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Biomedical subjects

P Weis

Publications and source records attributed to P Weis.

At least 37 records · Page 2Linked to original sources
PubMed1987

Effect of cimetidine on tissue distribution of some trace elements and minerals in the rat.

Cimetidine is a histamine H2-receptor antagonist that is used in the treatment of patients with gastric and duodenal ulcers and other hypersecretory conditions. This drug has a structure that suggests that it could act as a chelating agent. To examine its effects on trace metal and mineral metabolism, 38 weanling male Sprague-Dawley rats were assigned to one of five treatment groups. These were a high dose [(HD) 1750 mg/(kg X d)] group, HD pair-fed control (HDPF) group, intermediate dose [(ID) 875 mg/(kg X d)] group, ID pair-fed (IDPF) group and low dose [(LD) 87.5 mg/kg X d)] group. In a separate experiment, 20 female Sprague-Dawley rats were assigned to one of two treatment groups: a high dose cimetidine group [(HDFem) 1750 mg/kg X d)] and a pair-fed control group (PFFem). Cimetidine was administered intragastrically four times per week for 5 wk. Significant differences (P less than 0.05) found among groups for the male rats studied included higher plasma copper in the HD and the ID groups, higher plasma sodium, liver copper, heart calcium and heart zinc in the HD group and a lower percentage of fecal excretion of all the divalent metals studied in the HD and the ID groups than in their pair-fed controls. Pathologic examination of the liver revealed extensive fatty infiltration of liver cells, liver cell necrosis and disrupture of liver lobular architecture in the HD group. Cimetidine-dosed females had higher zinc in heart and plasma, higher copper in heart, kidney, liver, jejunum, ileum and uterus, higher manganese in stomach and ileum, lower iron in kidney and liver, lower kidney calcium and higher stomach calcium and lower liver magnesium compared with their pair-fed controls. Levels of liver and kidney metallothionein in the two groups were comparable. Male and female rats receiving high dose cimetidine experienced significant changes in tissue concentrations of some of the trace metals and minerals studied.

Animals↗
PubMed1987

Relationship between human prostatic epithelial cell protein synthesis and tissue dihydrotestosterone level.

To evaluate the role of small amounts of prostatic tissue dihydrotestosterone (DHT) as a stimulus to epithelial cell protein synthesis, we studied tissue from 27 patients given various androgen-blocking drugs for 1 week before transurethral resection of the prostate (TURP) and measured epithelial protein synthesis and DHT levels in the tissue specimens. Test drugs before TURP included megestrol acetate 160 mg per day, with and without Tamoxifen 40 mg per day, or ketoconazole 1200 mg per day. The tissue was processed immediately and epithelial cells separated by digestion of tissue with 0.5% collagenase. After separation, epithelial cells were labelled with either 3H-leucine or L-35S-methionine. The DHT level was measured in whole prostatic tissue. Megestrol acetate alone and with tamoxifen significantly decreased both the incorporation of 3H-leucine into protein and the tissue concentration of DHT; megestrol acetate plus ketoconazole significantly decreased L-35S-methionine incorporation into protein and the DHT level. When the data correlating DHT with protein synthesis using both labelling techniques were combined, the curves were parallel and a strong correlation was noted between DHT and protein synthesis over a wide range of values (P less than 0.001). These results suggest that in hormone-dependent prostatic cancer even small amounts of prostatic DHT such as may occur from adrenal androgens following castration may significantly stimulate protein synthesis of the tumour epithelial cells.

Aged↗
PubMed1987

Pollutants as developmental toxicants in aquatic organisms.

Pollutants, by disrupting metabolic processes, can interfere with development, and, at critical periods of development, can act as teratogens. Such interference with normal development can be used as a bioassay. Some screening tests are based on this phenomenon. As teratogens, pollutants are fairly nonspecific. Many different classes may elicit the same developmental responses. Mechanisms of teratogenicity include disruption of mitosis, interference with transcription and translation, metabolic disturbances in energy utilization, and nutritional deficits. These in turn interfere with cell interactions, migration, and growth. In aquatic organisms, environmental conditions can be critical. Interactions of pollutant effects with salinity and with temperature have been reported. Interactions between toxicants have also been studied; both synergism and antagonism have been reported. Most reports of teratogenesis have been qualitative. Quantitation has usually been in the form of percentages of embryos affected, but when severity of effect is indexed, more critical analysis is allowed. When effects of other developmental processes such as growth are analyzed, quantitation is readily achieved. Regeneration is an especially useful model of both differentiation and growth. These two components of regeneration can be separately analyzed. Dose-response relationships are readily apparent. In comparison to mammalian embryos, the use of embryos of many aquatic species for testing toxicants has certain advantages, including lower cost and maintenance and shorter development times. They respond to many of the same teratogens. A special advantage is availability for continual examination during development so that abnormalities can be observed and recorded as they arise.

Animals↗
PubMed1986

Cadmium acclimation and hormesis in Fundulus heteroclitus during fin regeneration.

We have previously demonstrated that exposure to cadmium at 0.1 and 0.5 mg/liter will retard the rate of fin regeneration in Fundulus heteroclitus. Since there is a body of literature indicating that preexposure to low levels of metals may increase tolerance during subsequent exposure, these experiments were designed to investigate the effects of preexposure to cadmium, using fin regeneration as the parameter of effect. Fish were exposed for 1 week to 0, 0.01, or 0.05 mg/liter Cd. Following this preexposure, the lower third of the caudal fin was amputated, and regrowth of the fins measured by ocular micrometer twice weekly for 2 weeks. During regeneration fish were maintained in either clean water (25% S, 23-25 degrees C) or in water with 0.1 mg/liter Cd. Fish newly placed in Cd (C----0.1 Cd) regenerated at the slowest rate, while the 0.01----0.1 Cd group approached the growth of control fish regenerating in clean water, indicating a protective effect or acclimation brought about by the preexposure. The 0.05----0.1 Cd group regenerated even more rapidly than controls, a phenomenon which has been termed "hormesis" and is believed to be due to an overcompensation by homeostatic regulatory mechanisms. In a second set of experiments in which regeneration took place in 0.5 mg/liter rather than 0.1 mg/liter, a protective effect of preexposure was again seen, but no hormesis was observed. Uptake data indicated that preexposed groups took up less Cd than the groups not preexposed.

Animals↗
PubMed1986

Hg- and Cu-induced hepatocellular changes in the mummichog, Fundulus heteroclitus.

To investigate mechanisms by which the mummichog (F. heteroclitus) successfully withstands heavy metal pollution, fish were treated with Hg2+ at up to 0.10 mg/L, Cu2+ at up to 1.0 mg/L, or combinations of Hg2+ and Cu2+. In earlier work, protein analysis of liver indicated that most of the cytosolic Cu is bound to the sulfhydryl-rich metallothionein, but that Hg is not associated with cytosolic proteins. Morphometric analysis indicates the Hg-treatment increases the lipid compartment of hepatocytes (ANOVA, F = 10.73, p less than 0.01). This lipid increase is correlated with the Hg content (analyzed by atomic absorption spectrophotometry) of individual liver samples (Spearman rank correlation, rs = 0.621, p less than 0.01). Cu treatment causes a reduction in the lipid compartment (F = 10.38, p less than 0.01), reduced cytoplasm in general (F = 18.55, p less than 0.001) and an increased lysosome count (F = 14.21, p less than 0.001). X-Ray microanalysis locates Cu in secondary lysosomes, but not in other organelles. Results of treatment with both Hg2+ and Cu2+ are similar to those of Hg2+ alone. Concentrations of Cu in liver varied too much to allow assessment of correlations with cytoplasmic changes. Usual mechanisms for handling toxic heavy metals include binding to metallothionein and sequestering in lysosomes. Our findings for Cu are in agreement with this. Fish, however, can methylate Hg. (We have found greater than 75% of killifish hepatic Hg to be methylated.) Increased cellular lipid may be a mechanism for sequestering the lipid-soluble methylmercury.

Animals↗
PubMed1984

Use of prenatal diagnosis among parents of infants with spina bifida in Atlanta, Georgia, 1976-1979.

A follow-up was made of the parents of a population-based cohort of 154 infants with spina bifida who were born in Atlanta during 1972-1979. We interviewed the parents of these infants and, for pregnancies after the spina bifida-affected birth, the ratio of use of prenatal diagnosis and the rate of recurrence of spina bifida were ascertained. Among 43 pregnancies which occurred in 1976 or later, and which occurred after a spina bifida-affected birth, prenatal diagnosis was used for 27 pregnancies (63%). For whites, among full siblings born after a spina bifida-affected birth, the recurrence rate for spina bifida was 2% (1/51). For blacks, among seven full siblings born after a spina bifida-affected birth, none was affected. Prenatal diagnosis appears to be well accepted among these parents of infants with spina bifida.

Adult↗
PubMed1978

In vitro interaction of L1210 cells with phospholipid vesicles.

The in vitro uptake of phospholipid vesicles by mouse leukemia L1210 cells was examined. Liposomes were generated by prolonged ultrasonic dispersion of aqueous dispersions of mixed lipids in the presence of radiolabeled inulin. Multilamellar vesicles were separated from unilamellar vesicles by column chromatography. Vesicle populations were examined by electron microscopy. Neutral vesicles were generated from egg yolk phosphatidylcholine and cholesterol, and surface charge was introduced via either phosphatidylserine or octadecylamine. Uptake, measured as cell-associated radioactivity, was temperature dependent and was strongly decreased by metabolic inhibitors. These results suggested that liposomes are taken up to a major extent by an energy-dependent mechanism. The uptake of liposomes by cells of a young culture was about 2-fold higher than was the uptake of liposomes by cells of a stationary culture. The uptake of positively charged liposomes by cells was about 20-fold higher than that of either neutral or negatively charged vesicles. About one-half of the cell-associated radioactivity transferred by positively charged liposomes could be removed by cell surface treatment with trypsin or neuraminidase or by a short exposure to 0.6 N NaCl.

Animals↗
PubMed1977

[Muscle bridges over the left anterior descending coronary artery: their influence on arterial disease (author's transl)].

A total of 711 hearts was studied and examined for coronary muscle bridges of the left anterior descending (LAD) macroscopically, angiographically and histologically. A muscular overbridging of the LAD was found in 22.9% of all hearts. The average distance from left artery bifurcation was 33.6 mm, the average length was 22.5 mm and the average thickness 2.8 mm. A thin layer of fat tissue is mostly to be found between the overbridged coronary artery and the myocardial bridge. The patient group with and without myocardial overbridging showed no difference in sex or age nor in average stature and the average heart weight. Statistically, there is significantly more atherosclerosis of the coronary artery proximal to the muscle bridge than there is under and distal to the bridge. A difference in frequency and extent of atherosclerosis in hearts with and without coronary muscle bridge could not be shown for this portion of the LAD. Nevertheless, there is a tendency for fewer anterior-wall infarctions in the patient group with a coronary muscle bridge of the LAD, because, when the whole branch is considered, there is a significantly lower incidence of atherosclerosis in hearts with myocardial overbridging of the LAD. The reason for the protective effect of a coronary muscle bridge is yet not clear.

Adipose Tissue↗
PubMed1977

Methylmercury teratogenesis in the killifish, Fundulus heteroclitus.

Exposure of developing eggs of the killifish, Fundulus heteroclitus, to 0.03 or 0.04 mg/l of methylmercuric chloride resulted in a variety of abnormalities. Percentage of axis formation was reduced somewhat, and many embryos developed cyclopia or intermediate conditions leading to cyclopia, reflecting interference with induction of the forebrain. Defects in the cardiovascular system also appeared in the form of failure of the heart to differentiate properly into chambers. The heart was a thin, feebly beating tube, incapable of causing the blood to circulate. Other tissues, however, continued developing fairly normally, and embryos showed spontaneous movement comparable to controls. Embryos with severe cardiovascular or optic defects did not hatch. Upon hatching, some embryos which had previously appeared normal were found to have skeletal malformations in the form of vertebral bends or the inability to uncurl from the position which they had while still inside the chorion. Exposure to the toxicant for shorter periods of time (6, 12, or 24 hours) reduced the incidence of abnormalities. The second day of development was found to be the most sensitive period.

Abnormalities, Drug-Induced↗
PubMed1975

Axonal transport of RNA during regeneration of the optic nerves of goldfish.

The distribution of radioactive RNA and RNA precursors in the goldfish optic tecta following intraocular injection of 3H-uridine has been studied during various stages of optic nerve regeneration. 3H-uridine was injected into the posterior chamber of the right eye 17, 30, or 60 days after both optic nerves were crushed. Five were sacrificed at time intervals ranging from 0.5 to 21 days after injection. One day prior to sacrificing, 14C-proline was also injected into the right eye as a marked of fast axonal protein transport. Seventeen to 23 days after crushing, the approximate time of nerve reconnection, the amount of radioactive RNA appearing in the left optic tectum was increased by more than ten times control values. Approximately 30 days after crushing the nerve, when the reconnected nerve is maturing, RNA values were still elevated, but significantly decreased from the earlier stage. By 60 days after crushing the optic nerve, the amounts of RNA in the left tectum was close to normal. Evidence suggesting that, at least, some of the radioactive RNA in the tectum originated from RNA transported along optic axons rather than from RNA synthesized locally in the tectum was provided by autoradiographic experiments. Autoradiograms of paraffin sections taken from the goldfish optic tecta after the intraocular injection of 3H-uridine showed a distribution of grains in a linear pattern, suggesting a distribution over the incoming fibers during the reconnection stage of regeneration. Electron microsocpic autoradiography of glutaraldehyde fixed epoxy sections confirmed that a significant number of grains (shown to be 3H-RNA) were, in fact, over regenerating optic axons. Intracranial injection of 3H-uridine, during the same stage of regeneration, on the other hand, resulted in a distribution of grains, specifically over cell perikaprya. These experiments suggest that during the reconnection phase of nerve regeneration, large amounts of RNA may be carried within regenerating optic axons as they enter the optic tectum.

Animals↗