Orotic aciduria. Differing enzyme patterns.
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Abnormalities, Multiple↗
Biomedical subjects
R M Fox
Publications and source records attributed to R M Fox.
Mechanisms of photochemotherapy-induced apoptotic cell death in lymphoid cells.
Previous studies we performed showed that 8-methoxypsoralen in combination with ultraviolet A light (photochemotherapy) caused DNA damage and that this caused nucleotide depletion in peripheral blood leukocytes, secondary to an active form of programmed cell death, poly(ADP-ribosyl)ation. Further studies revealed that 24 h after exposure to 10 J/cm2 ultraviolet A light and 8-methoxypsoralen (300 ng/mL), apoptotic cells increased from 3 (control) to 31% (p less than 0.001). Ultraviolet A light alone also significantly increased the number of apoptotic cells. These morphological changes were confirmed by parallel findings on DNA electrophoresis. Treatment with 2 to 5 J/cm2 of ultraviolet A light and 8-methoxypsoralen caused an approximately 30% increase in cytosolic free calcium levels in peripheral blood leukocytes 1 h after exposure. Associated with this was a 51% increase in 45Ca2+ uptake over the first 60 min. Similar findings in a different lymphoid cell (CCRF-CEM) confirmed the results obtained with peripheral blood leukocytes. The use of calcium-free medium prevented a rise in cytosolic free calcium and decreased the number of cells undergoing apoptotic cell death. Cycloheximide inhibited ultraviolet A light - 8-methoxypsoralen induced apoptosis in CCRF-CEM cells; it also decreased calcium levels in control CCRF-CEM cells. This study shows that ultraviolet A light - 8-methoxypsoralen caused apoptotic cell death in lymphoid cells; this appeared to be associated with calcium influx, presumably because of the requirement of endogenous endonucleases for calcium.
Calcium↗
Treatment of small cell bronchogenic carcinoma with VM-26.
VM-26 is active in small cell bronchogenic carcinoma even in patients resistant to previous chemotherapy. The overall response rate was 28%, with a response rate of 29% in patients resistant to previous chemotherapy. This response rate is similar to that obtained with other single agents including Adriamycin, vincristine, cyclophosphamide, and procarbazine. The mild subjective and objective toxic effects of the drug make it a potentially useful agent in the treatment of this tumor.
Adult↗
Mitolactol chemotherapy for malignant melanoma: a phase II study.
Fifty-one patients (43 evaluable) with malignant melanoma were treated with mitolactol in an intermittent oral schedule. There were four objective tumor responses, all occurring in patients previously treated with dacarbazine.
Adolescent↗
Gliotoxicity in brain reaggregate cultures caused by oxidants and excitatory amino acids can be prevented by alpha-tocopherol and MK-801.
Glutamine synthetase (GS) is a key enzyme involved in glutamate compartmentalisation which may be pivotal in the course of both central free-radical mediated and excitotoxic events. The ability of the oxidants FeCl2 and H2O2 and the excitatory amino acid, N-methyl-D-aspartate (NMDA) to induce changes in astrocytic GS and glial fibrillary acidic protein (GFAP), were assessed in whole rat brain reaggregate cultures. Both FeCl2 and H2O2 reduced GS activity whereas NMDA produced a large increase in enzyme activity. GFAP was not altered significantly by either oxidant although NMDA increased the level of this protein. These effects on such astroglial markers could be reversed in vitro following exposure to a-tocopherol (FeCl2 and H2O2) and MK-801. This study therefore demonstrates that inactivation of GS can be caused by free radical insult whereas stimulation of brain GS and reactive gliosis is produced by excitatory amino acids acting at neuronal NMDA receptors. The study of these gliotoxic events in 3-dimensional reaggregate cultures suggests that this model may be used to detect neuroprotective effects of novel pharmacological agents.
Animals↗
Combination chemotherapy with vincristine, bleomycin, and methotrexate for advanced head and neck cancers.
Thirty-three patients with a histologically confirmed diagnosis of advanced squamous cell carcinoma of the head and neck were treated with a combination of vincristine, methotrexate, and bleomycin. The regimen was as follows: Day 1, vincristine (2 mg iv) and methotrexate (200 mg/m2 iv over 24 hours); Day 2, bleomycin (15 mg/day by iv infusion for 48 hours). Folinic acid rescue began 36 hours after the start of methotrexate. The regimen was repeated at intervals of 3 weeks. Toxicity was minimal but the overall response rate was only 24% (three complete responses and five partial responses) and the median duration of remission was only 16 weeks overall. The combination of vincristine, methotrexate, and bleomycin in this dosage schedule has a response rate lower than that reported with single-agent treatment of advanced head and neck cancers.
Adult↗