Barriers to recovery for medical professionals: Assessing financial support through a survey of Physician Health Programs.

Background And Objectives: There is increasing focus on physician burnout, psychiatric problems, and substance use disorders. Costs of recovery for physicians enrolled in Physician Health Programs (PHPs) remain unexamined with little known regarding funding resources. We sought to elucidate perceived costs of recovery from impairing conditions and highlight resources for financial strain.

The role of diet and nutrition in cancer.

Experimental and epidemiologic studies in recent years are pointing to diet as an important contributor to the cancer death toll which in the US this year will reach nearly one half million. Obesity, high fat intake, low fiber content and a dearth of vitamin A- and C-containing fruits and vegetables have been identified as risk factors; but these are not independent variables. The complex network of metabolic mechanisms involved are still obscure and association is not necessarily causation.

5-Methylcytosine depletion during tumour development: an extension of the miscoding concept.

We propose a general model for neoplastic development which postulates that the loss of methyl groups from 5-methylcytosines (5-mC) involved in the control of gene expression may initiate neoplastic transformation and give rise to the aberrant phenotype of the transformed cell. Interference with normal patterns of methylation can be envisioned to occur by a number of mechanisms: as a result of carcinogen-induced G:C leads to A:T transition leading to a loss of potentially methylatable cytosines; by mutations or chromosome rearrangement which disrupt the integrity of active DNA methylase genes; by separating methylated repressor regions of the genome from the genes they control; by direct interference with DNA methylation, as proposed for ethionine and 5-azacytidine; by spontaneous deamination of 5-mC to thymine, leading to accumulation of 5-mC:G leads to T:A transitions, by virus-induced perturbations in host cell methylation patterns; and by activation of DNA demethylases.

Subcellular distribution of inorganic pyrophosphatase activity in various normal and neoplastic cell types.

Inorganic pyrophosphatase (PPiase) activity was measured in cell fractions of rat, mouse, and human erythrocytes; normal rat liver; Novikoff hepatoma; Morris 3924A hepatoma; and mouse Ehrlich and Sarcoma 37 ascites tumors. Despite high intracellular activities, when precautions were taken to maintain cell integrity, only negligible activities were found on the surface of intact erythrocytes, Novikoff ascites hepatoma, Ehrlich carcinoma, and Sarcoma 37 cells. Suspensions of intact Ehrlich and Sarcoma 37 cells exhibited low PPiase activity, but this was only about 1 to 2% of the intracellular activity and was completely accounted for by activity present in the suspension medium.

A microcolorimetric assay of inorganic pyrophosphatase.

A procedure is described for the assay of inorganic pyrophosphatase in tissues by a microcolorimetric procedure, taking advantage of the marked color intensification of phosphomolybdate by malachite green. Conditions are described for optimum enzyme activity, color stability, and sensitivity. With 1-cm cuvettes the AM660 is 100,000, allowing accurate measurement of Pi in the 1-nmol range.

Isozyme alterations, gene regulation and the neoplastic transformation.

Studies of isozyme composition in the rat liver-hepatocellular carcinoma model system have revealed wide-ranging abnormalities of gene expression. Isozymes geared for adult liver function are lost in tumors to varying degrees, depending on growth rate and degree of tumor dedifferentiation; whereas isozymes low or absent in normal adult liver become predominant or sole forms in fast growing, poorly differentiated hepatic tumors. The prevailing pattern is a switch from the adult to fetal forms, thereby indicating that genes coding for adult isozymes are suppressed in liver neoplasms, while genes active in fetal stages but inactivated during normal embryonic development become re-activated in cancer.

Purification and properties of inorganic pyrophosphatase of rat liver and hepatoma 3924A.

Inorganic pyrophosphatase (EC 3.6.1.

New dimensions in the biology of cancer.

A common thread interwoven throughout the literature of cancer biology is a wide-ranging abnormality of gene regulation, manifested by misprogramming of protein synthesis. This phenomenon encompasses virtually every means of identification of proteins, including antigens, hormones, growth factors, membrane components, and enzymes. Studies by the author and others of the activities of enzymes existing in multiple forms (termed isozymes) in a series of rat hepatomas ranging widely in growth rate, degree of differentiation, and other phenotypic properties has extended this concept and added to it a dimension of functional significance.

Formation of carbonyl chloride in carbon tetrachloride metabolism by rat liver in vitro.

In order to identify intermediates of CCl4 metabolism, whole, suitably fortified rat liver homogenates were incubated with 14CCl4 in the presence and absence of "pools" of unlabeled suspected intermediates. In the presence of NADH or NADPH, incorporation of radioactivity was rapid and substantial in CO2, lipid, protein, and the acid-soluble fraction. It was not influenced by the presence of large pools of unlabeled chloroform or formate, thus excluding these substances as obligatory intermediates.

Urea synthesis in Novikoff and Morris hepatomas.

The rates of urea synthesis in rat liver and in a series of rat liver neoplasms with widely different growth rates and degree of differentiation were investigated using tissue slices incubated in a Krebs-Ringer bicarbonate buffer. Urea synthesis did not occur in fast-growing, poorly differentiated Novikoff and Morris 3924A hepatomas, but it did occur in slow-growing, well- and highly differentiated hepatomas; however, there was no correlation with growth rate or degree of differentiation. Urea synthesis was comparable with normal liver, at about 32 mumoles/hr/g tissue, in the slow-growing Morris hepatomas 21, 28A, 47C, and 44; but it was very low in two other slow-growing, highly differentiated hepatomas, 9618A and 20.

Metabolism of [3H]-methylcholanthrene in the perfused rat liver.

The metabolism of [3H]-3-methylcholanthrene (3-MC) was studied in the isolated, perfused rat liver. Following addition of 250 mug to the perfusion fluid, 3-MC disappeared rapidly. After 2 hr, approximately 34% of the radioactivity was excreted in the bile, 6% remained in the perfusate, and 60% was found in the liver.