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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 1,603 records · Page 89Linked to original sources
PubMed1989

Biochemical toxicology of argemone oil. IV. Short-term oral feeding response in rats.

Consumption of edible oils contaminated with Argemone mexicana seed oil is known to cause various clinical manifestations. In the present study, the effect of dietary intake of argemone oil on histopathological changes, haematological indices and selected marker parameters of toxicity was investigated to observe the exact sites and mode of action of argemone oil in rats. Histopathological changes in the liver showed increased fibrosis, hyperplasia of bile ducts and congestion in a few portal tracts. Lungs of argemone oil-fed animals indicated congestion and thickening of interalveolar septa. Alveolar spaces were disorganised and irregular. Kidneys showed vascular and glomerular congestion and patchy tubular lesions. At 30 days only mild congestion was noted in the myocardium. Cardiac muscle fibres showed degenerative changes at 60 days which were more marked in the auricular wall. Haematological examination showed appearance of anaemia in experimental animals. Hepatic alkaline phosphatase, alanine transaminase and aspartate transaminase activities were inhibited by 30, 29 and 29% after 30 days of argemone intake along with concomitant enhancement in serum by 27, 29 and 66%, respectively. Liver showed decrease in glutathione (32-63%) content along with significant stimulation of lipid peroxidation (49-105%) in argemone-intoxicated animals. These results suggest that liver, lungs, heart and kidneys are the target tissues of argemone oil toxicity and that membrane destruction may be a possible mode of action.

Animals↗
PubMed1989

Noninvasive measurement of cardiac output during surgery using a new continuous-wave Doppler esophageal probe.

The ability of a new continuous-wave Doppler esophageal probe to measure cardiac output noninvasively during surgery under general anesthesia was tested and compared with simultaneously measured thermodilution cardiac output. A Doppler computer, calibrated for the aortic diameter and the transcutaneously measured cardiac output from the suprasternal notch, computed the Doppler cardiac output from the descending aortic blood flow velocity signal. A total of 246 paired Doppler cardiac output and thermodilution cardiac output measurements were made in 14 patients during surgery. The average thermodilution cardiac output was 5.90 +/- 3.27 (standard deviation) liters/min (range 1.20 to 19.18); the average Doppler cardiac output was 6.21 +/- 4.0 liters/min (range 2.30 to 28.20). The difference between the cardiac output measured by the 2 techniques was 1.38 +/- 2.2 liters/min (range 0.04 to 16.8). Two to 5 cardiac output measurements were averaged and arranged into "time periods." The average standard deviations for thermodilution and Doppler cardiac outputs within each time period were 0.64 and 0.47 liters/min, respectively. There was a correlation between the 2 measurements over a range of cardiac output values (r = 0.76, Doppler cardiac output = 0.93 x thermodilution cardiac output +0.7, standard error of the estimate = 1.76). Reproducible measurements of Doppler cardiac output were obtained during intraobserver (mean difference 0.64 +/- 0.52 liter/min) and interobserver (mean difference 0.41 +/- 0.36 liter/min) studies (n = 8). Cardiac output measurement by the Doppler esophageal probe could be used for hemodynamic monitoring during surgery in selected patients with cardiopulmonary disease.

Adult↗
PubMed1989

Biosynthesis of bacterial glycogen. Determination of the amino acid changes that alter the regulatory properties of a mutant Escherichia coli ADP-glucose synthetase.

The ADP-glucose synthetase of Escherichia coli K12 mutant 618 has a higher apparent affinity for the activator, fructose 1,6-P2 and a lower apparent affinity for the inhibitor, 5'-AMP, than the normal enzyme. The structural gene, glgC, of the mutant enzyme has been cloned and sequenced (Lee, Y. M., Kumar, A., and Preiss, J. (1987) Nucleic Acids Res. 15, 10603). Substitutions in the mutant enzyme were amino acid residues 296 (Lys to Glu) and 336 (Gly to Asp). Single mutant enzymes, Glu296 and Asp336, were constructed using oligonucleotide-directed mutagenesis. The Glu296 enzyme had the same allosteric kinetic constants as the wild type enzyme. The Asp336 enzyme was catalytically defective. Thus, the mutations at 296 and at 336 separately could not account for the allosteric alterations of the mutant enzyme. A hybrid glgC gene was prepared from genes of wild type and mutant 618 glgC using DNA recombinant techniques. The C-terminal portion of mutant 618 containing Glu296 and Asp336, combined with the N-terminal portion of wild type enzyme, showed allosteric and substrate kinetics similar to mutant 618 enzyme. Thus, alteration of the normal allosteric properties in mutant 618 are due to changes of both Lys296 to Glu and Gly336 to Asp.

Chromatography, Ion Exchange↗
PubMed1989

Activity and kinetic characteristics of glutathione reductase in vitro in reverse micellar waterpool.

The enzyme activity of glutathione reductase (NAD(P)H:oxidized-glutathione oxidoreductase, EC 1.6.4.2) incorporated in CTAB/H2O/CHCl3-isooctane (1:1, v/v) reverse micelles has been investigated. Enzyme follows the Michaelis-Menten kinetics within a specified concentration range. Effects of pH, waterpool (W0), and surfactant concentration on the activity of glutathione reductase have been studied in detail. Optimum pH for the maximum enzyme activity was found to be dependent on the size of the waterpool. Further, a substrate inhibition was observed when concentration of one of the substrates was present in large excess over the other substrate. Km values for the substrate, oxidized glutathione (GSSG) and NADPH in CTAB/H2O/CHCl3-isooctane (1:1, v/v) were determined at W0 values of 14.4, 20.0, 25.5 and 29.7, at pH 8.0. These values are close to those obtained in aqueous solution, whereas the kcat values vary with W0 values of 8.8 to 32.3. Studies on the storage stability in the reverse micelle at W0 29.7 and pH 8.0 showed that glutathione reductase retained about 80% of its activity even after a month. The enzyme showed a higher stability at high waterpool. Oxidized glutathione (GSSG) provides protection to glutathione reductase against denaturation on storage in reverse micellar solution. Apparently, the enzyme is able to acquire a suitable native conformation at waterpool 29.7 and pH 8.0 and thereby exhibits an activity and stability inside the micellar cavity that are almost equivalent to that in aqueous solution.

Cetrimonium↗
PubMed1989

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder.

The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.

Adolescent↗
PubMed1989

Reversal of bone marrow fibrosis and subsequent development of polycythemia in patients with myeloproliferative disorders.

Bone marrow fibrosis is a characteristic finding in agnogenic myeloid metaplasia and in the spent phase of polycythemia vera. It is commonly believed that the reticulin deposition is irreversible. However, we report four patients who demonstrated clinical and laboratory evidence of transition from myelofibrosis to polycythemia. The transition was documented by improvement in the hemoglobin concentration and by determination of the Cr51 red blood cell mass, accompanied by a resolution of the fibrosis on serial bone marrow biopsies. Two of the patients had been treated with alkylating agents and splenectomy, one with myelosuppressive therapy without splenectomy, and one with splenectomy alone. These findings indicate that bone marrow fibrosis in the chronic myeloproliferative disorders is not always an irreversible phenomenon. Pathogenetic implications will be discussed.

Aged↗
PubMed1989

Comparison of isotonic saline, distilled water and boiled water in irrigation of open fractures.

A prospective randomised study was carried out on 86 patients with first, second and third degree open fractures in order to compare the effect of isotonic saline, distilled water and boiled water as irrigating fluids. The standard management consisted of emergency surgical toilet, use of broad spectrum antibiotics and fracture immobilization. The results show that the outcome was not affected by the type of irrigating fluid used.

Amputation, Surgical↗
PubMed1989

The effect of levonorgestrel administered in large doses at different stages of the cycle on ovarian function and endometrial morphology.

In a pharmacokinetic study, levonorgestrel (L-NOG) 0.75 mg was administered orally to 10 swedish women in the early follicular phase of the menstrual cycle. L-NOG levels were measured after L-NOG administration. A peak level of 16 nmol/l was reached after 2 hours, T 1/2 was estimated to be 14.5 hours (8.5-18.5) in the 24-48-hour interval after dosing. Seventy-two women (in Stockholm, Bombay and Shanghai) were assigned to 4 treatment groups and studied during a control cycle, a treatment cycle and a posttreatment cycle when 0.75 mg L-NOG was administered orally for 4 days in the follicular phase, periovulatory period or luteal phase. Peripheral blood was drawn 3 times weekly during the entire study for the assay of estradiol and progesterone. In 22 women in Stockholm, an endometrial biopsy was obtained on cycle day 20-22 in all 3 cycles studied. When L-NOG was administered on periovulatory days 9, 11, 13, and 15, 3 women showed follicular activity only, 7 exhibited follicular activity followed by insufficient luteal function and 7 women ovulated normally. When L-NOG was administered on periovulatory days 11, 12, 16 and 19, 7 women ovulated during treatment, 6 women exhibited follicular activity followed by insufficient luteal function and 5 exhibited follicular activity only. When L-NOG was administered in the follicular or luteal phase, no effect on ovarian function was seen. No significant prolongation of the cycle lengths was seen when L-NOG was taken during the follicular phase. Only minor effects in the endometrium were observed during treatment.

Adult↗
PubMed1989

Development of a leukocytopenic baby guinea pig model with azathioprine and cyclophosphamide.

Immunosuppressive agents were given to baby guinea pigs to develop a leukocytopenic baby guinea pig model. Azathioprine in different doses, and cyclophosamide and methylprednisolone combinations did not result in predictable leukocytopenia without significant mortality. A combination of azathioprine 20 mg and cyclophosphamide 20 mg administered once daily for 5 days to 42 baby guinea pigs resulted in a mean white blood cell count of 2531/mm3 +/- 1198 (a reduction of 3931 +/- 1413 from pretreatment values). The mean counts for polymorphonuclear leukocytes and lymphocytes on day 6 were 398/mm3 and 2035/mm3, respectively. Only 7% mortality was seen in these animals. This model can be utilized to study a variety of bacterial and viral infections in "immunocompromised hosts".

Animals↗
PubMed1989

Identification of cellular proteins that bind to the human immunodeficiency virus type 1 trans-activation-responsive TAR element RNA.

Human immunodeficiency virus type 1 (HIV-1) trans-activator protein Tat activates the expression of its viral long terminal repeat (LTR) through a target transactivation-responsive element termed TAR. We have constructed cell lines that constitutively express the HIV-1 Tat protein. Analyses of nuclear proteins from these cells and from matched control cells that do not express Tat have identified three proteins that bind to a radiolabeled HIV-1 TAR RNA probe. These polypeptides are 100 kDa, 62 kDa, and 46 kDa in size. Competition experiments using a wild-type TAR RNA sequence, a biologically inactive mutant sequence of TAR, and an unrelated RNA species demonstrated that these proteins show higher binding affinity to wild-type TAR than to the other two non-trans-activatable sequences. We hypothesize that these cellular proteins may mediate a function necessary in Tat-dependent activation of the LTR. The fact that no differences were seen in the binding profiles of nuclear proteins to TAR RNA in Tat-producing and Tat-nonproducing cells suggests that Tat does not directly interact with TAR.

Base Sequence↗
PubMed1989

Antimalarial activity of demeclocycline against Plasmodium cynomolgi bastianellii in rhesus monkeys.

Demeclocycline was tested for causal prophylactic (at 25, 50 and 100 mg kg-1 dose levels), radical curative (at 25, 50, 100 and 200 mg kg-1 dose levels) and blood schizontocidal (at 25, 50 and 100 mg-1 dose levels) activities against Plasmodium cynomolgi B in rhesus monkeys. For causal prophylactic activity, demeclocycline extended the prepatent period at all dose levels. The maximum delay in patency was observed at 100 mg kg-1 (prepatent period = 40.66 +/- 14.57 days). For radical curative activity, relapse was also delayed at all dose levels tested, and the relapse interval was found to be 47.0 +/- 18.24 days at 200 mg kg-1. For blood schizontocidal activity, parasitaemia was initially cleared at all dose levels, followed by recrudescence in all monkeys. The recrudescence interval was found to be 17.0 +/- 5.2 days at 25 mg kg-1 and 31.0 +/- 2.7 days at 50 mg kg-1. However, three monkeys treated with 100 mg kg-1 did not show parasites in thin blood smears during the observation period, but parasites were present in thick blood smears of all the monkeys after the end of the observation period. On the other hand, all monkeys treated with 1 mg kg-1 of primaquine for causal prophylactic and radical curative activities and with 5 mg kg-1 chloroquine for blood schizontocidal activity were cured.

Animals↗
PubMed1989

Ciprofloxacin, imipenem and rifampicin: in-vitro synergy of two and three drug combinations against Pseudomonas cepacia.

The in-vitro activity of ciprofloxacin, imipenem and rifampicin, singly, and in two and three drug combinations was evaluated against 16 isolates of Pseudomonas cepacia. All 16 isolates were resistant to rifampicin; nine isolates were susceptible to ciprofloxacin; six were susceptible and seven had intermediate susceptibility to imipenem. The imipenem and rifampicin combination was synergistic for one of 16, imipenem and ciprofloxacin synergistic for seven of 16 and the three antibiotic combination was synergistic for 12 of 16 isolates. The three antibiotic combination demonstrated synergism with two isolates which were resistant to all three drugs. Combinations of two and three antibiotics resulted in enhanced killing of P. cepacia in this in-vitro study.

Ciprofloxacin↗