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Biomedical subjects

J Fried

Publications and source records attributed to J Fried.

135 records · Page 8Linked to original sources
PubMed1967

Studies of cellular proliferation in human leukemia. I. Estimation of growth rates of leukemic and normal hematopoietic cells in two adults with acute leukemia given single injections of tritiated thymidine.

Two adults with rapidly progressive acute myeloblastic and myelomonoblastic leukemia were given single injections of tritiated thymidine, and measurements were made of the growth rates of their leukemic and normal hematopoietic cells by radioautographic methods. Although almost all leukemic blasts in both marrow and blood were metabolically active as shown by their ability to incorporate tritiated uridine and leucine in vitro, only 5.6% and 6.1% of the blasts in the marrow and even fewer in the blood incorporated tritiated thymidine. The mitotic indexes of the marrow blasts were 0.66% and 0.52%; no circulating blasts were dividing. The mean generation times of the actively proliferating blasts were estimated to be 49 and 83 hours. This cannot be equated with the doubling time of the total leukemic population as there is evidence that many blasts fail to continue dividing and die. The mean durations of the phases of the blasts' mitotic cycles were as follows: DNA synthesis (S) = 22 and 19 hours, premitosis (G(2)) = 3 hours, mitosis (M) = 0.47 and 0.62 hour (minimal estimates), and postmitosis (G(1)) = 24 and 61 hours. In both patients the maximal mean transit time of the blasts in the blood was 36 hours, and the minimal numbers of actively dividing blasts present were 1.6 and 2.6 x 10(9) per kg of body weight.Estimates were also made of the rates of proliferation and maturation of the residual normal erythrocytic and granulocytic cells in these two patients. Although total production was markedly diminished because of reduction in the number of normal elements, the relatively few remaining normal cells appeared to be dividing and maturing at rates that are about the same or only slightly slower than those found in normal subjects. We conclude that main reason leukemic blasts displace normal hematopoietic precursors in acute leukemia is that the blasts largely fail to differentiate. Many die but many others persist in the marrow and elsewhere as primitive cells and continue to proliferate. As the blasts accumulate, they gradually displace the normal hematopoietic cells, most of which continue their normal course of differentiation and leave the marrow as nondividing mature cells. It is not known why the over-all production of normal cells is not adequately increased to compensate for the anemia, granulocytopenia, and thrombocytopenia that develop, but apparently the leukemic cells somehow interfere with the proliferation or differentiation or both of normal stem cells.

Autoradiography↗
PubMedDate not supplied

Isolated Candida parapsilosis arthritis in a heroin addict.

A case of isolated Candida parapsilosis arthritis involving the shoulder of a heroin addict is described. Amphotericin B successfully eradicated the infection after failure of flucytosine. Optimal therapy for this condition has not been determined.

Amphotericin B↗
PubMedDate not supplied

Kinetic and cytotoxic effects of cytarabine and daunorubicin on cells in culture.

To investigate the possibility that a significant kinetic basis exists for the improved clinical response often obtained using drug combinations, Chinese hamster ovary cells were exposed to cytarabine and daunorubicin in combination. Cell survival was determined by a colony-counting assay; kinetic perturbations were monitored by flow cytometry. No major synergistic effects of the conditions, each drug appeared to provide some protection against the lethal effects of the other. By pairing a moderately toxic concentration of one drug with a nontoxic concentration of the other, we observed sequence-dependent differences in survival. These differences could not be attributed simple to alteration of the cell cycle phase positions by the nontoxic drug, combined with phase-specific lethality of the toxic drug. It is likely, however, that daunorubicin provided partial protection from cytarabine-related cytotoxicity through its effect on the DNA synthesis rate.

Animals↗
PubMedDate not supplied

The contraceptive effects of etoprine on male mice and rats.

We had previously found that 2,4-diaminopyrimidines affected spermatogenesis, possibly through the inhibition of testicular dihydrofolate reductase (DHFR). The current study examined the effects of etoprine, a highly lipophilic 2,4-diaminopyrimidine that is also a potent DHFR inhibitor, on the fertility of male mice at various dosages (0.1-50 mg/kg/day) for 55 days and male rats at 5 mg/kg/day for 65 days. Two other substituted diaminopyrimidines were tested at dosages of 50 mg/kg/day for 55 days. Results of breeding trials along with assessment of various parameters indicative of male fertility were noted. We found that of the compounds tested, etoprine is a potent antifertility agent that causes complete infertility at doses of > or = 5 mg/kg/day in mice with a threshold of effectiveness occurring between 1 and 5 mg/kg/day. The antifertility action of etoprine may be related to its capacity to inhibit testicular DHFR and its high degree of lipophilicity.

Animals↗