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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 451 records · Page 25Linked to original sources
PubMed1981

Synthesis and processing of the alpha heavy chains of secreted and membrane-bound IgA.

We have compared the synthesis and processing of immunoglobulin alpha chains in two murine cell lines, a B cell lymphoma that expresses membrane-bound IgA and a hybridoma that secretes IgA. Results of biosynthetic labeling experiments demonstrated that membrane-bound and secreted alpha chains have two distinct intracellular precursors, of different molecular weights and isoelectric points. RNAs from both of these cell lines direct the synthesis in vitro of two alpha polypeptides of Mr 59,000 and 62,000, the larger one being the precursor for membrane-bound alpha chain and the smaller one being the precursor for secreted alpha chain. These cell lines each contain three RNAs, 1.7, 2.1, and 3.1 kilobases in length, which hybridize with cDNA for the alpha constant region and which are present in different concentrations. Our results suggest that the smallest RNA encodes the secreted alpha chain and one or both of the larger RNAs encode(s) the membrane-bound alpha chain.

Animals↗
PubMed1981

Enhancement of formation of the esophageal carcinogen benzylmethylnitrosamine from its precursors by Candida albicans.

Previous studies in Linxian, an area of China with a high incidence of esophageal carcinoma, showed that fungal infections are common in the esophageal epithelium of patients with either premalignant changes or early esophageal carcinoma. Fungi of the genus Candida were the most frequent invaders. In these areas nitrate and nitrite are often present in high concentrations in drinking water and staple grains. The present studies have established the ability of Candida albicans to augment the nitrosative formation of the esophagus-specific carcinogen, benzylmethylnitrosamine (NBMA; N-nitroso-N-methylbenzylamine). Stationary C. albicans cultures, with pH held at 6.8, were incubated with the precursors of NBMA, benzylmethylamine (BMA; N-methylbenzylamine) and NaNO(2). There was a significant increase in the amount of NBMA formed in these cultures, compared to precursors-only controls. The amount of NBMA synthesized depended on fungal cell number. Exponentially growing cultures were also able to cause NBMA formation. The identity of the NBMA was confirmed by high-performance liquid chromatographic coelution with authentic NBMA in three solvent systems and by mass spectroscopy. Boiled cells and conditioned medium in which cells had been incubated were not effective in enhancing nitrosation. Cultured Candida released acidic metabolites that reduced the pH of the medium when only a low concentration of buffer was present. Spontaneous nitrosation of BMA was enhanced under these acidic conditions. Thus, C. albicans infecting the esophageal epithelium could cause local formation of NBMA by both cell-mediated catalysis and extracellular decrease in pH.

Benzylamines↗
PubMed1981

Antibodies reactive with murine mammary tumor virus in sera of patients with breast cancer: geographic and family studies.

Sera of patients with breast cancer, of healthy women from the United States, East India, East Africa, and China, and of healthy women of American and Parsi families in which breast cancer occurred in several family members were assayed for levels of antibody reactive with the murine mammary tumor virus (MuMTV) by an enzyme-linked immunosorbent assay. Increased levels of antibody to MuMTV (absorbance greater than or equal to 0.4) were found in sera of 18.6% of American patients with breast cancer and of 2.8% of healthy American women and in 38% of patients from India and 61.9% from East Africa (healthy, 26.9%). In contrast, antibody reactive with MuMTV was found in less than 5 of women with breast cancer from mainland China (healthy Chinese, 5.0%). Differences in serum MuMTV antibody levels between breast cancer patients in the four groups were found to be significant (P less than 0.0001). Studies of two families from the United States and of one Parsi family from India with genetic propensity to breast cancer showed that high levels of antibody to MuMTV were found in 33%, 71%, and 23% of healthy family members, respectively. The antibody to MuMTV was readily absorbed with purified MuMTV and gp52. In contrast, fetal calf serum, murine type c retroviruses, or erythrocytes from various species failed to absorb the antibody.

Animals↗
PubMed1981

Growth of a pure population of mouse mast cells in vitro with conditioned medium derived from concanavalin A-stimulated splenocytes.

A pure population of mast cells was obtained after 14 days of culturing mouse bone marrow cells in the presence of medium derived from concanavalin A-stimulated mouse spleen cells. The cells were characterized as mast cells by their morphologic appearance and histologic staining, by their histamine content (450 ng per 10(6) cells) and by the demonstration of IgE receptors on their surface (150,000--440,000 receptor sites per cell). The histamine content and the number of IgE receptors remained constant for at least 7 wk of culture. These mast cells could be passively sensitized to mice hybridoma IgE. They then released 43% of their histamine content upon incubation with anti-mouse hybridoma IgE.

Animals↗
PubMed1981

Inhibition of specific cell-mediated cytotoxicity by monoclonal antibodies to human T cell antigens.

Human T lymphocyte subpopulations recently have been defined by monoclonal antibodies that recognize cell-surface antigens selectively expressed on functionally distinct T cell subsets. The majority (approximately 90%) of the peripheral blood sheep erythrocyte-rosette-forming cells carry the OKT3 antigen. Helper cells are OKT4(+), whereas cytotoxic/suppressor cells are OKT5(+) and OKT8(+). We investigated the effect of several monoclonal antibodies recognizing T cell antigens on certain proliferative responses of T cells and on the effector phase of the specific T cell-mediated cytotoxicity generated in mixed lymphocyte culture (MLC). In the absence of added complement, (i) OKT3 and OKT4 monoclonal antibodies inhibited the proliferative response to phytohemagglutinin (PHA), (ii) OKT3 monoclonal antibody inhibited the proliferative response to allogeneic cells in MLC, and (iii) OKT3 monoclonal antibody significantly and regularly inhibited the effector phase of the specific T cell-mediated cytotoxicity against allogeneic targets (P < 0.001) in a concentration-dependent manner. The OKT5 and OKT8 monoclonal antibodies, again in the absence of complement, inhibited moderately the specific cell-mediated cytotoxicity. This inhibition was observed in some experiments only. Inhibition of the specific cytotoxicity by these antibodies also was observed in secondary responses. In contrast, again in the absence of added complement, none of these antibodies had an effect on the nonspecific cytotoxicity generated in MLC against the K562 targets. The OKT4 antibody in the absence of added complement had no effect on either the specific or nonspecific cytotoxicity. Furthermore, treatment with OKT3 or OKT8 antibody and complement completely abrogated the specific T cell-mediated cytotoxicity but had no effect on the natural killer-like cytotoxicity against the K562 cells. Treatment with the OKT4 antibody and complement had no effect. These results suggest that (i) the T5/T8 and T3 antigens, present on cytotoxic T lymphocytes, may be involved directly or indirectly in the antigen recognition step(s) or the lytic mechanism of T cell-mediated lympholysis; and (ii) nonspecific cytotoxicity against the K562 targets generated in MLC is mediated by cells phenotypically different than those that mediate specific cytotoxicity.

Antibodies, Monoclonal↗
PubMed1981

Monoclonal antibody analysis of human T lymphocyte subpopulations exhibiting autologous mixed lymphocyte reaction.

In autologous mixed lymphocyte reaction (MLR), T cells proliferate in response to the stimulation by autologous non-T cells. In the present study, human T cell subpopulations, defined by murine monoclonal antibodies OKT4, OKT8, or 9.3, were examined for their capacity to proliferate in autologous and allogeneic MLR. It was observed that the treatment of responder T cells with OKT4 or 9.3 antibody (both defining helper/inducer T cells) and complement (C') ablated their proliferative response in autologous MLR and markedly reduced their allogeneic MLR proliferative response. In contrast, treatment of T cells with OKT8 antibody (defining suppressor/cytotoxic T cells) and C' had no or minimal effect on their proliferative response in autologous MLR. Furthermore, OKT4, 9.3, 9.6 (PAN), or 7.2 anti-human Ia (framework specific) but OKT8 antibody, when present during the entire culture period, in the absence of C' inhibited in a dose-dependent manner the proliferative response in both autologous and allogeneic MLR. Inhibition of proliferation was also observed when the responder T cells were pretreated with OKT4 or 9.3 antibody, washed, and then stimulated with irradiated autologous or allogeneic non-T cells. Pretreatment of T cells with OKT8 or 7.2 anti-Ia antibody in the absence of C' did not influence their proliferative response in autologous MLR. Thus, T cells containing cells with helper/inducer activity defined by OKT4 or 9.3 antibody appear to be the major responder T-cell subpopulation in autologous MLR.

Antibodies, Monoclonal↗
PubMed1981

Selective growth of a population of human basophil cells in vitro.

An initially homogeneous population of basophilic polymorphonuclear leukocytes was derived from human fetal liver cells grown in culture for 5-7 days. The cells were characterized as basophils by their morphology, histologic staining characteristics, and histamine content, and by the presence of IgE receptors on their surface. In this culture system the basophils were viable for up to 10 days.

Basophils↗
PubMed1981

In vitro differentiation of human marrow T cell precursors by thymic factors in severe combined immunodeficiency.

Marrow cells from 16 patients with severe combined immunodeficiency diseases (SCID) were examined for the presence of T cell precursors which could be induced to express surface markers and functions of T lymphocytes after exposure in vitro to thymic extracts or peptides of thymic origin (thymopoietin and thymopoietin32-36 (TP-5). Marrow cells from 14 patients studied before transplantation revealed three patterns of response. In five patients, inducible T cell precursors were not detected. In six patients, precursors were detected which could be induced to express a human T lymphocyte antigen (HTLA) but acquired little or no ability to rosette with sheep erythrocytes (SRBCs). Induction of HTLA-positive and E rosette-positive lymphocytes was normal in only two patients, both of whom were engrafted with maternal lymphocytes as an apparent result of an intrauterine infusion. Induction of mixed leukocyte reaction (MLR) responses following exposure to thymic hormones was also observed in one of these two patients. In no case could significant responses to mitogens be elicited. Following transplantation, marrow cells from fully engrafted, immunologically reconstituted patients could be induced to bear HTLA, to form E rosettes, and to respond to mitogens and allogeneic cells following exposure to thymic extracts, thymopoietin, or TP-5. Thus, most patients with SCID manifest differentiative abnormalities intrinsic to lymphoid precursors which are corrected following engraftment of functioning allogeneic lymphoid precursors from normal donors.

Antigens, Surface↗
PubMed1981

Serum zinc levels in patients with basal-cell carcinoma.

Basal-cell carcinoma is a malignant epithelial neoplasm that arises from the germinative cells of the epidermis and its appendages. Various causative factors have been implicated in its pathogenesis. In recent years, it has become increasingly apparent that alterations in serum zinc concentration may relate to neoplastic diseases. The objective of this study was to determine whether or not a relationship exists between abnormal serum zinc levels and basal-cell carcinomas. The data indicate that a statistically significant elevation in mean serum zinc levels is associated with this neoplasm. This may, however, not be of clinical significance because of variation in environmental or statistical sampling factors.

Basal Cell Carcinoma↗
PubMed1981

Lymphangiosarcoma after filarial infection.

A case of lymphangiosarcoma of a lower extremity is described in a patient with chronic lymphedema of that leg from a filarial infection in childhood. Histologically, the neoplasm resembled lymphangiosarcomas that arise in arms that become lymphedematous after mastectomies, but was different in that it also contained areas of calcification consistent with prior filarial infection. Calcifications were also present in muscle uninvolved by the lymphangiosarcoma of this case. The prolonged survival of this patient is unlike that of most patients with lymphangiosarcoma, which is generally shorter. Although lymphedema after filariasis is common, this is the first case of a lymphangiosarcoma arising in chronic lymphedema of filarial origin.

Filariasis↗
PubMed1981

Antigens and antibodies cross-reactive to the murine mammary tumor virus in human breast cyst fluids.

Human breast cyst fluids were shown to contain low concentrations of IgA (15-78 micrograms/ml) and IgG (33-145 micrograms/ml). The IgA:IgG ratios in individual breast cyst fluids ranged from 1:0.6 to 1:4. These levels are considerably higher than their ratio in serum (1:7). IgA from 33% of the 40 fluids examined, and IgG from 10% of the fluids, reacted with the murine mammary tumor virus (MuMTV). The reactivity was detected by an enzyme-linked immunosorbent assay that measures antibody binding to both the envelope glycoprotein and core protein of the virus. In a second series of experiments. IgA from 28% of 40 breast cyst fluids reacted only with MuMTV while IgA from 30% of the fluids was reactive with both MuMTV and the Rauscher murine leukemia virus. Antigen reactive with antiserum to the 28,000-dalton MuMTV core protein (p28), was also identified in a 165,000-g pellet fraction from breast cyst fluids. In individual fluids, the extent of IgA binding to MuMTV was positively correlated (P less than or equal to 0.01) with the binding of anti-p28 antibody to the pellet of the breast cyst fluid. Fractions with the buoyant density of retroviruses (1.16-1.18 g/ml) or their cores (1.21-1.25 g/ml) were isolated from breast cyst fluids. These fractions contained a DNA polymerase capable of utilizing the reverse transcriptase-specific template, dG12-18 x poly rCm. In addition, they reacted with antiserum to MuMTV p 28 but not with antiserum to the 30,000-dalton Rauscher murine leukemia virus core protein.

Animals↗
PubMed1981

Decreased in vitro humoral immune responses in aged humans.

Induction of antigen-specific and non-specific (polyclonal) humoral immune responses in vitro was investigated in peripheral blood mononuclear cells of aged (65-85 yr) and young (20-30 yr) volunteers. In vitro immunization of lymphocytes with antigen (sheep erythrocytes) was performed in a recently described microculture system, and anti-sheep erythrocyte plaque forming cells were quantitated in a direct hemolytic plaque assay. Immunoglobulin secreting cells, induced polyclonally with pokeweed mitogen, were quantitated in a reverse hemolytic plaque assay. Significant depressions of antigen-specific as well as polyclonal responses were noted in relation to advancing age. Antigen-specific responses were more frequently depressed than polyclonal responses. T cell mitogen concanavalin A (Con A) was used to amplify functions of autologous immunoregulatory T cells. Addition of 10 microgram/ml Con A to lymphocytes of young donors at culture initiation resulted in activation of suppressor cells and abrogated antigen-specific responses. Delayed addition of Con A, on the other hand, enhanced responses, presumably because of activation of helper T cells. Similar manipulations of lymphocyte cultures from aged donors showed failure of Con A to suppress antigen-specific responses in approximately half of the responders. In many nonresponders, responses within normal range were elicited by the delayed addition of Con A to their lymphocyte cultures. Deviations beyond the range of expected responses were noted in 32.5% of the co-cultures between pokeweed mitogen stimulated young and aged cells. Our findings suggest that age-related deficiencies of B cell function are frequently associated with dysfunction of immunoregulatory T cells and are only occasionally due to intrinsic defects of B cells.

Adult↗
PubMed1981

In vitro effects of two immunopotentiators, Isoprinosine and NPT 15392, on murine T-cell differentiation and function.

A new immunopotentiator, NPT 15392, was analyzed in vitro for its capacity to induce a T-cell marker (Thy-1 antigen) and to enhance the mitogen-induced lymphocyte proliferation. The activity was compared with that of Isoprinosine and a putative thymic hormone (thymosin Fr. V). Thymic hormone preparation (thymosin Fr. V) and the non-thymic agents (Isoprinosine and NPT 15392) induced significant percentages (20-30%) of Thy-1 positive cells in nylon wool-nonadherent nu/nu spleen cells. Maximum induction was observed the concentrations of 100 microgram/ml thymosin Fr. V, 1.0 microgram/ml Isoprinosine, and 0.1 microgram/ml NPT 15392. In addition, NPT 15392 or Isoprinosine significantly augmented proliferation of C57BL/6J spleen cells stimulated by the T-cell mitogens (Con A and PHA) and B-cell mitogen (LPS). The effect of both agents was greater on spleen cells from aged mice (18 mth) than on young mice (3 mth). The minimum effective concentration of NPT was lower than that of Isoprinosine. The data indicate that Isoprinosine and NPT 15392 have actions on precursor T cells, mature T cells, and probably B cells.

Adjuvants, Immunologic↗
PubMed1981

Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin.

The effect of continuous infusion into C57BL/6J mice of 2'-deoxycoformycin (DCF), a tight-binding inhibitor of adenosine deaminase, on the biological function of bone marrow stem cells and T- and B-lymphocytes was evaluated. Greater than 85% inhibition of adenosine deaminase in erythrocytes, thymus, and bone marrow was noted after DCF infusion at 0.4 mg per kg body weight per day, while lesser extents of inhibition were characteristic of spleen and lymph nodes. The reconstitution of lethally irradiated C57BL/6J mice with bone marrow cells from DCF- and 0.9% NaCl infused mice of the same strain was compared. The two groups of animals were virtually identical with respect to (a) the number of spleen colony-forming units, (b) the response of splenic lymphocytes to both B- and T-cell mitogens, (c) hematological analysis of peripheral blood elements, and (d) survival time, thus strongly supporting the lack of effect of DCF infusion on the capacity of stem cells to differentiate. In contradistinction, DCF infusion was highly lymphocytotoxic as noted by the severe necrosis in both B- and T-cell regions in lymph nodes and spleen and by the dramatic weight reduction in spleen and thymus. Histopathology of other tissues including bone marrow was normal except for the occurrence of hepatitis. A striking decrease in blastogenesis induced by the mitogens concanavalin A, phytohemagglutinin, and Escherichia coli lipopolysaccharides was also observed after DCF infusion. Consistent with these data, in vitro incubation of bone marrow cells with DCF did not impair the number of spleen colony-forming units produced in lethally irradiated mice. These data suggest a potential use for adenosine deaminase inhibitors in the prevention of graft-versus-host disease in hematopoietic transplantation.

Adenosine Deaminase↗
PubMed1981

Reciprocal transfer of abnormalities in clonable B lymphocytes and myeloid progenitors between NZB and DBA/2 mice.

Previous studies in this laboratory revealed that NZB mice have abnormalities of myeloid progenitor populations from an early age such that they are poorly responsive to a particular type of colony-stimulating activity (CSA). In addition, these mice develop abnormally high numbers of B cells that can be cloned in semisolid agar cultures and that are atypical in resisting inhibition by anti-mu antibodies. To investigate whether these abnormalities, like other autoimmune phenomena studied previously, are transferrable with hemopoietic cell grafts, we performed reciprocal bone marrow transplants between NZB and normal DBA/2 mice. Irradiated control mice given syngeneic marrow did not change with respect to any of the parameters that were measured. In contrast, DBA/2 recipients of NZB marrow were indistinguishable from NZB mice in terms of CSA responses and incidences of anti-mu resistant B cells. The proportions but not total numbers of clonable B cells ere elevated in these mice until at least 16 wk after grafting. Conversely, NZB mice given DBA/2 cells had all of the normal characteristics of DBA/2 mice. Transplantation did not cause significant changes in hematocrits, reticulocyte counts, or spleen weights. Therefore, all elements necessary for expression of these lymphoid and nonlymphoid abnormalities of NZB mice are intrinsic to radiosensitive hemopoietic cells.

Animals↗