PubMed Health⌕ Search

Biomedical subjects

H C Pitot

Publications and source records attributed to H C Pitot.

At least 469 records · Page 26Linked to original sources
PubMed1965

Effect of gamma radiation on dietary and hormonal induction of enzymes in rat liver.

The dietary induction of serine dehydrase, produced by the oral intubation of hydrolyzed casein to protein-depleted rats, is markedly inhibited by doses of gamma-radiation of 400 roentgens or higher provided the irradiation is given within an hour after the initial dose of casein. If the irradiation is delayed until 7 hours after the initial dose of casein, induction is not inhibited. In contrast, the cortisone induction of tyrosine alpha-ketoglutarate transaminase is not inhibited by doses of gamma-radiation up to 3200 roentgens; in some instances hormonal induction of this enzyme appears to be enhanced by irradiation.

Adrenalectomy↗
PubMedDate not supplied

Hazard assessment of chemical carcinogens: the impact of hormesis.

The recent report of reductions in the number and area of preneoplastic hepatic lesions in response to low doses of the tumor promoter phenobarbital provides important new support for the existence of hormetic responses to carcinogens. The presence of hormetic responses to carcinogenic agents and the corollary that beneficial doses of these compounds can be determined have several implications for the bioassay and hazard assessment of carcinogens as well as for public policy regulating exposure to these agents. To be adequately sensitive to detect and quantify hormetic or other non-linear dose-response functions, current study designs must be modified to include lower doses and sufficiently large numbers of animals. Short- or medium-term animal studies are a cost-effective means of addressing these needs and have been used recently to describe a classical hormetic response to the non-genotoxic carcinogen phenobarbital. These basic changes should be supported by a continuing emphasis on mechanistic research and the development of biologically based quantitative models of toxicant action. Linking these models with physiologically based pharmacokinetic model descriptions of target dose holds the greatest promise for improving the description of the dose-response curve at low doses. These approaches are generally encouraged by the USEPA in the form of The 1996 Proposed Carcinogen Risk Assessment Guidelines. However, there remain substantial questions regarding integration of the concept of hormesis into hazard testing and public policy that require careful consideration. Herein, we explore the issues that surround testing for hormetic responses and the implications for public policy.

Animals↗
PubMedDate not supplied

Electron microscopic and time lapse studies of mitosis in cultured rat hepatocytes.

Primary cultures of adult rat hepatocytes in a serum-free medium were observed by time lapse cinematography to proceed through mitotis and cytokinesis. An ultrastructural study of these cultures is presented with electron micrographs of each stage of mitosis and cytokinesis. The cultured hepatocytes begin to enter prophase about 48 hr after plating and proceed through mitosis in approximately 70 min not including cytokinesis. During this time, they remain somewhat flattened and joined to neighboring cells rather than rounding up. Both mononucleate and binucleate hepatocytes proceed through mitosis. Some mononucleate cells do not undergo cytokinesis, resulting in the formation of binucleate cells. In binucleate hepatocytes, both nuclei proceed through prophase simultaneously. Usually a single mitotic spindle with a large metaphase plate containing chromosomes from both nuclei is observed. Cytokinesis frequently occurs in binucleate hepatocytes which have a single mitotic spindle. Some binucleate cells form tripolar or 4-polar metaphase plates. In tripolar metaphases, some cells do not divide, resulting in multinucleate cells, whereas others undergo cytokinesis yielding three mononucleate cells or one binucleate and one mononucleate cell. Two mitotic spindles located perpendicularly to each other with microtubules intertwining have been observed in 4-polar metaphases. In this latter case, no cytokinesis has been observed. This study shows that both mononucleate and binucleate adult rat hepatocytes cultured in a serum-free medium in the presence of epidermal growth factor not only synthesize DNA, but progress through mitosis and often cytokinesis.

Animals↗
PubMedDate not supplied

Treatment of neuroendocrine cancer metastatic to the liver: the role of ablative techniques.

Carcinoid tumors and islet cell neoplasms are neuroendocrine neoplasms with indolent patterns of growth and association with bizarre hormone syndromes. These tumors behave in a relatively protracted and predictable manner, which allows for multiple therapeutic options. Even in the presence of hepatic metastases, the standard of treatment for neuroendocrine malignancy is surgery, either with curative intent or for tumor cytoreduction, i.e., resection of 90% or more of the tumor volume. Image-guided ablation, as either an adjunct to surgery or a primary treatment modality, can be used to treat neuroendocrine cancer metastatic to the liver. Image-guided ablative techniques, including radiofrequency ablation, alcohol injection, and cryoablation, can be used in selected patients to debulk hepatic tumors and improve patient symptoms. Although long-term follow-up data are not available, the surgical literature indicates that significant ablative debulking may improve patient survival. In this review, we discuss metastatic neuroendocrine disease and its treatment options, especially image-guided ablative techniques.

Catheter Ablation↗
PubMedDate not supplied

Quantitation of multistage carcinogenesis in rat liver.

A well characterized model of multistage carcinogenesis is that of hepatocarcinogenesis in the rat. The histopathology as well as the cell and molecular biology of the stages of initiation, promotion, and progression have been elucidated to varying degrees in this system. Putatively single initiated hepatocytes are identified by their expression of the ubiquitous marker of hepatocarcinogenesis, glutathione-S-transferase pi (GSTP). 0.5-1.0 x 10(6) GSTP-positive "initiated" hepatocytes developed within 14 days after initiation with a subcarcinogenic dose of diethylnitrosamine (DEN). Approximately 1% of these cells develop clonally into altered hepatic foci (AHF) in animals administered promoting agents, such as phenobarbital, chronically for 4-8 mo. Hepatocytes within AHF during the stage of promotion exhibit normal diploid karyotypes but various phenotypes depending on the chemical nature of the promoting agent. Continued administration of the promoting agent results in the infrequent development of hepatocellular carcinomas; however, administration of a complete carcinogen or a progressor agent during the stage of promotion results in substantial numbers of hepatic neoplasms. In order to quantitate the development of the stage of progression more accurately, markers selective for this stage have been sought. Transforming growth factor-alpha (TGF-alpha) appears to be such a marker of progression. About 500 TGF-alpha-positive lesions develop spontaneously following initiation and continued promotion, usually within GSTP-positive AHF, but administration of a single dose of a progressor agent such as ethylnitrosourea may increase this number 3-fold or more. Some agents such as gamma radiation and hydroxyurea, when administered as single or a few closely spaced multiple doses, result in no increased number in TGF-alpha-positive lesions but a markedly enhanced increase in their growth rate. By monitoring gene expression using quantitative stereology, the stages of hepatocarcinogenesis can be analyzed and quantified in sufficient detail so that the animal data can be utilized in biomathematical modeling to develop more accurate models for estimation of human cancer risks.

Animals↗