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Biomedical subjects

C Viswanathan

Publications and source records attributed to C Viswanathan.

9 recordsLinked to original sources

Molecular genetic analysis of cold-regulated gene transcription.

Chilling and freezing temperatures adversely affect the productivity and quality of crops. Hence improving the cold hardiness of crop plants is an important goal in agriculture, which demands a clear understanding of cold stress signal perception and transduction. Pharmacological and biochemical evidence shows that membrane rigidification followed by cytoskeleton rearrangement, Ca(2+) influx and Ca(2+)-dependent phosphorylation are involved in cold stress signal transduction. Cold-responsive genes are regulated through C-repeat/dehydration-responsive elements (CRT/DRE) and abscisic acid (ABA)-responsive element cis elements by transacting factors C-repeat binding factors/dehydration-responsive element binding proteins (CBFs/DREBs) and basic leucine zippers (bZIPs) (SGBF1), respectively. We have carried out a forward genetic analysis using chemically mutagenized Arabidopsis plants expressing cold-responsive RD29A promoter-driven luciferase to dissect cold signal transduction. We have isolated the fiery1 (fry1) mutant and cloned the FRY1 gene, which encodes an inositol polyphosphate 1-phosphatase. The fry1 plants showed enhanced induction of stress genes in response to cold, ABA, salt and dehydration due to higher accumulation of the second messenger, inositol (1,4,5)- triphosphate (IP(3)). Thus our study provides genetic evidence suggesting that cold signal is transduced through changes in IP(3) levels. We have also identified the hos1 mutation, which showed super induction of cold-responsive genes and their transcriptional activators. Molecular cloning and characterization revealed that HOS1 encodes a ring finger protein, which has been implicated as an E3 ubiquitin conjugating enzyme. HOS1 is present in the cytoplasm at normal growth temperatures but accumulates in the nucleus upon cold stress. HOS1 appears to regulate temperature sensing by the cell as cold-responsive gene expression occurs in the hos1 mutant at relatively warm temperatures. Thus HOS1 is a negative regulator, which may be functionally linked to cellular thermosensors to modulate cold-responsive gene transcription.

Acclimatization↗

Are our donors safe?

Blood is defined as a 'drug' under the Drugs and Cosmetics Act. The Standard of drugs is laid down in the Indian Pharmacopoeia. The first step towards blood safety is to encourage blood donations, which are voluntary, non-remunerated and obtained from low-risk and regular donors. A regular donor is one who donates blood two to three times a year and continues to donate at least once a year. Over the last 8 years, the Drug Control Authority has been taken up many steps to improve the quality of blood in circulation. As a result, blood centres are now equipped with minimum modern tests for making blood safer. The inspectors are also emphasising the need to employ uniform procedures for donor selection, donor deferral, validation of equipment, and so on. Over the last 5 years, quality control of diagnostic kits prior to their registration and marketing have been streamlined to ensure that blood centres use highly sensitive kits while testing for blood transmissible diseases. Therefore, current methods of donor screening and testing of donated blood have led to a remarkable decrease in the incidence of transfusion-transmitted infection and a blood supply that is very safe. The greatest threat to blood safety is donation by seronegative individuals during the infectious window period when they are undergoing seroconversion and infection cannot be detected by available laboratory tests. Look-backs is the process whereby blood collection facilities attempt to indentify prior recipients of blood donated by individuals who subsequently test positive TTD. This alone can assure safety.

Blood Banks↗

Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassaemia: Indian trial.

From August 1989 to May 1991, 52 patients with transfusion dependent thalassaemia major received L1 (1,2-dimethyl-3- hydroxypyrid-4-one), the oral iron chelator, for a period of 3-21 months (mean +/- SD: 14.2 +/- 6.8). Mean (+/- SD) urinary iron excretion varied from 6.2 +/- 4.6 mg/d on 25 mg/kg/d of L1 to 42.3 +/- 37.1 mg/d on 100 mg/kg/d of L1. Mean (+/- SD) drop in S ferritin was 1465 +/- 990 micrograms/l after 5.0 +/- 0.8 months to 3641.2 +/- 2299.3 micrograms/l after 20.1 +/- 0.9 months of therapy. There was no evidence of neutropenia, thrombocytopenia, ear or eye toxicity. L1-related arthralgia, which was reversible on dose reduction or stoppage, was seen in 20 patients (38.5%), while minor gastrointestinal (GI) tract symptoms occurred in seven (3.5%) cases. We conclude that although L1 is an effective iron chelator, further studies are required to understand the mechanism of L1 related arthralgia and also to find a safer but effective dose on which incidence of L1 related arthralgia is minimal.

Adolescent↗

Glanzmann's thrombasthenia.

During January 1981 to June 1991, 20 patients from 16 unrelated families were detected to have Glanzmann's thrombasthenia (GT). Twelve families (75%) had history of consanguinity, with 6 first cousins and 3 uncle-niece marriages; of these 7 were Muslims, 6 Hindus and 3 Christians. There were 12 girls and 8 boys; the mean age at diagnosis was 7.05 +/- 6.03 yr (range 1 day-22 yr). All cases had initial bleeding prior to the age of 5 yr with the mean age at the initial episode of bleeding being 2.21 +/- 1.34 yr (range 1 day-5 yr). Common pattern of bleeding included epistaxis, gingival bleeding, post-traumatic bruises, menorrhagia, gastrointestinal (2 cases), post-operative (2 cases) and spontaneous bleeding (2 cases). No patient showed hemarthrosis, intracranial bleeding or hemoptysis. Menorrhagia was a serious problem necessitating repeated transfusions and hormonal therapy. Twelve cases (60%) required 1-120 units of blood transfusions while five received platelet concentrates.

Child, Preschool↗

A simple technique for hemoglobin estimation to screen for anaemia.

Drabkins method has been modified enabling detection of anaemia in a large population. 132 samples of EDTA blood were subjected to hemoglobin estimation by (1) Direct Drabkin (DD) (2), Filter Drabkin (FD) and (3) Special Filter Drabkin (SFD). Hemoglobin estimations by DD and FD compared well on statistical analysis. SFD with a punch diameter of 10.6 to 10.7 mm compared well with DD and is ideal for screening anaemia in field studies.

Anemia↗

Anti-nuclear antibody positivity in multi-transfused thalassemia major.

The frequency of anti-nuclear antibodies (ANA) was evaluated in multi-transfused patients of thalassemia major. Twelve out of 83 patients (14.5%) had positive ANA at titres of 1:80 or above. The results were compared with age and sex matched healthy controls who showed positive results in only 1 of 52 cases (1.9%; p less than 0.05). Antibody against double stranded DNA was absent. ANA positivity was found to correlate with higher age (p less than 0.01), more amount of blood transfused (p less than 0.01), splenectomy status (p less than 0.01), higher levels of serum ferritin (p less than 0.01) and presence of hepatitis B surface antigen (p less than 0.01) and antihepatitis C antibody (p less than 0.01).

Adolescent↗

Efficacy and safety of 1-2, dimethyl-3-hydroxypyrid-4-one (L1) as an oral iron chelator in patients of beta thalassaemia major with iron overload.

Twenty-four patients with beta thalassaemia major, aged 8-22 years (mean 15.3 +/- 8.1) were given 1-2, dimethyl-3-hydroxypyrid-4-one (L1) orally for a period of three months. The drug was given in the dose of 25 mg/Kg/day for the first week and gradually increased to 100 mg/Kg/day which was continued until 3 months. The mean urinary iron excretion was 5.73 +/- 3.648 mg/day on 25 mg/Kg/day of L1; 15.2 +/- 11.225 mg/day on 50 mg/Kg/day; 24.2 +/- 12.69 mg/day on 75 mg/Kg/day and 36.3 +/- 19.4 mg/day on 100 mg/Kg/day of L1. Serum ferritin estimated by ELISA before and 3 months after L1 therapy in 21 patients showed significant drop in levels, the mean drop being 964.3 +/- 844.4 (P less than 0.001). The only side-effects noted were transient gastrointestinal symptoms in 5 patients and skeletomuscular pain in 3 patients. Both these groups of symptoms were of transient nature. The efficacy of L1 appears to be excellent and equivalent to the standard iron chelation therapy available at present i.e. desferrioxamine. It appears to be free of major toxicity. L1 is also a specific chelator for iron as it does not deplete trace metals. L1 appears to be a cheap and effective oral alternative to desferrioxamine for treating iron overloading.

Adolescent↗

Improved method for the analysis of furosemide in plasma by high-performance liquid chromatography.

Modifications of existing rapid high-performance liquid chromatographic procedures for the determination of furosemide in plasma were made in order to achieve greater sensitivity. To a small volume of plasma was added in internal standard structurally related to furosemide. Then, following previously described procedures, acetonitrile was added to precipitate the proteins and the clear supernatant was separated. However prior to injection of the supernatant the pH and composition of the sample were adjusted. This modification of the sample enabled an injection volume of up to 300 microliters of the supernatant to be injected onto the chromatographic column. The effluent was monitored spectrofluorimetrically. A standard linear calibration curve with a mean precision of +/- 4.4% was obtained for plasma samples containing 20--900 ng/ml of furosemide. Two structurally related compounds were used as internal standards in the furosemide assay.

Administration, Oral↗