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Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 505 records · Page 28Linked to original sources

Fatal disseminated adenovirus infection in a renal transplant recipient.

A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.

Adenoviridae↗

Cell surface antigen expression on chemically induced murine leukaemias.

The immunogenicity of murine leukaemias induced by chemical carcinogens or irradiation in C57Bl or (C57Bl times DBA2) F1 hybrid mice has been studied in vivo by transplantation and in vitro by indirect membrane immunofluorescence (IF) using syngeneic immune or allogeneic immune antisera. Two of 5 leukaemias tested for immunogenicity by assessment of the capacity of syngeneic mice specifically immunized with irradiated (3 Krad) cells to reject small challenge inocula (10(3)-10(4) cells) displayed weak neoantigenicity while 3 were non-immunogenic by this criterion. Antibodies directed against cell-surface antigens of the immunizing cells of 7 leukaemias were not detectable by immunofluorescence tests using sera from the respective immunized mice. H-2 histocompatibility antigens readily identified on normal lymphoid cells using reference Balb/c anti-C57Bl (H-2d anti-H-2b) alloantisera could neither be detected on the majority of transplanted leukaemias nor on 9 primary leukaemias in C57Bl mice induced by N-butyl-N-nitrosourea (BNU). Two of the transplanted leukaemias showed greatly diminished capacity for absorption of alloantibody compared with normal spleen cells. Transplantation to H-2 different recipients, in which the leukaemic cells were invariably rejected, generated a strong humoral antibody response, which was demonstrable against normal lymphoid cells. Failure to demonstrate significant antibody binding by indirect immunofluroescence tests with immune sera, or by absorption, is presented as evidency that H-2 antigen expression is substantially modified on BNU induced leukaemia cells. These findings have implications for the detection of tumour neoantigens on chemically induced leukaemias.

Animals↗

Inhibition of mitogen mediated lymphocyte blastogenesis by adenosine.

The effect of adenosine on the proliferative response of human peripheral circulating lymphocytes to stimulation by concanavalin A, phytohemagglutinin and pokeweed mitogen was evaluated. Increasing concentrations of adenosine substantially inhibited mitogen mediated lymphocyte blastogenesis. Erythro-9(2-hydroxyl-3-nonyl) adenine. HCl enhanced the inhibitory effect of adenosine. Inosine, the deamination product of adenosine, had an inhibitory effect which was less than that of adenosine. Inhibition by adenosine may be relevant to the normal regulation of immune function and may account in part for the pathophysiological relationship between severe combined immunodeficiency disease and adenosine deaminase deficiency.

Adenine↗

PHA stimulation of separated human lymphocyte populations.

Lymphocyte preparations from peripheral blood and tonsils were separated into populations enriched with T or B cells by formation of rosettes with SRBC and separation of the rosette-forming and non-rosette-forming populations. T cell-enriched populations were also prepared by nylon column filtration. Using these methods preparations were obtained which comprised 80--95% T or B lymphocytes as determined by E-rosette formation and surface immunoglobulin (Ig) staining. PHA responsiveness, measured by [3H]thymidine incorporation, varied between relatively wide limits and was critically dependent on the degree of separation obtained. Relatively pure B-cell populations (less than 12% T cells) from blood and tonsils gave low PHA responses while preparations from blood still containing 24--38% T cells gave responses equal to or even greater than those of unseparated controls (60--78% T cells). T cell-enriched populations (80--86% T cells) responded to an equal or greater degree than controls but more efficient separation (greater than 90% T cells) resulted in markedly reduced stimulation. There was thus no simple correlation between the degree of phytomitogen-induced transformation and the number of T cells present. It is concluded that the low response of relatively pure T-cell populations may be due to depletion of B cells or non-lymphoid cells (or both) during the separation procedures. These observations have implications for the use of PHA stimulation as a measure of T-cell activity in mixed populations such as those of human peripheral blood leucocytes.

B-Lymphocytes↗

Leucocytotoxicity in malignant and non-malignant colonic diseases.

The survival of cells from five different cultures of allogeneic malignant colonic carcinoma, two from normal adult colonic epithelium and eight from foetal colonic epithelium in the presence of leucocytes from patients with neoplastic and inflammatory disorders of the colon has been compared. Cytotoxicity assessed by the reduction of the number of adherent target cells in microplate wells compared with those surviving in wells treated with tissue culture medium alone was observed with leucocytes from donors in all categories examined including those from individuals without any known abnormality. Patients with ulcerative colitis were the only group to reveal consistent reactivity against cultures derived from all three sources, an observation which may reflect sensitization to organ-related antigens in this disease. In contrast, leucocytes from patients with bowel neoplasia showed reactivity for cells derived from colon carcinoma tissue, which was comparable to that of healthy donors. Evidence for tumour-specific cytotoxicity was therefore lacking in this study. It is suggested that the detection of tumour-associated antigens on cultured cells may be limited by a number of factors of which the wide variation in reactivity among controls and unspecified nature of the target cells are likely to be of greatest importance.

Antigens, Neoplasm↗

Studies on the mechanisms of chemical leukaemogenesis.

Following a single injection of MNU into "intact" mice, a high incidence of leukaemia (90%) is obtained, with a 50% induction time of 200 days. Immunological studies indicate that the θ antigen is expressed on the leukaemic cells. Thymectomized MNU treated mice had a 50% induction time of 500 days, and the incidence was somewhat lower. Leukaemias failed to develop in MNU treated T lymphocyte deficient animals and in lethally irradiated, or thymectomized lethally irradiated mice reconstituted with MNU treated bone marrow. It is suggested that the T lymphocytes rather than the haemopoietic stem cells or pre-T cells are the "target cells" in MNU leukaemogenesis.

Animals↗

Antigens of tumours induced by naturally occurring murine sarcoma virus (MSV-FBJ). I. Detection of group and type specific antigens by complement fixation.

Antigens associated with cells transformed in vivo by FBJ virus, a wild type murine sarcoma virus (MSV) complex originating from a spontaneously arising osteosarcoma in a CF1 mouse, have been partially characterized by complement fixation (CF). Using rat antisera against antigens specified by Gross leukaemia virus (GLV) the group specific (gs) antigen of C-type RNA murine tumour viruses was demonstrated in FBJ tumours as well as in GLV rat leukaemias, AKR lymphomata and sarcomata induced by MSV-H (Harvey), an MSV isolate of Friend-Moloney-Rauscher (FMR) subgroup specificity. Using mouse antisera against antigens present in FBJ cells the Gross (G) or wild type specificity of FBJ tumours was demonstrated by cross reactivity with antigens expressed on normal AKR lymphoid tissues and leukaemias. These antigens were absent from MSV-H induced sarcomata and in reciprocal tests mouse antisera to MSV-H failed to react with antigens present in FBJ tumour cells. No distinction between cellular and virion antigens expressed by FBJ cells was possible by CF although evidence for a cellular antigen with G specificity was obtained in tests using aged C57B1 antiserum containing a naturally occurring G antibody lacking significant virus neutralizing capacity. However, the likelihood that mouse FBJ antisera contain antibodies to type specific viral envelope antigens (VEA) as well as cellular antigen is discussed.

AKR murine leukemia virus↗

Antigens of tumours induced by naturally occurring murine sarcoma virus (MSV-FBJ). II. Detection of cell-surface antigens by indirect membrane immunofluorescence.

Cell surface antigens expressed by cells transformed in vivo by FBJ virus, a wild type murine sarcoma virus (MSV) complex derived from a spontaneously arising sarcoma in a CF1 mouse, have been studied by indirect membrane immunofluorescence (MIF). Using mouse antisera raised by immunization of syngeneic CBA mice with transplanted FBJ sarcomata an antigen common to all FBJ tumours was detected which was also present on Gross (G) antigen positive tissues, viz. leukaemic and preleukaemic AKR lymphoid cells, but absent from the tissues of mice of G negative strains. Failure to demonstrate antigenic cross-reactivity in reciprocal MIF tests using FBJ immune sera and antisera to MSV-H (Harvey), an MSV isolate of Friend-Moloney-Rauscher (FMR) sub-group specificity, established the virus type-specificity of antigens expressed by sarcoma cells transformed by the respective MSV.The presence of a cellular antigen with G specificity on FBJ sarcoma cells was confirmed in tests with aged exbreeding C57B1 antisera containing naturally occurring G antibody lacking significant virus neutralizing activity. However, evidence for a "sarcoma-non-leukaemia" antigen on cells transformed by MSV-FBJ was not obtained since absorption studies failed to reveal any specificity on FBJ sarcoma cells which was not also present on AKR leukaemic tissues.It is suggested that the major humoral component of the immune response to FBJ sarcoma cells is evoked against antigens specified by the associated non-pathogenic leukaemia virus (MLV-FBJ) and the relationship of antigens demonstrated by MIF to those detected previously by complement fixation (CF) and tumour rejection tests is discussed.

Animals↗