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Biomedical subjects

S Ganguli

Publications and source records attributed to S Ganguli.

At least 19 recordsLinked to original sources

Comparison of the galactopoietic response to pituitary-derived and recombinant-derived variants of bovine growth hormone.

Two studies were designed to examine the differences in galactopoietic potency of molecular variants of pituitary- and recombinant-derived bovine GH (bGH). The recombinant bGH molecules included amino-terminal and position-127 amino acid substitutions which are representative of two of the four natural pituitary variants or of partially degraded bGH molecules. Amino-terminal variants of bGH included methionine (Met1), alanine (Ala1), serine (Ser1) or deletion of four amino acids (delta 1-4). The delta 1-4 variants were representative of degradation products previously isolated in pituitary bGH preparations. In the first study, 54 lactating Holstein cows received i.m. injections of a buffer solution (control), pituitary-derived bGH, or recombinant-derived [Met1,Leu127]-bGH, [Met1,Val127]-bGH, [Ala1,Leu127]-bGH, or [Ala1,Val127]-bGH. Cows received 25 mg bGH/day for 21 days. Substitution of the amino-terminal alanyl residue with methionine did not affect milk response. GH variants with Val127 elicited a greater milk response (8.5 kg/day) than Leu127 bGH variants (6.5 kg/day). The average milk response to the four recombinant bGH variants was 7.5 kg/day greater than controls compared with 4.4 kg/day for pituitary-derived bGH. In contrast, blood bGH concentrations were equivalent for pituitary and recombinant bGH treatments, approximately 20 micrograms/l more than control levels at 3 h after injection. Blood free fatty acid concentrations were increased, but insulin and glucose levels were unaffected by bGH treatment. In the second study, 54 lactating Holstein cows received i.m. injections of a buffer control solution or recombinant-derived [Met1,Leu127]-bGH, [Ser1,Leu127]-bGH, [Ser1,Val127]-bGH, [delta 1-4,Leu127]-bGH or [delta 1-4,Val127]-bGH. Cows received 25 mg bGH/day for 28 days. The milk response to full-length bGH variants was 6.6 kg/day greater than the response to the amino-terminal deletion variants (P less than 0.05). Substitution of valine for leucine did not affect milk response to either the deletion (delta 1-4) or full-length (Met1 or Ser1) bGH molecules. In conclusion, the lowered galactopoietic potency of pituitary bGH preparations was demonstrated, at least in part, to be due to the presence of amino-terminal amino acid deletions rather than differences in amino acid sequences of recombinant bGH. Ala1 bGH variants with valine at position 127 elicited a greater milk response than Leu127 variants.

Amino Acid Sequence

Kwashiorkor and marasmus: changing hospital incidence of syndromic presentation (1957-88).

This clinico-epidemiological study was undertaken to substantiate the impression that the pattern of clinical presentation of protein-energy malnutrition causing kwashiorkor-marasmus syndrome (KMS) is changing over time. An analysis of data for the period 1964-88, obtained from the specialised Pediatric Clinic of the Calcutta School of Tropical Medicine serving mostly the city slums showed decrease (p less than 0.01) in the incidence of chronic edematous forms of severe KMS, less decrease (p less than 0.05) in the incidence of mild-moderate KMS and increase (p less than 0.01) in the incidence of nutritional marasmus and of chronic very severe forms of KMS characterised by extreme retardation in growth and development. Incidentally, a rising incidence of rickets was observed. In the hospitalised cases (1957-88) these observations were corroborated. Data for 1985-88 of NRS Medical College Hospital, Calcutta, a general hospital serving the city as well as the neighbouring rural areas, showed that among the hospitalised city children edematous KMS was proportionately fewer than marasmus. The situation was reverse in the children from the rural areas. The observations suggested that the syndromic presentation of KMS is changing over the last three decades with some rural-urban differences for which only some recent data could be available.

Child

Studies on the mechanism of action of prostaglandin F2 alpha induced luteolysis in rats.

The effects of prostaglandin F2 alpha (PGF2 alpha) administration on the utilization of low density lipoprotein (LDL) and progesterone secretion were examined in dispersed luteal cells from rat ovaries. Immature rats were rendered pseudopregnant with administration of pregnant mare serum gonadotropin and human chorionic gonadotropin. Animals were sacrificed at different times after PGF2 alpha (5 mg/kg) or vehicle administration on day-5 of pseudopregnancy. Administration of PGF2 alpha in vivo decreased human chorionic gonadotropin (hCG) binding to luteal cell membranes in vitro but enhanced binding of LDL. Utilization of labelled cholesterol for steroid synthesis from reconstituted LDL [(3H)-CL-LDL] by dispersed luteal cells was enhanced following PGF2 alpha administration. This suggests that the LDL pathway is not suppressed during prostaglandin induced luteolysis. Progesterone and total progestin secretion in response to N6-2'-0-Dibutyryladenosine 3'5'-cyclic monophosphate (cAMP) was decreased at 2, 4 and 24 hours following PGF2 alpha administration demonstrating a post-cAMP defect in steroidogenesis. Addition of the hydroxylated sterols, 20 or 25-OH cholesterol as substrate stimulated progesterone secretion in vehicle treated rats in a dose dependent fashion with 20-OH cholesterol being more potent. Progesterone secretion in response to stimulation with luteinizing hormone (LH) and cAMP from vehicle treated rats was less than that observed with 20 or 25-OH cholesterol, indicating that endogenous substrate may be a limiting factor in steroid synthesis. The maximal capacity of luteal tissue to produce progestins following PGF2 alpha administration was determined with 20-OH cholesterol as the substrate. The results suggest that the post-cAMP defect at 4 hours following PGF2 alpha administration may be due to failure of the cells to mobilize endogenous cholesterol. However at 24 hours following PGF2 alpha administration the decreased ability of luteal cells to convert cholesterol to pregnenolone may contribute to decreased progesterone synthesis.

Animals

Insulin stimulates amino acid and lipid metabolism in isolated fetal rat hepatocytes.

Although fetal hyperinsulinemia is associated with excessive deposition of glycogen in liver, both in vivo and in vitro studies show little effect of insulin on glycogen synthesis from glucose or the activity of the enzyme glycogen synthase in the fetus. To investigate whether lack of insulin effect extends to other fetal metabolic processes, we compared the influence of insulin on amino acid uptake (14C-alpha-aminoisobutyric acid) and lipid synthesis [14C-acetate) in freshly isolated hepatocytes from 21-day fetal (F) and adult (A) rats. Viability of F and A hepatocytes was documented by trypan blue exclusion (greater than 90%). In A, insulin stimulated 14C-alpha-aminoisobutyric acid uptake in a dose dependent manner with an apparent Km at 2 ng/ml and a Vmax at 10 ng/ml. When corrected for cell surface area, F cells responded to insulin in a similar dose response manner, although absolute values per 1 X 10(6) cells always remained lower. In contrast, whereas A cells demonstrated a typical dose dependent response of 14C-acetate incorporation into lipid with a Km at 5 ng/ml and Vmax at 10 ng/ml of insulin, F cells remained totally unresponsive when the concentration of acetate was 5 mM or less. However, at higher medium acetate concentrations (15-30 mM) fetal responses were equal to or greater than that of adult, both basally and with insulin. These findings suggest differences in the maturation of insulin-mediated processes in fetal rat hepatocytes; effects on amino acid uptake appear earlier than those on lipid or glycogen synthesis.

Amino Acids

Indomethacin and salicylate decrease epinephrine-induced glycogenolysis.

Epinephrine (E) produces an immediate (0-30 minutes) rise in hepatic glucose production (Ra), largely due to activation of glycogenolysis; thereafter, E-stimulated gluconeogenesis becomes the major factor maintaining glucose production. To investigate the possible role of arachidonic acid metabolites on Ra during E stimulation, we infused E in trained conscious dogs before and during administration of two inhibitors of arachidonic acid metabolism, indomethacin (INDO) and salicylate (S). On separate days, experimental animals were treated with both oral and IV INDO and oral acetylsalicylic acid and IV sodium salicylate. Ra and glucose utilization (Rd), both in mg x kg-1 min-1, were calculated by isotope dilution using 3-3H-glucose. After achieving steady state specific activity, control (C) and experimental animals (n = 6 per group) received E (0.1 ug x kg-1 min-1) for 150 minutes, raising plasma levels to approximately 1500 pg/mL in each group. In C, plasma glucose (G; mg/dL) rose by 17 +/- 5 at 10 minutes and 19 +/- 3 at 20 minutes due to an initial spike in Ra (2.7 +/- 0.2 to 4.9 +/- 0.5; P less than 0.01) at 10 minutes. INDO and S treatment attenuated this initial (10-20 minutes) rise in G (P less than 0.05) due to a lower stimulated Ra at 10 minutes (3.3 +/- 0.1 with INDO; 3.0 +/- 0.5 with S; P less than 0.05). After 20 minutes Ra was not different in the 3 groups; no overall differences in Rd, glucose clearance, or plasma insulin levels occurred with INDO or S treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Indomethacin and salicylate modulate effect of insulin on glucose kinetics in dogs.

We studied insulin's effects on glucose production (Ra) and utilization (Rd) in trained, conscious dogs before and during treatment with indomethacin (Indo) and salicylate (S). Ra and Rd (mg X kg-1 X min-1) were calculated by isotope dilution using [3-3H]glucose. Animals were treated with either oral Indo or acetylsalicylic acid for 1 day before the respective studies. On the study day, experimental animals were given a continuous infusion of either saline (control), Indo (5 mg/kg bolus followed by 0.05 mg X kg-1 X min-1), or sodium salicylate (0.45 mg X kg-1 X min-1) for 330 min on separate days; each animal participated in all three protocols. After establishing steady-state specific activity, control (C) and experimental animals (n = 6/group) received insulin, 0.275 mU X kg-1 X min-1 for 150 min, raising serum insulin levels two- to threefold above basal. During insulin infusion in C, plasma glucose (G) fell from 99 +/- 2 to 82 +/- 6 ml/dl (P less than 0.01), associated with a transient fall in Ra from 2.5 +/- 0.3 to 1.9 +/- 0.2 (P less than 0.01) at 30 min, returning to base line at 45 min; Rd did not change. In the Indo and S groups, G also fell by a similar extent. In contrast to C, however, the fall in G was associated with a rise in Rd, commencing at 30 min in the Indo group (P less than 0.05) and at 45 min in the S group (P less than 0.01); Ra did not fall and actually rose above basal (P less than 0.05), although it did not match the rise in Rd.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Use of a gait abnormality index for locomotion efficiency evaluation.

A number of gait curves obtained from 16 healthy, able-bodied adult males were selected as "normal" gait curves and thereafter analysed with a view to defining a "Gait Abnormality Index", which may be used as quantitative measure of human performance in locomotion. Similar studies on five groups of handicapped subjects, each group having 8 to 10 subjects with a particular type of handicap, indicate the suitability of this index for application in locomotion efficiency evaluation.

Adult

Bidirectional placental transfer of glucose and its turnover in fetal and maternal sheep.

Glucose biokinetics were assessed simultaneously in the pregnant ewe and its fetus by a primed constant infusion of 2-3H glucose and U-14C glucose. Late in gestation fetal glucose turnover was 27.3 +/- 3.7 mg/min; expressed in terms of fetal weight this is 6 to 10 mg/kg/min. In the fed state the results indicated that all of the fetal glucose turnover was derived from the mother via placental transfer and there was no evidence that the fetus was capable of glucose production. Maternal glucose turnover was 145.6 +/- 9.3 mg/min (2.8 mg/kg/min). There was a significant amount of glucose (16.3 +/- 2.3 mg/min) transferred from the fetus to the mother. This feto-maternal transfer of glucose accounted for 11% of the maternal glucose turnover and approximately 50% of the total glucose coming to the fetus from the mother. This study provides the first in vivo simultaneous quantification of the bidirectional glucose transfer across the placenta.

Animals

Studies in load carrying in BK amputees with a PTB prosthesis system.

This study was undertaken to assess the effects of certain common modes of load carrying by hand in the BK amputee-PTB prosthesis system. The energy costs of a test group consisting of BK amputees using PTB prostheses were compared to those of a control group made up of normal able-bodied individuals and the difference between the two groups was observed to be more marked when walking was performed on the level with load in one hand only in comparison with the both-hand carrying conditions. Single handed load carrying by either hand did not seem to make any observable difference. Stair ascending with equal load in both hands did not produce any appreciable difference between the two groups. Indications were obtained that the BK amputee with a PTB prosthesis system is capable of performing industrial tasks of "moderate" grade.

Adult

Performance evaluation of BK amputees through graded load carrying tests.

The ergonomic approach to performance evaluation in orthopaedic rehabilitation presents problems because of the cumbersome and time-consuming measurement and test procedures involved. This paper describes a method of performance evaluation through graded load carrying tests which makes it possible to set up regression equations which can be used in routine clinical practice for prediction of the performance of below-knee amputees.

Adult