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Biomedical subjects

J Kaye

Publications and source records attributed to J Kaye.

At least 127 records · Page 7Linked to original sources
PubMed1981

Attitudes of medical students and residents toward cancer.

Attitudes toward cancer and heart disease were evaluated in 99 freshmen medical students, 76 seniors, and 66 residents using the Cancer Attitude Survey and a Semantic Differential test. The Survey revealed a rise in positive attitudes towards patients' inner resources to cope with serious illness and toward personal immortality and a rise in negative attitudes toward early diagnosis of cancer as students progressed in their training. The Semantic Differential test demonstrated more negative attitudes toward cancer than heart disease in all groups (freshman, seniors, and residents in medicine, psychiatry, or surgery). The seniors had the most positive attitudes toward cancer and freshman the least positive attitudes. The residents had more positive attitudes than the freshmen but less positive attitudes than the seniors. The residents in psychiatry had more positive attitudes than the residents in medicine, who had more positive attitudes than the residents in surgery.

Attitude of Health Personnel↗
PubMed1981

The potential importance of soluble deoxynucleotidase activity in mediating deoxyadenosine toxicity in human lymphoblasts.

Deoxyadenosine and its nucleotides have been implicated in the pathogenesis of the immune dysfunction associated with a genetic deficiency of adenosine deaminase (ADA). We have previously shown that when ADA is blocked with a synthetic inhibitor, human T lymphoblastoid cell lines are more sensitive to deoxyadenosine toxicity, dephosphorylate deoxyadenosine nucleotides at a slower rate, and have much lower levels of ecto-5'-nucleotidase than most B cell lines. It seemed unlikely, however, that an enzyme on the outer surface of the lymphocyte plasma membrane could regulate intracellular deoxynucleotide catabolism. We now report that human lymphoblasts also contain a soluble deoxynucleotidase activity that is distinguishable from the plasma membrane enzyme by several criteria. In multiple human lymphoblastoid cell lines of varying origin and phenotype. soluble deoxynucleotidase correlated significantly (rs = 0.80, p < 0.001) with sensitivity to deoxyadenosine toxicity.

Adenosine Deaminase↗
PubMed1980

Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo.

An inherited deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) produces selective lymphopenia and immunodeficiency disease in humans. Previous experiments have suggested that lymphospecific toxicity in this condition might result from the selective accumulation of toxic deoxyadenosine nucleotides by lymphocytes with high deoxycytidine kinase, levels and low deoxynucleotide dephosphorylating activity. The present experiments were designed to determine if deoxyadenosine analogs which are not substrates for adenosine deaminase might similarly be toxic toward lymphocytes and lymphoid tumors. Two such compounds, 2-chlorodeoxyadenosine and 2-fluorodeoxyadenosine, at concentrations of 3 nM and 0.15 microM, respectively, inhibited by 50% the growth of human CCRF-CEM malignant lymphoblasts in vitro. Each was phosphorylated in intact cells by deoxycytidine kinase accumulated as the nucleoside triphosphate, and inhibited DNA synthesis more than RNA synthesis. Both deoxynucleosides had significant chemotherapeutic activity against lymphoid leukemia L1210 in mice.

Adenosine Deaminase↗
PubMed1980

DNA repair in human cells containing photoadducts of 8-methoxypsoralen or angelicin.

Photoactivated 8-methoxypsoralen (8-MOP) has been proven to be clinically effective for a number of dermatological conditions including lichen planus, mycosis fungoides, and psoriasis. 8-MOP forms two types of covalent photoproducts with DNA, monoadducts, and bifunctional adducts which cross-link the two DNA strands. Angelicin is a congener of 8-MOP which forms only monoadducts. We have used the combined density and isotopic labeling technique to study repair replication in cultured human fibroblasts treated with either of these compounds and exposed to near-ultraviolet light. In human diploid fibroblasts (WI-38), the time course of repair replication for both compounds is similar. Drug concentration and ultraviolet dose responses are also similar for 8-MOP and angelicin. No repair replication was stimulated by either compound in xeroderma pigmentosum cells from Complementation Group A (XP12BE). These results suggest that repair replication in response to 8-MOP is primarily a response to monoadducts and that the enzymatic pathway for this repair synthesis shares at least one step with the pathway for repair of pyrimidine dimers. Cross-link persistence in treated cells was assayed by use of the single-strand-specific S1 nuclease to digest DNA that did not renature readily following heat denaturation. Partial removal of cross-links was observed in normal, xeroderma pigmentosum variant, and Fanconi's anemia fibroblasts, but not in xeroderma pigmentosum Group A cells.

Cells, Cultured↗
PubMed1979

Biochemical basis for the enhanced toxicity of deoxyribonucleosides toward malignant human T cell lines.

Human malignant T cell lines have high levels of deoxyribonucleoside phosphorylating activity and low levels of deoxyribonucleotide dephosphorylating activity. When incubated with deoxyadenosine or thymidine, the malignant T cell lines rapidly accumulate toxic concentrations of dATP and dTTP, respectively. This unusual pattern of deoxyribonucleotide metabolism renders the malignant T cells especially vulnerable to the toxic effects of deoxyribonucleosides and related analogues.

B-Lymphocytes↗
PubMed1978

Deoxyribonucleoside toxicity in adenosine deaminase and purine nucleoside phosphorylase deficiency: implications for the development of new immunosuppressive agents.

The immunodeficient state associated with adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency may result from the selective phosphorylation by thymus-derived lymphocytes of the ADA substrate deoxyadenosine and the PNP substrate deoxyguanosine, leading to the intracellular trapping of toxic deoxyribonucleoside triphosphates. Agents such as deoxycytidine might be able to favourably modify the immunodeficient state by inhibiting deoxyribonucleoside phosphorylation. Deficiencies of other nucleotide catabolic enzymes, if selectively expressed by lymphocytes, might also lead to immunodeficiency via nucleoside trapping in lymphoid tissues. Purine deoxyribonucleoside analogues, either alone or in combination with ADA inhibitors, may have value as lymphospecific antimetabolites.

Adenosine Deaminase↗
PubMed1977

Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: possible role of nucleoside kinase(s).

Inherited deficiencies of the enzymes adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) and purine nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase; EC 2.4.2.1) preferentially interfere with lymphocyte development while sparing most other organ systems. Previous experiments have shown that through the action of specific kinases, nucleosides can be "trapped" intracellularly in the form of 5'-phosphates. We therefore measured the ability of newborn human tissues to phosphorylate adenosine and deoxyadenosine, the substrate of adenosine deaminase, and also inosine, deoxyinosine, guanosine, and deoxyguanosine, the substrates of purine nucleoside phosphorylase. Substantial activities of adenosine kinase were found in all tissues studied, while guanosine and inosine kinases were detected in none. However, the ability to phosphorylate deoxyadenosine, deoxyinosine, and deoxyguanosine was largely confined to lymphocytes. Adenosine deaminase, but not purine nucleoside phosphorylase, showed a similar lymphoid predominance. Other experiments showed that deoxyadenosine, deoxyinosine, and deoxyguanosine were toxic to human lymphoid cells. The toxicity of deoxyadenosine was reversed by the addition of deoxycytidine, but not uridine, to the culture medium. Based upon these and other experiments, we propose that in adenosine deaminase and purine nucleoside phosphorylase deficiency, toxic deoxyribonucleosides produced by many tissues are selectively trapped in lymphocytes by phosphorylating enzyme(s).

Adenosine Deaminase↗
PubMed1976

Adductor avulsive injuries near the symphisis pubis.

Avulsion injuries occurring near the symphisis pubis are related to the sites of origin of the adductor longus, adductor brevis, and gracilis muscles. Young athletes complain of pain near the symphisis which is increased by active adduction of the limb against resistance. Radiographic findings, similar to those found in infection and neoplasms, are mixed bone destruction and sclerosis on one side of the symphisis, frequently extending inferior pubic ramus.

Adolescent↗
PubMed1976

Standing roentgenograms in spondylolisthesis.

Lateral roentgenograms of 50 patients with spondylolisthesis were made in the recumbent and standing positions and compared. Thirteen (26%) showed an increase in the percentage of displacement on standing. Those patients with demonstrable change appeared to have a higher incidence of severe symptomatology. Apparent spondylolysis on recumbent roentgenograms may change to spondylolisthesis on standing lateral roentgenograms. Degenerative spondylolisthesis may be more apparent on standing lateral roentgenograms.

Adult↗
PubMed1975

Auditory and visual memory losses in aging populations.

Seventy-four men and women (age range, 44-77 years) were tested for short-term auditory and visual memory as part of a larger series of memory and cognitive function tests. All test scores for visual memory, including facial photograph recognition when a sequence requirement was adhered to, showed a significant decline (p smaller than .05) in a comparison of subjects aged 44-54 and subjects aged 55-64. This decline was not observed with the two tests of auditory memory. Thus the data indicate that short-term visual memory may be more susceptible to aging than is auditory memory.

Adult↗
PubMed1974

Adrenergic, coagulation, and fibrinolytic responses to heat.

Two groups of volunteers were exposed to heat in a sauna bath-one group for 10 minutes and the other for 15. There was no change in plasma adrenaline concentration until the subjects emerged from the sauna bath, when there was a slight increase in concentration. Factor VIII and thrombo-elastograph patterns did not change but marked activation of fibrinolysis was stimulated by exposure to heat. These findings support the concept that fibrinolysis is not mediated by direct adrenergic activity.

Adult↗