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Biomedical subjects

D M Bull

Publications and source records attributed to D M Bull.

At least 19 recordsLinked to original sources
PubMed1980

Natural killer activity of human lymphocytes against colon cancer cells.

A human colon cancer cell line, HCT-8, is shown to be an appropriate target cell for study of natural killer (NK) activity in man. In parallel experiments, effector cell characteristics for NK and antibody-dependent cellular cytotoxicity (ADCC) were found to be vested in a single lymphocyte subpopulation, which bore receptors for the Fc fragment of IgG, but lacked other surface receptors. The effector cell failed to adhere to glass and was inactivated by exposure to 3500 rad x-irradiation. Cells forming rosettes with SRBC and cells bearing receptors for complement were inactive in both systems. A wide distribution of NK activity was noted among individuals that correlated with the distribution of effector cell activity in ADCC (r = 0.8). Preincubation of NK effector cells with antibody-coated ADCC target cells markedly reduced NK activity. Neuraminidase treatment of effector cells led to increased NK and diminished ADCC, while trypsin treatment led to reduced NK activity and showed no effect on ADCC. Thus, NK and ADCC effector cells are highly overlapping if not identical populations, but different structures on the cell membrane may mediate the two activities.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1979

Cirrhotic hyperglobulinemia: increased rates of immunoglobulin synthesis by circulating lymphoid cells.

We have measured immunoglobulin (Ig) synthesis by circulating lymphoid cells of 20 patients with cirrhotic hyperglobulinemia (CH) and 20 age-matched controls. We used specific anti-Ig antisera to precipitate Ig synthesized from [14C] amino acid precursors in 13 controls and employed an electroimmunoassay of the "rocket" type to measure Ig elaborated by cultured cells in 4 patient-control pairs. In addition, we studied 3 patient-control pairs by absorption of elaborated Ig onto an anti-Ig-coated solid phase, bromoacetylcellulose. The synthetic index (SI; the ratio of Ig synthesis by a CH patient and a control) was elevated in every case. Mean SI by coprecipitation was 7.2 +/- 5.4 (mean +/- SD), by rocket" 7.3 +/- 3.0 for IgG and 2.2 +/- 0.8 for IgA, and by immunoabsorption 13.8 +/- 8.4 for IgG. Three cirrhotic nonhyperglobulinemic patient-control pairs showed a mean SI of 1.0 +/- 0.1. CH and control populations showed equal numbers of membrane Ig-positive B lymphocytes by immunofluorescence. We conclude that (1) peripheral blood lymphoid cells are appropriate for study of differences in Ig synthetic capacity among individuals; (2) CH is associated with increased in vitro Ig synthesis; and (3) CH lymphocytes may be an appropriate cell population for the study of control mechanisms in Ig synthesis.

B-Lymphocytes↗
PubMed1979

Characteristics of isolated intestinal mucosal lymphoid cells in inflammatory bowel disease.

Immunologic characteristics of intestinal mucosal lymphoid cells from patients with inflammatory bowel disease and controls have been compared. Mononuclear cells isolated by enzymatic means from intestinal tissues involved with inflammatory bowel disease were present in greater numbers, with increased proportions of macrophages and B-lymphocytes, particularly cells bearing intrinsic membrane immunoglobulin G. Synthesis of immunoglobulin G, measured by radioimmunoassay, was increased tenfold in inflammatory bowel disease, while immunoglobulin A synthesis per 10(6) cells was unchanged. "Null" or K-lymphocytes were absent from all populations, and antibody-dependent cellular cytotoxicity (a K-cell-mediated function) was not demonstrable. Taken together, the results fail to support a role for antibody-dependent cellular cytotoxicity or a defect in secretory immunoglobulin A, but rather focus attention upon possible forms of immunoglobulin G-mediated tissue damage in the pathogenesis or perpetuation of inflammatory bowel disease.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Isolation and functional characterization of human intestinal mucosal lymphoid cells.

Viable suspensions of human colonic mucosal lymphoid cells have been prepared by sequential treatment of tissue with dithiothreitol, EDTA in calcium- and magnesium-free salt solutions, and purified collagenase. The intestinal lymphocyte population, in comparison with that of peripheral blood, had greater numbers of bone marrow-derived cells, particularly cells bearing membrane IgA; showed spontaneous association with macrophages; underwent rapid rosette formation with sheep erythrocytes; and demonstrated increased in vitro synthesis of immunoglobulin. Total thymus-derived cells were equal in the two populations. Decreases were found in "null" cell numbers, in cells bearing membrane IgD and IgM, and in responsiveness to phytohemagglutinin. Macrophage/monocytes in the intestinal population were increased in size, granularity, motility, sustained glass adherence, and phagocytic activity. Human intestinal lymphoid cells appear to constitute a cell population that is more "mature" and/or "activated", in comparison with the lymphoid cells of peripheral blood. The method of preparation should lend itself to the study of inflammatory bowel disease, gastrointestinal cancer, and the intestinal secretory immune system.

Antibody Formation↗
PubMed1976

F-antigen: nature, liver specificity, and release in experimental liver injury.

F-antigen is a liver-specific antigen detected with antibody, raised in allogeneic (CBA) mice, to BALB/c mouse liver extract. The authors have confirmed the hepatic specificity of this antigen by showing it to be absent in extracts of extrahepatic organs of mouse and human origin. It is present in liver extracts of guinea pigs, rats, and rabbits, as well as in liver extracts from mouse and human sources. The antigen was present in the circulation of rabbits with acute carbon tetrachloride-induced hepatocellular injury. It was also demonstrated in the sera of 3 of 8 patients with acute hepatitis B antigen-positive hepatitis and in 1 of 4 patients with chronic active hepatitis. It was absent from the sera of 121 other patients with a variety of hepatic and nonhepatic diseases, and from the sera of 20 healthy subjects. The antigen is immunologically distinct from hepatitis B antigen, from the liver-specific lipoprotein antigen LP-2 of Meyer zum Buschenfeld, and from each of 15 individual human serum proteins tested.

Animals↗
PubMed1975

Cell-mediated immunity to liver in patients with alcoholic hepatitis.

Mononuclear-cell responses to liver extracts were studied by a migration-inhibition assay in patients with alcoholic liver disease, viral hepatitis, chronic alcoholism without evidence of liver disease, and in healthy individuals. Patients with acute alcoholic hepatitis demonstrated liver-antigen-induced inhibition of migration (migration index [M.I]equal 0-58 plus or minus 0-08, mean plus or minus S.D.), while patients with cirrhosis, alcoholism, and acute viral hepatitis, as well as healthy volunteers, did not demonstrate such a response (M.I. 0-92 plus or minus 0-13, 0-90 lus or minus 0-10, 0-86 plus or minus 0-18, 0-99 plus or minus 0-04, respectively). It is concluded that cell-mediated immunity to normal or damaged liver tissue may act to perpetuate alcoholic hepatitis and thereby contribute to the development of cirrhosis.

Adult↗
PubMed1975

Nutrition and tumor immunity: divergent effects of antitumor antibody.

Nutritional deficiency reduces antibody synthetic capacity. Antibody directed against tumor antigens, however, may serve either to heighten tumor immunity, as in antibody-dependent cellular cytotoxicity, or to diminish host resistance to cancer growth by "blocking" cell-mediated tumor immunity. Diets made deficient in specific amino acids are inimical to tumor growth, apparently through reduction of synthesis of blocking antibody. Thus, where tumor immune function is involved, complex and possibly paradoxical effects of nutritional status on tumor growth can be predicted.

Animals↗
PubMed1975

Diagnosis and prognosis in colon cancer based on a profile in immune reactivity.

An immunologic profile consisting of measurements of circulating carcinoembryonic antigen (CEA), tumor antigen-induced inhibition of monomuclear cell migration (IMM) and skin reactivity to purified protein derivative, streptokinase-streptodornase, and mumps was assessed as a diagnostic and prognostic tool in 16 patients with colon cancer. Preoperatively, 10 of 14 patients tested had elevated CEA, 12 of 12 showed tumor antigen-induced IMM, and 10 of 11 failed to react to 2 or more recall antigens. Potential surgical cure (7 patients) was accompanied by normal CEA in 4, absent tumor antigen-induced IMM in all 7, and increased skin-test reactivity in 6. Disseminated cancer (9 patients) was associated with elevated CEA in all 9, with absent IMM in all 7 and with suppressed skin-test reactivity in 6 of 9.

Adult↗
PubMed1973

Immunity to colon cancer assessed by antigen-induced inhibition of mixed mononuclear cell migration.

A purified preparation of mixed human peripheral blood lymphocytes and monocytes was used in an inhibition-of-migration assay for cell-mediated immunity to cancer of the colon. This preparation was reproducibly antigen-responsive and migrated with greater reliability than did a more complex cell mixture. Of 27 patients with this disease, cells from 24 showed inhibited migratio in response to colon carcinoma antigen. Uninhibited migration patterns were found in each of the 52 cancer-free controls, including eight patients with nonmalignant disease initially diagnosed as cancer of the colon, and in nine patients with surgically cured adenocarcinoma of the colon.

Adenocarcinoma↗