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Biomedical subjects

N Sharma

Publications and source records attributed to N Sharma.

At least 91 records · Page 5Linked to original sources

Interaction of alpha-synuclein and synphilin-1: effect of Parkinson's disease-associated mutations.

alpha-Synuclein is a major component of Lewy bodies, a neuropathological feature of Parkinson's disease. Two alpha-synuclein mutations, Ala53Thr and Ala30Pro, are associated with early onset, familial forms of the disease. Recently, synphilin-1, a protein found to interact with alpha-synuclein by yeast two hybrid techniques, was detected in Lewy bodies. In this study we report the interaction of alpha-synuclein and synphilin-1 in human neuroglioma cells using a sensitive fluorescence resonance energy transfer technique. We demonstrate that the C-terminus of alpha-synuclein is closely associated with the C-terminus of synphilin-1. A weak interaction occurs between the N-terminus of alpha-synuclein and synphilin-1. The familial Parkinson's disease associated mutations of alpha-synuclein (Ala53Thr and Ala30Pro) also demonstrate a strong interaction between their C-terminal regions and synphilin-1. However, compared with wild-type alpha-synuclein, significantly less energy transfer occurs between the C-terminus of Ala53Thr alpha-synuclein and synphilin-1, suggesting that the Ala53Thr mutation alters the conformation of alpha-synuclein in relation to synphilin-1.

Blotting, Western↗

Nitroglycerin: a NO donor inhibits TPA-mediated tumor promotion in murine skin.

Nitroglycerin (GTN), a nitric oxide (NO) generating vasodilator has been used in the present study to assess the role of NO during tumor promotion in murine skin. Administration of GTN to 12-O tetradecanoyl phorbol 13-acetate (TPA)-treated mice resulted in a dose-dependent inhibition in the level of glutathione and the activity of antioxidant enzymes by approximately 16-40% of acetone-treated control. We also observed that GTN application led to a significant reduction in the ornithine decarboxylase (ODC) activity and decreased the rate of [3H]thymidine incorporation into epidermal DNA when compared with the acetone-treated control (P < 0.001). Treatment of DMBA-initiated TPA-promoted mice with GTN increased the latency period, decreased the tumor incidence by 32% and there was a 2-fold decrease in tumor yield (tumor/mouse) as compared with the TPA (alone)-treated group by 20 weeks. From these data, it can be concluded that NO can abrogate the toxic and tumor promoting effects of TPA and GTN can be used as a chemopreventive agent to inhibit tumorigenesis in murine skin.

Animals↗

Analysis of contacts and V-defects in GaN device structures by transmission electron microscopy.

This paper describes the microstructure of ohmic contacts to an AlGaN/GaN heterostructure, of interest for high power transistors, and an analysis of V-defects in an InGaN/GaN multi-quantum well (MQW) light-emitting structure. A combination of different transmission electron microscopy (TEM) techniques has been employed, as they provide complementary information. These include bright field and dark field TEM, high-resolution electron microscopy, X-ray mapping, energy filtered TEM and high angle annular dark field. A full determination of the phase distribution in the ohmic contacts was achieved. The onset of low contact resistance was found to correspond with the formation of an interfacial layer containing both TiN and AlN, and of an intermetallic layer containing Al, Ti and Au in contact with it. The MQW structures were capped with a p-type GaN layer, and TEM and ADF studies of the samples show a number of V-defects 100-200 nm apart along the MQW. Each V-defect incorporates a pure edge (b = 1/3 <11-20>) dislocation, which runs through its apex up to the free surface. The defects contain GaN with no InGaN layers, suggesting the V-pits have been filled in by the capping layer.

Journal Article↗

Psychiatric morbidity in psoriasis and vitiligo: a comparative study.

The psychiatric morbidity in psoriasis patients was compared with that in vitiligo patients using the standardised Hindi (vernacular language) version of the General Health Questionnaire (GHQ-H). Thirty new and untreated patients each with psoriasis or vitiligo and between the ages of 18-60 yrs, constituted the study group. The prevalences of psychiatric morbidity as assessed by the GHQ-H were found to be 53.3% and 16.22% in the psoriasis and vitiligo patients respectively; the difference was statistically significant (p=0.0028). The prevalences of depression were 23.3% and 10% in psoriasis and vitiligo respectively and anxiety was observed in 3.3% of each group. Sleep disturbance was the most common complaint and was present in 56.6% of psoriasis patients and 20% of the vitiligo patients. However, the parameter of sleep disturbance showed a statistically significant difference between the two dermatoses (p=0.0034).

Adaptation, Psychological↗

Evaluation of techniques of single continuous suturing in penetrating keratoplasty.

AIM: To evaluate the three techniques of single continuous suturing-namely, torque, antitorque, and no torque in penetrating keratoplasty. METHODS: 53 eyes of 53 patients underwent penetrating keratoplasty using torque (17 patients), antitorque (18 patients), and no torque (18 patients) suturing techniques in this prospective study. Patients were followed up at 4 weeks, 3 months, and 6 months. Keratometric, videokeratographic, refractive astigmatism, and best corrected visual acuity were determined in all the three groups at each follow up visit. Post-keratoplasty suture adjustment was done at 4 weeks, if the astigmatism was >3 dioptres. RESULTS: The initial astigmatism in the torque group was higher than in the other two groups, although it was not statistically significant. Following suture adjustment, there was a significant decrease in astigmatism in all the three groups (p<0.0001). However, no significant difference in the postoperative astigmatism at 3 months and at 6 months was seen among the three groups. CONCLUSIONS: The three techniques of single continuous suturing-that is, torque, antitorque, and no torque produce a similar final astigmatic results. Suture adjustment is an effective method of reducing post-penetrating keratoplasty astigmatism.

Adult↗

An aggressive neuroendocrine tumour in a man with AIDS.

Pancreatic neuroendocrine tumours (PETs), though rare, are usually slow growing tumours with a relatively good prognosis. We describe a case of an aggressive malignant neuroendocrine tumour of the pancreas occurring in an AIDS patient, which has not been reported previously.

Acquired Immunodeficiency Syndrome↗

Isolated tubercular splenic abscess.

Splenic abscess due to tuberculosis is extremely rare in immunocompetent individuals. We report a case of tubercular splenic abscess (TSA) in an immunocompetent individual for its rarity.

Abscess↗

Multiple myeloma presenting as proptosis and sixth nerve palsy.

Cranial and intracranial locations are rare in multiple myeloma (MM). But their occurrence has a particular significance. Proptosis and 6th nerve palsy is very uncommon presentation. We report a case of MM with presenting features as proptosis and 6th nerve palsy.

Abducens Nerve Diseases↗

Drug resistance among tubercle bacilli from pulmonary tuberculosis cases in central India.

An estimate of drug resistance is extremely important in the epidemiology and control of tuberculosis. Data on drug resistance among mycobacterial isolates from sputum samples analysed at Microbiology dept. of Choithram Hospital and Research Centre, Indore, M.P. is presented here. Drug sensitivity testing was carried out on 1426 Mycobacterial isolates by the method of proportion using critical concentration in Lowenstein Jensen medium. Resistance for Isoniazid, streptomycin, and pyrazinamide was found to be high (54.2%, 41.5% and 50% respectively) and was followed by resistance to rifampin (25%) and ethambutol (22%). Resistance for kanamycin, p-aminosalicylic acid, thiacetazone and ciprofloxacin was much lower (18%, 13%, 6.5% and 3.6% respectively). Only 12% of the isolates were sensitive to all the anti-TB drugs while resistance to two, three, and four or more drugs was in the range of 20-25%. Pattern wise, simultaneous resistance to INF and Rifampin with or without resistance to other drugs was observed in 8.1% while resistance for Isoniazid + pyrazinamide and Isoniazid + streptomycin was 11.9 and 11.5% respectively. Resistance for Isoniazid + ethambutol was the lowest (5.1%). Growing multiple drug resistance among tubercle bacilli warrant urgent attention in tuberculosis control programme.

Antitubercular Agents↗

Primary multi-drug resistant tuberculous gumma.

A 28-year old lady presented with three discrete gummatous lesions on the anterior abdominal wall, one at the site of a previous laparoscopic scar. Skin biopsy showed epitheloid cell granulomas and a pus culture and sensitivity (for AFB) performed, showed growth of M. tuberculosis. The culture-isolate was resistant to all the essential anti-TB drugs. The patient was put on second line anti-TB chemotherapy and the gummas resolved.

Adult↗

Evaluation of emission characteristics and compliance of emission standards for in-use petrol driven vehicles in Delhi.

The tail pipe CO (carbon monoxide) and HC (hydrocarbon) emission characteristics of in-use petrol driven vehicles were evaluated between November 1996 through September 1997 in Delhi. A total of 4300 vehicles were checked at CRRI Pollution Checking Centre. Approximately 90% of the total vehicles meet the prescribed CO emission standards even without following routine I/M practices. The age of the vehicles appeared to have influence on the emission characteristics. The non-compliance level was found to be higher for older vehicles. Insignificant correlation was observed between CO and HC emissions for all categories of in-use petrol driven vehicles. The emission reduction (gain) in CO and HC emissions was observed for two wheelers equipped with four-stroke engines and four wheelers fitted with catalytic converters over their respective conventional vehicles. The observed high compliance levels indicate that existing tail pipe emission standards are lenient and need to be reviewed. The emission standards are proposed for different categories of in-use petrol driven vehicles.

Air Pollutants↗

Use of domain specific ligands to study urea-induced unfolding of bovine serum albumin.

Urea-induced structural transitions in different domains of bovine serum albumin (BSA) were studied fluorometrically using domain specific ligands; chloroform, bilirubin, and diazepam. Urea denaturation of BSA showed a two-step, three-state transition with the accumulation of an intermediate around 4.8-5.2 M urea. During first transition (0-5.0 M urea), a continuous decrease (starting from 1.0 M urea) in diazepam (a ligand for domain III) binding and a late (from 3.0 M urea onward) decrease in chloroform (a ligand primarily for domain I) binding suggested major conformational changes in domain III and partial but significant loss of native conformation in domain I prior to intermediate formation. Absence of any decrease in bilirubin (a ligand for domain II) binding up to 4.5 M urea indicated non-involvement of domain II in the unfolding of BSA in this region. However, decrease in bilirubin binding during second transition reflected the unfolding of domain II and its separation from domain I.

Animals↗

The Rac1/p38 mitogen-activated protein kinase pathway is required for interferon alpha-dependent transcriptional activation but not serine phosphorylation of Stat proteins.

The p38 mitogen-activated protein (MAP) kinase is activated during engagement of the type I interferon (IFN) receptor and mediates signals essential for IFNalpha-dependent transcriptional activation via interferon-stimulated response elements without affecting formation of the ISGF3 complex. In the present study, we provide evidence that the small GTPase Rac1 is activated in a type I IFN-dependent manner and that its function is required for downstream engagement of the p38 MAP kinase pathway. We also demonstrate that p38 is required for IFNalpha-dependent gene transcription via GAS elements and regulates activation of the promoter of the PML gene that mediates growth inhibitory responses. In studies to determine whether the regulatory effects of p38 are mediated by serine phosphorylation of Stat1 or Stat3, we found that the p38 kinase inhibitors SB203580 or SB202190 or overexpression of a dominant negative p38 mutant do not inhibit phosphorylation of Stat1 or Stat3 on Ser-727 in several IFNalpha-sensitive cell lines. Altogether these data demonstrate that the Rac1/p38 MAP kinase signaling cascade plays a critical role in type I IFN signaling, functioning in cooperation with the Stat-pathway, to regulate transcriptional regulation of IFNalpha-sensitive genes and generation of growth inhibitory responses.

DNA-Binding Proteins↗

Takayasu arteritis in children and young indians.

Twenty four patients of Takayasu arteritis (TA) aged less than 18 years were studied over a period of 20 years (1978-98). There were 4 males and 20 females with a male:female ratio of 1:5. The mean age of presentation was 14 years and the disease had a mean onset of time 4+/-1.5 months prior to admission to the hospital. Hypertension was the commonest mode of presentation seen in 83% of patients. 16% patients had congestive heart failure. Left ventricular hypertrophy was present in 54% patients. Angiographic findings showed that abdominal aorta was the commonest segment of aorta that was involved (71% cases). Renal artery was involved in 75% cases. Treatment modalities included antihypertensive drugs in 19 patients, antitubercular drugs in 7 patients and steroids in 7 patients. Renal angioplasty was performed in 2 patients with excellent results. On follow up 2 patients died. The causes of mortality were renal failure and heart failure in one patient each. The clinical profile of young patients with TA is similar to that of adults with this disease.

Adolescent↗

Sleep disordered breathing in patients with cluster headache.

OBJECTIVE: To study subjects with active or inactive cluster headache (CH) for occult sleep disordered breathing (SDB). BACKGROUND: CH frequently occurs during sleep. The authors previously found that symptoms of SDB predicted reported occurrence of CH in the first half of the night, which suggested that CH could be triggered in some cases by unrecognized SDB. METHODS: The authors performed polysomnography in 25 adults (22 men) with CH. Subjects were not selected for any sleep-related complaint. In addition to standard measures, studies included monitoring of end-tidal carbon dioxide (n = 22), and esophageal pressure (n = 20). RESULTS: The rate of apneas and hypopneas per hour of sleep was >5 in 20 subjects (80%; 95% CI, 64% to 96%), minimum oxygen saturation was <90% in 10 subjects, maximum negative esophageal pressure ranged from -13 to -65 cm H2O, and maximum end-tidal carbon dioxide was > or =50 mm Hg in eight subjects. The eight subjects with active (versus inactive) CH at the time of study had higher maximum end-tidal carbon dioxide levels (50 +/- 3 versus 44 +/- 5 mm Hg; p = 0.0007). More severe oxygen desaturation was associated with reports that CH typically occurred in the first half of the nocturnal sleep period (p = 0.008). CONCLUSIONS: SDB occurred in the majority of patients with CH. Evaluation of a patient with CH should include consideration that SDB may be present.

Adult↗