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Biomedical subjects

S Ghosh

Publications and source records attributed to S Ghosh.

At least 19 recordsLinked to original sources

Isolation of a cDNA clone for beta 1-4 galactosyltransferase from embryonic chicken brain and comparison to its mammalian homologs.

Based on the observed biochemical and immunological similarities between bovine beta 1-4 galactosyltransferase (GalT) and a developmentally regulated galactosyltransferase (GalT-4; UDP-Gal:Lc3 beta 1-4 GalT) from embryonic chicken brain, a genetic similarity between the two enzymes has been postulated. To test our hypothesis, we have employed a reverse transcription-polymerase chain reaction (RT-PCR)based approach and isolated a approximately 600 bp cDNA clone from embryonic chicken brain mRNA. Our results indicate that, within the approximately 600 bp fragment, the avian cDNA nucleotide sequence is 74% homologous to the human beta 1-4 galactosyltransferase cDNA. Similarity and identity between the predicted amino acid sequences of the two galactosyltransferases are 75% and 61%, respectively. Similar to its mammalian counterparts, the embryonic chicken brain galactosyltransferase gene appears to encode multiple mRNA transcripts (2.3 and 1.4 kb) and shows multiple bands on a Southern blot (18.6, 12.9, 10.5 and 3.7 kb) indicating that the avian gene is either polyexonic and/or it belongs to a multiple gene family.

Amino Acid Sequence

Effects of guava intake on serum total and high-density lipoprotein cholesterol levels and on systemic blood pressure.

There is evidence that inclusion of high fiber foods such as oats, fruits and vegetables in the diet can decrease fat intake and modulate blood lipids. To test this hypothesis, 61 group A and 59 group B patients with essential hypertension were administered guava fruit preferably before meals in a foods-to-eat approach rather than foods-to-restrict, in a randomized and single-blind fashion for 12 weeks. At entry into the study, mean age, male sex, mean body mass index, percentages of risk factors and mean levels of blood lipids were comparable between groups A and B. Adherence to guava consumption was assessed by questionnaires and weighing of guava intake by 24-hour recall after 12 weeks of follow-up. Nutrient intakes including saturated and total fat were significantly decreased; carbohydrates, total and soluble fiber and vitamins and mineral intakes were significantly higher in group A than in group B at 12 weeks. There was a significant net decrease in serum total cholesterol (9.9%), triglycerides (7.7%) and blood pressures (9.0/8.0 mm Hg) with a significant net increase in high-density lipoprotein cholesterol (8.0%) after 12 weeks of guava fruit substitution in group A than in group B. By adding moderate amounts of guava fruit in the usual diet, changes in dietary fatty acids and carbohydrates may occur, providing significant amounts of soluble dietary fiber and antioxidant vitamins and minerals without any adverse effects. There is a greater decrease in lipoprotein metabolism and blood pressures.

Blood Pressure

Effect of fat-modified and fruit- and vegetable-enriched diets on blood lipids in the Indian Diet Heart Study.

This study was designed to test the efficacy of the administration of fruits and vegetables for 12 weeks as an adjunct to a prudent diet in decreasing blood lipids in 310 (intervention; group A) and 311 (control; group B) patients with risk factors of coronary artery disease (CAD) in a parallel, single-blind fashion. At entry to the study, sex, mean age, body weight, body mass index, systolic and diastolic blood pressures, and blood lipoproteins were comparable between both groups. Tasty fruits and vegetables were given to patients to eat before major meals for better nutrient adherence and adequacy. Dietary intakes were determined by questionnaires and by weighing of fruit and vegetable intake. Fruits and vegetables decreased total cholesterol level by 6.5% and low-density lipoprotein cholesterol level by 7.3% in group A, whereas the levels were unchanged in group B. The high-density lipoprotein cholesterol levels that decreased during the diet stabilization period in both groups, increased by 5.6% in group A after 12 weeks. Serum triglycerides also decreased (7%) more in group A than B. Fasting blood glucose decreased by 6.9% in group A and by 2.6% in group B. The combined effect of a fat-modified diet plus fruits and vegetables was greater than these changes. Because tasty fruits were taken by the patients before meals (when they are hungry) and are easily available at reasonable cost in our marketing and buying capacity, the compliance was excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow up.

OBJECTIVE: To test whether a fat reduced diet rich in soluble dietary fibre, antioxidant vitamins, and minerals reduces complications and mortality after acute myocardial infarction. DESIGN: Randomised, single blind, controlled trial. SETTING: Primary and secondary care research centre for patients with myocardial infarction. SUBJECTS: 505 patients with suspected acute myocardial infarction. Those with definite or possible acute myocardial infarction and unstable angina based on World Health Organisation criteria were assigned to diet A (n = 204) or diet B (n = 202) within 24-48 hours of infarction. INTERVENTIONS: Both groups were advised to follow a fat reduced diet. Group A was also advised to eat more fruit, vegetables, nuts, and grain products. MAIN OUTCOME MEASURES: Mortality from cardiac disease and other causes. Serum lipid concentrations and compliance with diet. RESULTS: Blood lipoprotein concentrations and body weight fell significantly in patients in group A compared with those in group B (cholesterol fell by 0.74 mmol/l in group A v 0.32 mmol/l in group B, 95% confidence interval of difference 0.14 to 0.70, and weight by 7.1 v 3.0 kg, 0.52 to 7.68). The incidence of cardiac events was significantly lower in group A than group B (50 v 82 patients, p less than 0.001). Group A also had lower total mortality (21 v 38 died, p less than 0.01) than group B. CONCLUSIONS: Comprehensive dietary changes in conjunction with weight loss immediately after acute myocardial infarction may modulate blood lipoproteins and significantly reduce complications and mortality after one year.

Adult

Chromosomal alterations and sister chromatid exchanges induced by zirconium oxychloride in human lymphocytes in vitro with relation to age of donors.

Aqueous solutions of zirconium oxychloride were added to human peripheral blood lymphocyte culture. Cultures were set up from healthy donors of both sexes belonging to age groups of 0-10, 11-20, 21-30, 31-40, 41-50 and 51-60 years. Airdried Giemsa schedule was followed for preparation of chromosomal aberrations and micronuclei count. Flourescence plus Giemsa staining techniques were applied for the study of sister chromatid exchange. The endpoints screened were chromosome and chromatid breaks, dicentrics and rearrangements. The frequencies of chromosomal aberrations and sister chromatid exchanges induced were compared between the samples of different age groups. The frequency of CA could not be related to age of the donor. However, the frequency of SCE increased with increase in age of female donor.

Adolescent

Structural response of the hamster Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study.

Reproductively active hamsters were hypophysectomized and examined 6 or 20 days later in a combined morphometric and endocrine study of the Sertoli cell to determine 1) the morphological and endocrine effects of hypophysectomy of both short- and long-term duration, 2) if regression of Sertoli cells after hypophysectomy in a seasonal breeder resembles regression due to seasonal changes, and 3) if effects of hypophysectomy in a seasonal breeder are equivalent to the effects of hypophysectomy in a nonseasonal breeder. Six days after hypophysectomy, at a period when germ cell degeneration is first noted, there was a significant decrease in testis weight, interstitial space, tubule diameter and length, volume of seminiferous tubule, and tubular lumen. There were no significant changes in Sertoli cell nuclear and cytoplasmic volume although cell surface area was decreased significantly. Most organelles exhibited no significant change in volume or surface area except for secondary lysosomes which expectedly increased in volume as the result of phagocytosis of germinal cells. Thus at an early time period when functional changes in germ cells and Leydig cells are clearly evident (Russell et al. [1992] Endocrinology), the Sertoli cell shows minimal changes. Twenty days after hypophysectomy, the cell, nuclear and cytoplasmic volumes and surface area of the Sertoli cells, and volumes and surface areas of nearly all organelles were significantly decreased from values measured in normal and in short-term hypophysectomized hamsters. The exceptions were the total volumes of lipid which increased significantly and lysosomes which were similar to normal but significantly lower than short-term hypophysectomized animals. The long-term hypophysectomized hamster Sertoli cell, like that of the short-day hamster (Sinha Hikim et al. [1989b] Endocrinology, 125:1829-1843) is structurally regressed as a whole rather than exhibiting selective decreases in cellular and subcellular components. The size of the Sertoli cell in pituitary-intact, long- and short-term hypophysectomized animals showed positive and significant correlations with the volumes and surface areas of all its cytoplasmic organelles except the volume of lipid which showed a negative, significant correlation. Comparisons of long-term hypophysectomized hamsters (in long-day light exposure) and short-day exposed animals (Sinha Hikim et al. [1989b] (Endocrinology, 125:1829-1843) suggested that hypophysectomy, in general, resulted in similar, but slightly more severe regressive changes in the testis and germ cell population than those seen during seasonal regression.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The NF-kappa B p50 precursor, p105, contains an internal I kappa B-like inhibitor that preferentially inhibits p50.

The p50 subunit of NF-kappa B is apparently synthesized as a precursor molecule of 105 kDa (p105); subsequent processing releases the amino-terminal p50 polypeptide with rel homology, DNA binding activity and transcriptional activation potential. The carboxy-terminal region of p105 contains seven copies of an ankyrin-related sequence previously found in several genes involved in differentiation and cell cycle control. Two proteins with I kappa B activity, MAD-3 and pp40, have been cloned and found to contain five obvious ankyrin repeats that align with those in the carboxy-terminus of p105. Both proteins target their inhibitory activity to the p65 subunit of NF-kappa B and to c-rel. Here we show that the bacterially expressed and purified carboxy-terminal region (CTR) of p105 abolishes the binding of p50 homodimers to a kappa B motif but minimally affects the binding of p65 homodimers and NF-kappa B. By contrast, MAD-3 inhibits the binding of p65 and NF-kappa B but not p50. Both the CTR and MAD-3 interact with their respective targets through physical association both in vitro and in vivo. The CTR can be expressed as an independent entity and thus may play two roles, as a cis inhibitor built into the p105 molecule and as a trans regulator of p50.

Amino Acid Sequence

Crystal structures of a new oral iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone, and its solvates with acetic acid and formic acid.

The crystal structures of a new oral iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone (DMHP), and of its 1:1 solvates with formic acid (DMHP,F) and acetic acid (DMHP,A) were determined by single-crystal X-ray diffraction. The data were collected at temperatures of 23 +/- 1 degrees C for DMHP, -64 +/- 1 degrees C for DMHP,F, and -120 +/- 1 degrees C for DMHP,A. The iron chelator DMHP is orthorhombic [Pbca, a = 7.290(5) A, b = 13.046(4) A, c = 13.748(6) A, Z = 8]. The DMHP molecules form centric dimers, each in a 10-membered ring in which the OH group of one molecule is hydrogen-bonded to the CO oxygen of the other [O-H...O; 0.91(4) A, 153(3)degrees, 1.85(4) A]. In each DMHP molecule, the OH group and CO oxygen are insignificantly intramolecularly hydrogen-bonded [O-H...O; 0.91(4) A, 107(3)degrees, 2.33(4) A]. DMHP,F is monoclinic [C2/c, a = 21.825(9) A, b = 3.811(5) A, c = 20.491(6) A, beta = 92.80(3)degrees, Z = 8]. The fundamental intermolecular and insignificant intramolecular hydrogen-bonded dimer structure of DMHP is maintained but is distorted and is supplemented by hydrogen bonds between the CO oxygen of each DMHP molecule and the OH group of one formic acid molecule [O-H...O; 0.99(5) A, 176(3)degrees, 1.53(4) A]. However, the two DMHP and the two formic acid molecules are twisted out of plane like the blades of a four-bladed propeller. DMHP,A is triclinic [P1, a = 8.458(2) A, b = 8.471(2) A, c = 6.986(3) A, alpha = 104.33(2)degrees, beta = 92.57(2)degrees, gamma = 88.78(2)degrees, Z = 2].(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates

Responses of cat ventroposterolateral thalamic neurons to vibrotactile stimulation of forelimb footpads.

Responses of neurons in the ventroposterolateral nucleus of the thalamus to vibration applied to the forelimb footpads were analyzed in anesthetized cats in order to describe the signalling properties of thalamic neurons that received input from the different classes of tactile afferents innervating the glabrous skin of the distal forelimb. Seventy-six thalamic neurons, the majority of which (60 of 76) were positively identified as thalamocortical projection neurons, were classified into two broad groups according to their responses to 1-s step indentations of the skin. A minority (24%) comprised neurons that had slowly adapting (SA) responses, whereas the remainder (76%), the dynamically sensitive neurons, had transient responses to the onset and offset phase of the step and were further classified according to their sensitivity to cutaneous vibrotactile stimuli into those activated by low-frequency vibration (rapidly adapting, RA, neurons) and those activated by high frequencies (Pacinian afferent, PC, neurons). Thalamic RA neurons displayed phaselocked responses to vibration at frequencies up to approximately 100 Hz, while PC neurons displayed phaselocked responses to vibration up to 400-500 Hz. Thalamic SA neurons varied in their responses to vibrotactile stimuli; half were most sensitive to vibration frequencies of 50 Hz or less, while the others responded over a broader range of frequencies. Although three major classes of footpad-related thalamic neurons were identified, there was evidence of convergent input to a small proportion of them. The study demonstrates that thalamic neurons have the capacity for responding to cutaneous vibration with phaselocked, patterned impulse trains, which would enable them to encode information about vibrotactile frequencies up to approximately 300 Hz.

Anesthesia

Terodiline causes polymorphic ventricular tachycardia due to reduced heart rate and prolongation of QT interval.

Recent reports have suggested an association between terodiline hydrochloride and cardiac arrhythmias. We report 4 patients presenting over a six month period who developed polymorphic ventricular tachycardia (polymorphic VT) while receiving treatment with this agent. In each case there was prolongation of QT interval on electrocardiogram (ECG). Two patients had hypokalaemia associated with diuretic therapy. In the 3 cases in which follow-up ECG was available, QT interval returned to normal after discontinuation of terodiline. In order to define the effects of terodiline on corrected QT interval (QTc) and heart rate in the elderly, a prospective study was performed in 8 elderly in-patients treated with terodiline for urinary incontinence. After 7 days treatment with terodiline 12.5 mg twice daily, there was a significant increase in QT by a mean of 29 ms, QTc by 15 ms and a decrease in resting heart rate by a mean of 6.7 beats.min-1. Terodiline increases QTc and reduces resting heart rate in elderly patients. Both these effects may be associated with polymorphic VT, a potentially life threatening arrhythmia. This drug should be avoided in patients with other known risk factors for polymorphic VT, particularly hypokalaemia and cardiac disease.

Aged

The non-dosage compensated LSP1-alpha gene of Drosophila melanogaster lies immediately downstream of the dosage compensated L12 gene.

The X-linked gene LSP1-alpha of Drosophila melanogaster, expressed in the third larval instar, does not exhibit dosage compensation at its normal locus but does compensate when it is relocated to ectopic sites on the X chromosome. A transcription unit designated L12, which is active in the second larval instar and capable of encoding a putative protein of 28.5 kDa, lies immediately downstream from LSP1-alpha. We have determined that L12 is dosage compensated by measuring the steady-state level of its transcript in male and female larvae. The difference in response of these two adjacent genes should be taken into consideration when models of the mechanism of dosage compensation are formulated.

Animals

Interaction between two group IV metals--lead and zirconium--in bone marrow cells of Mus musculus in vivo.

The interaction between two group IV metals, the highly toxic lead and the relatively inactive and low toxic zirconium, was studied in the bone marrow chromosomes of Mus musculus in vivo. Low and high doses of zirconium oxychloride were fed orally to the experimental mice (i) 2 h before, (ii) 2 h after or (iii) together with different doses of lead nitrate. Protection against lead-induced clastogenicity was observed only when the lower dose of zirconium was administered prior to lead. All other combinations gave an additive or synergistic effect as was seen by significant increases in the frequencies of chromosomal aberrations.

Animals

Ising model for B-Z transition in supercoiled DNA.

The possible existence of nucleic acids in right-handed and left-handed helical forms is considered. A statistical mechanical model is developed to obtain an expression for a change in twist during helical transformation in terms of corresponding free energies and linking for a supercoiled DNA. The theoretically predicted values are compared with those determined experimentally. The physico-chemical significance of the parameters is discussed.

Base Composition

Zirconium. An abnormal trace element in biology.

The action of Zirconium (Zr) on biological systems presents an enigma. It is ubiquitous, being present in nature in amounts higher than most trace elements. It is taken up by plants from soil and water and accumulated in certain tissues. The entry into animal systems in vivo is related to the mode of exposure and the concentration in the surrounding environment. Retention is initially in soft tissues and then slowly in the bone. The metal is able to cross the blood brain-barrier and is deposited in the brain and the placental barrier to enter milk. The daily human uptake has been known to be as high as 125 mg. The level of toxicity has been found to be moderately low, both in histological and cytological studies. The toxic effects induced by very high concentrations are nonspecific in nature. Despite the presence and retention in relatively high quantities in biological systems, Zr has not yet been associated with any specific metabolic function. Very little information is available about its interaction with the compounds of the genetical systems, such as nucleic acids. Apparently, the metal is neither an essential nor toxic element in the conventional sense. However, the increasing exposure to this element through its increasing use in new materials and following radioactive fallout, has increased the importance of the study of its effects on living organisms. The tetravalent nature of the ionic state and the high stability of the compounds formed are important factors that need to be considered, as also the accumulation of this element in the brain, reminiscent of the relationship between Al3+ and Alzheimer's disease.

Animals