by the observation that in a yeast expression system ARA9 expression enhanced the response of AHR to the agonist beta-napthoflavone, decreasing the EC50 by greater than 5-fold and increasing the maximal response 2.5-fold. In contrast, co-expression of FKBP52 had no effect on AHR signaling. In addition, although ARA9 contains a domain similar to that found in other FK506-binding proteins, ARA9 binding to 3H-FK506 could not be detected. Finally, we have characterized the developmental and expression pattern of ARA9 in the developing mouse embryo and mapped the ARA9 locus to human chromosome 11q13.3.

Animals↗
PubMed1998

A possible role of sex in determining distribution of lesions in Takayasu Arteritis.

Sixty-nine female and 43 male patients of Takayasu Arteritis (TA) were analysed based on their clinical and angiographic features. Clinical manifestations included hypertension in 41 (95%), bruits in 37 (86%) and hypertensive retinopathy in 28 (65%) male patients as compared to 47 (68%), 45 (65%) and 39 (56%) female patients respectively. An increased number of male patients (11.6%) had higher serum creatinine than female patients (1.6%). Angiographic evaluation suggested that female patients had involvement of ascending aorta, arch and abdominal aorta in six (8.6%), 14 (20.5%) and 37 (53.6%) patients respectively as compared to six (13.6%), five (11.6%) and 34 (79.1%) male patients. This data suggests that Indian male patients with TA have a higher frequency of hypertension and abdominal aorta involvement while female patients have a tendency towards involvement of aortic arch and its branches.

Adolescent↗
PubMed1998

An autopsy study of Takayasu arteritis in India.

Autopsy findings of 10 patients with Takayasu arteritis (TA) are presented. These patients include six females and four males with a mean age of 22.6+/-10.2 years. Hypertension was the commonest mode of presentation. On autopsy, the vascular lesions in the aorta comprised of stenosis (eight), dilatation (six), aneurysm (two) and dissection of aorta involving its arch, thoracic and abdominal aorta (one). Abdominal aorta was the commonest site of involvement (nine patients) and renal artery was involved in six patients. Histologically, the three types of lesions were identified--active, fibrotic and combination of active and fibrotic lesions. Active inflammatory lesions in the arterial circuit were present despite a clinically chronic (silent) phase of the disease. Cardiac involvement included left ventricular hypertrophy (nine), right ventricular hypertrophy (four), biventricular hypertrophy (three), myocarditis (two) (rheumatic and Takayasu's myocarditis--one patient each) and involvement of coronary artery (one). The pulmonary artery was involved in two patients. Kidneys showed changes of malignant hypertension and benign nephrosclerosis in one patient each. Associated tuberculosis was present in four patients. The causes of mortality were congestive heart failure (four), chronic renal failure (two), intracranial bleed, aneurysmal rupture and pulmonary thromboembolism in one patient each. Thus, the major causes of morbidity and mortality in Indian patients with TA is due to severe uncontrolled hypertension and its effect on heart, kidney and brain. The disease appears to have a persistent activity for a prolonged period even when it appears to be clinically silent.

Adolescent↗
PubMed1998

Immunogenetic analysis of Takayasu arteritis in Indian patients.

The distribution of HLA-A, B, C and DR antigens was determined in a cohort of 104 unrelated Indian patients with Takayasu arteritis (TA) belonging to the North Indian states of Punjab, Haryana, Uttar Pradesh and Delhi. The data was compared with healthy controls belonging to the same ethnic group. In addition, polymorphism in the MHC class I chain related A (MIC A) gene was studied in a group of 25 TA patients and 40 healthy controls. The data revealed a strong association of the disease with HLA-B5 (chi2=22.5, P<1 x 10(-6), RR=3.08) as well as its two common serological subtypes, B51 (chi2=20.5) and B52 (chi2=18.5). No particular association was observed with any of the five alleles of the MIC A gene, nor any linkage disequilibrium could be established with these alleles and those of HLA-B locus in this population. The observation suggest that HLA linked genes are definitely involved in the development of Takayasu arteritis and that the disease in Indian subjects is associated with HLA-B5 and its two serological subtypes, B51 as well as B52.

Adolescent↗
PubMed1998

Stent supported angioplasty in Takayasu arteritis.

Eleven patients with Takayasu Arteritis (TA) underwent angioplasty and stent placement in aorta, renal, carotid, subclavian and coronary arteries. Five wall stents were deployed in aorta in four patients. Indications for angioplasty and stent placement in aorta included hypertension in four patients and claudication and erectile impotence in one patient each. Post-procedure the peak systolic pressure gradient across the stenotic segment in the aorta disappeared. Six patients underwent angioplasty and stent placement in carotid arteries. Indications were syncope in 6 patients, loss of vision, stroke, transient ischaemic attack and seizures in one patients each. There was a marked improvement in symptoms in the patients following the procedure. For chronic total occlusion of subclavian arteries, two stents were deployed in two patients. Following the stent placement pulses in upper limb reappeared. Stents were also deployed to treat near total occlusion of right coronary artery and flow limited dissection of renal artery in one patient each. Complications of the procedure included pain in the back, mild hypertension, transient bradycardia and conduction block in one patient each. In conclusion, the stenotic and obliterative vascular lesions in TA can be managed successfully with angioplasty and stent placement. A long term follow up is required to determine the re-stenosis rate.

Adolescent↗
PubMed1998

Variation at the MJD locus in the major psychoses.

Expansion of triplet repeats has been seen to underlie several disorders that manifest anticipation. Clinical evidence suggests that anticipation occurs in the major psychoses. We studied the distribution of repeat sizes at the Machado-Joseph disease (MJD) locus in a group of patients with the major psychoses. We did not find any large expansions, though 2 patients had alleles that were two repeats larger than in our controls. The difference in allele sizes was larger in the patient sample as compared to the controls. The effect of such large differences might be of functional significance.

Adult↗
PubMed1998

Hypertension and insulin resistance in a native unindustrialised rural population of India.

A cross-sectional survey of 2964 individuals aged 16-70 years from a rural area of North India was carried out to test the hypothesis that a rural unindustrialised hypertensive population of North India has central obesity and hyperinsulinemia. Oral glucose tolerance test was carried out on 68 newly detected hypertensives, 82 age- and sex-matched community controls and 58 genetically related members of hypertensives (family controls). Fasting blood samples were examined for plasma glucose, serum insulin and lipids. Postglucose-load blood samples were examined for plasma glucose and serum insulin. Three blood pressure readings were recorded using Random Zero Sphygmomanometer. Anthropometric measurements (waist-hip ratio, subscapular and triceps skinfold thickness) of all three groups of individuals (hypertensives, community controls and family controls) were also recorded. The hypertensives had significantly higher fasting and postglucose-load serum insulin levels (P<0.05), body mass index (21.3 vs. 19 kg/m2: P<0.05), waist-hip ratio (0.89 vs. 0.85: P<0.001), subscapular (18.5 mm vs. 12.7 mm: P<0.001) and triceps fold thickness (17.6 mm vs. 12.9 mm: P<0.05) than community controls. The family controls had significantly higher systolic blood pressure than community controls (P<0.05). The lipids were not significantly different in all the three groups. Multiple logistic regression showed that both fasting and postglucose-load serum insulin were significantly associated with hypertension independent of waist-hip ratio and body mass index. The results of the present study suggest that hyperinsulinemia is related to hypertension in a rural unindustrialised population of North India.

Adolescent↗
PubMed1998

Expression systems for study of mycobacterial gene regulation and development of recombinant BCG vaccines.

Successful genetic engineering of mycobacteria is crucial for developing new approaches to combat tuberculosis as well as for dissecting out the molecular basis of pathogenesis of Mycobacterium tuberculosis. We have constructed a Mycobacterium-Escherichia coli shuttle expression vector pSD5. It carries a modular expression cassette which provides sites for cloning of promoters, a ribosome binding site (RBS) with an appropriately placed initiation codon and multiple cloning sites for cloning the genes of interest. We also constructed pDK20, an integration proficient derivative of pSD5, by incorporating mycobacteriophage L5 integration signals in lieu of the origin of DNA replication for mycobacteria. This vector permits stable expression of genes in M.bovis BCG, M.smegmatis, and M.tuberculosis under the transcriptional control of a mycobacterial promoter. These vectors enable the expression of a gene to be regulated by several hundred fold depending upon the strength of mycobacterial promoter. We propose that expression of protective antigens using an appropriate promoter derivative of pDK20 should help in development of recombinant BCG vaccines that can induce an optimal immune response from the host. We have further employed the integration proficient expression system for comparing the efficiency and specificity of transcriptional recognition in M.bovis BCG, M.tuberculosis, and M.smegmatis. We show that fast growing M.smegmatis and slow growing M.tuberculosis and M.bovis BCG recognize mycobacterial promoters with comparable efficiency inspite of differences in their growth rates.

BCG Vaccine↗
PubMed1998

The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors.

We report that MOP3 is a general dimerization partner for a subset of the basic-helix-loop-helix (bHLH)-PER-ARNT-SIM (PAS) superfamily of transcriptional regulators. We demonstrated that MOP3 interacts with MOP4, CLOCK, hypoxia-inducible factor 1alpha (HIF1alpha), and HIF2alpha. A DNA selection protocol revealed that the MOP3-MOP4 heterodimer bound a CACGTGA-containing DNA element. Transient transfection experiments demonstrated that the MOP3-MOP4 and MOP3-CLOCK complexes bound this element in COS-1 cells and drove transcription from a linked luciferase reporter gene. We also deduced the high-affinity DNA binding sites for MOP3-HIF1alpha complex (TACGTGA) and used transient transfection experiments to demonstrate that the MOP3-HIF1alpha and MOP3-HIF2alpha heterodimers bound this element, drove transcription, and responded to cellular hypoxia. Finally, we found that MOP3 mRNA expression overlaps in a number of tissues with each of its four potential partner molecules in vivo.

Animals↗
PubMed1998

Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders.

The serotonin transporter is a compelling candidate gene to examine in bipolar and unipolar affective disorder, since drugs that specifically inhibit the serotonin transporter can successfully treat depression. Previous association studies of a VNTR polymorphism in intron 2 and a functional insertion/deletion polymorphism in the promoter of this gene have produced conflicting results. The present study examined allele and genotype frequencies for both of these polymorphisms and resulting haplotypes in 87 English Caucasian bipolar patients, 125 English Caucasian unipolar affective disorder patients, and 174 controls. No significant associations were detected when these unipolar or bipolar cases were compared either separately or as a pooled "affective disorder" group to the controls. A meta-analysis of over 1,400 individuals of European Caucasian origin was then performed, comprising 772 controls, 375 bipolar and 299 unipolar patients for the VNTR polymorphism, and 739 controls, 392 bipolar and 275 unipolar patients for the promoter polymorphism. A significant association of promoter allele 2 was shown with bipolar (estimated odds ratio 1.21; 95% confidence interval 1.00-1.45), unipolar (OR 1.23; 95% CI 1.01-1.42), and combined bipolar + unipolar groups (OR 1.22; 95% CI 1.04-1.42). There was no demonstrable allelic association of the VNTR polymorphism with affective disorder: for the combined bipolar + unipolar group the odds ratios for VNTR alleles 9 and 10, compared with the common allele 12 were 1.05 (95% CI 0.56-1.95) and 0.90 (95% CI 0.77-1.05). These results suggest that the promoter allele 2, which has previously been shown to result in lower levels of serotonin transporter transcription, may be associated with affective disorder risk.

Adult↗
PubMed1998

Risk assessment in cervical dysplasia patients by single cell gel electrophoresis assay: a study of DNA damage and repair.

Precancerous lesions of cervix, commonly known as dysplasia, present a complex problem because of their biological behavior. Increased genetic instability, either inherent or induced by some external mutagen, is considered as a primary event or a predisposing factor to neoplastic transformation. The relationship between genetic instability and susceptibility towards cervical cancer was evaluated with the comet or single cell gel electrophoresis (SCGE) assay. Among precancerous individuals, genomic instability was observed in cervical epithelial cells and peripheral blood leukocytes. The mean basal DNA damage and mean susceptibility to DNA damage by the mutagen (MNNG) treatment increased whereas repair capacity decreased with progression of the disease in a stepwise manner. Inter and intra individual variability was maximum in cancerous group. Risk was estimated by giving a predictive value for each precancerous individual. In combination with morphological, biochemical, and cytogenetic parameters, the SCGE assay may serve as a novel tool to predict the fate of cervical dysplasia.

Adolescent↗
PubMed1998

Gelatinase B and A expression after laser in situ keratomileusis and photorefractive keratectomy.

OBJECTIVE: To compare the expression of gelatinases in the corneal epithelium and stroma after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). METHODS: Rabbit eyes were treated with LASIK (n=11), PRK (n=12), or corneal flap construction (n=12); 4 eyes served as unwounded controls. Zymography was performed on the central epithelium and the stroma 1, 3, and 7 days after surgery to determine the expression of gelatinases. RESULTS: Epithelial expression of gelatinase B in the LASIK group (0%-25%) was lower than that in the PRK group at all time points (50%-100%) and was identical to the corneal flap group. Stromal expression of gelatinases A and B was similar after LASIK and PRK, but was minimal after corneal flap construction at all time points. Epithelial expression of gelatinase A was similar for the first 3 days after LASIK and PRK but not thereafter. CONCLUSIONS: Gelatinase B epithelial expression was up-regulated after PRK but not after LASIK. Gelatinase B stromal expression was up-regulated after both procedures. CLINICAL RELEVANCE: Differences in wound healing and subepithelial scarring after these 2 procedures may be related to gelatinase B.

Animals↗
PubMed1998

Flow-cytometric algorithm on fine-needle aspirates for the clinical workup of patients with lymphadenopathy.

To analyze the value and limitations of flow cytometry (FCM) in the investigation of patients with lymphadenopathy, a retrospective study of 196 patients, referred for fine-needle aspiration (FNA) cytology, was carried out in Canberra, Australian Capital Territory, Australia, between 1992-1997. Complete cytological, flow-cytometric, and outcome (clinical and histological) data were available on all the cases. The FNA appearances were read in conjunction with FCM findings. The following cytological categories were recognized: benign, 78 cases (39.8%); indeterminate, 9 cases (4.6%); and malignant, 109 cases (55.6%). None of the 78 cytologically benign cases had malignant outcome. All 109 cytologically malignant cases had malignant histology, and 8/9 of the cytologically indeterminate FNAs had malignant histology. The cytologically malignant category contained 106 B-cell lymphomas and three T-cell lymphomas. All 65 B-cell lymphomas with K light chain predominance had K/L ratio greater than 3/1, and all 34 B-cell lymphomas with L light chain predominance had an L/K ratio greater than 2/1. Clonality was therefore established for K/L and L/K at 3/1 and 2/1, respectively. When K/L and L/K ratios were below these figures (7 cases), other parameters, including the proportion of CD20 and the dual expression of CD19/CD10 and CD20/CD5, were used to determine the nature of the aspirate. In the B-cell lymphomas without demonstrable light chain restriction, CD20 positivity in excess of 85%, CD19/CD10 positivity of more than 18%, or CD20/CD5 positivity greater than 35% were independently diagnostic of B-cell lymphoma. In the T-cell lymphomas, greater than 90% of the cells were T cells, and aberrant T-cell antigen expression with loss of at least one pan-T-cell antigen was detected. In conclusion, the sensitivity of diagnosis of malignancy, false-negative rate, and predictive value of malignant diagnosis with combined FNA cytology and FCM were 99%, 0%, and 100%, respectively.

Algorithms↗
PubMed1998

Differential expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) and its coactivators steroid receptor coactivator-1 and PPAR-binding protein PBP in the brown fat, urinary bladder, colon, and breast of the mouse.

Peroxisome proliferator-activated receptors (PPARs) regulate genes involved in lipid metabolism and adipocyte differentiation. Steroid receptor coactivator-1 (SRC-1) and PPAR-binding protein (PBP) interact with PPARgamma and act as coactivators to enhance ligand-dependent transcription. We report here that PPARgamma, SRC-1, and PBP are differentially expressed in the brown fat, transitional epithelium of the urinary bladder, colonic mucosa, and mammary epithelium of the adult mouse. PPARgamma and PBP are expressed in the transitional epithelium of urinary bladder and in brown adipose tissue, but not SRC-1. In the colonic mucosa, PPARgamma expression occurs throughout the villi, whereas the expression of both SRC-1 and PBP is confined mostly to the crypts. The expression of both SRC-1 and PBP is prominent in the breast epithelium of nonpregnant, pregnant, and lactating mice, whereas PPARgamma expression appeared prominent during lactation. During early embryonic development, PPARgamma, SRC-1, and PBP are differentially expressed, with only limited cell types displaying overlapping expression. PPARgamma and PBP expression overlapped in the brown fat and urogenital sinus at stage E15.5 of embryogenesis, whereas SRC-1 expression occurred mostly in neuroepithelium and cartilage between stages E9.5 and E13.5 of embryogenesis.

Adipose Tissue, Brown↗
PubMed1998

Ventilation of patients with asthma and obstructive lung disease.

Mechanical ventilation in a patient with obstructive airway disease may be a lifesaving measure; however, it may also be associated with significant morbidity and mortality. It is important for a physician to be familiar with the potential complications of mechanical ventilation in this group of patients and to know how to avoid them by carefully applying safe ventilator strategies. The cornerstone of such strategies is to minimize minute ventilation, maximize time for expiration, and avoid hyperinflation of the lung. Several bedside parameters (iPEEP, VEI, Pplat) that reflect presence of gas trapping and potential hyperinflation may be measured. In addition to mechanical ventilation, management should include inhaled bronchodilators and systemic corticosteroid therapies. In the event controlled hypoventilation is necessary, sedation with or without the use of muscle relaxants may be required. Unconventional therapies such as the use of Heliox, magnesium sulfate, ketamine, and inhalational anesthetics may be attempted in severe cases that do not respond to conventional management. With appropriate use of ventilator strategies, a reduction in the mortality and morbidity of patients with obstructive airway disease requiring mechanical ventilation has recently been noted.

Algorithms↗