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Biomedical subjects

J Leibowitz

Publications and source records attributed to J Leibowitz.

36 records · Page 2Linked to original sources
PubMed1991

Monoclonal antibody analysis of a unique macrophage procoagulant activity induced by murine hepatitis virus strain 3 infection.

A panel of 24 IgG2ak monoclonal antibodies was produced against murine hepatitis virus strain 3 (MHV-3)-induced procoagulant activity (PCA) from murine macrophages. The antibodies were specific and did not react in an enzyme-linked immunosorbent assay with purified MHV-3; lipopolysaccharide-induced PCA; crude mouse, human, or rabbit tissue factor, or unstimulated murine macrophages. Sixteen of 24 monoclonal antibodies inhibited functional PCA expression in a one-stage clotting assay. More detailed studies on one monoclonal antibody, 3D4.3, demonstrated that it inhibited prothrombin cleavage at concentrations of greater than or equal to 0.1 microgram/ml, and by Western blot this antibody reacted with proteins of a molecular mass of 140, 74, and 70 kDa on nonreduced gels and 74 and 70 kDa on reduced gels distinct from tissue factor known to have a molecular mass of 47 kDa. Induction of PCA was dependent on both host RNA and protein synthesis. Immunofluorescence studies showed specific binding to MHV-3-stimulated PCA-positive macrophage membranes. Both numbers of positive macrophages and intensity of staining correlated with multiplicity of infection. These monoclonal antibodies will be useful in isolation and characterization of the unique viral-induced PCA as well as in determining its biologic role in MHV infection and other diseases in which the prothrombinase has been implicated.

Animals↗
PubMed1991

Cellular and metabolic requirements for induction of macrophage procoagulant activity by murine hepatitis virus strain 3 in vitro.

The cellular basis for the variation in induction of monocyte procoagulant activity (PCA) by murine hepatitis virus strain 3 (MHV-3) was examined using a set of recombinant inbred strains of mice derived from the resistant (A/J) and susceptible C57B1/6J (B) progenitors. Induction of PCA by MHV-3 required live virus and host protein and RNA synthesis. Absolute restriction for induction of PCA was observed at the level of the macrophage. Peritoneal macrophages from resistant parental A/J and RI strains (AXB5) could not be induced to express PCA when stimulated by MHV-3 alone or in the presence of lymphocytes from susceptible and H-2 compatible RI mice (AXB3) although they did respond to endotoxin (LPS). In contrast, macrophages from both susceptible (AXB3) and semisusceptible (AXB1) RI strains of mice expressed a similar increase in PCA after stimulation with MHV-3 in the absence of lymphocytes. The levels of PCA expressed by macrophages in the presence of Thy-1.2+ lymphocytes correlated with susceptibility to disease. Thy-1.2+ lymphocytes from susceptible RI AXB3 mice could induce levels of PCA in macrophages from semisusceptible RI AXB1 mice equivalent to that seen in cultures of macrophages and lymphocytes from susceptible mice. Further subfractionation of Thy-1.2+ cells demonstrated that L3T4+ cells instructed macrophages to produce PCA. Thy-1.2+ cells from MHV-3 immunized resistant AXB5 mice, but not from non-immunized mice, were able to suppress induction of PCA. This suppressor cell activity could be detected 4 days after immunization, reaching maximal activity at day 7 with significant suppression even at 28 days. The PCA was shown to have direct prothrombin cleaving activity (prothrombinase) by ELISA and immunofluorescence staining using the mAb 3D4.3. These results demonstrate that induction of a unique PCA (prothrombinase) is restricted at the level of the macrophage and define a regulatory role for T lymphocytes in its induction.

Animals↗
PubMed1990

A community mental health team to serve revolving door patients. The Doddington Edward Wilson (DEW) Mental Health Team 1984-1988.

This is a descriptive paper. It outlines the running of a specialist service aimed to meet the needs of long-term mentally ill patients who live in community settings in an inner urban district of London. The service functions in an outreach model from an office base on a large public housing estate. No patient care premises are available on site, consequently all patient activities are carried out in public rooms and other non-mental-health venues. The staffing of the Team and details of its organisational practice are described: demographic and clinical statistics for two years' working are presented. Advantages and disadvantages of the outreach model are discussed. The need for such a specialist service in contrast to the traditional generic service model is argued. The paper is intended as a basic description to underlie current evaluative studies. No evaluation data are presented here.

Catchment Area, Health↗
PubMed1987

Theiler's murine encephalomyelitis: a model of demyelination and persistence of virus.

Theiler's murine encephalomyelitis virus (TMEV) causes immune-mediated demyelination in susceptible mice which is similar to human demyelinating disorders such as multiple sclerosis. In addition, the picornavirus persists within the central nervous system throughout the course of the chronic demyelinating disease. This article reviews the neuropathology, virology, immunology, and molecular biology of the model system. We analyze the possible mechanisms by which this virus induces demyelination and persists in the nervous system. Finally, we provide a hypothesis that the specificity of primary white matter destruction in the TMEV model depends on immune-sensitized cells which interact with viral antigen plus major histocompatibility complex (MHC) antigens on the surfaces of oligodendrocytes or myelin sheaths.

Acute Disease↗
PubMed1986

Susceptibility to Theiler's virus-induced demyelination. Mapping of the gene within the H-2D region.

Demyelination induced by Theiler's virus was examined in mouse strains with congeneic recombinant haplotypes. Light and electron microscopy of spinal cord sections from mice with s, q, v, p, and f H-2D alleles showed perivascular inflammation and primary demyelination. The presence of susceptible haplotypes in the K or I region did not correlate with pathologic abnormalities. The Qa, Tla, PgK, and UpG genes did not appear to be critical in determining susceptibility to disease. However, mutation in the H-2D genes altered the susceptibility to virus-induced demyelination. B10.D2dm1 mice, which have deletions in the 3' end of Dd and the 5' end of Ld, showed prominent demyelination and clinical deficits. In contrast, BALB/c-dm2, which have a deletion of the entire L gene, showed no pathologic changes. Central nervous system virus titers correlated with susceptibility to demyelination; both resistant and susceptible strains had a strong humoral immune response to the virus. The findings in the congeneic recombinant mice and in mice mutant in the H-2D region strongly suggest that at least one of the genes critical for determining virus-induced demyelination maps to the 3' end of the H-2D gene.

Animals↗
PubMed1986

Partial suppression of Theiler's virus-induced demyelination in vivo by administration of monoclonal antibodies to immune-response gene products (Ia antigens).

In vivo administration of monoclonal antibody reactive with major histocompatibility complex-encoded Ia molecules (I-As) partially suppressed inflammation and demyelination in the spinal cord of SJL/J (H-2s) mice persistently infected with Theiler's murine encephalomyelitis virus. Demyelination was decreased if antibody was given at the time of virus inoculation or after inflammation had been established in the spinal cord. The decrease in demyelination was independent of isolation of infectious virus from the CNS or of serum titers of immunoglobulin to purified viral antigen. Thus, Theiler's virus-induced demyelination is mediated, in part, by immune cells that carry Ia class II molecules.

Agglutination Tests↗
PubMed1986

Leporine acquired immune deficiency disease.

We have identified a recombinant leporipoxvirus that produces disseminated fibromas and a severe combined immune deficiency disease of sudden onset. The virus is recombinant between the SFV and the MV. MV was identified as a trace contaminant in stocks of SFV (Patuxent strain). Rabbits inoculated with the original uncloned stock of SFV prepared in vitro develop local tumors that subsequently regress. However, tumor extracts prepared from these animals, when injected into a second group of rabbits, produced MV syndrome. Rabbits with MV syndrome develop severe, usually lethal, Pasteurella or Bordetella infections and have disseminated fibroxanthosarcomas more similar to those produced by myxoma virus. The virus that induces this syndrome has been isolated by two cycles of plaque purification. This virus is indistinguishable from SFV using cross-neutralization and electron microscopy. Analyses of restriction enzyme digests of MV and plaque-purified SFV show them to be quite dissimilar and indicate that MV is recombinant between SFV and myxoma virus. This recombinational event resulted in approximately 5.5 kb of myxoma virus DNA within each of the inverted terminal repeats being replaced by a similar amount of DNA derived from the corresponding region of the SFV genome. Thus, MV contains approximately 149 kb of myxoma sequences and 11 kb of SFV sequences. Immunofluorescent studies of spleen and lymph nodes from MV-infected rabbits demonstrate that viral antigens are present predominantly in the sinusoidal lining cells in lymph nodes and in phagocytes in the splenic cords. This contrasts with the distribution of antigen observed in myxoma virus-infected rabbits where myxoma-specific antigens are present in large amounts in hyperplastic epithelium overlying tumors, particularly in the nasal mucosa and in spleen and lymph node cells. MV-infected rabbits essentially lose their lymphocyte proliferative response to T and B cell mitogens and are unable to initiate an antibody response to SRBC, as determined by a modified Jerne plaque assay. In vitro MV severely depresses the mitogen responses of normal B and T lymphocytes after two days of culture. Lymphoid cells and lysates of lymphoid cells from MV-infected rabbits will suppress mitogen- and antigen-induced responses in vitro. MV can grow in lymphocytes, but replication of MV is less efficient in lymphocytes than in RK-13 cells. Thus, MV produces a disseminated viral infection, systemic myxofibromas, and a severe combined immune deficiency in rabbits. The molecular and immunologic basis for these effects is now under study.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Recombinants of Mahoney and Sabin strain poliovirus type 1: analysis of in vitro phenotypic markers and evidence that resistance to guanidine maps in the nonstructural proteins.

A neutralizing monoclonal antibody-resistant variant of the Sabin vaccine strain of poliovirus type 1 and a guanidine-resistant variant of the virulent parent Mahoney strain were derived. The two variants were used, in a coinfection, to generate recombinant virus containing both resistance markers. Recombinants appeared on the order of 1.0 PFU for every 10(4) total PFU. Two independently derived recombinant viruses were isolated. Each isolate contained the P1 (structural protein) gene region of the Sabin strain virus and the P3 (nonstructural replicase protein) gene region of the Mahoney strain virus. The recombinant virus phenotypes were compared with certain characteristic in vitro phenotypes of both parents. It was found that the slow growth in cell culture, temperature sensitivity, and virion surface charge characteristics of the Sabin virus mapped entirely to the structural protein gene region whereas the phenotype of the actinomycin D sensitivity of the Sabin virus mapped to the gene region specifying the nonstructural replication proteins. Sequence analysis of the recombinant RNA revealed that the crossover occurred 3' of nucleotide 3919. This result showed that the resistance of poliovirus mutants to growth in 2 mM guanidine hydrochloride maps in the 3'-terminal region of the viral genome specifying the nonstructural proteins.

Antigens, Viral↗
PubMed1981

Comparison of biological and behavioral activities of alpha- and gamma-melanocyte stimulating hormones.

The biological and behavioral activities of gamma-MSH (gamma-MSH) and alpha-MSH (alpha-MSH) were compared using three different tests: darkening of the skin of Anolis, grooming behavior of rats, and performance of a visual discrimination task by rats. When incubated with the Anolis skin, both peptides cause skin darkening. However, alpha-MSH is much more potent than gamma-MSH. The alpha-MSH effect is not antagonized by coincubation with gamma-MSH. When given intraventricularly to rats, alpha-MSH induces a marked grooming behavior. This effect was not noted upon administration of gamma-MSH. Injection of gamma-MSH with the alpha-MSH did not produce a grooming response significantly different from alpha-MSH alone. In the visual discrimination task, the two peptides had opposite effects on the rate at which rats learned the initial discrimination and a subsequent reversal. The peptides were injected intraperitoneally prior to behavioral testing. Following alpha-MSH, rats learned the discrimination and subsequent reversal faster than the control rats. Following gamma-MSH, rats learned the initial discrimination at approximately the same rate as controls, and learned the reversal much slower. These results are discussed in terms of the similarity and differences in the mechanisms of action of alpha-MSH and gamma-MSH.

Animals↗
PubMed1978

Citrullinemia.

The pathological findings in two cases of neonatal citrullinemia are reported. One patient survived for eight months with treatment using alpha keto-analogues of essential amino acids. The untreated patient expired at eight days of age. Necropsy findings in these two cases are compared. The major histopathological changes were present in the brain and liver. They were much less prominent in the treated patient. Changes in a section of rib from the untreated patient were consistent with growth arrest and suggest than damage may occur in utero in neonatal citrullinemia.

Amino Acid Metabolism, Inborn Errors↗