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Biomedical subjects

J C White

Publications and source records attributed to J C White.

At least 127 records · Page 7Linked to original sources
PubMed1978

Lack of stereospecificity at carbon 6 of methyltetrahydrofolate transport in Ehrlich ascites tumor cells. Carrier-mediated transport of both stereoisomers.

Nonlabeled and tritiated stereoisomers of 5-methyltetrahydrofolate were prepared and were both shown to be substrates for the high affinity H4 folate cofactor membrane transport carrier in Ehrlich ascites tumor cells. Both the enzymically active form and the isomer having the opposite configuration at carbon 6 inhibited the influx of enzymically synthesized (+)-5-methyltetrahydrofolate, methotrexate, and aminopterin. When added to the media of cells preloaded with methotrexate, both isomers stimulated a net efflux of the antifolate from the cell. Influx of the natural and unnatural isomers followed Michaelis-Menten kinetics with comparable Km values. Each isomer competitively inhibited influx of the other.

Aminopterin↗
PubMed1978

Acute leukemia in Malaysian children.

A review of acute childhood leukemia in the University Hospital, Kuala Lumpur reveals no significant differences in either the epidemiological or clinical features between Malaysian and Caucasian children. BCG does not appear to have conferred any protection against the occurrence of leukemia. With the introduction of total therapy 4 of 10 patients with good prognostic features and 3 of 15 patients with poor prognostic features have survived 3 years. Prognosis appears to correlate with adopted clinical criteria.

Antineoplastic Agents↗
PubMed1978

Occurrence of haemoglobin H in leukaemia: a further case of erythroleukaemia.

Erythroleukaemia in an elderly Caucasian male was associated with the presence of 15% of haemoglobin H (Hb-H; Hb-beta4) in the haemolysate, identified by electrophoretic analysis, isolation and 'finger-printing'. The peripheral blood picture was dimorphic, with 40% of hypochromic and morphologically abnormal red cells. Inclusion bodies indicative of the presence of Hb-H occurred in 30% of the red cells after supravital staining. The rare occurrence of Hb-H in leukaemic conditions and its distribution in the red cells is discussed in relation to the possible clonal origin of leukaemia and the involvement of red cell precursors.

Aged↗
PubMed1978

A basis for fluoropyrimidine-induced antagonism to methotrexate in Ehrlich ascites tumor cells in vitro.

The inhibitory effect of methotrexate on [3H]deoxyuridine incorporation into DNA is reduced as the basal rate of this reaction is inhibited by pretreatment of Ehrlich ascites tumor cells with fluoropyrimidines. This observation is a basis for fluoropyrimidine-methotrexate antagonism in anticancer regimens and supports the concept that the sensitivity of thymidylate synthesis in tumor cells to methotrexate is related, in part, to the basal rate of thymidylate synthesis from deoxyuridylate.

Animals↗
PubMed1977

Haemoglobin H disease and pregnancy in a Malaysian woman.

A case of haemoglobin H (HbH) disease associated with pregnancy is presented and discussed in the light of reports in the literature. The variable symptomatology is commented upon, although mild to moderate chronic haemolytic anaemia seems to be a constant feature. The roles of folic acid supplements and of splenectomy; the avoidance of oxidant drugs, and the mode of inheritance in HbH disease are briefly commented upon. Available reports indicate that HbH disease probably has no adverse effect on pregnancy. However, the association of the two conditions is uncommon, and reports are too few, therefore, to allow definite conclusions on the outcome in all instances.

Adult↗
PubMed1977

Benign epileptiform transients of sleep. Clarification of the small sharp spike controversy.

Electroencephalograms were performed on 120 normal subjects sleep deprived for 24 hours. Twenty-four percent of the volunteers exhibited one or more epileptiform transients during stages 1 or 2 of non-rapid eye movement sleep. These potentials usually appeared as monophasic or diphasic spikes unaccompanied by sharp waves or focal slowing. When abundant, they occurred sporadically and independently over both hemispheres but were best developed in the anteromesial temporal regions. A 20 percent incidence of similar spikes was found in 599 consecutively referred patients recorded under the same conditions. We conclude that these epileptiform transients of sleep, which have been called "small sharp spikes," are normal and are of no diagnostic value in the evaluation of patients with seizures.

Adolescent↗
PubMed1977

Delayed paralysis after cervical fracture-dislocation. Case report.

The authors describe the late development of ascending damage to the spinal cord after a cervicothoracic fracture-dislocation that produced no evidence of cord or nerve injury other than transient mild paresthesia in the arms. After 16 years, progressive quadriplegia developed with subsequent ascending dissociated sensory loss in the upper cervical dermatomes. The presence of a central syrinx was verified at operation 18 years after the injury.

Adult↗
PubMed1976

Cryoimmunoglobulin IgGk with microtubular ultrastructure associated with pyoderma gangrenosum.

Recurrent gangrenous leg ulcers were associated with a monoclonal IgGk cryoglobulinaemia, though without overt myeloma. Cryoprecipitation of the serum in vitro gave a reversible gel with microtubular structure, built from the monomer and with a high degree of order. The same structure was found distending the superficial vessels of the ulcer biopsy, as well as extravascularly. There was no vasculitis, and luminal obstruction appeared responsible for the ulceration. Microtubular structures occur in nature among diverse proteins and viruses. The protein studied here is similar to a reported instance of myeloma cryo-IgGk.

Blood Vessels↗
PubMed1976

Aspects of obstetrical defibrination in West Malaysia.

Five patients illustrate various aspects of obstetrical defibrination in West Malaysia, resulting from exaggeration of changes in fibrinolytic-coagulation equilibrium that occur at delivery. Hypofibrinogenaemia and fibrinolysis may occur in association or either feature predominate. These patients are from a population in which a variety of genetic and environmental factors may interact, e.g. abnormal haemoglobins, cold agglutinins, viral and other infections, introducing additional complications.

Abortion, Spontaneous↗
PubMed1976

Exchangeable intracellular methotrexate levels in the presence and absence of vincristine at extracellular drug concentrations relevant to those achieved in high-dose methotrexate-folinic acid "rescue" protocols.

Studies were undertaken to (a) assess intracellular methotrexate (MTX) levels at extracellular drug concentrations comparable to those achieved in high-dose MTX-folinic acid rescue protocols and (b) establish whether there is a rationale for the use of vincristine in these regimens. The data indicate that only low levels of exchangeable MTX (intracellular MTX in excess of the tightly bound fraction) accumulated in Ehrlich ascites tumor cells at high extracellular MTX concentration. For instance, the exchangeable steady-state intracellular MTX level was approximately 6.5 muM when the extracellular drug concentration was 85 muM. Over the interval of these experiments, exchangeable intracellular MTX did not exceed approximately 10 muM even when extracellular MTX was raised to 250 muM. These exchangeable intracellular MTX concentrations are comparable to those levels required experimentally to suppress (a) tetrahydrofolate synthesis from dihydrofolate and (b) tetrahydrofolate-dependent purine, pyrimidine, and amino acid synthesis in these cells in vitro. Vincristine (10 muM) augmented net MTX accumulation when the extracellular MTX level was 10, 100, or 250 muM. The limited capacity of cells to accumulate exchangeable intracellular MTX and the apparent role for this intracellular MTX component in achieving the metabolic effects of this agent may account for the necessity for high MTX blood levels in the treatment of some tumors and may be the basis, in part, for the enhanced chemotherapeutic efficacy of high-dose MTX regimens. These studies provide a rationale for the combined use of vincristine and MTX in high-dose MTX protocols. The addition of vincristine may permit the achievement of the level of exchangeable intracellular MTX that is required to critically inhibit tetrahydrofolate synthesis without an increase in the extracellular MTX concentration. This may permit a reduced MTX dose, diminishing the excretory load on the kidney and minimizing nephrotoxicity due to deposition of MTX in the renal tubule and interstitium. While the data indicate that the ratio of the concentration of exchangeable intracellular MTX to the extracellular drug concentration may be very low under steady-state conditions at high extracellular drug levels, further studies are required to establish that these steady-state gradients for MTX represent nonequilibrium conditions.

Animals↗