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Biomedical subjects

J W Harris

Publications and source records attributed to J W Harris.

At least 109 records · Page 6Linked to original sources

Hemoglobin Hofu or alpha 2 beta 2 [126 (H4) Va1 leads to Glu] found in combination with hemoglobin S.

Hb Hofu, alpha 2 beta 2 [126 (H4) Va1 leads to Glu], was found in 10 members of 2 apparently unrelated Valmiki families in central India. None showed evidence of hemolysis and hemoglobin levels were normal in most. In two individuals, Hb Hofu occurred in combination with Hg S, but neither had clinical manifestations of sickle cell disease. In samples containing Hb Hofu, the isopropanol precipitation test was positive. Quantitation of the hemoglobin fractions by DEAE-cellulose chromatography showed that Hb Hofu constituted a mean of 23--25% of the total whether in combination with Hb A or Hb S.

Female↗

Gingival biopsy in thrombotic thrombocytopenic purpura.

Gingival biopsy has been advocated as a readily available, safe, rapid histologic confirmation of the clinical diagnosis of thrombotic thrombocytopenic purpura. Eighteen gingival biopsies from 16 patients with proven thrombotic thrombocytopenic purpura were reviewed. Seven (39%) showed characteristic histologic changes: [1] subendothelial hyalinelike deposits; [2] intraluminal deposits; [3] lack of inflammatory change in vessels and stroma. To assess specificity, gingival sections from 154 patients with oral pathology only and from 50 unselected autopsies were reviewed: 10% to 20% of biopsies from patients with oral pathology only (primarily inflammation) and three of 50 autopsy specimens showed occasional intraluminal deposits but no subendothelial deposits. In addition, other histologic features permitted them to be distinguished from thrombotic thrombocytopenic purpura. We conclude that gingival biopsy in thrombotic thrombocytopenic purpura, although helful in confirming the diagnosis, is less often positive than has been suggested. Biopsy of grossly inflamed gingiva should be avoided.

Biopsy↗

Sickle cell anemia and trait in a population of southern India.

In an ethnic group in southern India, the Irula, seven individuals with sickle cell anemia were found to manifest only mild illness. Although a relatively high level of fetal hemoglobin was present in one, none of the factors thought to ameliorate the course of sickling disorders could be identified in the remaining six. In a random population survey, sickle hemoglobin was found in 90 of 292 Irula (31%). In those with sickle cell trait, the proportion of sickle hemoglobin in hemolysates (mean = 26%, range 19-32%) was substantially lower than that reported for any other population.

Anemia, Sickle Cell↗

Secondary gout in hemoglobinopathies: report of two cases and review of the literature.

Although patients with hemolytic hemoglobinopathies characteristically are over-producers of urate, and hyperuricemia is frequently recognized, clinical gout has rarely been reported in such patients. Our evaluation of 2 premenopausal women with gout led to the diagnosis of previously unrecognized hemoglobinopathies (SC disease and CC disease). Investigation of these 2 patients and review of the reported cases of gout in patients with hemoglobin S or C disorders suggest that relatively minor abnormalities of renal function in these patients may lead to early development of significant hyperuricemia. With increasing lifespan of patients with hemolytic hemoglobinopathies and the likelihood of increased occurrence of renal function abnormalities, it is anticipated that gout will more frequently be responsible for joint symptoms in such patients.

Adolescent↗

Response of extremely hypoxic cells to hyperthermia: survival and oxygen enhancement ratios.

Chinese hamster V79 cells and mouse EMT6 cells were made extremely hypoxic with a chamber technique that relies upon gas exchange rather than respiration-assisted oxygen depletion. Cells in these chambers were treated with heat (43degrees C) or heat plus x-irradiation, and colony-forming ability was determined. Hyperthermia: (a) kills exponentially growing V79 cells more efficiently than plateau-phase cells; (b) kills euoxic and extremely hypoxic cells equally; and (c) radiosensitizes euoxic and extremely hypoxic cells to the same degree, leaving the oxygen enhancement ratio unchanged.

Animals↗

Interactions of the trophoblast and maternal tissues in three closely related primate species.

The confluence of maternal and fetal tissues to form the placenta causes a wide variety of alterations in cells of both origins. Three closely related primate species were studied for similarities and differences in the interrelationships formed during various stages of placental development in the areas of implantation, decidualization, and trophoblastic involvement in the spiral arteries. Although certain similarities exist among the three species a surprising number of distinct differences were found to shed doubt on the common practice of assuming species-to-species similarity, particularly among primates.

Animals↗

Neuropathology of experimental vitamin B12 deficiency in monkeys.

We have produced severe vitamin B12 deficiency in rhesus monkeys by feeding them a defined experimental diet under controlled conditions. Five years after institution of the deficient diet, the morphology and counts of peripheral blood and bone marrow are normal. Gross visual impairment appeared in five of the monkeys between 33 and 45 months after the institution of the vitamin B12 deficient diet. Subsequently, in three of the visually impaired animals, a gradually progressive spastic paralysis of their hind limbs developed. Autopsies of six deficient animals showed degeneration of the peripheral visual pathway in all and of white matter in the spinal cord in four. Degeneration of several cranial nerve roots was found in four monkeys and a mild diffuse degeneration of cerebral white matter in four. The lesions in all affected parts of the central nervous system were bilaterally symmetrical and were indistinguishable from those due to B12 deficiency in the human. No abnormalities were found in one B12 supplemented control animal.

Animals↗

Increased cytolytic T lymphocyte activity induced by 2-mercaptoethanol in mixed leukocyte cultures: kinetics and possible mechanisms of action.

The 20- to 50-fold increase in cytolytic T lymphocyte (CTL) activity caused by the addition of 50 muM 2-mercaptoethanol (2-ME) at the onset of a one-way murine mixed leukocyte culture (MLC) between C57BL/6 and DBA/2 splenic lymphocytes appears to be unrelated to early events in the culture: if 2-ME was present for the first 24 hr of culture only, there was no increase on day 4, but if addition of 2-ME was delayed until the last 24 hr of culture, the CTL activity was almost as high as that of cultures that were exposed to 2-ME for the entire 4-day culture period. The increase of CTL activity caused by delayed addition of 2-ME ("2-ME rescue") was used to investigate the mechanism by which the thiol induces differentiation of CTL from precursor cells. 2-ME rescue was mimicked by two other thiols, dithiothreitol and cysteamine phosphate, but at higher concentrations. Because the latter compound has no free sulhydryl group until it diffuses into cells and is enzymatically dephosphorylated, we conclude that thiols may increase the differentiation of CTL from precursor cells by an intracellular process involving free sulphydryl groups rather than by interaction with membrane sulfhydryls or destruction of inhibitor cells or their products. Cell separation experiments indicated that 2-ME rescue was independent of the presence of B lymphocytes and of adherent cells (macrophages) and was restricted to a subpopulation of T lymphocytes that developed into large lymphoid precursor cells during the first 3 days in culture even without 2-ME. The development of this subpopulation required DNA synthesis between 24 nad 72 hr after the onset of MLC. When 2-ME was added to day-3 MLC, CTL activity increased slightly as early as 4 hr later, but the major increase occurred during the second half of the 24 hr "rescue"period. Because this increase was inhibited by cytosine arabinoside (ARA-C), it seems likely that DNA synthesis is associated with and may be required for the differentiation of large precursor lymphoid cells into CTL after the addition of 2-ME.

Animals↗

Effects of Tumor-like assay conditions, lonizing radiation, and hyperthermia on immune lysis of tumor cells by cytotoxic T-lymphocytes.

Cytotoxic T-lymphocytes (CTL's) harvested from mixed splenic lymphocyte cultures (DBA/2 + C57BL) were tested for their ability to lyse allogeneic P815 mastocytoma cells under various tumor-like assay conditions, with or without previous exposure to ionizing radiation or hyperthermia (43 degrees). There was little or no decrease of immune cytolysis when CTL's were assayed by 51Cr release under tumor-like conditions (plateau-phase target cells, low pH, or anoxia) or after irradiation, but cytolytic activity was greatly reduced when CTL's were exposed to heat; 45 min of hyperthermic treatment decreased activity by greater than or equal to 99% while reducing the apparent cell viability (as indicated by trypan blue exclusion) by only 30%. When the P815 target cells rather than the CTL's were exposed to heat their susceptibility to immune lysis was not affected even after treatment times that were lethal to the tumor cells. Despite the dissimilar heat sensitivities of CTL and P815 cells, the dose-response curves for inhibition of protein synthesis by heat, as indicated by [3H]leucine incorporation, were similar for both cell types: neither the depression of protein synthesis in heated CTL's nor the decreased cytolytic ability of these cells was reversed within 3 hr. When irradiated or heated P815 cells were incubated with CTL's, the resulting survival curves were always additive, indicating that neither irradiation nor heat treatment affected the susceptibility of the tumor cells to immune attack. The extreme heat sensitivity of cytotoxic T-lymphocytes raises important questions about the possible effects of hyperthermic treatment on the immune competence of cancer patients.

Animals↗