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Biomedical subjects

E Murray

Publications and source records attributed to E Murray.

At least 127 records · Page 7Linked to original sources

Blocking factors against melanoma leucocyte-dependent antibody: relationship to disease activity in melanoma patients.

Previous studies have shown that many melanoma patients have cytotoxic leucocyte-dependent antibody (LDA) which is inhibited by factors in their sera. These factors were shown to be small molecular weight glycoproteins which could also be identified in the supernatants of melanoma cultures, and which were therefore most likely to be melanoma cell surface antigens. The present studies have shown that these blocking factors against melanoma LDA can be detected in patients with primary melanoma, and that the levels of this activity show an inverse correlation with the levels of LDA in the sera of melanoma patients. The appearance of melanoma LDA after surgery for localized melanoma was shown in approximately a third of the patients, and this pattern was shown to result from the disappearance of the LDA blocking activity after surgical removal of the melanoma. Assays were designed specifically to measure the melanoma LDA blocking factors by plasmapheresis. It is not yet known whether the melanoma LDA blocking activity has correlation with tumour growth in melanoma patients. The potential value of measuring this activity to assess response to therapy was shown by studies designed to remove the blocking factors by plasmapheresis. It is not yet known whether the melanoma LDA blocking activity has biological significance in regard to tumour growth, but these studies appear to indicate that measurement of these factors in the sera of melanoma patients may provide a useful in vitro monitor of tumour growth in melanoma patients.

Adult↗

Average heterozygosity revisited.

The estimate of heterozygosity and proportion of polymorphic loci for 33 red blood cell loci has been updated by the elimination of some loci of questionable status and the addition of data on 33 loci. The new figures for heterozygosity and proportion of polymorphic loci, .105 and .283, respectively, are based on 60 red blood cell loci of European origin populations. These values are less than those calculated by Lewontin in 1967, and furthermore they do not appear to be reaching an asymptote. At the present time, the red blood cell data and allozyme data for European populations have similar estimates of heterozygosity and proportion of polymorphic loci.

Blood Group Antigens↗

Blocking factors against leucocyte-dependent melanoma antibody in the sera of melanoma patients.

Previous studies, using plasmapheresis to remove blocking factors of cell-mediated cytotoxicity to melanoma cells from the circulation of melanoma patients, suggested that leucocyte-dependent antibody to melanoma cells may also be blocked by factors in their sera. The present study confirms these findings, by showing that most patients with disseminated melanoma had melanoma LDA activity in the IgG fraction when this was separated from their sera. This also applied to a high percentage of patients with primary melanoma. Evidence that the blocking factors may be immune complexes was shown by experiments in which LDA activity to melanoma cells was revealed after acidification of melanoma sera to dissociate immune complexes, followed by ultrafiltration through membranes retaining molecules of size greater than 100,000 daltons. Blocking of LDA activity in the retentate recurred when the retentate was recombined with the filtrate. Further studies indicated that the blocking activity showed affinity for the target cell and not the effector cell. Preliminary analysis of the specificity of the blocking suggests that this was similar to that of melanoma antisera. These results appear to show that blocking of LDA activity to melanoma cells is common in melanoma patients and that the assay system may provide a quantitative method for their analysis that may yield information of biological importance in the management of melanoma patients.

Antibodies, Neoplasm↗

Antibody-dependent cell-mediated cytotoxicity against melanoma cells induced by plasmapheresis.

Patients with disseminated melanoma were treated by repeated plasmapheresis using a continuous-flow blood-cell separator, as part of a study to investigate methods of removing factors from tissue fluids which block cell-mediated immunity. Using 51Cr release cytotoxic assays, it was found that plasmapheresis resulted in removal of serum blocking activity. Post-plasmapheresis sera taken from several patients also increased cell-mediated cytotoxicity by induction of antibody-dependent cell-mediated killing. This effect may have resulted from removal or alteration of circulating immune complexes in the serum. It is not known whether cytotoxic activity induced in this way improves the patient's immune response against their tumours. However, the procedure is well tolerated and these preliminary in-vitro results indicate that this form of therapy could act as an adjunct to other forms of treatment of advanced melanoma.

Antigen-Antibody Complex↗

Clinical effects and pharmacokinetics of different dosage schedules of adriamycin.

Adriamycin was administered to 60 adults and 21 children by 3 different dosage schedules: 22.5 mg/sq m (0.6 mg/kg) daily for 4 days, 15 mg/sq m (0.4 mg/kg) every 8 hr for a total of 6 doses, and 50 to 120 mg/sq m as a single dose every 3 to 4 weeks. Objective responses lasting more than 1 month occurred in 5 subjects with acute leukemias or lymphoma, 3 with transitional cell carcinomas, 2 with sarcomas, 2 with Ewing's sarcoma and 1 each with bronchogenic carcinoma, orchidoblastoma, and thymoma. Toxic reactions included nausea, vomiting, stomatitis, alopecia, and hematopoietic depression, but significant cardiac toxicity occurred in only 1 patient. Pharmacokinetic data, collected in 25 patients by fluorometric and chromatographic assay, suggested a biphasic plasma clearance of drug with initial and secondary half-lives of about 1.5 and 14 to 21 hr, respectively. When drug was given every 8 hr there was evidence of loss of an initial very rapid phase of distribution of adriamycin and its metabolites. Urinary excretion accounted for 3.4 to 38.1% of administered fluorescence over a 72-hr period; in the first 24 hr, between 48.2 and 100% of this urinary material was in the form of adriamycin; leter, this fraction declined. No adriamycin or its fluorescent metabolites could be extracted from the stools.

Blood Cells↗

Protein requirements of man: comparative nitrogen balance response within the submaintenance-to-maintenance range of intakes of wheat and beef proteins.

Sixteen young male students participated in two studies designed to determine the nitrogen balance response to beef or stone-ground, whole wheat protein over the submaintenance-to-maintenance range of protein intake. The objective of the studies was to evaluate the relative capacities of these proteins to meet the minimum protein needs in young adult males. A modified Latin-square design was used to allocate subjects to the four 15-day metabolic balance diet periods in each study. The last 10 days were used for fecal nitrogen determination and the last 5 days for evaluation of urinary nitrogen excretion. The diet periods were separated by a 4-day break period and began with 1 day on a "protein-free" diet. The levels of protien (N times 6.25) intake tested were 0.2, 0.3, 0.4, and 0.5 g/kg body weight/day in the beef study. The results have been compared with those obtained in a previous similar study with egg protein. The regression of estimated "true" nitrogen balance (Y) (mg N/kg/day) on nitrogen intake (X) (mg N/kg/day) was: Y equals 0.51(plus or minus 0.08)X minus 41.9(plus or minus 4.6) for beef and Y equals 0.27(plus or minus 0.06)X minus 33.6(plus or minus 5.0) for whole wheat protein. The amounts of beef and wheat proteins estimated to be requried to support body nitrogen balance in 97.5% of the population supplied 96 and 178 mg N/kg/day, respectively. The relative protein value of beef and wheat proteins, in comparison with egg protein, was 78 plus or minus 12 and 41 plus or minus 10, respectively. It is concluded that the variations in dietary protein quality should be taken into account in assessing the protein adequacy of diets for individuals and population groups.

Adolescent↗