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Biomedical subjects

H S Gilbert

Publications and source records attributed to H S Gilbert.

11 recordsLinked to original sources
PubMed1992

Polycythemia vera. II. Hypersensitivity of bone marrow erythroid, granulocyte-macrophage, and megakaryocyte progenitor cells to interleukin-3 and granulocyte-macrophage colony-stimulating factor.

Polycythemia vera (PV) is a clonal disease of the hematopoietic stem cell characterized by a hyperplasia of marrow erythropoiesis, granulocytopoiesis, and megakaryocytopoiesis. We previously reported that highly purified PV blood burst-forming units-erythroid (BFU-E) are hypersensitive to recombinant human interleukin-3 (rIL-3). Because these cells may be only a subset, and not representative of marrow progenitors, we have now studied partially purified marrow hematopoietic progenitor cells. Dose-response experiments with PV marrow BFU-E showed a 38-fold increase in sensitivity to rIL-3 and a 4.3-fold increase in sensitivity to recombinant human erythropoietin (rEpo) compared with normal marrow BFU-E. In addition, PV marrow colony-forming units-granulocyte-macrophage (CFU-GM) and CFU-megakaryocyte (CFU-MK) also showed a marked hypersensitivity to rIL-3 and to human recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). Dose-response curves with rGM-CSF and blood BFU-E showed a 48-fold increase in sensitivity. No effect of rIL-4, rIL-6, human recombinant granulocyte-CSF (rG-CSF), or macrophage-CSF (rM-CSF) was evident, nor was there any effect of PV cell-conditioned medium on normal BFU-E, when compared with normal cell-conditioned medium. Autoradiography with 125I-rEpo showed an increase in Epo receptors after maturation of PV BFU-E to CFU-E similar to that shown with normal BFU-E, but no increase of specific binding of 125I-rIL-3 by PV CD34+ cells was seen compared with normal CD34+ cells. These studies show that PV marrow hematopoietic progenitor cells are hypersensitive to rIL-3 and rGM-CSF, similar to PV blood BFU-E. While the mechanism does not appear to be due to enhanced binding of rIL-3, the hypersensitivity of PV progenitor cells to IL-3 and GM-CSF may be a key factor in the pathogenesis of PV.

Bone Marrow↗
PubMed1979

Increased circulating neutrophils with surface receptor activity for immunoglobulin G in polycythemia vera and myeloid metaplasia.

Reports of heterogeneity of IgG receptor activity of normal circulating neutrophils prompted measurements in myeloproliferative disease to determine if dysplasia of the hematic stem cell resulted in an abnormality of this membrane property. IgG receptors were assayed by rosette formation in suspension with human Rh-positive erythrocytes sensitized with high-titer Rh antiserum. IgG receptors were detected on 19 +/- 1.6% (mean +/- SEM) of neutrophils from 45 normal subjects. A significant increase in IgG-receptor-bearing neutrophils was found in polycythemia vera (PV) and myeloid metaplasia (MyM), with values of 70 +/- 3.6% and 69.7 +/- 4.3%, respectively. Normal values were observed in polycythemic states not due to myeloproliferative disease and in chronic myelocytic leukemia. Rosette-forming neutrophils were increased to 52.3 +/- 3.7% in infection and inflammatory disease, but this value was significantly lower than those in PV and MyM. Increased IgG receptors in PV and MyM may be related to the activated state of the neutrophil and may result from an intrinsic cellular abnormality of the proliferating clone or from altered bone marrow release. Quantitation of neutrophil IgG receptors may be of value in the differential diagnosis of PV and MyM and may offer insights into the derangement of hematopoiesis that underlies these myeloproliferative disorders.

Antibody Specificity↗
PubMed1978

Effects of acute endotoxemia and glucose administration on circulating leukocyte populations in normal and diabetic subjects.

Effects of intravenous endotoxin and glucose administration on circulating leukocyte populations were compared in seven normal subjects and seven patients with juvenile-onset diabetes by means of automated cytochemical differential counting to quantitate each cell type. Both groups had comparable control cell counts that were unaffected by glucose tolerance testing but altered significantly by endotoxin. Different patterns of response to endotoxin were observed for different circulating cell types. The response of diabetics was parallel to that of normals but showed lower neutrophil and monocyte rebound, longer lasting depression of lymphocytes and eosinophils, and greater rebound of basophils on the day following endotoxin exposure. Characterization of distinctive normal response patterns of circulating leukocyte populations to endotoxin and comparison with responses in diabetes revealed abnormalities under conditions of stress that may impair the diabetic's ability to cope with acute infection.

Adult↗
PubMed1977

Partial trisomy of the long arm of chromosome 1 in myelofibrosis and polycythemia vera.

We have identified partial trisomy 1q in 2 patients with different hematologic disorders. The first patient was a 55-year-old female with myelosclerosis and myeloid metaplasia diagnosed at age 38 years presenting with anemia, fatigue, bruising, fever, and splenomegaly. At age 56, she had 50--95% myeloblast cells and 95--100 nucleated RBC precursors per 100 WBC. Chromosome analysis of unstimulated leukocytes with Q, G, and C banding showed 46,XX,-6,+t(1;6) (q25;p22) in all metaphase cells. In vitro incorporation of Fe55 was demonstrated 90% of metaphases by autoradiography. The second patient, a 49-year-old male, was diagnosed as having polycythemia vera at age 30 during a regular checkup. He since developed hepatosplenomegaly. Chromosome analysis from a direct bone marrow preparation at age 44 and 45 showed grossly normal karyotypes. At age 49, his marrow by Q and G banding showed almost 100% of cells with 46,XY,-13,+t(1;13) (q12;p12). Eleven cases of trisomy of 1q have been reported in various hematologic disorders. It is apparent that partial trisomy 1q represents another nonrandom chromosomal abnormality, in addition to the most common nonrandom chromosomal aberrations, such as the Philadelphia chromosome, trisomy 8, trisomy 9, and monosomy 7 in hematologic disorders.

Chromosomes, Human, 1-3↗
PubMed1977

Inhibition of vitamin B12 binding to transcobalamin II at low pH: basis of a procedure for quantitation of circulating TC II and R binders.

A diminution in the binding of exogenous vitamin B12 by serum or plasma at pH 1.5 to 2 (acid-resistant binding capacity, ARBC) as compared with the binding capacity at neutral pH (unsaturated vitamin B12 binding capacity, UBBC) was observed. This phenomenon was found to be attributable to the absence of transcobalamin II (TC II)-associated vitamin B12 from serum labeled at low pH, as demonstrated by gel chromatography on Sephadex G-200. Further confirmation was obtained by demonstration of a significant correlation between the ARBC and the R binder content, quantitated as resistance to precipitation by ammonium sulfate at a 2M concentration. Serum labeled at acid pH failed to deliver vitamin B12 to Hela cells indicating absence of a "functional" TC II-B12 complex. The differing vitamin B12 binding capacities of neutral and acidified material was utilized to fractionate the unsaturated vitamin B12-binding proteins of serum and plasma. The ARBC was used to measure the R binder content, and TC II was calculated from the difference between UBBC and ARBC. The fractionation procedure was performed on 75 sera and showed increased ARBC in patients with myeloproliferative disorders and decreased ARBC in leukopenia. The content of unsaturated vitamin B12-binding protein was compared in 75 paired samples of serum and plasma collected from EDTA-anticoagulated blood containing sodium fluoride to inhibit release of granulocyte binders. The ARBC content of fluoridated plasma was significantly lower, due to decreased in vitro R binder release. Plasma also contained less TC II, possibly related to in vitro cellular uptake of this binder in fluoridated plasma.

Blood Proteins↗
PubMed1976

Increased circulating levels of transcobalamin ii in gaucher's disease.

The presence of several serum protein abnormalities in Gaucher's disease prompted a study of vitamin B12 binding proteins, in which 14 of 15 consecutive patients displayed increased circulating transcobalamin II unassociated with elevations of serum vitamin B12 or other vitamin B12 binders. Transcobalamin II levels were most significantly increased in nine patients with disease severe enough to require splenectomy (P less than 0.01), but were not correlated with liver size or levels of any other laboratory feature of Gaucher's disease studied. Splenectomy, per se, did not alter circulating transcobalamin II. Chracterization of the binder in Gaucher's disease revealed identity with normal serum transcobalamin II in acid inhibition of vitamin B12 binding, chromatographic behavior, immunologic specificity and functional integrity in vitamin B12 delivery. This observation suggests a relation between reticuloendothelial-cell activity and transcobalamin II metabolism. Elevated transcobalamin II levels may provide an additional means for diagnosis and assessment of Gaucher's disease.

Adolescent↗
PubMed1975

Isolation and characterization of a novel vitamin B12-binding protein associated with hepatocellular carcinoma.

High levels of a novel vitamin B12-binding protein (hepatoma B12 BP) have been observed recently in plasma obtained from three adolescent patients with hepatocellular carcinoma. This protein has now been isolated in homogeneous form from the plasma and pleural fluid of two of these patients by the use of affinity chromatography with vitamin B12-Sepharose. The hepatoma B12 BP belongs to the R-type group of B12-binding proteins and is essentially indistinguishable from the recently isolated human milk and saliva R-type proteins in terms of: (a) immunologic properties based on immunodiffusion and immunoprecipitation assays; (b) amino acid composition; (c) molecular weight based on amino acid and carbohydrate content; and (d) absorption spectra. Both hepatoma B12 BPs contain more sialic acid and less fucose than the milk and saliva B12 BPs. All four proteins contain similar amounts of galactose, mannose, galactosamine, and glucosamine. Differences in sialic acid content appear to account for the differences in electrophoretic mobility that were observed among the four proteins. Differences in total carbohydrate content appear to account for the differences in apparent molecular weight that were observed with both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor tissue from one of the patients contained 10 times as much R-type protein as did normal liver tissue from the same patient. This suggests, although it does not prove, that synthesis by the tumor is the cause of the high levels of R-type protein found in the plasma of certain patients with hepatocellular carcinoma. Plasma survival studies performed with rabbits indicate that the hepatoma B12 BP has a prolonged plasma survival and suggests that his parameter is also of importance.

Aged↗
PubMed1975

Abnormal liver function and elevated hemoglobins in heroin addicts.

Reports dealing with medical problems of heroin dependency contain conflicting data regarding hemoglobin concentration. Medical evaluation of a large group of asymptomatic heroin users undergoing screening for participation in a methadone maintenance treatment program revealed a significant number of patients with elevated hemoglobin levels. The presence of increased hemoglobin concentrations in the addict population was highly correlated with the presence of abnormalities in liver function. In a preliminary serial study, a diminution of elevated hemoglobin values toward normal was observed in heroin users undergoing methadone maintenance therapy. These findings suggest the presence of deranged mechanisms responsible for the regulation of plasma volume and/or erythropiesis which may have pathophysiologic consequences of importance in the medical management of the heroin addict.

Adult↗
PubMed1975

Basophil counting with a new staining method using alcian blue.

Difficulties in obtaining reproducible and accurate enumeration of circulating basophils with existing techniques have hampered investigation of this infrequent cell population. A new basophil staining method is described that employs alcian blue dye for staining of heparin within basophils at low pH and in the presence of lanthanum ions. Basophil recognition is facilitated by reducing nonspecific nuclear staining. This objective is achieved because of the differences in stability of alcian blue-heparin, alcian blue-nucleic acid, lanthanum-heparin, and lanthanum-mucliec acid complexes. Reduction of pH after staining also favors solubilization of leukocyte cytoplasmic proteins, providing greater contrast between stained and unstained cells by reducing light scattering of the unstained leukocytes . The alcian blue staining method is suitable both for chamber basophil counting and automated basophil counting using continuous-flow sampling and electro-optical detection. The new staining method was evaluated by comparing it with the chamber counting method using toluidine blue in a triple-blind study in which the results of basophil counting by the alcian blue chamber method, alcian blue automated instrument method, and the toluidine blue chamber method were analyzed for reproducibility and compared with an indirect basophil count obtained from a 1000-cell leukocyte differential and a total leukocyte count. Both alcian blue staining methods gave greater reporducibility that toluidine blue and were more accurate, as evidinced by a significantly higher correlation with the indirect basophil count. The improved reproducibility, accuracy, and convenience of this method over existing methods should facilitate the collection of more meaningful information about circulating basophil levels in health and disease.

Alcian Blue↗