Search PubMed⌕ Search

Biomedical subjects

R Abraham

Publications and source records attributed to R Abraham.

At least 109 records · Page 6Linked to original sources

Nuclear ploidy of neonatal rat livers: effects of two hepatic carcinogens (mirex and dimethylnitrosamine).

The effect of two hepatic carcinogens, dimethylnitrosamine (DMN) (genotoxic) and mirex (epigenetic), on polyploidization in 12-d-old neonatal rats was investigated by Coulter counteranalysis and [3H] thymodine uptake in isolated hepatic nuclear classes. DMN disturbed the normal ploidy development in the neonatal liver and the proportion of nuclei in the ploidy classes by inducing the premature formation of a significant population of tetraploids with a concomitant reduction in diploids. A great proportion of the replicative activity was present in tetraploid nuclei as measured by the incorporation of [3H] thymidine. The labeling index and number of mitoses were also increased. In contrast to DMN, mirex had no influence on polyploidization. The neonatal rats used in these studies thus offer an opportunity to investigate in vivo the mode of action of genotoxic versus epigenetic compounds with reference to their effect on DNA.

Animals↗

Zinc and copper in Asian pregnancies--is there evidence for a nutritional deficiency?

In 92 Hindu Asians, 59% of them vegetarian, and 51 Europeans longitudinal measurements were made during pregnancy of the zinc and copper concentrations in plasma and hair together with urinary zinc excretion, as indices of their zinc and copper status. Maternal diets were assessed once at booking. Zinc intakes ranged from 3.1 to 16.9 mg/day, with average intakes least in vegetarian Hindus and most in Europeans. Average copper intakes ranged between 1.48 and 1.80 mg/day and were similar in the three patient groups. Both ethnic groups showed the pregnancy-associated fall in the plasma concentration of zinc and rise in that of copper but throughout the study Hindus had statistically significant lower levels of zinc and higher levels of copper than Europeans. Urinary zinc excretion was not only significantly lower throughout the study in Hindus than in Europeans but the increase in excretion which occurred after 20 weeks gestation was smaller. There were no ethnic differences in the zinc content of hair. Urinary zinc excretion correlated with both plasma zinc levels and dietary zinc. Mean birthweight in the Hindus was 2912 g and 34% of infants were below the 10th centile, using the Aberdeen standards, compared with 6% of the European babies (mean birthweight 3349 g). No association was found between crude or adjusted birthweight and any of the measures of zinc or copper status in either ethnic group. The Hindus had an apparently lower average zinc status than the Europeans, but there was no evidence that this had acted as a nutritional constraint and was the cause of their slower rate of intrauterine growth.

Adult↗

Electrophysiological effects of ethmozine in perfused rabbit hearts.

His-bundle electrocardiography was used to evaluate the effects of ethmozine on cardiac conduction in isolated perfused rabbit hearts electrically driven at cycle lengths of 320 and 250 ms. There was no significant change in conduction until high concentrations of ethmozine were reached. His-Purkinje and atrioventricular (AV) nodal conduction were slowed significantly at 0.1 microgram/mL and atrial conduction at 1.0 microgram/mL. Conduction block occurred at 10.0 micrograms/mL in all the hearts treated. Effects of the drug (0.1 and 0.01 microgram/mL) on conduction of extrasystoles were also studied in hearts driven at a basic cycle length of 270 ms. No significant change was observed in atrial conduction of extrasystoles throughout the coupling intervals tested at both concentrations. Ethmozine (0.01 and 0.1 microgram/mL) caused slowing of His-Purkinje conduction of extrasystoles but the effect of the drug did not change as a function of the coupling interval. An interval-dependent increase in AV-nodal conduction time was observed, with the maximum slowing of conduction occurring at coupling intervals close to the effective refractory period of the AV node. AV-nodal functional refractory period was increased significantly by ethmozine (0.01 and 0.1 microgram/mL). The effective refractory period was significantly increased only at the higher concentration.

Animals↗

Agenesis of the corpus callosum: magnetic resonance imaging.

Three patients who had complete agenesis and two patients who had partial agenesis of the corpus callosum (ACC) underwent magnetic resonance (MR) imaging. In addition to excellent visualization of the indirect signs of ACC, direct vivid display (short T1) of the corpus callosum on sagittal images allowed better evaluation of subtle abnormalities than has been possible with other modalities. Associated abnormalities were also well-displayed. MR is the initial procedure of choice in evaluation of the corpus callosum.

Agenesis of Corpus Callosum↗

Comparative changes in rat liver cytosolic proteins by mirex, diethylnitrosamine, and dimethylnitrosamine exposure.

Using a newborn rat model for carcinogenesis, changes in liver cytosolic proteins at three stages of tumorigenesis, on Days 21, 97, and 120, by mirex (dodecachloropentacyclo-1,3,4-metheno-2H-cyclobuta[cd] pentalene), and diethyl- and dimethylnitrosamines (DEN and DMN) were studied. Following multiple exposure to the hepatocarcinogens, groups of weanling rats were given dietary phenobarbital (PB) up to 120 days. SDS-PAGE separation of cytosolic proteins showed that at 21 days, prior to PB, two proteins of 26K and 23K mol wt were significantly induced by mirex and DMN while a high mol wt 63K protein was induced only by DEN and DMN. During the period of PB treatment up to 97 days, these proteins were well sustained at a higher level. A marked increase in 21K protein band was also observed at this point. In tumor tissues obtained from DEN and DMN rats continued on PB diet for 120 days, the high level of 63K protein was seen only in DEN and not in DMN tumor. The tumors also showed a significant reduction in 25K protein compared to 21- and 97-day groups. The presence of even lower mol wt proteins of 14-21K was seen in tumors. The early detection and further characterization of these low mol wt proteins may provide clues as to whether they are preneoplastic markers or oncogene products as speculated by other investigators. Moreover, certain similarities in the induction of cytosolic proteins by "epigenetic" and "genotoxic" carcinogens raise more interesting questions regarding the mechanisms of action of these distinct classes of carcinogens.

Animals↗

Diet during pregnancy in an Asian community in Britain--energy, protein, zinc, copper, fibre and calcium.

Dietary intake of 813 pregnant Harrow Asians of mainly Gujarati descent was compared with the intake of 54 pregnant Europeans living in the same area. The diet of the Europeans had more protein and zinc but less fibre and fat that that of the Harrow Asians. The average rate of weight gain and the energy intakes were similar in both groups. Hindu non-vegetarians and Muslim non-vegetarians differed somewhat, because the Hindus, who are more recent converts to meat-eating, have diets with a lactovegetarian basis to which small amounts of meat have been added. Among the Hindu vegetarians, those who ate eggs and cheese had higher protein and zinc intakes, but otherwise Hindu vegetarians can be regarded as a fairly homogeneous group. Although the protein and zinc intakes of the Asians, particularly the vegetarians, were lower than those of the Europeans, there was no evidence of adverse consequences to the mother and fetus.

Adult↗

Pharmacokinetics and pharmacodynamics of d-tubocurarine and metocurine in the elderly.

The effects of age (older than 70 yr) on the pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) and metocurine (MTc) were evaluated in studies of 21 patients aged 70-87 and 21 patients aged 29-59. There was a significant difference in the pharmacokinetic parameters of all elderly patients compared with younger controls. With both dTc and MTc, the elderly exhibited a decreased plasma clearance, decreased initial volume of distribution, decreased volume of distribution, and a prolonged elimination half-life. After 0.3 mg/kg of dTc, the times for 50% return of twitch and recovery index (25-75% return of twitch response) in the elderly were significantly longer than in the young (P less than 0.02). A similar observation was made for the elderly patients receiving 0.15 mg/kg of MTc. No significant difference was seen in the log plasma concentration-twitch response relationship between 20-80% paralysis in young and in elderly patients receiving dTc. There was a similar lack of significant difference between the log plasma concentration-twitch response lines for elderly and young patients receiving MTc. Because there was no difference between the plasma concentration-response relationships in the elderly and young, altered sensitivity to dTc or MTc cannot explain the longer duration of action seen in the elderly. The most likely explanation for this difference is the altered pharmacokinetics of these two drugs in the elderly.

Adult↗

Factors affecting birthweights in Hindus, Moslems and Europeans.

The birthweights of 664 Hindu and 132 Moslem babies were compared with those of 486 European babies born at the same hospital. The mean birthweight of the Europeans was 3362 g, compared with 3146 g for the Moslems and 2960 g for the Hindus. The Asian women were smaller than the European and tended to have a shorter length of gestation. Forty-four per cent of the Asians and 46% of the European mothers were of social classes I and II; 28% of the Europeans and 2% of the Asians smoked. There were no significant differences between Asians and Europeans in the effects of maternal size, parity, gestational age and fetal sex on birthweight. After adjustment for these variables and for cigarette smoking there was no significant difference in birthweight between the Moslems and the Europeans, but the mean birthweight of the Hindus was about 190 g lighter than that of the Europeans. Hindus from East Africa had lighter babies than those from India.

Asia↗

Ploidy patterns in hepatic tumors induced by Mirex.

The effects of chronic exposure to dietary Mirex was investigated in rat livers over a 13 month period. The distribution of ploidy (diploid and tetraploid nuclei) in nodular and nonnodular areas was analyzed in a Coulter Counter fitted with a Channelizer. The nodules, such as adenomas and carcinomas, were identified in histologic sections obtained from companion samples, part of which was used for analysis of nuclear ploidy. The carcinogen disturbed the distribution of nuclei in the ploidy classes, selectively reducing the number of tetraploid cells. This reduction in tetraploid cells corresponded to the nature of the tumor, the most significant effect being noted in hepatocellular carcinomas.

Animals↗

Paternal effects of ethanol in the long-evans rat.

Ten male Long-Evans rats were given 20% v/v ethanol in the drinking water for 60 consecutive days. Ten other males were given distilled water and served as controls. Each male was then allowed to mate with three virgin female Long-Evans rats, once per week for three consecutive weeks. The males were necropsied after the third mating, the females were killed on d 20 of gestation, and the offspring were examined for parameters of fetal growth, skeletal ossification, and soft-tissue anomalies. Ethanol caused testicular weight reductions and gross testicular atrophy in 1 of 10 males. Five matings of alcoholic male rats proved infertile. Total embryonic deaths (resorptions and preimplantation loss) were increased by ethanol, while implantations and litter size were significantly decreased. Fetuses fathered by alcoholic male rats were malformed: 55% had soft-tissue anomalies (microcephalus, microphthalmia, cranial fissure, and hydronephrosis). Litter weight and average pups weights were also reduced by paternal ethanol consumption. No recovery in reproductive function was evident over the 21-d post-ethanol mating period.

Animals↗

Preferential fluorescent staining of heterochromatic regions in human chromosomes 9, 15, and the Y by D 287/170.

The utility of a newly synthesized chemical variation of DAPI (4'-6-diamidino-2-phenyl-indole), D 287/170, for differential staining of constitutive heterochromatin in man is demonstrated. Direct staining of human chromosomes with D 287/170 results in brilliant fluorescence of the paracentromeric C-band of chromosome 9, of a proximal short-arm segment of chromosome 15, and of certain heterochromatic regions in the Y. Bright, but less conspicuous fluorescence is occasionally seen at the centromeres of other chromosomes. The staining differentiation obtained by D 287/170 is very distinct, and the intensity of the fluorescent light is unusually high. The new fluorochrome should prove particularly useful for detecting and analyzing human chromosome 9 heterochromatin at various stages of the cell cycle in normal and structurally altered chromosomes.

Chromosomes, Human↗