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Biomedical subjects

N E Kay

Publications and source records attributed to N E Kay.

At least 109 records · Page 6Linked to original sources
PubMed1982

Heterogeneity of human melanoma-associated antigens defined by monoclonal antibodies and conventional xenoantisera.

Immunochemical analysis of cultured human melanoma cell detergent extracts and spent culture medium with conventional xenoantisera and monoclonal antibodies identified four types of 94,000 (94K) dalton molecules and two types of high-molecular-weight melanoma-associated antigens by the following characteristics: (1) association with other components, (2) mobility in SDS-PAGE under reducing and nonreducing conditions, (3) antigenicity, and (4) presence in spent culture medium. Conventional xenoantisera were found to contain antibody populations to antigenically distinct structures, some of which have similar apparent molecular weights. Immunodepletion studies showed that the antigenic determinant detected by the monoclonal antibody 225.28S to a high-molecular-weight melanoma-associated antigen was expressed on a subpopulation of the antigens defined by the conventional xenoantiserum #8995. These data prove that antibodies reactive with antigens of similar molecular weight cannot be assumed to identify the same structures, and indicate that tumor-associated antigens may be heterogeneous in the expression of antigenic determinants defined by monoclonal antibodies.

Animals↗
PubMed1982

Effect of therapy on T cell subpopulations in patients with chronic lymphocytic leukemia.

We have previously demonstrated functional and quantitative imbalances in two human thymic (T) cell subpopulations, T gamma and T mu, in chronic lymphocytic leukemia (CLL) patients. Serial evaluations of the numbers of T gamma and T mu subsets in CLL were performed in order to delineate more completely the patterns of T cell abnormalities two groups of CLL patients were studied: (I) previously untreated (n = 3) and (II) stable CLL on chemotherapy (n = 12). In Group I, two of three patients had significantly increased percentages of T gamma cells (mean +/- S.E.M. = 57 +/- 5 vs 18 +/- 2 for controls). There was defective in vitro appearance of T mu cells in both groups. In Group II, repeated studies of T cell subsets revealed persistently elevated T gamma cells despite various modes of oral chemotherapy. In three CLL patients who required splenectomy a dramatic decrease in the percentages of T gamma cells was noted post-splenectomy (51 +/- 3 to 15 +/- 3). In all cases the spleen was diffusely involved with CLL. These findings indicate: (1) abnormalities of T cell subsets are present early in CLL, (2) chemotherapy does not affect the levels of T gamma cells in stable patients and (3) removal of infiltrated CLL spleens results in a dramatic decrease in the proportion of T gamma cells. This latter finding plus the increase in T gamma cells in progressive disease post-splenectomy suggest T gamma cells may be an important determinant of the course of CLL.

Follow-Up Studies↗
PubMed1982

Human T-cell function in experimental ascorbic acid deficiency and spontaneous scurvy.

Studies in animal models suggest that ascorbic deficiency impairs T-cell-mediated immunity. We studied five normal volunteers hospitalized on a metabolic unit and consuming a strictly controlled diet deficient in ascorbic acid I) after a 5-wk control period of ascorbic acid supplementation (75 mg/day) and 2) after a 9-wk period of no supplementation. Three of the subjects were restudied after a 5-wk period of ascorbic acid supplementation after the deficient period. At the end of both control periods ascorbic acid levels in plasma ranged from 0.9 to 1.3 mg/dl and in leukocytes from 19 to 30 microgram/10(8) cells. At the end of the deficient period levels of ascorbic acid in plasma ranged from 0.09 to 0.15 mg/dl and in leukocytes from 6.2 to 10 microgram/10(8) cells, levels at or below those frequently found in frank scurvy. None of the T-cell parameters tested including mitogen responsiveness to phytohemagglutinin and percentage of T-cells bearing receptors for IgM (helper cells) and IgG (suppressor cells) was different in the deficient period compared to the control periods. One patient with spontaneous scurvy (plasma ascorbic acid 0.07 mg/dl, leukocytic ascorbic acid 4.9 microgram/10(8) cells) was studied at the time of admission and after vigorous ascorbic acid repletion. All T-cell parameters after repletion were unchanged from admission. We conclude that in man ascorbic acid deficiency, even at the scorbutic level, does not alter T-cell numbers or impair in vitro T-cell function.

Adult↗
PubMed1982

Zinc and T-lymphocyte function in hemodialysis patients.

Thirteen patients maintained on long-term hemodialysis were studied with respect to their serum zinc concentration and T-lymphocyte response to phytohemagglutinin. Six patients demonstrated depression of T-cell mitogen response, while seven patients demonstrated a normal response. The mean serum zinc concentration of the patients with abnormal response was lower than those patients with a normal response (63 +/- 11 versus 75 +/- 14 microgram/di, respectively). There was no significant correlation between an individual's serum zinc concentration and T-cell response (r = 0.16). Five patients whose T-cell responses were depressed were given intravenous zinc chloride during each dialysis run for 6 wk (10 mg intravenous zinc, three times weekly) and were evaluated before and after therapy. All five patients remained anergic to four skin tests antigens. Only one patient (who had the lowest pretreatment serum zinc concentration at 48 micrograms/dl) demonstrated significant improvement in mitogen response after zinc therapy. Although dialysis patients commonly have low serum zinc concentrations and depressed mitogen response, in our patients these two findings were generally unrelated. Additionally, supplemental zinc did not change base-line measurements of T-lymphocyte mitogen response in four of five patients studied.

Chlorides↗
PubMed1982

Enhanced T cell suppression is directed toward sensitive circulating B cells in multiple myeloma.

Multiple myeloma, a disorder typically accompanied by monoclonal immunoglobulin excess and hypogammaglobulinemia was evaluated to delineate the status of T cell regulation on malignant B cell proliferation. Intact T cells and T cell subsets previously noted by us to be suppressor (T gamma) and helper (T non-gamma) were isolated from 10 controls and 10 myeloma patients. Various concentrations of control and patient T cell subsets were mixed with control and patient B cells and stimulated with PWM. T cell effect on B cell proliferation as measured by [3H]thymidine incorporation was then determined. Myeloma T gamma cells were more effective than control T gamma cells in suppressing control or myeloma B cell [3H]thymidine incorporation. Interestingly, myeloma B cells, when added to myeloma T gamma cells, were suppressed to a greater extent than were control B cells when mixed with a similar concentration of myeloma T gamma cells. These in vitro studies suggest a complexity of B and T cell abnormalities in multiple myeloma; first, the myeloma B cells are extremely sensitive to T gamma cell suppression, and second, myeloma T gamma cells have excessive suppressor capacity. It is yet unclear whether these results are associated with an immunoregulatory response to this malignancy or represent part of the basic disease process.

B-Lymphocytes↗
PubMed1982

Monoclonal CLL B-cells may be induced to grow in an in vitro B-cell colony assay system.

A simple reproducible in vitro B-cell colony assay system was used to evaluate B-cell growth in controls and patients with chronic lymphocytic leukemia (CLL). All six CLL patients studied formed B-cell colonies. The number of colonies was significantly less in patients than controls (66 +/- 18 versus 127 +/- 8). CLL colonies were shown to be monoclonal and appeared to reflect the circulating malignant B-cell clone in our patient group, while the six controls studied formed polyclonal B-cell colonies. Wright-Giemsa staining showed typical plasma cells to have developed in the controls but not in the patients. Cells from CLL patients retained a more lymphoid appearance. It is believed that investigations with this B-cell assay will provide the means for further in vitro evaluation of malignant B-cell proliferation in other lymphoproliferative disorders.

B-Lymphocytes↗
PubMed1982

Fibronectin enhances in vitro monocyte-macrophage-mediated tumoricidal activity.

Control of neoplastic proliferation reflects in part monocyte/macrophage destruction of target cells--destruction that evidently requires cell-cell interaction. We herein show it to involve the natural plasma opsonin, fibronectin. With two cultured human tumor lines--Malme melanoma and CAK-I renal carcinoma cells--addition of fibronectin, purified to homogeneity, enhances macrophage-mediated cytotoxicity 2--4-fold (p less than 0.01). Both fresh human monocytes or the U-937-cultured macrophage line become more lethal to tumor cells with added fibronectin. The fibronectin-enhanced monocyte and U-937 tumoricidal activity occurred in a dose-dependent fashion. Specificity of fibronectin's action was validated by use of affinity-purified rabbit antifibronectin antibody, which completely abated its enhancement of tumoricidal activity. Enhancement of tumoricidal activity did not occur when monocytes or U-937 were exposed to fibronectin-coated plates. However, the addition of soluble fibronectin to fibronectin-coated plates was then capable of enhancing cytocidal activity. These studies demonstrate that human fibronectin is capable of increasing both fresh and cultured human monocyte tumor-directed cytotoxicity. Fibronectin appears to be a potentially important circulating molecule that may favorably influence human monocyte tumor cell cytotoxicity.

Cell Communication↗
PubMed1981

Deficiency of natural killer cell activity in patients with chronic lymphocytic leukemia.

Natural killer (NK)6 cell activity of peripheral blood lymphocytes against human leukemia cell lines was measured in patients with chronic B-cell lymphocytic leukemia (CLL) and age- and sex-matched controls. In order to remove the leukemia cells that interfere with the in vitro assay we (1) isolated lymphocytes that form rosettes with sheep red blood cells (SRBC) or (2) lysed the CLL cells with a monoclonal anti-B cell antibody and complement. NK activity in either lymphocyte preparation from nine of 10 patients with advanced disease was not detectable and, when calculated in terms of lytic units per ml of blood, as at least seven times lower than in controls; only one of these patients exhibited activity within the control range. Two patients with early disease had measurable, but low, NK-cell activity. Prolongation of the NK cell assay from 6 to 18h gave rise to significant killing in the CLL patients lacking NK cell activity in the 6-h assay; however, the activity still was six times lower than in controls. Treatment of leukemia cell-depleted lymphocytes from CLL patients with human fibroblast interferon or the interfeon inducer poly 1:C enhanced NK-cell activity in the two early stage patients but this treatment was ineffective in three later stage patients. The percentage of cells with characteristics of NK cells, i.e. those with receptors for SRBC and Fc-portion of IgG, was four times higher in CLL patients and the percentage of lymphocytes binding to NK-sensitive target cells was equal to that in controls despite the fact that, in the majority of patients, lysis of the target cells by the lymphocytes does not ensue. The NK deficiency may be responsible for the increased incidence of secondary malignancies in CLL patients.

Aged↗
PubMed1981

T-cell subpopulations in multiple myeloma: correlation with clinical disease status.

T-lymphocyte subpopulations bearing Fc receptors for IgM (T mu) or for IgG (T gamma) were studied in blood specimens obtained from 40 normal volunteers and from 16 patients with multiple myeloma. The myeloma patients showed a significant imbalance in T-cell subpopulations characterized by an increase in the percentages of T gamma cells to 30.0 +/- 3.9% (mean +/- SEM) compared with 12.0 +/- 3.0% for the controls (P less than 0.001). The patients exhibited a decreased proportion of T mu cells (13.4 +/- 4.1%) compared with the control value of 55 +/- 7% (P less than 0.001). When the results were analysed according to clinical status it was the patients with indolent or well-controlled disease and not those with progressive disease who exhibited an elevated proportion of T gamma cells. The elevation of T gamma cells or of a subpopulation of suppressor cells should be further studied as a possible mechanism of disease control in multiple myeloma.

Aged↗
PubMed1981

Detection of shedding of human blood monocyte Fc receptor during in vitro culture.

Human monocytes, isolated from peripheral blood and placed in culture, produce supernatants that have Fc receptor activity. This activity is detectable using a complement-dependent hemolytic assay. Inhibition of hemolysis is detected with undiluted supernatants, is temperature-dependent and is not demonstrable with culture supernatants from Fc-receptor-negative endothelial cells. To more completely determine their monocyte supernatants contained shed Fc receptors, inhibition of direct Fc rosettes by the same supernatants was demonstrated. The supernatants are most active for Fc receptor activity after monocytes are cultured for 7-9 days. The activity of Fc receptor material varied among donors. Monocyte culture supernatants may be utilized as sources of monocyte Fc receptor material for future evaluation.

Adult↗
PubMed1981

Severe zinc deficiency in humans: association with a reversible T-lymphocyte dysfunction.

Two patients developed severe zinc deficiency with acrodermatitis during parenteral hyperalimentation. The response of circulating T-lymphocytes to phytohemagglutinin was assessed both during the episode of clinical zinc deficiency and after intravenous zinc supplementation as the sole means of nutritional intervention. Maximum T-cell response to phytohemagglutinin, expressed as percent of simultaneous normal control response, was 2.1% and 27.9% in Patients 1 and 2 respectively. After 20 days of intravenous zinc supplementation (12 mg/d), repeat studies showed the T-cell response of Patient 1 to be 221% of the control, and that of Patient 2 to be 139% of control. In addition, Patient 1 was anergic during the period of zinc deficiency and normally reactive after zinc supplementation. These findings agree with extensive animal studies showing the detrimental effect of zinc deficiency on cellular immunity.

Acrodermatitis↗
PubMed1981

Abnormal T-cell subpopulation function in CLL: excessive suppressor (T gamma) and deficient helper (T mu) activity with respect to B-cell proliferation.

T-cell function directly influences several B-cell functions. The effect of T-cell subgroups on B-cell function (DNA synthesis) was evaluated for controls and patients with B-cell type of CLL. Control and CLL intact T cells, T cells with receptors for IgG (T gamma), and T cells without Fc receptors at isolation (T non-gamma) were admixed with control B cells. Two predominant differences between control and CLL T cells were observed. First, CLL T gamma cells were excessively effective at suppressing B-cell DNA synthesis, and secondly, control T non-gamma cells were more efficient than CLL T non-gamma at promoting control B-cell DNA synthesis. While it is unclear whether the qualitative and quantitative T-cell abnormalities are part of the CLL disease process, it is possible that excessive T gamma cell numbers and function may reflect an appropriate immune response to a malignant B-cell clone.

B-Lymphocytes↗
PubMed1981

Production of erythroid potentiating factor(s) by a human monocytic cell line.

U-937 is a human monocytic cell line that has been to elaborate factors that affect normal human hematopoiesis in vitro. Studies on the effects of these factors demonstrated an erythroid potentiating factor (EPF) and a potent inhibitor of granulocyte-macrophage (CFU-GM) colony growth. The EPF was present in both serum-containing and serum-free U-937 conditioned media, had a dose-dependent effect on erythroid colony formation and was remarkably heart stable. The CFU-GM inhibitory activity was also detected in serum-free conditioned medium, was dose-dependent, heart labile and its effect was reversed by Indomethacin. Indomethacin (Sigma, St. Louis, Mo.) did not alter the erythroid effects of the U-937 conditioned medium. No colony stimulating factor (CSF) or erythropoietin (Ep) could be detected in this medium. The existence of a human cell line capable of production EPF without simultaneous CSF production will permit further studies on the biochemical and biologic nature of these factors.

Animals↗
PubMed1981

Cell-cell interaction in human granulopoiesis: role of T lymphocytes.

T lymphocytes have been implicated in the pathogenesis of granulocytopenias. We studied the effects of unstimulated and pokeweed mitogen (PWM) activated intact (Ti) and partially purified T cell subpopulations (T gamma and Tnon gamma, i.e., T mu plus T0) on in vitro granulocyte-macrophage colony formation (CFUGM) by autologous normal human bone marrow (BM). Coculture of BM and Ti, T gamma, or Tnon gamma caused only a slight decrease in the numbers of colonies and clusters; however, when cultured with a mixture of T gamma and Tnon gamma, the inhibition was significant. In contrast, activation of T cells or T cell subsets with PWM resulted in a marked decrease in colony formation. These results demonstrate that: 1) PWM-activated T cells or its subpopulations will inhibit autologous BM colony formation in vitro. The suppression seen with admixes of unstimulated T gamma and Tnon gamma is presumptive evidence that prior cell-cell interaction(s) may be required for the generation of inhibitory cells in this system; and 2) this model may represent an in vitro counterpart of immune-mediated cytopenias in man.

Animals↗
PubMed1981

Lysozyme enhances monocyte-mediated tumoricidal activity: a potential amplifying mechanism of tumor killing.

The mononuclear phagocyte is well established as an in vitro cytotoxic effector cell for certain human tumors. The mechanism(s) for this action remains unclear. Increased levels of lysozyme, a cationic enzyme synthesized in large amounts by mononuclear phagocytes, are associated with increased resistance to transplantable animal tumors. In this study, we provide evidence that human lysozyme, isolated from the urine of leukemic patients, has marked potentiating effects on human monocyte-tumor-cell cytocidal activity. In addition, lysozyme-exposed monocytes incorporate increased quantities of leucine, suggesting that monocytes are capable of amplifying their own metabolic activation by secreting an endogenous constituent. Tri-N-acetyl-glucosamine, a competitive inhibitor for the active site of lysozyme, inhibits cytocidal activity. Conversely, protamine, an extraneous albeit similarly positively charged molecule, increases monocyte-mediated tumor cytotoxicity; this protamine effect is negated by heparin. We conclude that lysozyme, at least partially by its positive charge, is capable of enhancing in vitro monocyte tumor cell cytotoxicity; its in vivo secretion may potentiate monocyte-tumor-cell interaction.

Acetylglucosamine↗