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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 469 records · Page 26Linked to original sources

Reconstitution of normal megakaryocytopoiesis and immunologic functions in Wiskott-Aldrich syndrome by marrow transplantation following myeloablation and immunosuppression with busulfan and cyclophosphamide.

Three patients with Wiskott-Aldrich syndrome received transplants of marrow from their HLA-A, B, C, D identical siblings after myeloablation with busulfan, 2 mg/kg/day x 4 days, followed by immunosuppression with cyclophosphamide, 50 mg/kg/day x 4. Sustained engraftment of lymphoid and hematopoietic elements was documented in each case. Platelet counts in excess of 100,000/cu mm were restored 20--50 days posttransplant and remain in the normal range 6--12 mo later. Platelets exhibit normal size and in vitro aggregation. The patients produce isoagglutinins and antibodies to other polysaccharides. The use of busulfan in moderate dosages as a myeloablative agent, coupled with cyclophosphamide, may offer an improved alternative to the use of lethal total body irradiation as a preparative regimen for complete correction of Wiskott-Aldrich syndrome by marrow transplantation.

Bone Marrow Transplantation↗

Adenosine-5'-triphosphate-(ATP) mediated stimulation and suppression of DNA synthesis in lymphoid cells. I. Characterization of ATP responsive cells in mouse lymphoid organs.

The effects of various nucleotides and nucleosides on DNA synthesis of mouse lymphocyte populations were studied. Significant stimulation of DNA synthesis was observed in the cells from bone marrow or the thymus in the presence of ATP. In contrast, the DNA synthesis of the cells from spleen, lymph nodes, and peripheral blood was markedly inhibited by ATP. Guanosine 5'-triphosphate had nonspecific stimulatory effects on the DNA synthesis of various lymphoid cells, whereas cytidine triphosphate had no effect. When thymocytes or bone marrow cells were separated by 1 x g velocity sedimentation, a distinct cell population was identified as being responsible for the ATP-mediated stimulation of DNA synthesis. Further characterization of ATP-responsive cells revealed that the highest concentration of terminal deoxynucleotidyl transferase, a marker enzyme for precursor T cells, was present in these cells. ATP-mediated stimulation of DNA synthesis may, therefore, serve as a specific marker restricted to a certain population of differentiating T cells.

Adenine↗

Demonstration of 11S IgA antibody to spermatozoa in human seminal fluid.

Spontaneous sperm agglutination was observed in the ejaculate of a 39-year-old male (patient Z). Using an enzyme-linked immunosorbent assay (ELISA) with spermatozoa fixed to wells of a microtitre plate it was determined that IgA was associated with patient Z's spermatozoa but not with a pooled sample of spermatozoa from fertile men Z's seminal fluid agglutinated human spermatozoa (titre 1:16). In contrast, no sperm-agglutinating or immobilizing activity was present in the patient's serum. Agglutination was prevented by preincubation of the seminal fluid with anti-IgA antibody but not with anti-IgA antibody. IgG from Z's seminal fluid readily bound to human spermatozoa, as determined by the ELISA assay. IgA from a pool of seminal fluids from fertile men or from 18 human sera bound to spermatozoa to a much lesser extent. By sucrose-gradient velocity centrifugation it was demonstrated that the anti-sperm IgA in patient Z's seminal fluid was 11S. Finally, antibody to secretory component removed the anti-sperm IgA from Z's seminal fluid. These data provide evidence that secretory IgA with anti-sperm activity is produced in the male genital tract. Furthermore, a new methodology is presented for the determination of antibodies to spermatozoa.

Adult↗

Autoimmunity in selective IgA deficiency: relationship to anti-bovine protein antibodies, circulating immune complexes and clinical disease.

To test the possibility that autoimmunity could be related to increased levels of anti-bovine antibodies and/or circulating immune complexes in selective IgA deficiency, we studied the sera of 30 consecutive patients for the quantitative level of antibody to bovine milk, the presence of antigen--antibody complexes and 10 selected autoantibodies. Higher titres of anti-milk antibody and circulating immune complexes were to be correlated with positive serological tests of autoimmunity in these patients, and rheumatoid arthritis (three cases) and neurological disease (four cases) were found in individuals who had both milk precipitins and circulating immune complexes. We suggest that the chronic excessive permeability of the gastrointestinal tract in selective IgA deficiency may permit the excessive absorption of many food proteins, leading to the formation of antigen--antibody complexes and autoimmunity.

Adolescent↗

Serum zinc, copper, and the Cu/Zn ratio in patients with benign and malignant breast lesions.

Serum zinc, copper, and the Cu/Zn ratio were evaluated in 80 patients with breast lesions prior to surgery. There were 37 patients with benign and 43 with malignant breast lesions. There was no evidence of weight loss, impaired appetite, or change in eating pattern in any of the patients. There was a statistically significant difference for the mean SCL and Cu/Zn ratio between controls, age 66-94, and patients with malignant breast lesions. This difference was also observed between the ages of 20-45 and 66-94 among controls, suggesting that this is age related rather than disease related. The range of distribution for SZL and SCL were similar for all groups studied. Neither SZL, SCL, or the Cu/Zn ratio were of value in discriminating between controls and patients with benign or malignant breast lesions. We were unable to demonstrate the value of these parameters as markers of disease activity in patient with benign or malignant breast lesions.

Adenocarcinoma↗

The effect of diet on autogenous immunity to mouse mammary tumor virus in C3H/Bi mice.

Antibody levels to mouse mammary tumor virus (MuMTV) in sera of C3H/Bi, C57BL/6 and AKR mice were assayed by an enzyme-linked immunosorbent assay (ELISA). It was found that antibody levels to MuMTV were highest in sera of C3H/Bi females which have a high incidence of breast cancer and low in male C3H/Bi and female C3H/Bi foster-nursed on C57BL/6 females. Sera of C57BL/6 and AKR mice showed very low or undetectable levels of antibody to MuMTV. Reduction of caloric intake sufficient to inhibit mammary tumor formation strikingly inhibited formation of antibody against MuMTV. The lowest levels of antibody were observed in sera of mice fed 10 cal/day of a defined diet. Significantly higher levels developed in the sera of mice fed 16 cal/day of the same defined diet. The highest antibody levels against MuMTV, however, were seen in sera of mice fed lab chow ad libitum but no correlation was evident between levels of antibody and tumor size. These studies indicate that dietary caloric restriction has a profound influence on the development of both mammary adenocarcinoma and antibody responses to MuMTV.

Age Factors↗

Pre-B cells and other possible precursor lymphoid cell lines derived from patients with X-linked agammaglobulinemia.

A group of unique Epstein-Barr virus-containing cell lines was derived from the bone marrow of three patients with X-linked agammaglobulinemia. Efforts to obtain cell lines from the peripheral blood of these patients were uniformly unsuccessful. Immunofluorescence analyses as well as biosynthetic studies with [(35)S]methionine indicated unusual patterns of Ig synthesis in many of these bone marrow derived lines. Seven of the lines were of particular interest in that two produced no Ig of any type; two others showed no Ig by fluorescence but small amounts by [(35)S]methionine labeling; one expressed only cytoplasmic mu chains without any evidence of light chain synthesis, and two produced primarily mu chains with only slight amounts of light chains. One of the lines without membrane or cytoplasmic Ig studied in detail grew like a typical lymphoid line and was carried in intermittent culture over a period of 2 yr without Ig expression. One line grew quite differently and resembled the round cell type described previously, which has been obtained from a variety of sources. The cell line with cytoplasmic mu chains and no light-chain expression had the characteristic properties of pre-B cells. Three normal type Ig-producing cell lines also were obtained from the patients. The accumulated evidence obtained in the present study indicates that these unusual cell lines represent normal precursor cells of the B-cell lineage; these grew out in these cases because of the virtual absence of mature B cells that ordinarily overgrow the culture system. However, the possibility that in certain instances they reflect abnormal Ig synthesis characteristic of the disease has not been ruled out.

Agammaglobulinemia↗

Analysis of multiple cell markers in acute leukemia complicating Hodgkin's disease.

A multidisciplinary methodology was applied to study 6 patients with acute leukemia (AL) following treatment for Hodgkin's disease. All 6 patients developed acute monocytic leukemia according to cytochemical criteria; morphologically, 3 cases were undifferentiated monoblastic leukemia; 3 cases were partially differentiated monocytic leukemia. In 3 of the 6 cases, cell suspensions from peripheral blood and/or bone marrow bore predominantly surface receptors for the Fc fragment of IgG and/or C-3 fraction of complement and exhibited variable degrees of phagocytosis. Two cases lacked any recognizable membrane markers or phagocytic activity. Terminal transferase enzymatic activity was not diagnostically elevated. Soft agar bone marrow culture studies revealed no growth or a characteristic leukemic cluster pattern. Chromosome analysis done in 1 of the 2 patients studied revealed hypodiploidy and structural rearrangement. Prospective studies, done serially, will help determine whether development of AL in patients with Hodgkin's disease results from the influence of intensive and potentially oncogenic therapy or represents progression from a preleukemic stage inherent to the original tumor.

Adult↗

Subpopulations of human T lymphocytes. VI. Analysis of cell markers in acute lymphoblastic leukemia with special reference to Fc receptor expression on E-rosette-forming blasts.

A variety of surface markers, terminal deoxynucleotidyl transferase (TdT) activity, morphologic appearance, and cytochemical composition were studied in a group of 16 patients (13 children, 3 adults) with acute lymphoblastic leukemia (ALL). In 9 children, no surface markers were detected on lymphoblasts (null-type ALL). Leukemic blasts of 4 children formed E-rosettes. These E-rosette-forming blasts from 3 adult patients with ALL, were studied for the presence of Fc receptors. Of the leukemic blasts from these 7 patients, 2--76% expressed receptors for IgG Fc. Only 3 of 7 patients showed 9--42% receptors for IgM Fc. In addition, complement receptors were investigated in 6 of those 7 patients with T-cell ALL. Complement receptors were detected on 9--70% of the E rosette forming blasts from all 6 patients. TdT activity was elevated in T-cell ALL and in children with null-type ALL. The heterogeneity of Fc receptor expression on leukemic blasts in these patients demonstrates a malignant proliferation of T cells in different stages of differentiation or maturation. This observation might be helpful in subclassifying T-cell leukemias with regard to prognosis and the response to therapy.

Adult↗

Antibodies reactive with the mouse mammary tumor virus in sera of breast cancer patients.

IgG binding to purified mouse mammary tumor virus (MuMTV) was quantitated by an enzyme-linked immunoassay (ELISA) using sera from patients with breast cancer or benign breast disease, or from healthy age-matched controls. Significantly greater binding (p<0.01) was found in breast-cancer-derived sera than in the other categories. In addition to IgG reactivity, three breast cancer sera also possessed IgA and IgM reactive with MuMTV by the ELISA assay. Only IgG was reactive in the majority of sera while two sera possessed MuMTV binding activity only in the IgM fraction. Both IgG binding and virolysis of MuMTV were greatly reduced by preincubation of sera with MuMTV. The specificity for MuMTV was further explored with IgG of serum from one breast cancer patient. Human antibody reactive with MuMTV was progressively diminished by preincubating the human serum with increasing concentrations of MuMTV but not by incubation with the type-C AKR murine leukemia virus. Preincubation of MuMTV with a breast cancer serum partially blocked the reactivity of gp52 antiserum with the virus. The results suggest that an antigen related to an MuMTV envelope component is expressed in breast cancer.

Antibodies, Viral↗

Identification of a p69,71 complex expressed on human T cells sharing determinants with B-type chronic lymphatic leukemic cells.

In the course of generating monoclonal antibodies to human thymus-dependent differentiation antigens, we were able to define specificities shared by T cells and by cells from patients with chronic lymphatic leukemia that were not detectable on normal B cells. In particular, one of these antibodies was reactive by indirect immunofluorescence with greater than 95% of the thymocytes and 80--95% of nonadherent sheep erythrocyte-rosetting peripheral blood lymphocytes (PBL), but was unreactive with normal B cells or cell lines derived from PBL by Epstein-Barr virus transformation. However, the leukemic cells from 11 of 14 patients with B-type chronic lymphatic leukemia were found to express detectable concentrations of this surface determinant. The target antigen recognized by this monoclonal antibody was shown by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be a p69,71 complex. Our findings suggest a possible relationship between this antigen and the previously described GIX system in the mouse.

Animals↗

Bone marrow transplantation for the therapy of refractory adult T cell acute lymphoblastic leukemia.

Two adult patients with T cell acute lymphoblastic leukemia (ALL) received an intensive multiagent therapeutic regimen and failed to enter remission. Following cytoreduction with cyclophosphamide (60 mg/kg x 2) and total body irradiation (1000 rads) they underwent bone marrow transplantation. One patient received marrow from his identical twin brother and the other from his HLA-matched sister. Both patients promptly went into remission. The identical twin recipient is alive and free of disease at 20+ months, but the allogeneic patient died of P. carinii pneumonia at eight months with no evidence of leukemia. These results suggest that even some refractory patients whose disease has multiple negative prognostic features may respond to pretransplant chemoradiotherapy and attain a clinically useful complete remission. Additional patients with longer follow-up will be necessary before the curative potential of bone marrow transplantation in T cell ALL can be assessed.

Adult↗

Suppressor cells in healthy relatives of patients with hereditary colon cancer.

Patients with sporadic or hereditary colon cancer (cancer family syndrome) demonstrate in vitro defects of cellular immunity characterized by decreased lymphocyte responsiveness in mixed leukocyte culture, which can frequently be attributed to the influence of suppressor macrophages. Healthy relatives of affected patients with hereditary colon cancer can show the same defects of cellular immunity. Affected members with polyposis coli or healthy relatives do not show these defects, whereas individuals with Gardner's syndrome can. These defects of cellular immunity may be an important etiologic component of, or marker for, the cancer family syndrome. These defects could also serve to differentiate the colonic polyposis syndromes.

Colonic Neoplasms↗

Association of Kaposi's sarcoma with second primary malignancies: possible etiopathogenic implications.

The association of Kaposi's sarcoma (KS) with second primary cancers, especially of the lymphoreticular system, has been frequently noted. To confirm these reports in a systematic way, data on a series of 92 patients with KS treated at Memorial Sloan-Kettering Cancer Center (MSKCC) 2949-1975 were subjected to extensive statistical analysis. Use was made also 4517 double primaries including all sites, diagnosed at MSKCC 1949-1974, and 1959 simultaneous double primaries from the Third National Cancer Survey. Some key results: (1) of KS patients had toher primary malignancies; (2) there was a 20-fold increase in the incidence of lymphoreticular malignancies after diagnosis of KS; (3) in the MSKCC series double primaries, lymphoreticular malignancies were involved in 8% of cases; for KS alone the corresponding figure was 58%. Our findings provide evidence in support of possible etiopathogenic mechanisms that may be involved in the natural course of KS.

Adult↗