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Biomedical subjects

R Madhavan

Publications and source records attributed to R Madhavan.

8 recordsLinked to original sources

Calmodulin specifically binds three proteins of the dystrophin-glycoprotein complex.

Dystrophin is the approximately 400,000 Da. protein (p400K) product of the Duchenne muscular dystrophy gene locus. In the sarcolemma membrane, it is associated with several other proteins, many of which are glycoproteins (abbreviated gp) and include gp156K, p59K, gp50K, gp43K, gp35K, and p25K. Here, we show that dystrophin, gp156K, and p59K are calmodulin-binding proteins, the binding is Ca(2+)-dependent, and of high-affinity similar to that seen with calmodulin-activated enzymes. Two putative calmodulin-binding sequences were identified, one at either end of the dystrophin sequence.

Animals

Effect of bed time intermediate acting insulin in NIDDM subjects refractory to a combination of sulphonylureas and biguanides.

The effect of a single dose of intermediate acting (Lente) insulin given subcutaneously at 9.00 P.M. in 22 NIDDM subjects refractory to a combination of Sulphonylureas and Biguanides was analysed. Euglycemia was achieved and maintained during the study period of three months with a mean insulin requirement of 14.22 +/- 5.98 units/day. Plasma FFA, Total cholesterol, triglyceride and VLDL-cholesterol also showed significant reduction. The level of FFA modulates hepatic glucose production, which in turn correlates positively with the fasting blood glucose. The therapeutic modality of bed time Lente Insulin based on physiological principles is an effective way of achieving glycemic control in NIDDM subjects who have become non-responsive to oral hypoglycemic agents.

Biguanides

Subcutaneous insulin pulse therapy.

Subcutaneous Insulin Pulse Therapy (SIPT) consists of administration of small doses of regular insulin hourly or two hourly in the subcutaneous tissue of anterior abdominal wall through a scalp vein needle. Fifteen Non-Insulin Dependent Diabetes Mellitus (NIDDM) subjects, 8 males and 7 females with mean ages 58 +/- 8.7 years and mean duration of diabetes 11.7 +/- 9.1 years and mean BMI 25.2 +/- 5.64 were admitted for elective surgery. Glycemic control was attempted preoperatively with multiple pre-meal doses of Actrapid MC with a single injection of Monotard MC at bed time. The mean fasting plasma glucose in the 15 subjects with this insulin regimen was 321.28 +/- 69.32 mgm% and the insulin requirement per day was 106.87 +/- 35.77 units. The subjects were put on SIPT for 48 to 72 hours. During SIPT the mean fasting plasma glucose dropped to 123.2 +/- 74.11 mgm% and this marked decline in fasting plasma glucose value was statistically significant (P < .05). The insulin requirement during SIPT was 96.42 +/- 31.36 units, similar to the previous regimen (NS). The subjects were switched back to conventional insulin therapy after SIPT during which period the mean fasting plasma glucose was 125.82 +/- 34.50 mgm% and this value was again significantly lower than the pre SIPT fasting plasma glucose value (P < .05). Insulin requirement during conventional insulin therapy after SIPT was reduced to 71 +/- 21.89 units/day. This dose was significantly lower than the insulin dose administered during SIPT (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles

Calmodulin-binding proteins also have a calmodulin-like binding site within their structure. The flip-flop model.

The flip-flop model is a mechanistic model proposed to describe how calmodulin activates enzymes. One prediction based upon this model is that calmodulin-activated enzymes would contain a calmodulin-like binding site which, among other attributes, would bind the peptide melittin. Five purified calmodulin-activated enzymes, namely calcineurin, myosin light chain kinase, phosphorylase b kinase, phosphodiesterase, and NAD kinase, were all found to bind biotinylated melittin and to also bind an antimelittin antibody and biotinylated calmodulins. Using gel blots of crude tissue extracts (rat brain and Arabidopsis), most proteins did not bind any of the probes and thus do not have these characteristics. However, among those which bind any of these probes, a strong correlation was found between those proteins which bind biotinylated calmodulins and those which bind melittin and antimelittin. Gel blots of phosphorylase b kinase demonstrate that the alpha, beta, and gamma subunits all bind calmodulin and melittin. A putative calmodulin-like binding site sequence was identified in eight enzymes or subunits which may play an important role in both melittin binding and calmodulin-dependent regulation of these enzymes.

Amino Acid Sequence

Progressive systemic sclerosis in south India.

Seventy eight patients with progressive systemic sclerosis (PSS) were seen over a period of 14 years. They were analysed after clinical, haematological, biochemical, immunological and radiological investigations for comparison with other Indian and Western studies. Nine of the 78 were cases of childhood PSS. There was a female preponderance (3.9:1) and the peak age of occurrence was the 4th decade (32.1%). Arthralgia (53.8%) and skin thickening (70.5%) were the common presenting symptoms. Raynaud's phenomenon (28.2%) was less common. Involvement of the skin was present in all the patients and skin biopsy was positive in 96% of the cases. Joints were affected in 66.7%; internal organs were involved in 52.6%. Antinuclear antibody was positive in 56.8%. Abnormal echocardiography (37.6%) and barium studies (20.4%) were seen. Restrictive airway pattern by pulmonary function test was present in 55%. Death occurred in 5 patients, of whom 3 died of severe pulmonary hypertension.

Adolescent

Pattern of rheumatic diseases in south India. IV. Clinical profile of juvenile rheumatoid arthritis.

An analysis of 100 consecutive cases of juvenile rheumatoid arthritis from South India revealed a male preponderance (62%), a lower incidence of the systemic onset variety (10%) and equal incidence of systemic features when compared with the West. Knees and ankles were the joints commonly involved. The incidence of elevated erythrocyte sedimentation rate and C reactive protein, with haemoglobin levels below 10 g/dl was highest in the systemic onset variety. The polyarticular and systemic onset group responded well to aspirin, while the pauciarticular group responded well to indomethacin.

Arthritis, Juvenile

Pattern of rheumatic diseases in south India. V. Ankylosing spondylitis. A clinical and radiological study.

One hundred and two patients from South India with primary ankylosing spondylitis (AS) were analysed clinically and radiologically. The mean age of onset was 26 years, with a male to female ratio of 16:1. Eleven patients presented as juvenile ankylosing spondylitis. The mode of presentation of AS included axial involvement in 59, peripheral arthritis in 38, heel pain in 18 and acute anterior uveitis (AAU) in 11. The overall incidence of extra axial features was high (90 patients). These included subjects with peripheral arthritis (49), heel pain (35), AAU (14), rib pain (11), aortic regurgitation (8), apical pulmonary fibrosis (5), mitral regurgitation (2) and conduction defects (2). Peripheral arthritis was characteristically asymmetrical and oligo articular, and involved lower limb joints. No renal involvement was noticed. Radiologically, bilateral sacroilitis was seen in 80% of cases.

Adolescent

Fibrodysplasia (myositis) ossificans progressiva in Dominica.

Fibrodysplasia (myositis) ossificans progressiva is a rare but severely disabling disease in which ossification forms within muscle and leads to progressive restriction of the movements of the jaw, neck, shoulders and hips. Shortening of the big toes is usually present. It is important to recognise this disease as avoidance of intra-muscular injections, surgery and trauma reduces the risk of further ossification.

Adult