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Biomedical subjects

R Handa

Publications and source records attributed to R Handa.

At least 91 records · Page 5Linked to original sources

Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase.

Binding of type I interferons (IFNs) to their receptors induces rapid tyrosine phosphorylation of multiple proteins, including the alpha and beta subunits of the receptor, the polypeptides that form the transcriptional activator ISGF3 alpha (Stat113, Stat84, and Stat91), and the p135tyk2 and Jak-1 tyrosine kinases. In this report, we demonstrate that the alpha subunit of the type I IFN receptor (IFN-R) corresponds to the product of a previously cloned receptor subunit cDNA and, further, that the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit. Glutathione S-transferase (GST) fusion proteins encoding the different regions of the cytoplasmic domain of the alpha subunit can bind the p135tyk2 contained in human cell lysates. The association between the alpha subunit and Tyk2 was demonstrated by immunoblotting with anti-Tyk2 and antiphosphotyrosine antibodies and by using an in vitro kinase assay. Analogous experiments were then performed with recombinant baculoviruses encoding constitutively active Jak family tyrosine kinases. In this case, p135tyk2, but not Jak-1 or Jak-2 protein, binds to the GST-IFN-R proteins, suggesting that the interaction between these two proteins is both direct and specific. We also demonstrate that Tyk2, from extracts of either IFN alpha-treated human cells or insect cells infected with the recombinant baculoviruses, can catalyze in vitro phosphorylation of GST-IFN-R protein in a specific manner. Deletion mutants of the GST-IFN-R protein were used to localize both the binding and tyrosine phosphorylation site(s) to a 46-amino-acid juxtamembrane region of the alpha subunit, which shows sequence homology to functionally similar regions of other cytokine receptor proteins. These data support the hypothesis that the Tyk2 protein functions as part of a receptor complex to initiate intracellular signaling in response to type I IFNs.

DNA-Binding Proteins↗

Alteration in blood gases in tetanus.

Tetanus is an important cause of patient mortality. Hypoxia is an important determinant of poor prognosis in tetanus. Oxygen saturation (Sa02) determines effectiveness of muscle relaxants. We performed arterial blood gas (ABG) studies in 20 patients with tetanus and 20 controls. All patients had hypoxemia and metabolic acidosis at admission. The mortality rate in patients with admission PaO2 < 70mm Hg was higher compared to those with PaO2 > 70mm Hg (P < 0.01). Patient with pH < 7.2 had higher mortality compared to those with pH > 7.2 (p < 0.05). Severe hypoxemia and severe metabolic acidosis connoted poor prognosis.

Acidosis↗

Clinical, hematological and electrophysiologic study of megaloblastic anemias.

Thirty one cases of megaloblastic anaemia were studied clinically and electrophysiologically. Eight patients had clinical evidence of peripheral neuropathy. MNCV, distal sensory latency, la fibre conduction velocity, proximal conduction velocity and H-reflex amplitude and latency were compared with fourteen age and sex matched healthy controls. MNCV, proximal conduction velocity and H-reflex amplitude were significantly decreased in anaemic subjects while distal sensory latency was increased. No change was seen in la fibre conduction velocity and H-reflex latency. There was no correlation between severity of anaemia and the electrophysiologic abnormalities. MNCV and la fibre conduction velocity improved after correction of anemia.

Adolescent↗

Serum, CSF, RBC & urinary levels of magnesium & calcium in idiopathic generalised tonic clonic seizures.

Serum, cerebrospinal fluid (CSF) and urinary levels of magnesium and calcium and RBC magnesium levels were studied in 100 patients of idiopathic generalised tonic clonic seizures and 95 healthy controls matched for age and sex. There was a significant reduction in serum, CSF and RBC magnesium levels and a rise in serum and CSF calcium levels in epileptic patients. The 24 h urinary excretion of calcium and magnesium in the epileptics did not differ from controls. Post ictal (within 24 h of seizure) serum and CSF magnesium levels were significantly lower and calcium levels significantly higher as compared to inter ictal levels (4 wk after seizure). There was no correlation between serum magnesium, serum calcium and CSF calcium levels and the frequency, control or duration of fits. Low CSF magnesium levels correlated with increased frequency, poor control and longer duration of fits. Patients with status epilepticus and those in the EEG abnormalities had low CSF magnesium levels.

Adolescent↗

Aluminium phosphide poisoning.

Aluminium phosphide is a solid fumigant pesticide widely used in the Indian subcontinent as a grain preservative. Over the last 5 years there has been a dramatic increase in the number of cases of aluminium phosphide poisoning in India. Ninety-two patients with aluminium phosphide poisoning due to ingestion were studied over a period of 3 years. Abdominal pain, vomiting and restlessness were the common initial features followed by alteration in sensorium and shock unresponsive to conventional treatment. Electrocardiographic abnormalities were very common and highly variable. Routine serum biochemistry was usually unremarkable. Severe metabolic acidosis was common and mortality high (49%). The survivors recover completely without any residual organ damage. There is no known antidote.

Adolescent↗

Erythrocytic glucose-6-phosphate dehydrogenase deficiency in the Bania community of Punjab.

Five hundred members belonging to the Bania community of Punjab were screened for erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The incidence of enzyme deficiency in males was 2.84 per cent and in females 2.75 per cent, with an overall incidence of 2.80 per cent. No correlation between age and G-6-PD deficiency was found. The mean values for haemoglobin and haematocrit did not differ significantly in the normal and deficient subjects. Study of the deficiency pattern amongst family members of the enzyme deficient subjects confirmed the X-linked inheritance of G-6-PD deficiency.

Age Factors↗

Kala-azar--new developments in diagnosis and treatment.

Kala-azar is an endemic disease in many parts of India. Traditionally, diagnosis of this disease was based on demonstrating the parasites in various tissues like bone marrow or splenic aspirates. However, lack of high sensitivity of these methods led to the use of various immunodiagnostic methods in the diagnosis of kala-azar. Antigen detection and polymerase chain reaction to detect parasitic DNA have been found to be useful in patients with an underlying immunosuppressive disease like AIDS. For treating kala-azar, pentavalent antimonial compounds are still the first-line agents. However, due to increasing resistance to this agent, many patients at present require other drugs including amphotericin B and pentamidine. Toxic effects of these second-line agents have led to development of drug delivery systems like liposomal amphotericin B, which has shown uniform efficacy in clinical trials. Combining stibogluconate with either paromomycin or interferon-gamma has also been shown to be useful in many patients with drug-resistant kala-azar.

Amphotericin B↗

Awareness of brain death and organ transplantation among high school children.

The objective of this study was to assess the awareness of the concepts of brain death and organ transplantation among high school children. One hundred and eighty eight students of class 12th of a reputed public school were studied. Structured questionnaires were used to assess their knowledge in various aspects of brain death and organ transplantation. Following the questionnaire, they were provided with educational information on brain death and organ transplantation. This was followed by similar questionnaires to assess any change in awareness of brain death and organ transplantation. Results spoke of widespread awareness and acceptance of organ transplantation in the high school children. However, the awareness of various aspects of brain death was quite low. There was significant increase in awareness and acceptance of brain death after educating the students. Education about various aspects of brain death, its immense importance for organ donation and legality of brain death needs to be highlighted.

Adolescent↗

Atherosclerosis in Asian Indians with systemic lupus erythematosus.

OBJECTIVES: Atherosclerosis has emerged as an important late complication of systemic lupus erythematosus (SLE). Asian Indians, as an ethnic group, are known to be metabolically predisposed to development of early atherosclerosis. No data on this aspect of SLE are available from Asia. This study was undertaken to find the frequency of atherosclerosis in Indian lupus patients and the factors affecting such an occurrence. METHODS: Carotid artery intimo-medial thickness (IMT) and plaque were used as markers of atherosclerosis. High-resolution B-mode ultrasonography was used to compare carotid IMT and plaque in 50 patients with SLE and 50 age- and sex-matched healthy controls. RESULTS: Patients with lupus (age 31.6+/-10.05, median 30.5 years; disease duration 52.3+/-36.7, median 46 months) exhibited a significantly greater IMT than controls (0.417+/-0.07 vs. 0.362+/-00.07 mm; p = 0.003). Carotid plaques were seen in seven (14%) cases. None of the control population had plaques (p = 0.006). On bivariate analysis, the IMT was significantly affected by age, systolic blood pressure (SBP), disease duration and menopausal status. On multivariate analysis, the only factor significantly affecting IMT was SBP. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) score was the sole factor found to significantly affect the occurrence of plaque. CONCLUSIONS: Asian Indian lupus patients in our study, despite being relatively young and with shorter disease duration, exhibited premature atherosclerosis in the form of significantly thicker intimo-media and plaque. The factors found to affect accelerated atherosclerosis in our cohort were age, SBP, disease duration, postmenopausal status and the SLICC/ACR score.

Adolescent↗