PubMed Health⌕ Search

Biomedical subjects

W H Butler

Publications and source records attributed to W H Butler.

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

The ultrastructural effects of di-n-pentyl phthalate on the testis of the mature rat.

A sequential morphological study has been carried out to examine the ultrastructural effects of di-n-pentyl phthalate (DPP) on the mature rat testis. A single oral dose of 2.2 g DPP/kg body wt was administered, and testes, perfuse-fixed 3-48 hr after dosing, were examined by transmission electron microscopy. By 3 hr, rarefaction of the basal Sertoli cell cytoplasm was seen and the basal plasma membranes separating adjacent Sertoli cells were thrown into a series of convoluted profiles with the appearance of interdigitating cell processes. The subjacent ectoplasmic specializations that normally face these membranes were disrupted, and by 12 hr the inter-Sertoli junctions showed numerous membrane discontinuities. The lateral processes of Sertoli cell cytoplasm, which separate germ cells, showed retraction and fragmentation, resulting in direct contact between adjacent germ cells or the isolation of germ cells unapposed by Sertoli cell plasma membrane. In addition, the ectoplasmic specializations associated with Sertoli-spermatid and Sertoli-pachytene spermatocyte junctions were often disrupted or absent. The mitochondria in the Sertoli cells were enlarged and, in some tubules, increased in number. The changes seen were restricted to tubules in the successive stages XI-XIV, I, and II of the spermatogenic cycle. Elongating spermatids (steps 12-15) showed cytoplasmic condensation and vacuolation by 12 hr and were necrotic by 24 hr. A small proportion of zygotene and early pachytene spermatocytes showed necrosis by 24 hr after dosing. By 48 hr, the cytoplasmic rarefaction and convoluted plasma membranes had regressed and ectroplasmic specializations had reformed along Sertoli-Sertoli junctions.

Animals↗
PubMed1987

Chronic toxicity/carcinogenicity study of carmine of cochineal in the rat.

Carmine was fed continuously to groups of 54 males and 54 females at dietary levels providing 50, 150 or 500 mg/kg body weight/day for up to 109 wk. As a control, groups of 90 males and 90 females were fed the basal diet for the same period. The rats were derived from parents fed the same dietary levels for 60 days before mating and throughout pregnancy and were thus potentially exposed in utero. There were no adverse effects upon survival, growth or intakes of food and water. No changes associated with treatment were found during the periodic measurement of haematology or renal function, or in the serum chemistry or organ weights at the end of the study. Tumour incidence was not affected, and variations in the distribution of the non-tumour pathology were not considered to be due to treatment. It was concluded that carmine administered to rats in utero and for up to 109 wk is not carcinogenic and that the no-untoward-effect level is 500 mg carmine/kg body weight/day.

Animals↗
PubMed1987

Long-term toxicity study of amaranth in rats using animals exposed in utero.

Groups of 90 (control) and 54 (treated) rats of each sex were given amaranth in their diet to provide daily intakes of 0 (control), 50, 250 or 1250 mg/kg for 111 wk (male) and 112 wk (female) after weaning. The rats had also been exposed to the same dose levels in utero, and their parents were exposed for 60 days before mating. The colouring had no adverse effects on fertility, haematological parameters, serum chemistry or incidence of tumours. All treated animals showed contamination of the fur and red colouring of the faeces and at the high dose only the faecal pellets were poorly formed. Rats in the high-dose group produced more pups, and the average pup weight was lower than that of the controls. Rats of the F1 generation given the highest dose level were slightly lighter than the controls despite a small increase in food and water intake. Both sexes given the highest dose level and males given 250 mg/kg/day had increased caecal weight. High-dose females excreted more protein in the urine after 18 months and on histopathological examination females in all treated groups showed an increased incidence of renal calcification and pelvic epithelial hyperplasia with degenerative changes. It is concluded that amaranth fed to rats at dose levels of up to 1250 mg/kg/day in the diet did not have any carcinogenic effect. However, because of the effect on the kidneys of the females it was not possible to establish a no-untoward-effect level in this study.

Amaranth Dye↗
PubMed1987

A study of the effects of vigabatrin on the central nervous system and retina of Sprague Dawley and Lister-Hooded rats.

Vigabatrin (gamma-vinyl GABA), an enzyme-activated, irreversible inhibitor of GABA transaminase, was administered orally to albino Sprague Dawley and pigmented Lister-Hooded rats. A dose-dependent retinal lesion characterized histologically by disruption of the outer nuclear layer was observed in the Sprague Dawley rat but not in Lister-Hooded rats, indicating that this alteration is related to the absence of pigment. The lesion is similar to that induced in albino rats by light and certain drugs. In addition, myelin vacuolation of the brain was observed in both rat strains, consistent with the findings of other toxicity studies with vigabatrin. In all cases, the vacuolation was limited to myelinated tracts and resulted from separation of the myelin sheath at the intraperiod line. There was no evidence of demyelination, axonal degeneration or damage to contiguous structures in the affected areas. The vacuolation is histologically similar to that induced in rats by certain other compounds such as isoniazid, hexachlorophene, and triethyltin, but differs in that it is focal in distribution, it is limited to the brain, and is reversible upon cessation of treatment.

4-Aminobutyrate Transaminase↗
PubMed1987

Dose-response relationships in chemical carcinogenesis: renal mesenchymal tumours induced in the rat by single dose dimethylnitrosamine.

A single intraperitoneal dose of dimethylnitrosamine (DMN) given to weanling rats after 3 days' treatment with a protein-free diet results in the induction of renal mesenchymal tumours, the incidence of which is related to the dose of DMN in a sigmoid dose-response curve. The number of tumours per kidney is small, most animals given 40 mg/kg DMN (the TD100) having either one or two tumours in each kidney. However, within a few days of dosing a large number of small proliferative foci of mesenchymal cells, which resemble the tumours, appears in the renal cortex. The number of these foci is linearly related to the dose of DMN. By 12 weeks, the majority of these foci have disappeared, leaving an essentially normal kidney with only one or two developing tumours. The initial amount of methylation of guanine at the O6 and 7 positions in the kidney DNA measured 18 h after dosing is also linearly related to the dose of DMN. Thus, the formation of the early lesions is directly proportional to the amount of DNA alkylation, but the eventual tumour incidence is not. It is suggested that the mechanisms which operate to remove the majority of the early proliferative foci determine the shape of the dose-response curve for the tumours, which is independent of the initial alkylation levels.

Alkylation↗
PubMed1987

A possible mechanism for the dose-response relationship observed for renal mesenchymal tumours induced in the rat by a single dose of N-nitrosodimethylamine.

The incidence of renal mesenchymal tumours induced in rats by N-nitrosodimethylamine (NDMA) is related to the dose in a sigmoidal dose-response curve. Each kidney bears only one or two tumours at 20-24 months. In contrast, one week after dosing, a large number of preneoplastic proliferative foci is present, the incidence of which is linearly related to dose and directly proportional to methylation of DNA by NDMA. It is suggested that most of these foci are removed by host defense mechanisms before they can progress to tumour, thus accounting for the sigmoid shape of the dose-response curve for the tumours.

Animals↗
PubMed1986

An ultrastructural study of ethylene glycol monomethyl ether-induced spermatocyte injury in the rat.

Previous studies have shown that administration of ethylene glycol monomethyl ether (EGM) to the rat results in testicular damage with the spermatocyte being the primary cellular site for toxicity. An ultrastructural study has now been carried out to characterize the early subcellular changes following a single dose of 250 or 500 mg EGM/kg body weight. At 12 and 18 hr after dosing, large membrane bound intracellular vacuoles filled with flocculent or granular material were observed in the basal region of the tubules. These mostly appeared to originate as rarefaction and swelling of Sertoli cell processes. Necrosis of spermatocytes was evident at 12 hr but the process of cell death was rapid with cells either appearing normal or in an advanced state of necrosis. Many of the spermatocytes which appeared otherwise normal, showed areas of plasma membrane dissolution, a change which was also seen affecting the facing Sertoli cell plasma membrane resulting in continuity of the cytoplasm between the two cells. This membrane change was seen in the absence of any other morphological abnormality in the affected spermatocyte, although slight mitochondrial condensation was sometimes also present. By 24 hr after dosing, most of the spermatocytes in the spermatogenic stages which had shown the earlier membrane changes, had become necrotic while Sertoli cell vacuolation had largely regressed. Although the membrane dissolution was an early and specific effect, it is regarded as part of the phagocytic response of the surrounding Sertoli cell. It is suggested that the vacuolar changes in the Sertoli cell may be causally associated with spermatocyte injury.

Animals↗
PubMed1986

The histology and development of hepatic nodules in C3H/He mice following chronic administration of phenobarbitone.

Male C3H/He mice were given 0 (control) or 85 mg/kg/day phenobarbitone (PB). Groups of five control and five treated animals were killed at 5, 10, 25, 40 and 55 weeks; additional animals were allowed to live out their natural life span or killed at the termination of the experiment at 100 weeks. Small nodules of basophilic cells were seen in control animals at 55 weeks. These increased both in size and number so that at term nodules were found in 17/35 animals examined. Animals given PB showed typical centrilobular hypertrophy. Basophilic nodules were also seen in the treated animals and these were similar in form and in number to those seen in control animals. The total number of liver nodules seen in animals given PB was, however, greater than the number seen in control animals. The increased nodule burden was a result of the development of a second nodule type that was first seen in animals killed at 40 weeks. These nodules were formed of large eosinophilic cells that had a similar appearance to the hypertrophied cells of the centrilobular region. In contrast the incidence of carcinoma in PB-treated animals was not increased over that of the control group.

Animals↗
PubMed1985

Acute toxicity and recovery in the hemopoietic system of rats after treatment with ethylene glycol monomethyl and monobutyl ethers.

Male rats were given ethylene glycol monomethyl ether (EGM) or ethylene glycol monobutyl ether (EGB) po for 4 consecutive days at doses of 100 or 500 mg/kg body wt/day for EGM, and 500 or 1000 mg/kg body wt/day for EGB. Animals were killed on Days 1, 4, 8, and 22 after the final treatment. Both EGM and EGB produced thymic atrophy and lymphocytopenia and, in the case of EGM, neutropenia also. Hemolytic anemia induced by EGB resulted in splenic extramedullary hemopoiesis, hyperplasia of both spleen and bone marrow, and reticulocytosis. Apart from residual slight increases in spleen weight, mean red cell volume, and mean corpuscular hemoglobin at the end of the recovery period, other effects were reversible. With EGM, reduction in the numbers of circulating red cells was only slight. Treatment with EGM also abolished splenic extramedullary hemopoiesis which partially recovered on Day 4, followed by a marked response on Day 8, and return to the moderate control values on Day 22. Femoral bone marrow was hemorrhagic 1 day after treatment with EGM which appeared to be associated with sinus endothelial cell damage. By Day 4 the histologic appearance of the marrow was normal. Testicular atrophy was also produced in EGM-treated animals which persisted for the duration of the experiment. It is concluded that EGM and EGB differ considerably in the spectrum of toxic changes induced, and apart from testicular atrophy, these changes were largely reversible within a short time of the end of treatment.

Animals↗
PubMed1979

Zonal changes in the rat liver after chronic administration of phenobarbitone in ultrastructural, morphometric and biochemical correlation.

Alterations in the liver of rats subjected to 24 days of continuous administration of phenobarbitone have been supplied bu subcellular fractionation, conventional electron microscopy and morphometric analysis. The increase in wet weight of the liver was found to result from a combination of cellular hypertrophy, hyperplasia and an enlarged hepatic blood space. In the centrilobular zone all the hepatocytes underwent a substantial proliferation of total ER, became enlarged and had an increased blood supply. However, in the periportal zone phenobarbitone caused changes in only 45% of the hepatocytes, the remainder being apparently resistent or tardy. An overall dramatic increase in hepatic RER was both measured and observed but the response involved hepatocytes in which the RER had proliferated as well as those which were depleted of RER or had stacks and cisternae that were severely shortened and dispersed. These alterations are discussed in relation to changes in RER after administration of agents causing hepatonecrosis. Possible reasons for the inability of other workers to detect a phenobarbitone-induced increase in RER are also put forward. After subcellular fractionation and corection for centrifugation losses into the 9500 g pellet, using the microsomal marker cytochrome P-450, phenobarbitone-induced increase in total ER was substantially less than that found by morphometric analysis. This indicates that during the preparation of microsomes a substantial proportion of intracellular membranes, having different metabolic and synthetic properties to those finally isolated, are discarded and emphasizes the need to exercise care when using microsomal preparations.

Animals↗
PubMed1979

Cellular progression of neoplasia in the subcutis of mice after implantation of 3,4-benzpyrene.

An implantation model has been used to investigate the cellular progression of chemically induced subcutaneous neoplasia in the mouse. Implantation of 3,4-benzpyrene induced persistent changes in the normal process of connective tissue formation around the implant. Light-microscope and autoradiographic studies have shown a temporal progression from aberrant filter- or muscle-associated cells through proliferative foci to large invasive sarcoma. Electron microscopy revealed that presarcomatous cell foci consisted of one of two different cell types. These were either spindle cells with ultrastructural characteristics similar to foreign-body-induced sarcoma, or cells with the ultrastructural features of rhabdomyosarcoma. The subsequent appearance of two histological groups of sarcoma that were ultrastructurally similar to the cells of the early proliferative foci indicated that both elements may progress to form tumours. However, the constituent cells of both groups of tumours displayed a broad histological and ultrastructural spectrum and the marked similarity between the undifferentiated cells of each suggested that both may have arisen from diverse differentiation of a common pluripotential cell such as the pericyte.

Animals↗
PubMed1978

Histochemical observations on nodules induced in the mouse liver by phenobarbitone.

This study describes the histochemical reactions seen in nodules of the mouse liver. The nodules were obtained from 13 animals treated for over 80 weeks with phenobarbiotone and three untreated mice. The morphology of the lesion depends upon the preparative techniques and only two lesions with persistent abnormal trabecular pattern metastasised. A varying pattern of histochemical reaction was seen. The aniline hydroxylase reaction was dense in simple nodules and in centrilobular areas of phenobarbitone-treated mice but was weak in the abnormal trabecular lesions. These results suggest that it is possible to predict behavioural characteristics of mouse hepatic nodules on the basis of certain morphological characteristics.

Animals↗
PubMed1978

The hepatotoxicity of 3-amino-1,2,4-triazole and carbon disulphide in phenobarbitone-treated starved rats.

In phenobarbitone-treated starved male rats 1 g/kg 3-amino-1,2,4-triazole produced moderate liver necorsis and increased the serum glutamic-pyruvic transaminase activity. If half an hour after the administration of aminotriazole animals were exposed for 4 h to 2.0 mg/l CS2, the necrotic damage in the liver was larger and the serum glutamic-pyruvic transaminase activity higher than in rats not exposed to CS2. Carbon-disulphide in phenobarbitone-treated starved male rats caused only a very slight increase in the serum transminase activity in spite of the widespread hydropic degeneration in the liver. These experiments indicated that increase in serum transaminase activity is the consequence of necrosis and not hydropic degeneration; aminotriazole is hepatotoxic in rats when microsomal enzymes are induced and the hepatotoxicity of aminotriazole and carbon disulphide is potentiated by the administration of the other compound.

Alanine Transaminase↗
PubMed1978

Long-term effects of phenobarbitone-Na on male Fischer rats.

Male inbred Fischer rats were fed phenobarbitone-Na at a level of 500 parts/10(6) in the diet for 1 week, followed by 1000 parts 10(6) for 103 weeks at which time the survivors were killed. Thirty-three treated rats survived to 80 weeks. Before 80 weeks, no animals showed hyperplastic lesions. Of the 33 rats surviving 80 weeks and more, 11 had foci of nodular hyperplasia. These foci were usually small, but one animal killed at 102 weeks had a lesion of 0.75 cm diameter, which compressed the surrounding liver. In one case was evidence of local invasion or metastasis found. All the livers had evidence of parenchymal cell damage. No evidence of nodular hyperplasia was found in the controls. It is concluded that there is no evidence to suggest that phenobarbitone-Na induced neoplasm in the liver of male Fischer rats.

Animals↗
PubMed1978

A comparison of the changes induced in rat liver by feeding low levels of aflatoxin B1 or an azo dye.

(1) Rats have been given 6 weeks' feeding with low levels of the hepatocarcinogens aflatoxin B1 and 2-methyl dimethyl aminoazobenzene (2-Me-DAB). (2) It has been confirmed that 3 weeks' feeding with either toxin is sub-carcinogenic, whereas 6 weeks' feeding results in a high incidence of hepatocarcinoma. (3) The changes occurring in the liver during this feeding have been monitored by histological examination and zonal rotor centrifugation. (4) Marked similarities have been observed between the time courses of development of changes induced in the liver by the two carcinogens. Little change is observed after 2 weeks' feeding with the toxins. The greatest change occurs after 3 weeks' feeding, which results in tissue necrosis and the loss of a large proportion of the tetraploid hepatocyte nuclei. (5) A compensatory proliferation of predominantly diploid hepatocytes takes place in the presence of a continuing supply of either of the carcinogens. This indicates that not only does feeding each carcinogen induce the production of a population of hepatocytes resistant to the cytotoxicity of the inducing agent, but that the population is also resistant to the cytotoxicity of the other carcinogen.

Aflatoxins↗
PubMed1977

Hepatic structure and function after modified jejunoileal bypass surgery for obesity.

The most serious adverse effect of standard intestinal bypass for obesity is the high incidence of hepatic dysfunction and death from hepatic failure. We therefore examined the long-term effects of a modified form of jejunoileal bypass (in which a greater continuous length of ileum is retained), on liver function in 120 patients. Substantial weight loss (119-0+/-SD 23-3 kg to 82-3+/-18-8 kg) occurred during the first nine months after surgery, accompanied by a significant rise in serum concentrations of bilirubin, alanine transferase, and alkaline phosphatase, and a significant reduction in albumin concentrations. Biochemical changes were unrelated to weight loss or halothane anaesthesia. After weight stabilisation liver function reverted to normal, and four years after bypass sulphobromophthalein retention and hepatic histology did not differ from those in obese controls. There were two postoperative deaths. Three other patients died during the period of rapid weight loss with severe hepatic steatosis. While transient mild impairment of liver function is common after modified jejunoileal bypass, clinically significant hepatic dysfunction is a rare and unexplained early complication.

Adult↗