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Biomedical subjects

S Ramachandran

Publications and source records attributed to S Ramachandran.

At least 109 records · Page 6Linked to original sources
PubMed1996

Assessment of iodine deficiency disorders using the 30 cluster approach in the National Capital Territory of Delhi.

OBJECTIVE: Iodine Deficiency Disorders (IDD) are a major public health problem in India. The National Capital Territory (NCT) of Delhi is a known iodine deficiency endemic area. The Delhi Government banned the sale of non-iodised salt since 1989. The present study was conducted to assess the status of IDD after 7 years of salt iodisation programme in the state. DESIGN: Cross sectional. METHODOLOGY: The recent indicators recommended by the World Health Organization-United Nations Childrens Fund-International Council for the Control of Iodine Deficiency Disorders (WHO-UNICEF-ICCIDD) were utilized for the assessment of IDD. A total of 30 clusters were selected using population proportionate to size cluster sampling procedure. In each identified cluster, one primary school was selected using random sampling. A total of 6911 school children in the age group of 8-10 years were included for the study. RESULTS: The total goiter prevalence rate was 8.6% while 2.1, 8.4, 17.6 and 71.9% of the children had urinary iodine excretion levels of < 2, 2-4.9, 5-9.9 and 10 and above mcg/dl, respectively. The median urinary iodine excretion was 17 mcg/dl. Of the 1854 salt samples analyzed, salt with a nil iodine content was consumed only by 1.4% of the beneficiaries. Forty one per cent of families consumed salt with an iodine content of less than 15 ppm. CONCLUSION: IDD continues to be a public-health problem in the NCT of Delhi. There is a need of strengthening the existing monitoring system for the quality of iodised salt.

Child↗
PubMed1995

Catalysis sensitive conformational changes in soybean lipoxygenase revealed by limited proteolysis and monoclonal antibody experiments.

Soybean lipoxygenases catalyze lipid hydroperoxidation of polyunsaturated fatty acids. Putative ligand mediated conformational changes in soybean lipoxygenase 3 (L3) were studied by a combination of limited proteolysis and a series of monoclonal antibodies that recognize discontinuous epitopes and alter catalysis (inhibition and activation). Trypsin cleaved L3 (97 kDa) into C-terminal 60 kDa and N-terminal 37 kDa fragments. The 37 kDa fragment was obtained from a 38 kDa fragment formed initially. Using protein footprinting, the epitopes of the antibodies were mapped to the 37 kDa fragment. Proteolysis in the presence of a substrate analog inhibitor, oleic acid, generated the 60 and the 38 kDa fragments only. No further proteolysis of the 38 kDa fragment was seen even after prolonged incubation. This was not a detergent effect since the altered proteolysis was not obtained in the presence of SDS or Tween 20. Binding of a monoclonal antibody to L3 in the presence of oleic acid was substantially reduced providing additional evidence for a conformational change induced by the oleic acid-lipoxygenase interaction. These observations are interpreted using the recently solved three-dimensional structure of L3. It is apparent that while the protein is composed of a small N-terminal beta-barrel domain and a large principally alpha-helical C-terminal domain, proteolysis does not take place at a linking region between the two domains. The proteolysis results makes it clear that the smaller domain is connected across the entire length of the larger domain to a narrow, tongue-like projection that extends into the vicinity of the entrance to the proposed substrate binding channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1995

The relationship of TAP1 and TAP2 dimorphisms to multiple sclerosis susceptibility.

Transporters associated with antigen processing and presentation (TAP1 and TAP2) have been considered candidate genes in MS susceptibility based on evidence from experimental animal models confirming antigenic peptide selection by transporter polymorphisms and by the proximity of these transporter genes to the DR- and DQ-associated alleles known to confer disease risk in man. We report here an association study examining the influence of TAP gene polymorphisms on MS susceptibility in a Canadian patient population. Our results do not support a role for the five polymorphisms examined in the etiology of this disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Prevention of oxidative damage to rat lens by pyruvate in vitro: possible attenuation in vivo.

Studies have been conducted to assess the possible preventive effect of pyruvate against lens protein oxidation and consequent denaturation and insolubilization. Rat lens organ culture system was used for these studies. The content of water insoluble proteins (urea soluble) increased if the lenses were cultured in medium containing hydrogen peroxide. Incorporation of pyruvate in the medium prevented such insolubilization. The insolubilization was associated primarily with loss of gamma crystallin fraction of the soluble proteins. PAGE analysis demonstrated that insolubilization is related to -S-S- bond formation which was preventable by pyruvate. Since pyruvate is a normal tissue metabolite the findings are considered pathophysiologically significant against cataract formation. This was apparent by the prevention of selenite cataract in vivo by intraperitoneal administration of pyruvate.

Adenosine Triphosphate↗
PubMed1995

Electroencephalographic abnormalities in patients with snake bites.

Electroencephalograms (EEGs) were obtained for 26 patients with snake bite to observe the cerebral impact of snake venom. All snakes were identified; 19 (73%) were Russell's vipers, one (4%) was a common cobra, five (19%) were hump-nosed vipers, and one (4%) was a dog-faced fresh water snake. The EEG was abnormal in 25 patients (96%) and these results included all the snake species identified. The EEG abnormalities observed were reduced alpha activity, increased theta/beta activity or sharp waves (grade 1), sharp waves or spikes and slow waves (grade 2), or diffuse delta activity (grade 3). Grade 1 changes occurred in 16 patients (62%), grade 11 in eight patients (31%), and grade 111 in one patient (4%). Thus, grade 2 and 3 changes, which were moderately severe to severe abnormalities, occurred in nine patients (35%). One patient had acute renal failure and two others had mild jaundice and hyponatremia. These three patients had EEG abnormalities that were similar to those observed in the remaining 22 patients. The altered EEG, suggestive of an encephalopathy, appeared within hours of the bite and persisted for several days without clinical neurologic effects. The changes were seen mainly in the temporal lobe. Similar changes occurred in both patients with and without antivenom therapy. It appeared that the EEG abnormalities are a consequence of the effects of venom from the bites of a variety of snakes.

Adolescent↗
PubMed1995

The mechanism of force generation in myosin: a disorder-to-order transition, coupled to internal structural changes.

We propose a molecular mechanism of force generation in muscle, based primarily on site-specific spectroscopic probe studies of myosin heads in contracting muscle fibers and myofibrils. Electron paramagnetic resonance (EPR) and time-resolved phosphorescence anisotropy (TPA) of probes attached to SH1 (Cys 707, in the catalytic domain of the head) have consistently shown that most myosin heads in contracting muscle are dynamically disordered, undergoing large-amplitude rotations in the microsecond time range. Some of these disordered heads are bound to actin, especially in the early (weak-binding, preforce) phase of the ATPase cycle. The small ordered population (10-20%) is rigidly oriented precisely as in rigor, with no other distinct angle observed in contraction or in the presence of intermediate states trapped by nucleotide analogs. These results are not consistent with the classical model in which the entire head undergoes a 45 degree transition between two distinct orientations. Therefore, it has been proposed that the catalytic domain of the myosin head has only one stereospecific (rigor-like) actin-binding angle, and that the head's internal structure changes during force generation, causing the distal light-chain-binding domain to rotate. To test this model, we have performed EPR and TPA studies of probes attached to regulatory light chains (RLCs) in rabbit and scallop myofibrils and fibers. The RLC results confirm the predominance of dynamic (microsecond) rotational disorder in both relaxation and contraction, and show that the different mechanisms of calcium regulation in the two muscles produce different rotational dynamics. In rabbit myofibrils, RLC probes are more dynamically disordered than SH1 probes, especially in rigor and contraction,indicating that the light-chain-binding domain undergoes rotational motions relative to the catalytic domain when myosin heads interact with actin. An SH1-bound spin label, which is sensitive to myosin's internal dynamics, resolves three distinct conformations during contraction, and time-resolved EPR shows that these transitions are coupled to specific steps in the ATPase cycle. We propose that force is generated during contraction by a disorder-to-order transition, in which myosin heads first attach weakly to actin in a nonstereospecific mode characterized by large-scale dynamic disorder, then undergo at least two conformational transitions involving large-scale structural (rotational) changes within the head, culminating in a highly ordered strong-binding state that bears force.

Adenosine Triphosphate↗
PubMed1995

Retinopathy of prematurity: a study.

A total of 50 infants of less than 2000 gm birth weight were screened for retinopathy of prematurity (ROP) by binocular indirect ophthalmoscopy. The incidence of ROP was found in 19 patients (38%). Of these, 8 patients (16 eyes) had threshold disease. Significantly, occurrence of threshold ROP was seen in both 1600 gm birth weight in one infant and in the absence of oxygen administration in 2 infants. Ten of the 16 eyes underwent therapeutic intervention while 6 eyes did not receive treatment for lack of consent from the parents. The treatment consisted of indirect laser photocoagulation (8 eyes) and transconjunctival cryopexy (2 eyes). Good regression of the disease (favourable outcome) was noted in all the treated eyes.

Birth Weight↗
PubMed1994

Nucleotide sequence organisation and analysis of the nuclear ribosomal DNA circle of the protozoan parasite Entamoeba histolytica.

We have sequenced the extrachromsomal ribosomal DNA (rDNA) circle of the human protozoan parasite Entamoeba histolytica HM-1:IMSS and present here the complete sequence organisation of the 24.5-kb molecule. Each circle contains two 5.9-kb rDNA transcription units organised as inverted repeats. The regions downstream (3543 bp) and upstream (9216 bp) of the rDNAs contain various families of short tandem repeats. Some of the upstream repeats share extensive sequence homology with the downstream repeats. In addition to the rDNAs themselves, the rDNA circle appears to code for only one other transcript which is 0.7 kb in size as seen in Northern blots. From DNA sequence analysis, no open reading frame could be assigned to the transcript. Extrachromosomal rDNA circles also exist in other E. histolytica strains. Restriction enzyme maps of rDNA circles were constructed from E. histolytica strains 200:NIH, HK-9 and Rahman; and Entamoeba moshkovskii strain Laredo. Striking differences were observed in the organisation of some of them, e.g. the HK-9, Rahman and Laredo circles contained only one rDNA unit and lacked the 0.7-kb transcript sequence. The short repeat sequences upstream and downstream of rDNAs were present in HK-9 and Rahman but absent in Laredo. Circles with one rDNA unit may be derived from those with two units by homologous recombination at direct repeat sequences located upstream and downstream of the two rDNAs.

Animals↗
PubMed1994

Transcription factors in plant growth and development.

The target DNA sequences of several classes of plant transcription factors, including basic leucine zipper (bZIP) proteins and Myb-related factors, have been characterized in vivo as well as in vitro. The bZIP proteins, for example, act at ACGT elements, the flanking nucleotides determining their binding specificities. Overexpression, co-suppression, and antisense technology studies of factor genes in transgenic plants have uncovered the roles of bZIP, homeodomain, and MADS box factors in plant growth and development; for example, ectopic expression of pMADS1 alone in early Petunia development is sufficient for homeotic conversion of sepals into petaloid organs.

Base Sequence↗
PubMed1994

Measurement of lamotrigine under conditions measuring phenobarbitone, phenytoin, and carbamazepine using reversed-phase high-performance liquid chromatography at dual wavelengths.

A reverse-phase high-performance liquid chromatographic (HPLC) method for the measurement of lamotrigine (LTG) simultaneously with phenobarbitone (PB), phenytoin (PHT), and carbamazepine (CBZ) is described using hexobarbital as the internal standard. The method uses the chromophore at 307 nm to detect LTG in the presence of interfering CBZ-10,11-epoxide detected at 220 nm, the wavelength used to measure the other drugs. This method requires < 10 min/sample for completion. Simultaneous monitoring of the chromatographs at 220 and 310 nm with a simple calculation allows LTG to be measured virtually identically to a routine method for monitoring of the other anticonvulsants. Between-batch precisions for LTG at 2 and 6 mg/L were < 5%. Accuracy of LTG estimation was assessed by comparison with known values of samples supplied by an external quality assessment scheme.

Anticonvulsants↗
PubMed1994

Myonecrosis due to Russell's viper bites in Sri Lanka.

Scattered or diffuse myonecrosis is the histopathologic basis for muscle pain and tenderness due to bites by Vipera russelli pulchella in Sri Lanka. These lesions may even occur without any clinical symptoms. Subclinical lesions may form one end of continuous spectrum, with the other being severe pain and muscle tenderness with rhabdomyolysis and myoglobinuria. Electromyographic abnormalities, when present, are suggestive of a myopathic pattern, rather than inflammatory muscle disease. A subclinical motor neuropathy may also occur. Hence, there is evidence for subclinical envenomation following bites by Russell's viper. Early antivenom therapy does not prevent the histologic, electromyographic, or nerve conduction abnormalities.

Adult↗
PubMed1992

Limited proteolysis and active-site labeling studies of soybean lipoxygenase.

Soybean lipoxygenase 1 was studied using limited proteolysis and active-site labeling to begin the structural characterization of the enzyme in solution. The serine proteases trypsin and chymotrypsin cleaved the large monomeric protein (95 kDa) into two large polypeptides, a C-terminal fragment of about 30 kDa and an N-terminal fragment of about 60 kDa. Under conditions that led to complete cleavage of the protein as judged by SDS-polyacrylamide gel electrophoresis, the catalytic activity of the protein was either reduced slightly (chymotrypsin) or enhanced (trypsin). The characteristics of the cleaved enzymes were the same as for native lipoxygenase 1 in all aspects examined: insensitivity to cyanide, fluoride, and EDTA, regiochemical and stereochemical consequences of catalysis, and EPR spectroscopy upon oxidation by product. The two fragments apparently were tightly associated as they could not be resolved under conditions which preserved the catalytic activity. Both native and protease-cleaved lipoxygenase 1 formed covalent adducts when treated with either 14C-phenylhydrazine or 4-nitrophenylhydrazine. The label was found only in the 60-kDa fragment and following complete trypsin digestion was associated with a peptide beginning after Lys-482 in the primary sequence. Therefore labeling occurred in the vicinity of the conserved histidine cluster which has been postulated as the iron-binding site. From these observations it appears that lipoxygenase 1 exists as a pair of tightly associated domains with the iron-binding site located in the larger of the two.

Amino Acid Sequence↗
PubMed1992

Prevention of galactose cataract by pyruvate.

The effect of pyruvate on the progress of galactose cataract has been studied. Pyruvate was administered topically in the form of eye drops. Such treatment was found to delay the onset of the cataractous changes. Cataract formation was studied by visual inspection with pen light, as well as with slit lamp biomicroscopy in the intact animal. The delay in the formation of cataract was associated with the preservation of the levels of lens ATP, soluble proteins and the decreased accumulation of galactitol. In vitro organ culture experiments yielded similar results.

Adenosine Triphosphate↗