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Biomedical subjects

N E Kay

Publications and source records attributed to N E Kay.

At least 127 records · Page 7Linked to original sources

Abnormal erythrocyte metabolism in hepatic disease: effect of NADP repletion.

Erythrocytes from ten patients with severe liver disease displayed low methylene blue-stimulated hexose monophosphate (HMP) shunt activity and glucose recycling despite elevated total glucose consumption when compared to controls. Heinz body formation was increased and reduced glutathione concentration significantly decreased. After hemolysis, no differences in methylene-blue estimulated HMP shunt activity or glucose recycling could be demonstrated between patients and controls. The addition of 2- and 4-mM NADP to the hemolysates produced significantly greater HMP shunt activity and glucose recycling in the patients' hemolysates. The addition of NADPH to the incubation mixture produced no significant stimulation of either HMP shunt activity or glucose recycling, unless methylene blue was also added. Omission of NAD or phosphate from the incubation mixture produced no change in shunt metabolism. The absence of supplemental ATP resulted in extremely low shunt metabolism and refractoriness to NADP stimulation in both patients and controls. In the absence of additional magnesium, a reduction of shunt metabolism was noted. These data suggest that the defect in stimulated shunt metabolism in the intact erythrocytes of patients with hepatic disease does not result from an absolute enzyme deficiency, but rather from an unavailability of NADP or other cofactor.

Adult↗

Chronic lymphocytic leukemia in association with a second lymphoproliferative disorder: response to chemotherapy in two cases.

The development of either histiocytic lymphoma or Hodgkin disease in association with pre-existing chronic lymphocytic leukemia has been described in the literature as a terminal event. We describe two patients in whom the diagnosis of a second malignant lymphoma was made during life and who achieved objective clinical response after a change in therapy to a more aggressive combination of drugs. We conclude that patients with chronic lymphocytic leukemia who have had a sudden change in their clinical course should have thorough reevaluation, looking specifically for the development of a second lymphoproliferative disorder. If this is discovered, more aggressive therapy should be initiated.

Aged↗

Human neutrophil migratory function: modulatory effect of interactions with opsonized particles.

Human polymorphonuclear neutrophils preexposed to cytotaxin or to phagocytizable particles exhibited reduced spontaneous and chemotactic migratory responses. This influence of cytotaxin appears to be related to toxic effects of by-products of hexose monophosphate shunt stimulation. To determine whether a phagocytic stimulus may inhibit subsequent neutrophil migratory functions by the same mechanism, we assessed spontaneous and chemotactic migratory functions of neutrophils from individuals with chronic granulomatous disease exposed to antibody-opsonized sheep erythrocytes. Our results showed that phagocytosis of such particles did not alter these migratory responses of chronic granulomatous disease neutrophils and suggest that phagocytic stimulation of normal neutrophils may modulate migratory function by some mechanism dependent upon hexose monophosphate shunt stimulation.

Cell Movement↗

Modulation of neutrophil function by lysozyme. Potential negative feedback system of inflammation.

Host responses to infectious organisms should be modulated so that tissue-damaging products of inflammatory cells do not produce excessive destruction of normal tissue. Lysozyme, which is continuously secreted by monocytes, which, in turn, migrate relatively late to inflammatory areas, was found to significantly dampen several responses of neutrophils to inflammatory stimulants. Thus, human lysozyme obtained and purified from the urine of patients with monocytic leukemia (but not its structurally similar and comparably cationic analogue, eggwhite lysozyme) depresses chemotaxis of normal neutrophils to activated complement, bacterial supernate, and N-formylmethionyl-phenylalanine. In addition, human (but not eggwhite) lysozyme depresses oxidative metabolism (hexose monophosphate shunt activity) and superoxide generation of neutrophils. The specificity of the suppressive effects was indicated by inhibition studies with rabbit antihuman lysozyme antibody, and with the trisaccharide of N-acetylglucosamine, a specific inhibitor of lysozyme. The results suggest that lysozyme, a product of inflammatory cells themselves, may function in a negative feedback system to modulate the inflammatory response.

Cell Migration Inhibition↗

Prolactin suppression of leukocyte chemotaxis in vitro.

Leukocyte chemotaxis in vitro was studied for cells from patients with pituitary adenomas. Leukocytes obtained preoperatively from two of three patients with elevated serum prolactin levels demonstrated chemotaxic alterations described in other malignant disease. Statistically significant suppression of chemotaxis occurred in the leukocytes of four of 12 specimens from normal donors at concentrations of 1000 ng/ml, and in four of eight specimens at 2000 ng/ml of prolactin in preincubation media. Thus prolactin concentration may influence the motility of leukocytes. The variable neoplastic behavior of morphologically similar pituitary adenomas may, in part, reflect a neurohormonally altered host response to the presence of these lesions.

Adenoma↗

T-cell subpopulations in chronic lymphocytic leukemia: abnormalities in distribtuion and in in vitro receptor maturation.

Purified human thymus-derived (T) lymphocytes were analyzed by detection of Fc receptors for either IgG or IgM in healthy controls and in patients with chronic lymphocytic leukemia (CLL). There was a significant and persistent increase in the numbers of T cells bearing receptors for IgG (Fc gamma) in CLL patients in comparison to the controls. After an in vitro culture period, there was a significantly decreased appearance of cells with IgM receptors (Fcmu) in CLL patients in comparison to the control group. These results indicate an imbalance in circulating T-cell subpopulations for CLL patients. In addition, an in vitro defect in CLL T-cell membrane receptor appearance is present.

Binding Sites↗

Autoimmune hemolytic anemia in association with monoclonal IgM(kappa) with anti-i activity.

A patient with a warm autoimmune hemolytic anemia with an immunoglobulin G (IgG) panagglutinin, also had monocional IgM(kappa) cold agglutinin with anti-i activity. Ninety per cent of the peripheral blood lymphocytes had surface immunoglobulin and the number of T cells was diminished. A subpopulation of the patient's lymphocytes formed rosettes with cord (i) erythrocytes and not with adult (l) erythrocytes. The finding of increased lymphocytes bearing i-binding sites and a monoclonal antibody with anti-i activity could be related to shared idiotypic determinants between antigen-binding sites and serum antibody. The occurrence of two autoantibodies in this patient suggests an immune regulatory disorder.

Anemia, Hemolytic, Autoimmune↗

Lymphocyte-mediated antibody-dependent cytolysis: role in immune hemolysis.

Peripheral blood lymphocytes obtained from normal volunteers were capable of lysing Rh(D)-positive human erythrocytes in the presence of IgG anti-Rh(D) antibodies. The percent cytotoxicity produced by peripheral blood lymphocytes was approximately equivalent to that produced by unfractionated peripheral blood mononuclear cells. Neither peripheral blood mononuclear cells nor peripheral blood lymphocytes lysed Rh(D)-negative human erythrocytes in the presence of IgG anti-Rh(D) antibody.

Antibody-Dependent Cell Cytotoxicity↗

Blood-group antigens and antibodies in human brain-tumor cysts.

Cyst fluids from 12 human brain tumors were studied for their blood-group content and compared to autologous saliva, serum, and cerebrospinal fluid (CSF). Lewisa substance, which is a fucolipid, was present in four of 12 cysts studied. Lewisb, which differs from Lewisa by a single fucose, was found in eight of 12 sera and/or saliva and in one CSF specimen; Lewisb substance, however, was not detected in any corresponding cyst fluids. Isohemagglutinins, blood-group antibodies anti-A and/or anti-B, were present in nine of nine cyst fluids studied, were of lower titers as compared to autologous serum, and occurred as either IgG or IgM immunoglobulins. The results further delineate the biochemical requirements necessary for molecular penetration into human brain-tumor cysts.

Adolescent↗

Effect of phagocytosis and Fc receptor occupancy on complement-dependent neutrophil chemotaxis.

Neutrophil migration was assessed following cell interaction with IgG or after phagocytosis of antibody-coated EA or latex. The migration of these neutrophil preparations was markedly impaired as studied in an agarose medium with ZAS as the chemoattractant. Neutrophils which had interacted with EA retained some capacity for directed migration toward synthetic tripeptides and E. coli filtrate. Rosette formation with EA(IgM)C3 did not impair cell movement. The reduced cell migration observed after immune or nonimmune ingestion was reversible following a prolonged incubation period. The results suggest that phagocytosis or Fc receptor occupancy transiently blocks the ability of neutrophils to migrate.

Adult↗

Neutrophil chemotaxis in cerebral astrocytoma.

Neutrophil chemotaxis was evaluated for five patients with a primary intracerebral malignancy. All patients had intratumor cysts and these fluids with corresponding serum and cerebrospinal fluid were tested for their chemotactic ability. The ability of cyst fluid to effect neutrophil chemotaxis was diminished in comparison to serum from either patients or control population. Cyst fluids had lower complement levels than serum and did not have a humoral chemotactic inhibitor. The neutrophils for both the patient and control groups had similar chemotaxis to a given chemotactic stimulus suggesting that this malignancy does not have an accompanying peripheral blood phagocytic cell chemotactic defect. Chemotaxis, the migration of phagocytic cells, is a fundamental requisite for the inflammatory and the immune response.

Adolescent↗