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Biomedical subjects

H S Gilbert

Publications and source records attributed to H S Gilbert.

At least 37 records · Page 2Linked to original sources
PubMed1985

Myeloproliferative disorders.

Myeloproliferative disorders result from monoclonal proliferation of the pluripotential hematic precursor cell, with preservation of its capacity to differentiate and mature into functional progeny. Phenotypic expression varies with the degree of involvement of each derivative cell type and the extent to which growth is hyperplastic, dysplastic, or malignant. Hyperplastic bone marrow with increased circulating erythrocytes and platelets, reactivation of hematopoiesis in long bones and extramedullary sites, and the development of secondary marrow fibrosis are responsible for complications of thrombosis, hemorrhage, splenic infarction, hypersplenism, and anemia. A predilection for the geriatric population, chronicity, and great variability in phenotypic expression present a challenge in diagnosis and management. Individualized treatment based on thorough understanding of the pathophysiology of myeloproliferative disease is required to maximize complication-free survival by avoiding both the risk of the disease and its therapy and utilizing all available supportive measures in the prevention and treatment of complications.

Aged↗
PubMed1984

A method to correct for errors caused by generation of interfering compounds during erythrocyte lipid peroxidation.

A commonly used method for quantification of lipid peroxidation depends upon measurement of a malonaldehyde-thiobarbituric acid derivative with absorbance at 532 nm. Investigation of this assay demonstrated that erythrocyte peroxidation produces compounds that react with thiobarbituric acid to interfere with the malonaldehyde assay. Interference results from carryover absorbance at 532 nm, equivalent to 20% of the intensity of the maximum absorption peak at 453 nm. These compounds are not products of lipid peroxidation but are derived from erythrocyte hemolysate and reduced glutathione. A specific HPLC assay for malonaldehyde corroborated the improved accuracy of measuring absorbance at 453 nm and correcting for the absorbance of the interfering compounds at 532 nm when assaying erythrocyte malonaldehyde production.

Chromatography, High Pressure Liquid↗
PubMed1984

The pyrogallol assay for superoxide dismutase: absence of a glutathione artifact.

Reduced glutathione was found to affect the assay for superoxide dismutase when autooxidation of epinephrine, but not pyrogallol, was used as the indicator. Glutathione concentrations in the micromolar range, which correspond to levels in erythrocyte extracts, were capable of perturbing the epinephrine assay method and causing overestimation of enzyme content. The pyrogallol method was not significantly affected by large excesses of glutathione and appears to be a superior method for tissue extracts likely to be rich in glutathione.

Epinephrine↗
PubMed1984

The effect of chronic hypocholesterolemia in myeloproliferative disease on the distribution of plasma and erythrocyte tocopherol.

The presence of hypocholesterolemia and increased erythrocyte lipid peroxidation susceptibility in myeloproliferative disorders raised the possibility of coexistent tocopherol deficiency. Plasma and red blood cell (RBC) alpha-tocopherol, beta- + gamma-tocopherol, and free cholesterol were determined simultaneously by high performance liquid chromatography in 22 patients and 26 controls. Plasma alpha-tocopherol was correlated most highly with plasma free cholesterol and secondarily with RBC alpha-tocopherol in both groups. Plasma-free cholesterol and alpha-tocopherol were significantly reduced in myeloproliferative disease, although the ratio between the two remained normal. Erythrocyte tocopherol and free cholesterol concentrations were normal in myeloproliferative disease. High relative retention of tocopherol by erythrocytes was most pronounced in patients with the lowest plasma alpha-tocopherol and free cholesterol levels. The normal RBC tocopherol levels in these patients with chronic hypocholesterolemia indicate that the observed increase in RBC peroxidation susceptibility is not explainable by a deficiency of RBC vitamin E.

Cholesterol↗
PubMed1984

Reduced plasma concentrations of total, low density lipoprotein and high density lipoprotein cholesterol in patients with Gaucher type I disease.

Plasma lipid and serum apoprotein concentrations were determined in twenty-nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a group of matched control subjects. Total, LDL and HDL cholesterol were lower in males than in females with Gaucher disease. These sex differences appeared to be inversely correlated with the severity of disease manifestations which were greater in the males. Serum levels of apoprotein-B and apoprotein-AI, the major structural apoproteins of LDL and HDL, respectively, were decreased in the subjects with Gaucher disease. Thus, the reductions in LDL and HDL cholesterol were associated with reduced numbers of lipoprotein particles in plasma. In contrast, apoprotein-E, a protein which is secreted by several tissues, including activated macrophages and which may mediate hepatic catabolism of lipoproteins, was elevated in the patients. Since macrophages may also catabolize lipoproteins, Gaucher disease may serve as a model for the effect of activated macrophages upon human lipoprotein metabolism.

Adolescent↗
PubMed1984

Myelofibrosis revisited: characterization and classification of myelofibrosis in the setting of myeloproliferative disease.

In describing the various forms of myeloproliferative disease in which myelofibrosis develops, it becomes clear that certain cellular and biochemical abnormalities are shared by all forms of reactive myelofibrosis. Of possible etiologic significance are megakaryocytosis, monocyte-macrophage hyperplasia and activation, altered immunologic status, and proliferation of mast cells and basophils. The mechanisms by which these abnormalities could mediate fibrosis and the methodology that makes assessment and monitoring of fibrosis possible during the course of myeloproliferative disease are discussed in the subsequent contributions to this volume. Opportunities for further study and elucidation of the pathogenesis of myelofibrosis abound and should stimulate the generation of new knowledge that has direct relevance to the management of myeloproliferative disease.

Bone Marrow↗
PubMed1984

Increased erythrocyte susceptibility to lipid peroxidation in myeloproliferative disorders.

The recognition of abnormal lipoprotein metabolism that produces chronic hypocholesterolemia in myeloproliferative disorders and the known influence of altered plasma lipid levels on erythrocyte membranes prompted a study of erythrocyte susceptibility to lipid peroxidation in myeloproliferative disease. Malonyldialdehyde generation during an oxidant challenge of erythrocyte suspensions of standardized hemoglobin concentration with H2O2 was significantly greater in 32 patients with myeloproliferative disease than in 47 hematologically normal subjects. The myeloproliferative disease group had significantly lower plasma total, HDL-, and LDL-cholesterol, erythrocyte indices, and erythrocyte deformability, and higher reticulocyte counts and serum lactic dehydrogenase. In the myeloproliferative disease group, mean corpuscular hemoglobin concentration, reticulocyte count, and erythrocyte count were significant variables in accounting for the observed variation in peroxidation susceptibility. Erythrocytes of patients with myeloproliferative disease had elevated concentrations of reduced glutathione, normal glutathione stability, and normal alpha-tocopherol content. These studies demonstrate increased susceptibility to oxidative damage in myeloproliferative disease despite normal or increased concentrations of the major antioxidant compounds of the erythrocyte. The presence of reticulocytosis, elevated serum lactic dehydrogenase, and decreased erythrocyte deformability suggests that lipid peroxidation susceptibility is associated with in vivo hemolysis and may contribute to the anemia that complicates myeloproliferative disease.

Cholesterol↗
PubMed1983

Hypocholesterolemia as a manifestation of disease activity in chronic myelocytic leukemia.

A patient with chronic myelocytic leukemia and hypocholesterolemia displayed marked fluctuations in plasma cholesterol in response to several therapeutic maneuvers. During chemotherapy there was a reciprocal relation between low density lipoprotein (LDL) cholesterol levels and the degree of leukocytosis and splenomegaly. LDL cholesterol increased after splenectomy, but continued to cycle inversely with the leukocyte count. Receptor-mediated degradation of 125I-labeled LDL (125I-LDL) by mononuclear cells in vitro also showed cyclical changes which were unrelated to the number of immature myeloid cells in the population or the level of plasma cholesterol. 125I-LDL degradation rate was normal or slightly increased during relapse and after remission was achieved, but was greatly increased when tested during periods of remission induction. This patient illustrates that significant changes in plasma total and LDL cholesterol occur in chronic myelocytic leukemia in association with alterations in proliferative state. Tumor load, the presence of an enlarged spleen, and changes in lipid metabolism of circulating cells all appear to contribute to the reduction in LDL cholesterol levels.

Adult↗
PubMed1983

Failure of mean red cell volume to serve as a biologic marker for alcoholism in narcotic dependence. A randomized control trial.

Mean red cell volume, mean red cell hemoglobin, and mean red cell hemoglobin concentration were measured in a prospective, longitudinal, single-bind study of alcoholism and its treatment in 625 patients receiving methadone. Mean red cell volume and mean red cell hemoglobin were significantly elevated in alcoholic as compared with nonalcoholic patients (p less than 0.001), with a sensitivity of 40 and 51 percent, respectively. The ability of an elevated mean red cell volume and mean red cell hemoglobin to exclude active alcoholism (specificity) was 86 and 76 percent, respectively. Development of excessive consumption of alcohol during the course of the study was not associated with significant elevations over baseline values of either mean red cell volume or mean red cell hemoglobin. Similarly, the mean red cell volume and mean red cell hemoglobin in the small number of patients whose consumption of alcohol markedly decreased did not significantly change from baseline values. These findings suggest that although the specificity of mean red cell volume may be helpful in eliminating those persons who are not actively alcoholic, its sensitivity does not permit its use as a biologic marker for alcoholism. The inclusion of an elevated mean red cell volume as a major criterion for the diagnosis of alcoholism should be reconsidered.

Alcohol Drinking↗
PubMed1982

Increased low-density-lipoprotein catabolism in myeloproliferative disorders.

Hypocholesterolemia reported in patients with myeloproliferative disorders prompted our investigation of lipoprotein metabolism in these patients. The production and fractional catabolic rates of very-low-density lipoprotein (VLDL) apoprotein-B were measured using 131I-VLDL; those of VLDL triglyceride, using 3H-glycerol; and those of low-density lipoprotein (LDL) apoprotein-B, using 125I-LDL. Plasma total and LDL cholesterol levels (mean +/- SD) were significantly reduced in seven patients with myeloproliferative diseases, compared to five normal subjects (93.1 +/- 20.3 mg/dL versus 166.8 +/- 24.6 mg/dL and 50.3 +/- 14.8 mg/dL versus 107 +/- 20.8 mg/dL, respectively). The production rates of VLDL apoprotein-B and VLDL triglyceride were normal in the patients. The fractional catabolic rate of LDL apoprotein-B was increased in the patients with myeloproliferative diseases (0.89 +/- 0.32/d versus 0.52 +/- 0.10/d; p less than 0.05); this increased rate was associated with reduced plasma LDL apoprotein-B levels (41.7 +/- 7.1 mg/dL versus 57.0 +/- 11.3 mg/dL; p less than 0.05) despite normal or elevated LDL apoprotein-B production (16.7 +/- 5.3 mg/kg body weight . d versus 12.9 +/- 1.2 mg/kg body weight . d). The site (or sites) of increased LDL catabolism in these hypocholesterolemic patients with myeloproliferative disorders is under investigation.

Adult↗
PubMed1981

Characterization of hypocholesterolemia in myeloproliferative disease. Relation to disease manifestations and activity.

Characterization of the hypocholesterolemia observed in polycythemia vera and agnogenic myeloid metaplasia revealed significant reductions in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol in an age- and sex-matched comparison with the Framingham population. Men with myeloproliferative disease also had significantly lower total and LDL cholesterol levels than did those with relative or secondary polycythemia. LDL and HDL cholesterol were significantly correlated, suggesting a generalized disturbance of cholesterol metabolism, unexplained by nutritional status. Evaluation of the relationship among hematic cell proliferation, degree of myeloid metaplasia and hypocholesterolemia by multiple regression analysis revealed that spleen size was the variable of most significance in explaining the variation in plasma total, LDL and HDL cholesterol levels. Uncontrolled disease activity was accompanied by a decline in LDL cholesterol levels. Splenectomy or control of proliferation with chemotherapy or splenic irradiation reversed this abnormality. Levels of plasma total and lipoprotein cholesterol provide information that may be of value in diagnosis and assessment of myeloproliferative disease activity.

Aged↗
PubMed1980

L-Ethionine as an inducer of differentiation in human promyelocytic leukemia cells (HL-60).

The methionine analog, L-ethionine, induces morphological and biochemical changes in cultured HL-60 cells which are indicative of myeloid maturation. After 3 to 5 days of growth in the presence of L-ethionine, the majority of cells have enhanced phagocytic ability. The percentage of cells in the culture which bear complement receptors and which can respond to 12-O-tetradecanoylphorbol-13-acetate with respiratory burst activity increases more than 3-fold. Since the cells fail to become adherent and lose nonspecific esterase activity, we conclude that L-ethionine, like dimethyl sulfoxide, induces granulocytic differentiation of HL-60 cells.

Animals↗
PubMed1980

Long-term treatment of systemic mastocytosis with histamine H2 receptor antagonists.

A patient with systemic mastocytosis, accompanied by gastric hypersecretion and duodenal ulcer, was treated with metiamide followed by daily cimetidine for 44 months. Treatment with cimetidine resulted in healing of the ulcer, without recurrence and marked amelioration of the cutaneous symptoms of mastocytosis. Complete suppression of basal gastric hypersecretion was documented after 33 months of treatment and cimetidine and Vitamin B12 absorption remained normal. Cimetidine reduced the patient's cutaneous response to intradermal histamine without affecting leucocyte histamine release. No cimetidine toxicity was observed. These results indicate that effective long-term control of histamine-induced gastric hypersecretion can be achieved with cimetidine. They suggest that some of the cutaneous symptoms of mastocytosis are mediated via histamine H2 receptors in the skin.

Adult↗