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Biomedical subjects

J F Weiss

Publications and source records attributed to J F Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Radioprotection by vitamin E: injectable vitamin E administered alone or with WR-3689 enhances survival of irradiated mice.

Radioprotection by injectable vitamin E (alpha-tocopherol) was investigated in mice exposed to 60Co radiation (0.2 Gy/min). Vitamin E injected subcutaneously either 1 hr before or within 15 min after irradiation significantly increased 30-day postirradiation survival in CD2F1 male mice. A dose reduction factor (DRF) of 1.11 (95% confidence interval [1.08, 1.14]) was observed for vitamin E at a dose of 100 IU/kg body weight administered within 15 min after irradiation. Combination studies with the phosphorothioate WR-3689 (S-2([3-methylaminopropyl]amino)ethylphosphorothioic acid) were undertaken to determine whether radioprotection by WR-3689 could be enhanced by vitamin E. Mice were given WR-3689 (150-225 mg/kg, intraperitoneally) 30 min before irradiation and were given vitamin E (100 IU/kg) either 1 hr before or within 15 min after irradiation. Survival was significantly increased in mice given vitamin E and WR-3689 before irradiation as compared to mice given WR-3689 alone: the DRF for WR-3689 (150 mg) was 1.35 [1.32, 1.38]; for WR-3689 combined with vitamin E (100 IU), the DRF was 1.49 [1.45, 1.53].

Amifostine↗
PubMed1990

Influence of whole body irradiation and local shielding on matrix-induced endochondral bone differentiation.

Subcutaneous implantation of demineralized bone matrix into allogeneic rats induces endochondral bone formation. We have investigated the effects of irradiation on the sequelae of the interaction of collagenous matrix and mesenchymal cells and on cartilage and bone differentiation. Rats were irradiated in a vertical direction with a midline dose of 850 rad. Radiation entered the rats ventrally while a small area of the upper thorax was locally shielded. After irradiation, bone matrix was implanted in shielded and nonshielded sites, and the implants were studied at various stages. On day 3, [3H]thymidine incorporation, an index of cell proliferation, was inhibited by 70% in the nonshielded sites compared to nonirradiated control rats. The degree of inhibition (35%) was less pronounced in shielded sites. Furthermore, there was recovery of cell proliferation in the shielded sites as opposed to the nonshielded contralateral site. A similar pattern was observed on day 7 as assessed by 35SO4 incorporation into proteoglycans during chondrogenesis. Bone formation and mineralization were quantified on day 11 by alkaline phosphatase activity and 45Ca incorporation. In nonshielded sites, there was a 73% inhibition of alkaline phosphatase activity. In conclusion, radiation impaired progenitor cell proliferation which resulted in decreased cartilage and bone differentiation. These findings imply that local mesenchymal cells proliferate and differentiate into bone in response to implanted collagenous matrix.

Animals↗
PubMed1990

Advances in radioprotection through the use of combined agent regimens.

The most effective radioprotective agents exhibit toxicities that can limit their usefulness. It may be possible to use combinations of agents with different radioprotective mechanisms of action at less toxic doses, or to reduce the toxicity of the major protective compound by adding another agent. With regard to the latter possibility, improved radioprotection and reduced lethal toxicity of the phosphorothioate WR-2721 was observed when it was administered in combination with metals (selenium, zinc or copper). The known mechanisms of action of potential radioprotective agents and varying effects of different doses and times of administration in relation to radiation exposure must be considered when using combined-agent regimens. A number of receptor-mediated protectors and other biological compounds, including endotoxin, eicosanoids and cytokines, have at least an additive effect when administered with thiol protectors. Eicosanoids and other bioactive lipids must be administered before radiation exposure, whereas some immunomodulators have activity when administered either before or after radiation exposure. For example, the cytokine interleukin-1 administered simultaneously with WR-2721 before irradiation or after irradiation enhances the radioprotective efficacy of WR-2721. The most effective single agents or combinations of protectors result in a decrement in locomotor activity, an index of behavioral toxicity. Recent evidence indicates that administration of the CNS stimulant caffeine mitigates the behavioral toxicity of an effective radioprotective dose of the phosphorothioate WR-3689 without altering its radioprotective efficacy. These examples indicate that the use of combinations of agents is a promising approach for maximizing radioprotection with minimal adverse effects.

Animals↗
PubMed1979

Serum acute-phase proteins and immunoglobulins in patients with gliomas.

Cellular immune competence was found to be impaired in previous studies of patients with malignant brain tumors. In patients with nonneural tumors, we recently found that serum levels of acute-phase proteins were related to immune status as well as to tumor extent. To determine whether the serum proteins in patients with central nervous system tumors show similar changes, levels of acute-phase proteins (alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, C-reactive protein) and immunoglobulins (immunoglobulins G, M, and A) were assayed in patients with gliomas prior to treatment. Compared to normals, significant increases (p less than 0.001) in the acute-phase proteins were found, and the levels were similar to those in patients with nonneural solid neoplasms. Serum immunoglobulins were not significantly increased in patients with gliomas.

Alpha-Globulins↗
PubMed1978

Effect of maleic anhydride-vinyl ether on the lymphocyte subpopulations of tumor-bearing, irradiated mice.

The splenic T- and B-lymphocyte populations of BALB/c mice were determined in Madison lung carcinoma 109-bearing animals. Concurrently, some groups of tumored mice were exposed to 500 rads of whole-body irradiation and were treated with one dose of maleic anhydride-vinyl ether (MVE). By direct immunofluorescence, it was found that the percentage of splenic T lymphocytes was significantly depressed in the tumored-irradiated mice. Mitogenic studies revealed that the T lymphocytes were more depressed in the tumored-irradiated mice than in the corresponding nonirradiated tumored mice. MVE was relatively effective in reconstituting the T-cell compartment of these splenic T lymphocytes. The B-cell compartment of the splenic lymphocytes of the tumored-irradiated mice was found to be extremely radiosensitive. Utilizing a specific anti-B serum, no B lymphocytes were detected during the testing. Blastogenic studies using lipopolysaccharide as the mitogenic probe revealed that the incorporation of 3H-TdR of the tumored-irradiated mice was just slightly higher than background values. MVE proved to be relatively ineffective in reconstituting the splenic B cells of the tumored-irradiated mice.

Animals↗
PubMed1977

Correlations among serum protein-bound carbohydrates, serum glycoproteins, lymphocyte reactivity, and tumors burden in cancer patients.

Levels of glycoprotein-associated carbohydrates (neutral hexoses, hexosamine, sialic acid and fucose) were determined in the serum of patients with either local, regional or metastatic cancer, patients clinically cured of cancer, and controls (smokers and nonsmokers). Total protein-bound carbohydrates were compared with levels of 17 normal serum glycoproteins, carcinoembryonic antigen (CEA), and with lymphocyte reactivity to phytohemagglutin (PHA). Tumor burden was directly related to protein-bound carbohydrate levels in patient groups. Levels of bound carbohydrates reflect the sum of all the changes in serum glycoproteins, but primarily changes in the acute-phase proteins (alpha 1-acid glycoprotein, alpha 1-antitrypsin, haptoglobin, ceruloplasmin) found in the alpha-globulin fraction of serum. Increases in protein-bound carbohydrates in tumor-bearers were not related to increases in CEA. Increased levels of the acute-phase proteins occurred in individuals with depressed in vitro lymphocyte reactivity to PHA. A significant positive correlation was found between lymphocyte reactivity and level of alpha 2HS-glycoprotein. The results suggest that serum protein-bound carbohydrates or glycoproteins may be of adjunctive value is assessing tumor burden and immune reactivity in cancer patients.

Carbohydrates↗
PubMed1976

Desmosterol in human and experimental brain tumors in tissue culture.

Desmosterol, a possible chemical indicator of brain tumors, was detected in cells of neurogenic, nitrosourea-induced rat tumors (neurinomas and gliomas, C6 cell line) and in human astrocytomas grown in lipid-poor media. A further increase in the amount of cell desmosterol was obtained when triparanol was added to media containing delipidized serum. Cholesterol was replaced almost completely by desmosterol in tumor cells grown in media containing nontoxic levels of 20,25-diazacholesterol. Desmosterol did not accumulate when these inhibitors of desmosterol-reductase were added to culture media containing cholesterol and other lipids (whole fetal calf serum). The results demonstrate that tumors of the nervous system grown in tissue culture are capable of sterol synthesis, and indicate that a central mechanism of cholesterol synthesis is operative in these cells, which may be related to the availability of exogenous cholesterol. It is concluded that these findings are relevant to clinical studies on the use of cholesterol inhibitors as tools for the detection of brain tumor activity.

Animals↗