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Biomedical subjects

I Chakravarty

Publications and source records attributed to I Chakravarty.

At least 19 recordsLinked to original sources

Micronutrient malnutrition--present status and future remedies.

Micronutrient deficiency is a serious public health concern in most of the developing countries which leads to malnutrition syndromes. The micronutient deficiencies which are of greatest public health significance include iron deficiency, vitamin A deficiency and iodine deficiency disorder. National Pilot Programme on Control of Micronutrient Malnutrition was launched in 1995 and the department of biochemistry and nutrition of the All India Institute of Hygiene and Public Health, Calcutta was entrusted to co-ordinate the activities. It presently covers five eastern and north-eastern states. Baseline situation analysis was conducted mainly on iron deficiency anaemia, iodine deficiency disorder and vitamin A deficiency. Comparing with WHO cut off figures, point prevalence of anaemia in various age groups was found to be high. Bitot's spot was mainly noted in the age group of 6-71 months. Nightblindness was found in the children of the age group of 24-71 months. High prevalence of nightblindness in pregnant women is a point of concern. Action needed to control micronutrient deficiency includes: Intervention strategies, extensive nutrition and health education, to support the problem specific programmes, to stregthen various state government programmes and strengthen role of NGOs.

Adult↗

Effect of subacute administration of three organophosphorus pesticides on the hepatic phosphatases under various nutritional conditions.

In developing countries, extensive use of pesticides to meet with increased agricultural needs is inevitable and the indiscriminate use has led to several toxicological implications in humans. The toxic effects, however, to a large extent depend on the nutritional status of the individuals. In the present work, the hepatic susceptibility to pesticide toxicity has been studied in experimental animals maintained on diets containing different levels of protein for a period of 3 weeks. Along with protein deprivation, the rats were also exposed to three organophosphorus pesticides, viz., parathion, malathion, and phosalone, individually at various doses for the same time period. Phosphatases, the functionally important enzymes of the liver, were estimated and the results obtained indicated that protein deprivation further aggravated the pesticide-induced effects on the hepatic phosphatases.

Acid Phosphatase↗

Protein synthesis in rabbit reticulocytes. A study of the mechanism of Co-eIF-2 action.

The characteristics of component activities in Co-eIF-2 (where eIF is eukaryotic initiation factor) protein complex have been studied. (i) At limiting concentrations, Co-eIF-2 promoted rapid GDP binding to eIF-2 and also GDP displacement from eIF-2 X GDP during ternary complex formation in the presence of GTP and Mg2+ (Co-eIF-2C activity) but did not significantly stimulate ternary complex formation by eIF-2. (ii) At higher concentrations, Co-eIF-2 significantly enhanced ternary complex formation by eIF-2 and also rendered the complex stable to aurintricarboxylic acid presumably as Co-eIF-2 became physically bound to the ternary complex (Co-eIF-2A activity). (iii) Ternary complex preformed in the presence of Co-eIF-2 and without Mg2+ dissociated upon subsequent addition of Mg2+ (Co-eIF-2B activity). This dissociation reaction was presumably due to loss of interaction of the Co-eIF-2A component in Co-eIF-2 with the ternary complex (reversal of Co-eIF-2A activity) as the complex became increasingly sensitive to aurintricarboxylic acid with increasing Mg2+ concentration. In another study, purified eIF-2 was freed of bound GDP by treatment with alkaline phosphatase and the characteristics of native and GDP-free eIF-2 were compared. (i) One mM Mg2+ inhibited (60%) ternary complex formation by native eIF-2 but not by GDP-free eIF-2. Addition of exogenous GDP rendered GDP-free eIF-2 sensitive to Mg2+ indicating that Mg2+ inhibition is due to eIF-2-bound GDP. (ii) In the presence of Mg2+, Co-eIF-2 stimulated similarly ternary and Met-tRNAf X 40 S X AUG complex formation by both native and GDP-free eIF-2. Such stimulatory activity in each case was strongly inhibited by prior phosphorylation of eIF-2 alpha subunit by heme-regulated translational inhibitor. (iii) Ternary complexes preformed using either native and GDP-free eIF-2 and excess Co-eIF-2A80 in the absence of Mg2+ did not form Met-tRNAf X 40 S X AUG complex. They required trace amounts of Co-eIF-2 for such activity.

Alkaline Phosphatase↗

Protein synthesis in rabbit reticulocytes. Purification and properties of an Mr 80,000 polypeptide (Co-eIF-2A80) with Co-eIF-2A activity.

The high molecular weight protein complex, Co-eIF-2, contains both Co-eIF-2A and Co-eIF-2C activities (Bagchi, M. K., Banerjee, A. C., Roy, R., Chakravarty, I., and Gupta, N. K. (1982) Nucleic Acids Res. 10, 6501-6510). Co-eIF-2A stimulated Met-tRNAf binding to eukaryotic initiation factor-2 (eIF-2) both in the presence and absence of Mg2+. Co-eIF-2C stimulates Met-tRNAf binding to eIF-2 in the presence of Mg2+ by relieving Mg2+ inhibition of ternary complex formation from eIF-2. Co-eIF-2 protein complex contains several polypeptides including Mr 80,000 and 50,000 polypeptides. Three polypeptides (Mr 80,000, 50,000 and 25,000) are present in 0.5 M KCl ribosomal salt wash and each possesses Co-eIF-2A activity. Mr 80,000 polypeptide (Co-eIF-2A80) has been purified to homogeneity and its properties studied. 1) Co-eIF-2A80 stimulated Met-tRNAf binding to eIF-2 and the complex formed was resistant to aurintricarboxylic acid. 2) Co-eIF-2A80 activity was N-ethylmaleimide-resistant and heat-labile; it was destroyed by heating at 55 degrees C for 4 min. 3) Antibodies prepared against homogeneous Co-eIF-2A80 strongly inhibited protein synthesis in reticulocyte lysates and, also, eIF-2 and Co-eIF-2 promoted Met-tRNAf binding to 40 S ribosomes. Inhibition of protein synthesis in reticulocyte lysates was overcome by preincubation of anti-Co-eIF-2A80 with homogeneous Co-eIF-2A80 and was partially overcome by similar preincubation with Co-eIF-2. 4) Upon limited digestion with Staphylococcus aureus V8 protease, the homogeneous Co-eIF-2A80 gave two major polypeptide fragments (Mr 50,000 and 25,000). Upon similar treatment, an Mr 80,000 polypeptide band isolated from the sodium dodecyl sulfate-gel of the Co-eIF-2 protein complex gave four major polypeptide fragments, and two of these fragments (Mr 50,000 and 25,000) were similar to those given by Co-eIF-2A80, indicating that this Mr 80,000 polypeptide band contains the Co-eIF-2A80 component. We suggest that Co-eIF-2A80 is a component of Co-eIF-2 and is also essential for Co-eIF-2 activity and overall peptide chain initiation.

Animals↗

A comparative study of the characteristics of eIF-2 and eIF-2-ancillary factor activities from yeast Saccharomyces cerevisiae and rabbit reticulocytes.

The characteristics of yeast eukaryotic initiation factor 2 (eIF-2) and Co-eIF-2A have been studied and compared with those of the corresponding factors from rabbit reticulocytes. 1) Unlike eIF-2r, purified eIF-2y did not contain bound GDP. 2) Purified eIF-2y preparation contained GTPase activity and dephosphorylated GTP to GDP. 3) An anti-eIF-2r preparation which predominantly precipitated the gamma-subunit (Mr 54,000) of eIF-2r also precipitated the larger subunit (Mr 54,000) of eIF-2y. 4) Unlike eIF-2r, ternary complex formation by eIF-2y was not inhibited by Mg2+. 5) Both Co-eIF-2A20y and Co-eIF-2r significantly enhanced Met-tRNAf binding to eIF-2y and, again, Mg2+ did not have any effect on this stimulated Met-tRNAf binding to eIF-2y. 6) Both Co-eIF-2A20y and Co-eIF-2r were similarly effective in stimulating Met-tRNAf binding to eIF-2r in the absence of Mg2+. However, in the presence of Mg2+, Co-eIF-2A20y was significantly less effective than Co-eIF-2r as Co-eIF-2A20y did not promote displacement of GDP from eIF-2r X GDP. 7) eIF-2y bound [3H]GDP and this binding was significantly enhanced in the presence of Mg2+. Also, [3H]GDP in the preformed eIF-2y X [3H]GDP complex was rapidly exchanged with exogenously added unlabeled GDP in the presence of Mg2+. Co-eIF-2A20y had no effect on GDP binding to eIF-2y nor on GDP exchange reactions. 8) Reticulocyte heme-regulated protein synthesis inhibitor, which phosphorylated almost completely (in excess of 80%) the alpha-subunit (Mr 38,000) of eIF-2r, also phosphorylated similarly the smaller subunit (Mr 36,000) of eIF-2y. However, such phosphorylation had no significant effect on ternary complex formation, GDP binding, and GDP exchange reactions.

Animals↗

Protein synthesis in rabbit reticulocytes. A study of the roles of Co-eIF-2, Co-eIF-2A80, and GDP in peptide chain initiation.

The roles of Co-eIF-2, Co-eIF-2A80, and GDP in ternary complex and Met-tRNAf X 40 S initiation complex formation were studied. 1) Partially purified eukaryotic initiation factor 2 (eIF-2) (50% pure) preparations contained 0.4-0.6 pmol of bound GDP/pmol of eIF-2. eIF-2 purity was calculated from ternary complex formation in the absence of Mg2+ and in the presence of excess Co-eIF-2. 2) In the absence of Mg2+, approximately 30% of the potentially active eIF-2 molecules formed ternary complexes, and both Co-eIF-2 and Co-eIF-2A80 were equally effective in full activation of the eIF-2 molecules for ternary complex formation. 3) In the presence of Mg2+, approximately 10% of the potentially active eIF-2 molecules formed ternary complexes in the absence of ancillary factors, and the ancillary factors Co-eIF-2A80 and Co-eIF-2 raised the incorporation to 20 and 50% of the eIF-2 molecules, respectively. 4) In the absence of Mg2+, [3H]GDP in preformed eIF-2 X [3H]GDP was readily displaced by GTP during ternary complex formation. 5) In the presence of Mg2+, [3H]GDP remained tightly bound to eIF-2 and ternary complex formation was inhibited. Co-eIF-2, but not Co-eIF-2A80, was effective in promoting [3H]GDP displacement and the former was more effective in promoting ternary complex formation than the latter. 6) eIF-2 X [3H]GDP was converted to eIF-2 X [3H] GTP by incubation in the presence of nucleoside-5'-diphosphate kinase and ATP, but the eIF-2 X [3H]GTP thus formed did not bind Met-tRNAf in the presence of Mg2+ and required exogeneous addition of Co-eIF-2 and GTP for ternary complex formation and GTP displacement. 7) In the absence of Mg2+, the increased ternary complex formed in the presence of eIF-2 X [3H] GDP and Co-eIF-2A80 (with accompanying loss of [3H] GDP) was inactive in a subsequent reaction, which involves Met-tRNAf transfer to 40 S ribosomes (in the presence of Mg2+), and required trace amounts of Co-eIF-2 for such activity. Based on the above observations, we have suggested a two-step activation of eIF-2 molecules by the Co-eIF-2 protein complex for functional ternary complex formation. One of these steps involves the Co-eIF-2A component of Co-eIF-2. This activation results in stimulated Met-tRNAf binding to eIF-2 and is most apparent in the absence of Mg2+ and with aged eIF-2 molecules.(ABSTRACT TRUNCATED AT 400 WORDS)

Eukaryotic Initiation Factor-2↗

Assessment of the carcinogenic potential of a proposed food coloring additive, laccaic acid, using short-term assays.

Laccaic acid is a red colored natural dye produced by the insect Laccifer lacca or Coccus lacca. It is obtained in large amounts as a by-product of the shellac industry and has been considered for general use as a food coloring agent. Laccaic acid is found to have no mutagenic activity as assessed by two short-term assays: the Salmonella/microsome mutagenicity test, and the phi X fidelity assay. However, laccaic acid did inhibit metabolic cooperation in Chinese hamster V79 cells. These results suggest that laccaic acid should be tested in animals with particular emphasis on in vivo models for tumor promotion.

Animals↗

Augmented hepatic susceptibility to malathion toxicity in rats on low-protein diets.

With an increasing world population, use of pesticides is unavoidable. However, indiscriminate use of these chemical agents has resulted in several incidents of human intoxication. Toxic effects of human exposure may be influenced by their nutritional status. Effects of malathion, an organophosphorus insecticide, on the hepatic lipid and protein levels and GOT, GPT, and beta-glucuronidase activities in rats maintained on 16, 6, and 1% protein diets for a period of 3 weeks is reported. The doses of malathion used were 5, 50, 250, and 500 mg/kg body wt, administered 24 hr prior to decapitation. The results obtained indicated that malathion induced alterations in enzyme activity; lipid and protein levels were further perturbed by the dietary protein deficiency.

Alanine Transaminase↗

Protein synthesis in rabbit reticulocytes: a study of the mechanism of action of the protein factor RF that reverses protein synthesis inhibition in heme-deficient reticulocyte lysates.

A eukaryotic initiation factor 2 (eIF-2)-ancillary protein factor Co-eIF-2 promotes displacement of GDP from eIF-2 X GDP and facilitates ternary complex (Met-tRNAf X eIF-2 X GTP) formation in the presence of Mg2+. Heme-regulated protein synthesis inhibitor, HRI, phosphorylates the alpha-subunit of eIF-2 and thus inhibits ternary complex formation as Co-eIF-2 does not displace GDP from eIF-2 alpha (P) X GDP. RF, a high molecular weight cell supernatant factor, reverses protein synthesis inhibition in heme-deficient reticulocyte lysates and also reverses HRI inhibition of ternary complex formation. RF contains Co-eIF-2 activity. In addition, an active RF preparation contains excess alpha-subunit of eIF-2 in the free and unphosphorylated form and this alpha-subunit of eIF-2 is not phosphorylated by HRI and ATP. In this paper we report (i) an active RF preparation contains excess alpha-subunit of eIF-2 and this alpha-subunit can be phosphorylated by HRI and ATP in the presence of GDP; (ii) RF promotes ternary complex formation by eIF-2 X [3H]GDP with accompanying GDP displacement; (iii) in the presence of HRI and ATP, RF promotes ternary complex formation by eIF-2 X [3H]GDP without accompanying GDP displacement; (iv) in the presence of HRI and ATP, the ternary complex formed using RF is active in Met-tRNAf X 40S initiation complex formation; (v) both the ternary complex and the Met-tRNAf X 40S complex formation in the presence of HRI and ATP are completely inhibited by prior incubation of RF with GDP; (vi) upon further fractionation of an active RF fraction, a preparation can be obtained that contains HRI-sensitive Co-eIF-2 activity. However, this preparation does not efficiently reverse protein synthesis inhibition in heme-deficient reticulocyte lysates and does not contain excess alpha-subunit of eIF-2. Based on these observations, we have suggested (a) RF provides the unphosphorylated alpha-subunit to eIF-2 alpha (P) X GDP and restores eIF-2 activity. This RF activity is inhibited as the alpha-subunit in the RF preparation becomes phosphorylated by HRI and ATP in the presence of GDP; (b) RF contains Co-eIF-2 activity, which has dual functions: (i) stimulation of ternary complex formation by eIF-2 and (ii) GDP displacement from eIF-2 X GDP during ternary complex formation. In the presence of HRI and ATP, Co-eIF-2 but does not displace GDP from eIF-2 alpha(P) X GDP.

Adenosine Triphosphate↗

Effect of nutritional status on the circulatory gonadotrophin levels in girls before puberty.

Circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were investigated in prepubertal girls (aged 6 to 10 years) showing evidence of varying degrees of either stunting and wasting or both, due to protein-energy malnutrition (PEM). Both serum LH and FSH levels in all the subjects with either grade 1 or 2 type of stunting and no wasting, or grade 1 type of wasting and no stunting, showed no noticeable variations from the corresponding hormonal levels of the normals. However, a low serum FSH level was observed in one subject with grade 3 type of stunting. Amongst the subjects with both stunting and wasting, those with a combination of grade 1 type of stunting and wasting, serum hormonal levels were comparable to the normals. On the other hand, those with more severe degrees of wasting and stunting had low levels of serum LH and FSH, particularly of FSH. It is suggested that the low levels of these gonadotrophins may be responsible for the delay in the onset of menarche commonly encountered in cases of PEM.

Body Height↗

Enzymatic changes in the male reproductive organs by delta-9-tetrahydrocannabinol.

Like most psychoactive agents, cannabis and its active component delta-9-tetrahydrocannabinol (delta 9-THC) have been reported to affect the neuroendocrine axis in animals. The effect of delta 9-THC on some of the functionally important enzymes of the male reproductive organs are reported. The study indicates that delta 9-THC reduces the activities of the enzymes, beta-glucuronidase, alpha-glucosidase acid phosphatase and fructose-6-phosphatase in a dose related manner in the testis, prostate as well as in the epididymis. It may be concluded that delta 9-THC may interfere with the normal functioning of the male reproductive organs.

Acid Phosphatase↗

Circulating gonadotropin profile in severe cases of protein calorie malnutrition.

The circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were studied in children of both sexes between 2 and 14 years of age who were suffering from severe protein calorie malnutrition (PCM), namely, kwashiorkor, marasmic kwashiorkor, and marasmus. LH and FSH levels in all the age groups and in all forms of PCM were found to be significantly lowered, thereby explaining the possible delay in the onset of puberty in these children. Circulating PRL levels, on the other hand, were significantly raised in all patients with PCM studied, with values in children with kwashiorkor and marasmic kwashiorkor higher than in children with marasmus, possibly accounting for the presence of edema in the former cases. The present work, therefore, proposes a possible correlation between gonadotropin levels and PCM in children.

Adolescent↗

Delta-9-tetrahydrocannabinol: its effect on hypothalamo-pituitary system in male rats.

Subcutaneous administration of delta-9-tetrahydrocannabinol (delta 9-THC) in adult male rats caused a decrease in serum luteinizing hormone (LH) levels with unchanged serum prolactin, pituitary LH and pituitary prolactin content. Response of pituitary to in vitro gonadotropin releasing hormone (GnRH) remained unaltered while the response to in vivo GnRH treatment was markedly increased with the drug indicating the pituitary to be functionally normal. Differences in the in vitro and in vivo response could be due to the endogenous steroid levels. The hypothalamic LH-RH content concommitantly increased. Delta-9-tetrahydrocannabinol may inhibit the release of luteinizing hormone releasing hormone (LHRH).

Animals↗