Search PubMed⌕ Search

Biomedical subjects

S Pradhan

Publications and source records attributed to S Pradhan.

At least 73 records · Page 4Linked to original sources
PubMed1997

Interpatient variability: genetic predisposition and other genetic factors.

Polymorphisms and other genetic factors related to enzymes metabolizing drugs and xenobiotic chemicals are well known. This article focuses on selected molecular mechanisms and introduces some of the clinical implications arising from genetically determined interpatient variability or expression in some of these enzymes. Selected are the polymorphic enzymes of cytochromes P-450 (CYP) as examples of phase I enzymes and methyl transferases, n-acetyl transferases, and glutathione-s-transferases as examples of phase II enzymes. The polymorphism surrounding arylhydrocarbon hydroxylase induction is briefly described. Phase I enzymatic reactions are predominantly oxidative, whereas phase II reactions often couple with the byproducts of phase I. Overall, in poor metabolizers, whether phase I or phase II, there is limited metabolism in most patients unless another major metabolic pathway involving other enzymes exists. Drug metabolism also depends on whether the parent compound is a prodrug that forms an active metabolite, and poor metabolizers under this condition will form only trace amounts of an active compound. Therefore, the clinical significance of genetic polymorphisms and other genetic factors may be related to substrate, metabolite, or the major elimination pathway.

Cytochrome P-450 Enzyme System↗
PubMed1997

Proportion and pattern of dystrophin gene deletions in north Indian Duchenne and Becker muscular dystrophy patients.

Population-based variations in frequency and distribution of dystrophin gene deletions have been recognized in Duchenne/Becker (DMD/BMD) muscular dystrophy patients. In the present study, DNA samples from 121 unrelated DMD/BMD patients from North India were analyzed for deletional studies with multiplex PCR and Southern hybridization. A total of 88 (73%) patients showed intragenic deletions in the dystrophin gene. The observed proportion of gene deletions is relatively high, particularly compared with that of Asian counterparts. However, the distribution of breakpoints across the gene does not show significant variations.

Dystrophin↗
PubMed1997

Parainfectious myelitis: three distinct clinico-imagiological patterns with prognostic implications.

Seventeen parainfectious myelitis patients were studied for site, extent and severity of lesions. Three patterns were observed each having distinct clinical, electrophysiological and MRI features: 1) focal segmental myelitis--focal cord lesion with long tract signs and good prognosis; 2) ascending myelitis--continuous lesion from conus to mid-cord with upper and lower motor neuron signs (not necessarily spinal shock), dysautonomia and poor outcome; 3) disseminated myelitis--discrete lesions scattered throughout the cord with subtle signs in spinal segmental distribution, above and below the transverse level and moderate outcome. Severe autonomic dysfunction, denervation of paraspinal muscles, "dense" lesion on imaging and often (but not always) the absent somatosensory evoked potentials carried poor outcome. In conclusion "parainfectious myelitis" is a better term to describe transverse myelitis, as the lesion extends to a large vertical extent. Further classification into 3 subgroups may improve understanding of anatomical and physiological dysfunction and prediction of outcome.

Adolescent↗
PubMed1997

Genotype-phenotype correlation in Duchenne/Becker muscular dystrophy patients seen at Lucknow.

The molecular basis of two allelic forms of muscular dystrophy, Duchenne (DMD) and Becker (BMD), has been explained by frame shift hypothesis. In order to test this hypothesis, deletional mutations in 59 patients confirmed to have DMD and 11 BMD patients were analysed using multiplex polymerase chain reaction and Southern hybridization with dystrophin cDNA probes. Translational reading frame of the dystrophin gene was derived from 'Border type' analysis of exons flanking the intragenic deletions. The correlation between genotype (reading frame) and phenotype (clinical severity) showed higher number of DMD patients (approximately 20%) deviating from the frame shift hypothesis. The patients who deviated had deletions at the central hot spot region of the dystrophin gene. The presence of these deviations in a large number of DMD patients highlights the difficulties in predicting the clinical progression of the disease based only on DNA profile.

Gene Deletion↗
PubMed1995

DNA binding and methyl transfer catalysed by mouse DNA methyltransferase.

By using a purified fraction of mouse DNA methyltransferase we have shown, by gel-retardation analysis, that the enzyme forms a low-affinity complex preferentially with hemimethylated DNA; the complexes formed with unmethylated or with fully methylated DNA are of even lower affinity, and only very weak interaction occurs with DNA lacking CG dinucleotides. Interaction is inhibited by N-ethylmaleimide. Methyl transfer from S-adenosyl-methionine is associated with the release of the fully methylated product from the complex. Complexes formed with the intact enzyme are extremely large, but limited trypsin treatment allows a major complex to enter the gel. DNA binding is not inhibited by this limited proteolysis of the native enzyme.

Animals↗
PubMed1995

CG and CNG methyltransferases in plants.

We have purified two distinct DNA methyltransferases from pea shoot tips and analysed their sequence specificity using synthetic oligodeoxyribonucleotide substrates and chemical sequencing methods. One methylates only CG target sequences, whereas the other methylates only CAG or CTG target sequences. We have found no evidence for methylation of the 5' cytosine in CCG target sequences either in vivo or in vitro. Using amino-acid sequence data, PCR-amplified fragments from conserved sequences and heterologous probes, we have isolated several cDNA clones that react with mRNA molecules of different sizes.

Base Sequence↗
PubMed1995

Urinary tract infection in patients of gynecological malignancies undergoing external pelvic radiotherapy.

A total of 216 midstream urine (MSU) samples from 36 patients with gynecological malignancies undergoing external pelvic radiotherapy (RT) were studied periodically every week for any evidence of urinary tract infection (UTI). UTI was detected in 33.3% patients of whom 8.3% had infection at the onset of RT and the rest developed UTI during the course of therapy. All three patients who had UTI at the onset of RT underwent cystoscopy as a part of routine pretreatment workup. A higher preponderance of UTI was observed in patients of stage III carcinoma cervix (33.3%) compared to stage II (16.7%) during the course of RT. Half of the patients with UTI had repeated episodes of infection despite appropriate antibiotic treatment. The study emphasizes the importance of conducting periodic MSU examination in patients with gynecological malignancies during RT and its treatment with appropriate antibiotics to minimize the risks of further injury to the already susceptible uroepithelium following radiotherapy.

Adult↗
PubMed1995

Infraspinatus muscle hypertrophy and wasting of axillary folds as the important signs in Duchenne muscular dystrophy.

Eighty-four patients with Duchenne muscular dystrophy (DMD) were examined clinically for hypertrophy and wasting in different muscles, parts of the muscles or muscle groups. Some muscles were examined under mild contraction to bring out any subclinical pseudohypertrophy. Findings revealed infraspinatus muscle hypertrophy to be significantly frequent (88%) and closely second to well known calf hypertrophy (94%). Infraspinatus hypertrophy was noted in 5 such DMD patients in whom calf hypertrophy was unremarkable. The wasting was consistently observed in the muscles forming anterior and posterior axillary folds. In conclusion, infraspinatus muscle hypertrophy and wasting of axillary folds are the important supportive clinical evidences during the examination of DMD patients.

Adolescent↗
PubMed1995

Central pontine myelinolysis following 'slow' correction of hyponatremia.

Two patients with central pontine myelinolysis are described for the peculiar mode of development. Both patients were in chronic renal failure and admitted in a stuporous state due to hyponatremia. Both developed central pontine myelinolysis during the hospital stay following slow and judicious correction of hyponatremia. The role of chronicity of hyponatremia prior to its correction, in the genesis of central pontine myelinolysis, particularly in the patients who have chronic debilitating illness, septicemia or malnutrition, is highlighted.

Adult↗
PubMed1995

Distinct CG and CNG DNA methyltransferases in Pisum sativum.

DNA methyltransferase activity, present in low salt extracts of nuclei from young pea shoot apices, has been fractionated into two different species by assaying with model substrates. The CG methyltransferase (an unstable enzyme believed to be of 140 kDa) methylates cytosine only in oligonucleotides with CG and Cl dinucleotide targets while an enzyme of 110 kDa (the CNG methyltransferase) methylates the cytosines in 5'-CAG-3' and 5'-CTG-3' target sequences, especially when hemimethylated, but not in 5'-CCG-3' nor in 5'-CGG-3' target sequences present in oligonucleotides.

Base Sequence↗
PubMed1994

New clinical sign in Duchenne muscular dystrophy.

A new sign in Duchenne muscular dystrophy is described. The sign demonstrates a unique characteristic of this disorder: selective hypertrophy and wasting in different muscles of the same region. The patients were asked to abduct their arms to about 90 degrees with elbows flexed to 90 degrees and hands directed upwards. Those who could not abduct the arm to 90 degrees were asked to do so to the maximum that they could. In this posture, all patients had examination of pectoral girdles from behind. Some patients with spinal muscular atrophy and other forms of muscular dystrophies were also examined in the same manner. In this posture, patients with Duchenne muscular dystrophy demonstrated a linear or oval depression (due to wasting) of the posterior axillary fold with hypertrophied or preserved muscles on its 2 borders (i.e., infraspinatus inferomedially and deltoid superolaterally), as if there were a valley between the 2 mounts. The sign was specific to Duchenne muscular dystrophy with sensitivity of about 90%. It was most remarkable in patients 8-11 years of age.

Child, Preschool↗
PubMed1993

DNA substrate specificity of pea DNA methylase.

DNA methylase, present in low-salt extracts of nuclei prepared from Pisum sativum shoot tips, methylates model DNA substrates containing CNG trinucleotides or CI dinucleotides only. The binding to the hemimethylated trinucleotide substrates is very much stronger and more persistent than the binding to the unmethylated substrates or to the hemimethylated dinucleotide substrate. When the DNA concentration is limiting, the rate of methyl-group transfer with the hemimethylated CNG substrate is much greater than that with the unmethylated CNG. However, the Vmax. is similar for the two CNG substrates. On fractionation using Q-Sepharose, two peaks of activity are seen with different relative activities using the di- and trinucleotide substrates. The relative activity with these substrates changes during purification, during plant growth and on heating at 35 degrees C as well, indicating that more than one enzyme or more than one form of the enzyme may be present.

Chromatography, Gel↗
PubMed1993

Prevention of postischemic injury in immature intestine by deferoxamine.

Free radical-mediated reperfusion injury has been demonstrated in ischemic neonatal bowel necrosis, but the mechanism of injury remains elusive. To determine whether such an injury can be prevented, 76 weaning rats were studied to test the effects of deferoxamine, an iron chelator, in postischemic injury. Group I (N = 20) had a sham laparotomy without vascular occlusion. Group II (N = 21) was subjected to 90 min of superior mesenteric artery occlusion prior to reperfusion. Group III (N = 35) received deferoxamine 15 mg/kg intravenous prereperfusion, in addition to ischemia and reperfusion as in group II. Survival profiles for each group were determined and a scale of pathologic severity was applied and compared. Group I had 100% long-term survival and group II, 14%. Group III had an overall survival of 28% and demonstrated a prolonged postreperfusion survival profile (P < 0.002) compared to group II. Histology was nearly identical to human necrotizing enterocolitis in degrees of bowel wall destruction and relative paucity of neutrophils. Group III showed a significant reduction in severity of injury compared to group II (P < 0.003). We conclude that neonatal bowel ischemia conditions such as necrotizing enterocolitis may be reperfusion injuries wherein free iron plays an important role in tissue injury. Administration of an iron chelating agent under such conditions has a beneficial effect on survival and histology.

Animals↗
PubMed1993

Tibialis anterior R-1 response: physiological behaviour, normative data and clinical utility in L4-L5 radicular compression.

A modified H-reflex, known as R-1 response, was recorded in healthy subjects by averaging 200 responses from the moderately contracting tibialis anterior muscle (TA) after repetitive submaximal stimulation of common peroneal nerve. Physiological changes to different modes of stimulation and recording were studied and normative data obtained at the most reliable parameters. Subsequently, the test is applied to 36 patients with clinical and myelographic evidences of L5 or L4-L5 radicular compression (with or without S1 radicular compression). Increasing the force of muscle contraction resulted in increase in amplitude up to a certain limit, with no change in latency. Increasing the current from subliminal to submaximal stimulation caused initial increase and subsequent fall in the amplitude without change in the latency. The change in the stimulus frequency from 0.5 to 3 Hz did not alter latency or amplitude but the higher frequencies sometimes did. On changing the position of the foot from plantarflexed to dorsiflexed, an increase in amplitude and reduction in duration of the response was noted. Fifty subjects were studied using stimulus intensity just enough to produce 200-400 microV M-response, stimulus duration of 1.0 msec, stimulus rate of 3 Hz and the muscle force sufficient to keep the foot in complete dorsiflexion. The tibialis anterior R-1 response (TAR-1) could be recorded reliably from both legs in all the subjects. The take-off point was sharp and in no subject was there any difficulty in measuring the latency to onset point. On repeating the test, the onset point of the response was superimposable. Latency showed linear correlation with height and age. Among the patients, 21 out of 25 cases of unilateral (84.0%) and 10 out of 11 cases of bilateral (90.9%) radicular compression had abnormal findings. Abnormalities included significant a right-left latency difference within the normal range of absolute latencies, unilateral or bilateral prolongation of latency to onset point and attenuation or absence of the response. It was concluded that the TAR-1 is an important and reliable test for the study of functional integrity of L4-L5 spinal segments in lumbo-sacral sensorimotor root lesions.

Adolescent↗