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Biomedical subjects

D Abraham

Publications and source records attributed to D Abraham.

118 records · Page 7Linked to original sources
PubMed1978

Metabolism and cytotoxicity of 5-azacytidine in cultured Novikoff rat hepatoma and P388 mouse leukemia cells and their enhancement by preincubation with pyrazofurin.

5-Azacytidine transport into cells was measured in the absence of metabolism in adenosine triphosphate-depleted and uridine kinase-deficient Novikoff cells. Azacytidine is transported with about the same efficiency as uridine and cytidine by the facilitated nucleoside transport system of these cells. The phosphorylation of azacytidine in untreated, wild-type cells, however, is much more inhibited by uridine and cytidine than is its transport into the cell. This inhibition seems to be responsible for the specific protection of cells by these nucleosides from azacytidine toxicity. Azacytidine is incorporated by Novikoff and P388 cells into both RNA and DNA, and this incorporation seems to be responsible for its cytotoxicity; an inhibition of de novo pyrimidine nucleotide synthesis is not a major contributory factor. Incorporation of azacytidine into nucleic acids is relatively slow, but it is enhanced 3 to 4 times when cells are preincubated with pyrazofurin. Pyrazofurin inhibits de novo pyrimidine synthesis and thus causes a depletion of cellular pyrimidine nucleotides. Azacytidine is largely cytostatic for Novikoff and P388 cells, but a sequential treatment with pyrazofurin and azacytidine markedly increases the cytotoxicity over that observed with drug alone or when administered together with drug, even at higher concentrations. Increased cytotoxicity correlates with the increased incorporation of azacytidine into nucleic acids.

Amides↗
PubMed1976

Neocarzinostatin (NSC 157365) a new cancerostatic compound.

Neocarzinostatin is a new anticancer drug developed by Japanese investigators. In order to delineate the potential usefulness of this drug, we have reviewed the preclinical data and summarized the Japanese clinical data on 462 patients. The bulk of these patients had carcinoma of the stomach or pancreas and acute leukemia. Neocarzinostatin was administered intravenously in a daily dose of 2-3 mg for five to 15 day periods. Significant antitumor activity was observed in acute leukemia. A few responses were also reported in pancreatic adenocarcinoma, but the drug was inactive against gastric carcinoma. The side effects observed included nausea, vomiting, myelosuppression, fever, and occasional hypersensitivity reactions. The Investigational Drug Branch of the National Cancer Institute has recently sponsored an investigational new drug application with the Food and Drug Administration, and phase I studies are expected to begin soon in the United States.

Amino Acids↗
PubMedDate not supplied

Mechanism for national distribution of delta 9-tetrahydrocannabinol (NSC-134454).

The National Cancer Institute (NCI) is initiating a national THC distribution program by applying to the FDA for its classification as a Group C investigational agent. Since THC is also a Schedule I drug, the distribution system requires strict adherence to Drug Enforcement Agency (DEA) security and safety regulations. Contrary to the usual distribution of Group C drugs, THC will not be available directly to physicians. THC will be made available to hospital pharmacies which are: (1) an NCI recognized Cancer Center (P-30 grant supported), (2) an NCI designated New Drug Study Group, (3) a member of the Council of Teaching Hospitals. Hospital pharmacies that are located in inadequately represented geographic areas when certain criteria are met by them will also be considered. Physicians desiring to prescribe THC need not have Schedule I registration, but should (1) have experience in cancer chemotherapy, (2) have a current DEA registration number, (3) agree to abide by the Guidelines for Use of THC, and (4) be registered with a participating pharmacy. A registered physician may prescribe THC by writing a Research Order for Medication on a usual prescription blank, including, in addition to normal required information, confirmation that patient consent has been obtained and the name of the hospital at which the physician is registered to prescribe THC.

Antineoplastic Agents↗
PubMedDate not supplied

Clinical optimization and multicenter validation of antigen-specific cut-off values on the INNO-LIA ANA update for the detection of autoantibodies in connective tissue disorders.

OBJECTIVES: The INNO-LIA ANA Update is a qualitative multiparameter line immunoassay for detection of autoantibodies to several different antigens associated with connective tissue disorders. We sought to optimize and validate the cut-off values for its antigen-specific components: SmB, SmD, RNP-70k, RNP-A, RNP-C, SSA/Ro52, SSA/Ro60, SSB/La, Cenp-B, Topo-I, Jo-1, ribosomal P, and histones. Our aim was to achieve 98% specificity for each of the markers, with respect to differential disease controls, while maintaining sensitivity. METHODS: For optimization, the cut-off value of the different antigen lines was fixed to achieve this specificity using an in-house set of 955 patient samples. Specificity was validated at multiple sites using a different set of 330 samples obtained from 158 apparently healthy blood donors, 100 patients with a variety of infections, 20 each with Wegener's granulomatosis, inflammatory bowel disease, and primary antiphospholipid syndrome, and 12 with psoriatic arthritis. Sensitivity was evaluated, using this optimized cut-off control, in 147 patients with scleroderma, 93 with Sjögren's disease, 40 with systemic lupus erythematosus, 40 with rheumatoid arthritis, 39 with mixed connective tissue disease, and 19 with polymyositis. Sensitivity and specificity of the INNO-LIA ANA Update were determined using the clinical diagnosis as reference. RESULTS: The optimized cut-off values resulted in a specificity 98% or more for all LIA markers except one (histones 97.8%) in the validation set of 330 samples. The sensitivity for each marker tested in 378 samples from the target patient groups was comparable to that reported in the literature. CONCLUSION: The INNO-LIA ANA Update shows uniformly high specificities combined with sensitivities very similar to those of reference assays, in a single test format.

Antigens↗
PubMedDate not supplied

Coronary risk factors in a rural community.

A cross-sectional health examination survey was carried out among a random sample of 406 people of 30 years and above from a rural community to investigate the prevalence of coronary heart disease risk factors. Prevalence of smoking and tobacco use was 16%, alcohol intake 9.4 %, daily Salt intake (> or = 5 gram) 34.2%, daily saturated fat intake ( > or =10 % of daily energy intake) 47.0 % and physical inactivity 18.5 %. BMI was > or =25 Kg /m(2) in 18 percent and it was > or =30 Kg / m(2) in 3.2 percent population. Truncal obesity (WHR: men> 0.9; women > 0.8) was found 18.5 percent more in case of males (20.7). Abdominal obesity(men > or =102; women > or = 88)was found 15.7 percent more in case of males (20.6).18.5 percent population was found suffering from systolic hypertension> or =140 mm Hg )and 15 percent from diastolic hypertension(> or =90 mm Hg). Awareness of CHD risk factors was present in 30.0 percent population. Differences in prevalence of riskfactor in male and female were found statistically significant in case of smoking, alcohol consumption and abdominal obesity. The present study shows that prevalence of CHD risk factors increases significantly in men and women having BMI equal or more than 25 Kg /m(2) so this cutoff, should be used to determine obesity in Indian population.

Adult↗