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J C Klock

Publications and source records attributed to J C Klock.

At least 37 records · Page 2Linked to original sources
PubMed1981

Chemical characterization of neutral glycolipids in the human myeloid leukemias.

Human neutrophils and lymphocytes have been shown to have different classes of neutral glycolipids. We have investigated alterations of glycolipids in the human myeloid leukemias to see how their neutral glycolipids differ from those of normal neutrophils. The chemical structures of the neutral glycolipids from large numbers of homogeneously purified leukemia cells were determined using column and thin-layer chromatography, gas-liquid chromatography (GLC), GLC-mass spectrometry, and direct probe mass spectrometry. Our results showed that cells from patients with acute myelogenous leukemia (AML) had less than half the amount of neutral glycolipid per cell than did cells from patients with chronic myelogenous leukemia (CML). Chromatographic mapping of the neutral glycolipids from these cells showed that AML cells had less of the polar, long-chain neutral glycolipids than did CML cells. The studies confirmed that over 99% of the neutral glycolipids were contained in a population of compounds with 1, 2, 3, and 4 sugar-containing neutral glycolipids whose structures are: Glc 1 --> 1 ceramide; Gal 1 --> 1 ceramide; Gal 1 --> 4 Glc 1 --> 1 ceramide; Gal 1 --> 4 Gal 1 --> 1 ceramide; GlcNAc 1 --> 3 Gal 1 --> 4 Glc 1 --> 1 ceramide; and Gal 1 --> 4 GlcNAc 1 --> 3 Gal 1 --> 4 Glc 1 --> 1 ceramide. Lactosyl ceramide was the major glycolipid in both AML and CML cells. The studies show that human myeloid leukemia cells have the same neutral glycolipids as normal neutrophils. The alterations in neutral glycolipid distribution in leukemia suggest that they might be useful as "differentiation markers", with the morphologically more "mature" leukemias having more complex glycolipids. We were unable to detect novel or "malignancy-associated" neutral glycolipids in any of the leukemias we studied.-Klock, J. C., J. L. D'Angona, and B. A. Macher. Chemical characterization of neutral glycolipids in the human myeloid leukemias.

Carbohydrate Conformation↗
PubMed1981

Complex carbohydrates as differentiation markers in malignant blood cells: glycolipids in the human leukemias.

This article summarizes the data on chemical sequencing of human leukocyte cell surface glycolipids that we have obtained over the last 3 years. The purpose of the work was to determine if these cell surface glycoconjugates differ among different leukocyte populations and at different stages of development. In homogeneous form we purified large numbers of leukocytes from normal persons and persons with acute and chronic leukemias of myeloid and lymphoid types, using continuous flow centrifugation leukapheresis. We extracted the glycolipids from these cells and used thin-layer chromatography, gas-liquid chromatography, gas chromatography-mass spectrometry, direct probe mass spectrometry, and enzyme treatment to obtain complete structural information on these compounds. Twenty glycolipids were identified and sequenced, representing over 99% of the glycolipids of human leukocytes. The major findings are that human leukocytes possess glycolipid patterns that distinguish them from other blood cells. Additionally, leukocytes of "myeloid' and "lymphoid' types can be distinguished by their glycolipid type. Glycolipids in human leukemic cells show two main features: (1) even though the cells appear morphologically "undifferentiated', all leukemias can be classified on the basis of their glycolipids as "myeloid' or "lymphoid'; (2) the complexity of their cell surface glycolipids is correlated with their degree of morphologic "differentiation', the more differentiated leukemias having more complex structures. No glycolipids were found in leukemic leukocytes that were not found in the normal cells. Glycolipids would therefore appear to be useful as both cell- and possibly differentiation-specific markers in human blood cells. The antigenic differences seen in human leukemic cells may be due in part to an altered distribution of complex carbohydrates at the cell surface.

Antigens, Surface↗
PubMed1980

Isolation and chemical characterization of neutral glycosphingolipids of human neutrophils.

Six neutral glycosphingolipids were isolated from purified preparations of human neutrophils. The chemical structure of each compound was characterized by degradation with exoglycosidases, methylation analysis, and electron impact/desorption mass spectrometry. The following structures were assigned on the basis of these detailed analyses: Glc beta 1 leads to 1Cer Gal beta 1 leads to 1Cer Gal beta 1 leads to 4Glc beta 1 leads to 1Cer Gal alpha 1 leads to 4Gal beta 1 leads to 1Cer GlcNAc beta 1 leads to 3Gal beta 1 leads to 4Glc beta 1 leads to 1Cer Gal beta 1 leads to 4GlcNAc beta 1 leads to 3Gal beta 1 leads to 4Glc beta 1 leads to 1Cer. Neutral glycosphingolipids containing N-acetylgalactosamine were not detected in human neutrophils. The major neutral glycosphingolipids were lactosylceramide and lactoneotetraosylceramide. Although lactoneotriaosylceramide accounts for only 10% of the neutral glycosphingolipid fraction, neutrophils are the most readily available source of this compound. We may conclude that human neutrophils, in contrast to human erythrocytes and platelets, contain as their major neutral glycosphingolipids lactoneo-type structures and smaller amounts of gala-type structures. These findings are discussed in terms of blood group antigens and glycosphingolipid changes due to malignancy.

Carbohydrate Conformation↗
PubMed1979

Cholesterol, phospholipids, and fatty acids of normal immature neutrophils: comparison with acute myeloblastic leukemia cells and normal neutrophils.

The lipid composition of immature myeloid cells from the bone marrow of normal persons and myeloblasts from patients with acute myeloblastic leukemia was studied and compared with the lipid composition of normal mature human neutrophils. Total cholesterol, phospholipid, and fatty acid composition was determined on each cell type. The leukemic cells showed decreased total cholesterol and cholesterol-to-phospholipid ratio, increase phosphatidylcholine and phosphatidylinositol, decreased phosphatidylethanolamine, and an increased percentage of unsaturated fatty acids when compared to normal mature neutrophils. A nearly identical pattern was seen in the normal immature myeloid precursors from normal bone marrow. We conclude that the altered lipid composition of acute myeloblastic leukemia cells is related to unexplained factors related to cell age and not to malignancy per se.

Bone Marrow↗
PubMed1979

Nylon-fiber-induced neutrophil fragmentation.

We have investigated the effects of mechanical elution of neutrophils from nylon-wool fiber (NWF) using the scanning electron microscope and biochemical analysis of elution fractions. We have determined that mechanical removal of neutrophils from nylon-wool fiber disrupts neutrophils adherent to nylon-wool fiber and augments release of granules, release of peripheral cytoplasmic fragments, and release of lactic dehydrogenase, a soluble cytoplasmic enzyme. Mechanical shearing of the adherent cell, and not adherence per se, causes the fragmentation. The extent of fragmentation is proportional to the NWF surface area available to neutrophils and is maximal at the temperature for optimal adherence and spreading. Agents that decrease cell spreading (n-ethylmaleimide and cold) diminish fragmentation. Cytochalasin B, an agent that destabilizes the neutrophil cortex, increases fragmentation. Fragmentation may be an important contributing cause of the abnormal morphology, function, and in vivo survival of nylon-wool-fiber procured human neutrophils. The prevention of fragmentation would appear to be necessary to insure the procurement of optimally functioning cells. Elution of NWF-adherent neutrophils in the cold might be a practical way to diminish neutrophil damage during clinical filtration leukapheresis.

Cell Adhesion↗
PubMed1977

Detection, pathogenesis, and prevention of damage to human granulocytes caused by interaction with nylon wool fiber. Implications for filtration leukapheresis.

Granulocytes collected by reversible adhesion to nylon wool fiber (NWF) function relatively well in standard in vitro tests; however, they have an abnormally shortened survival time in the circulation. Assuming that this rapid disappearance represents clearance and that recognition by phagocytes is important for such clearance, we used an autologous in vitro cell:cell recognition assay to determine whether phagocytes can detect cellular changes induced by exposure of normal granulocytes to NWF. Human granulocytes incubated with NWF 1 h at 37 degrees C, eluted with 20% acid citrate dextrose plasma, and washed stimulated the hexose monophosphate shunt activity of normal granulocytes an average of twofold (193+/-40% of controls), indicating a recognition response. NWF-induced granulocyte recognition was not dependent on plasma factors or activated complement components but was dependent on the time that the granulocyte was on the NWF and was maximal by 60 min of exposure. After elution from NWF, granulocytes demonstrated resting glucose oxidation rates only slightly higher than normal; however, during the first 20 min of exposure to NWF, granulocytes increased their rate of (14)CO(2) production from [1-(14)C]glucose three- to five-fold. Therefore, experiments were performed to determine whether toxic oxygen metabolites produced by NWF-adherent cells might contribute to recognition. The results showed that (a) normal granulocytes exposed to NWF in the presence of scavengers of superoxide anion (superoxide dismutase) or free radicals (ascorbate, mannitol, or benzoate) and washed before assay did not stimulate glucose oxidation of indicator granulocytes; and (b) NWF granulocytes prepared from cells unable to generate high levels of toxic oxygen metabolites, i.e. cells prepared anaerobically or from a patient with chronic granulomatous disease, also failed to stimulate indicator granulocytes. Human granulocytes placed in contact with NWF show an oxidative burst and become recognizable to other phagocytes. Free radical scavengers are effective in minimizing this recognition conferred on NWF-procured granulocytes.

Animals↗
PubMed1976

Febrile neutrophilic dermatosis in acute myelogenous leukemia.

Three patients with acute myelogenous leukemia and adequate granulocyte reserves developed fever and painful indurated erythematous plaques on their extremities and faces. The plaques became studded with vesicles or bullae and occasionally became necrotic. Histologic examination revealed dermal edema, infiltration with granulocytes, and formation of intraepidermal vesicles. Efforts to relate the skin reaction to infiltration of leukemic cells, microorganisms, or allergic phenomena were unsuccessful. Empiric antibiotic therapy was without effect. The symptoms and signs responded dramatically to systemic administration of corticosteroids. These lesions, which may cause diagnostic confusion and needless therapy with potent antibiotics, may represent another previously uncharacterized nonspecific skin reaction in patients with acute myelogenous leukemia.

Adrenal Cortex Hormones↗
PubMed1976

Degranulation and abnormal bactericidal function of granulocytes procured by reversible adhesion to nylon wool.

Granylocyte bactericidal capacity, chemotaxis, hexose monophosphate shung activity (before and after phagocytic stimulus), and quantitative nitroblue tetrazolium reduction and enzyme content were examined in cells obtained by filtration leukaphresis (FL) and continuous-flow centrifugation (CFC). A decrease in the bactericidal efficiency of FL-produced cells compared to that of both normal and CFC-procured granulocytes was found; the decrease was 17% with a cell-to-bacteria ratio of 5:1, and 55% with a 1:1 ratio. Moreover, FL-acquired cells were often vacuolated and consistently contained less acid phosphatase and beta-glucuronidase than did normal granulocytes. When normal cells were incubated for 1-2 hr with nylon wool, 30% of the total acid phosphatase and beta-glucuronidase was released, with no evidence of cell death, thus suggesting degranulation. Similar results were obtained with glass, cotton, or polysulfone plastic fibers. Electron microscopic and peroxidase cytochemical studies of the adherence of normal granulocytes to nylon fibers were also carried out. After 30 min of incubation, cell-to-fiber attachment and cellular aggregation had occurred, although the cells per se appeared normal. After 60 and 120 min, other changes became apparent: (1) a decrease in the amount of cytoplasmic granules; (2) large, intracytoplasmic vaculoles; and (3) extracellular peroxidase on fiber surfaces. We conclude that granulocytes obtained by adherence to nylon fibers show both morphological and biochemical evidence of degranulation and diminished bactericidal capacity, and that these abnormalities may be causally related to decreased granulocyte survival in transfusion recipients.

Acid Phosphatase↗
PubMed1975

Nonocclusive coronary disease after chronic exposure to nitrates: evidence for physiologic nitrate dependence.

A 38-year-old man, exposed to notroglycerin in his work as an explosives expert, developed non-occlusive ischemic heart disease after withdrawal of exposure to organic nitrates. Despite the severity of his symptoms and the documented spasm of his right coronary artery, his electrocardiogram was at all times normal, as were results of a wide panel of laboratory tests. Sublingual nitroglycerin amerliorated the symptoms which have decreased with time.

Administration, Oral↗
PubMed1975

Coma, hyperthermia, and bleeding associated with massive LSD overdose, a report of eight cases.

Eight patients were seen within 15 min of intranasal self-administration of large amounts of pure D-lysergic acid diethylamide (LSD) tartrate powder. Emesis and collapse occurred along with sign of sympathetic overactivity, hyperthermia, coma, and respiratory arrest. Mild generalized bleeding occurred in several patients and evidence of platelet dysfunction was present in all. Serum and gastric concentrations of LSD tartrate ranged from 2.1 to 26 ng/ml and 1000 to 7000 mug/100 ml, respectively. With supportive care, all patients recovered. Massive LSD overdose in humans is life-threatening and produces striking and distinctive manifestations.

Adult↗
PubMed1974

Coma, hyperthermia and bleeding associated with massive LSD overdose. A report of eight cases.

Eight patients were seen within 15 minutes of intranasal self-administration of large amounts of pure D-lysergic acid diethylamide (LSD) tartrate powder. Emesis and collapse occurred along with signs of sympathetic overactivity, hyperthermia, coma and respiratory arrest. Mild generalized bleeding occurred in several patients and evidence of platelet dysfunction was present in all. Serum and gastric concentrations of LSD tartrate ranged from 2.1 to 26 nanograms per ml and 1,000 to 7,000 mug per 100 ml, respectively. With supportive care, all patients recovered. Massive LSD overdose in man is life-threatening and produces striking and distinctive manifestations.

Adult↗