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Biomedical subjects

T R Moench

Publications and source records attributed to T R Moench.

36 records · Page 2Linked to original sources
PubMed1989

Epidemiologic observations on feline immunodeficiency virus and Toxoplasma gondii coinfection in cats in Baltimore, Md.

Five hundred eighty-five serum samples obtained between 1980 and 1981 from a diverse population of cats were tested by use of an indirect immunoperoxidase assay for antibodies to feline immunodeficiency virus (FIV). Results of 14 of the samples were positive (prevalence, 2.4%). The FIV-positive cats were markedly older than the overall population and frequently were coinfected (57%) with Toxoplasma gondii. The Toxoplasma titers of the FIV-positive cats were significantly (P less than 0.03) higher than those of the FIV-negative cats. The FIV-positive cats were not coinfected with FeLV. Our findings suggested that FIV-associated immunosuppression may be a factor in active Toxoplasma infection in adult cats.

Age Factors↗
PubMed1989

Characterization of the local and systemic B cell response of normal and athymic nude mice with Sindbis virus encephalitis.

During Sindbis virus (SV) encephalitis in mice B cells are an important component of the mononuclear inflammatory response and recovery depends primarily on the development of antiviral antibody. To begin to characterize various parameters of the local B cell response during SV encephalitis we have defined B cell isotype expression in brain sections, splenocytes and peripheral blood mononuclear cells (PBMC) in normal and athymic nude mice using an immunoperoxidase technique. Early (days 3-5) in SV encephalitis brain perivascular B cells are IgM or IgM/IgD-bearing lymphocytes, later (days 10-14) most B cells express one of the IgG isotypes or IgA. The pattern of isotype expression seen in the brain during the course of the encephalitis is reflected in the spleen and blood. The data suggest that progressive isotype switching results in an increasingly higher percentage of certain isotypes, especially IgG2a. Isotype switching of most B cells may occur outside of the brain, or may arise in situ from the IgM/IgD-bearing B cells found in the brain throughout the course of encephalitis. In athymic nude mice numbers of B cells in brain were markedly decreased and the cells present were primarily IgM-bearing, although IgG isotypes and IgA did appear late (day 14). The data suggest that T cells are required for recruitment of B cells into the inflammatory response as well as for normal isotype switching and peripheral B cell maturation during SV encephalitis.

Animals↗
PubMed1988

Acute measles in patients with and without neurological involvement: distribution of measles virus antigen and RNA.

Using peroxidase immunohistochemistry and in situ hybridization to localize viral antigen and RNA, we studied autopsy tissues from 20 cases of acute fatal human measles (including seven patients with acute encephalomyelitis) and peripheral blood mononuclear cells from 16 patients with acute, nonfatal measles. In immunologically normal patients, virus was detected in five of nine who died five days or less after the onset of rash but in none of 11 who died later. Virus was localized to epithelial cells of lung, gut, bile duct, bladder, and skin and to lymphoid organs. Neither viral antigen nor RNA was detected in brain sections from 14 patients, including seven with acute encephalomyelitis and four with virus identified in other tissues, a finding supporting an indirect pathogenesis of post-measles encephalomyelitis. These data show that measles virus replicates in cells previously not recognized to be involved (capillary endothelium of lymph node and thymus, Hassall's corpuscles, and hepatic duct epithelium) and that invasion of the brain parenchyma during acute measles is uncommon.

Acute Disease↗
PubMed1988

Basis of neurovirulence in Sindbis virus encephalomyelitis of mice.

Neuroadapted Sindbis virus (NSV) was selected by serial passage of wild-type Sindbis virus (SV) in mouse brain. After intracerebral inoculation of weanling mice, NSV causes a severe encephalomyelitis with hindlimb paralysis and high mortality; SV causes nonfatal mild disease. In order to determine the biologic basis of neurovirulence in vivo, these viral infections have been compared by using infectivity assays, light and electron microscopy, in situ hybridization, immunohistochemistry, and double-labeling for neural cell markers and viral RNA. More infectious virus is present in the central nervous system during NSV than during SV infection. After intracerebral inoculation, both viruses enter the central nervous system via the ependyma and spread to gray matter areas, including the ventral horns of the spinal cord. Their cellular targets are not different, and neuronal infection is prominent. NSV infects more neurons, and causes more severe injury than SV. In NSV infection, there is marked swelling of lumbar and thoracic neurons and their processes in the ventral horns. Relatively mild changes are detected in SV infection only by electron microscopy. Neuroadaptation likely occurs by increasing the efficiency of viral replication in neurons, rather than by a fundamental change in the cellular tropism or the topography of the infection in the central nervous system.

Animals↗
PubMed1987

In vitro studies of the role of monocytes in the immunosuppression associated with natural measles virus infections.

Measles is associated with suppression of mitogen-induced proliferative responses. The role of monocytes in depressed responses to phytohemagglutinin during measles was assessed. Depleting peripheral blood mononuclear cells of adherent cells decreased, increased, and did not change proliferative responses in essentially equal numbers of individuals. Inhibition of prostaglandin synthesis by indomethacin significantly increased proliferation (P = 0.009) but often not to normal values. Addition of supplemental interleukin 1 had little effect. Addition of supplemental natural interleukin 2 significantly increased proliferation (P = 0.002) even in patients with very low responses. These data suggest that monocyte function is abnormal in some individuals with measles, that the abnormality is variable, and that lymphocyte response to monocyte signals is probably suboptimal as well.

Biomechanical Phenomena↗
PubMed1987

In situ hybridization.

In situ hybridization is the hybridization-mediated detection of specific nucleic acid sequences within structurally intact cells or tissues. As such it uniquely provides localization of nucleic acid superimposed on observable cellular and subcellular structural detail, allowing analysis unobtainable by other hybridization techniques. The technique is highly sensitive, particularly when the target nucleic acid is contained within a small percentage of a sample of cells. Innovations have increased the versatility of in situ hybridization which is now capable of specific detection of DNA, or RNA of sense or anti-sense polarity, application to samples prepared with a variety of fixation and embedding procedures, and analysis at the macroscopic, light microscopic, or electron microscopic level. These characteristics have made in situ hybridization a powerful and important means of analysis in a diversity of scientific fields.

Animals↗
PubMed1987

Immune responses in the central nervous system.

Immune responses occurring within the central nervous system (CNS) have unique features attributable to the cellular and functional organization of the CNS and to the presence of the blood-brain barrier. Immune responses to viral infection of the CNS involve the participation of most immunologically important cells: T and B lymphocytes, monocytes, and natural killer cells. Normally, helper/inducer T lymphocytes are predominant in the cerebrospinal fluid (CSF) and in perivascular cuffs. After stimulation with antigen in tissue, these cells produce lymphokines, which stimulate mast cells to open capillary tight junctions, stimulate proliferation of lymphocytes, and attract monocytes and B lymphocytes. B lymphocytes mature into immunoglobulin-producing cells that secrete antibody locally which appears in the CSF. Cytotoxic/suppressor T lymphocytes, which damage antigen-containing cells, are predominant in immunopathologic reactions. In other situations the immune response targets normal CNS tissue rather than foreign antigens. Two general types of reactions may be seen: (1) vasculitis with destruction of vessel walls and infarction, and (2) perivascular inflammation with demyelination. The former is associated with immune complex deposition, and the cellular infiltrate includes polymorphonuclear leukocytes. The inflammation associated with perivenular demyelination is composed almost exclusively of mononuclear leukocytes. In the diseases for which pathogenetic mechanisms are understood, cells become sensitized to myelin constituents and induce local demyelinating lesions in which the damage is effected by macrophages. It is not clear whether macrophages are directed in this destructive effort by lymphokines or immunoglobulins or both.

Animals↗
PubMed1987

The pathogenesis of spinal cord involvement in the encephalomyelitis of mice caused by neuroadapted Sindbis virus infection.

Weanling mice develop an acute encephalomyelitis with high mortality after intracerebral inoculation of neuroadapted Sindbis virus. The mice develop kyphoscoliosis and hindlimb paralysis. Immunohistochemical and in situ hybridization studies have demonstrated virus in the gray matter of the brain and spinal cord. Ventral horn cells are prominently infected, providing an anatomical basis for the clinical poliomyelitis. A novel route of spread of inoculated virus within the central nervous system has been found. The virus enters the ventricular system, and then travels caudally in the central canal of the spinal cord where ependymal cells are infected. The virus subsequently spreads into the gray matter. The distribution of virus in the spinal cord is likely dependent both on variations in the susceptibility of neural cells and on this route of entry and subsequent spread.

Animals↗
PubMed1986

Peripheral blood mononuclear cells during natural measles virus infection: cell surface phenotypes and evidence for activation.

Peripheral blood mononuclear cells from 25 patients with measles and 13 patients with other diseases from Lima, Peru, were studied by immunocytochemical staining for cell surface antigens indicating the type of cell (Leu 4, Leu 3, T8, B1, M1, or esterase) and the state of cell activation (T10 and IL-2 receptor). Measles patients were studied during the first 2 weeks of disease and had no alteration in the proportion of cells which were positive for any subset marker or in the ratio of helper/inducer to cytotoxic/suppressor T cells compared to controls. Measles patients, however, had a greater number of cells expressing the activation antigens T10 and IL-2 receptor than controls. Incorporation of [3H]thymidine was also higher in measles patients when exogenous natural or recombinant IL-2 was added to unstimulated cultured cells. We conclude that the peripheral blood mononuclear leukocytes of patients with measles have normal proportions of helper/inducer and cytotoxic/suppressor T lymphocytes, B lymphocytes, and monocytes but that an increased number of these cells are in an activated state.

Adolescent↗
PubMed1985

Identification of the inflammatory cells in the central nervous system of patients with adrenoleukodystrophy.

Adrenoleukodystrophy is a disorder of long-chain fatty acid metabolism associated with adrenal cortical insufficiency and central nervous system demyelination. The central nervous system disease is unusual in that it is abrupt in onset and accompanied by a considerable infiltration of mononuclear inflammatory cells. To determine the nature of these inflammatory cells, immunocytochemical staining was carried out on the mononuclear cells in the brain and cerebrospinal fluid of patients with adrenoleukodystrophy. Monoclonal antibodies to T lymphocytes (T11), the helper/inducer (T4) and cytotoxic/suppressor (T8) subsets of T lymphocytes, B lymphocytes (B1), and monocyte/macrophages (M1 or esterase) were used. Mononuclear cells in the perivascular cuffs of autopsy material from 4 patients were, on average, 59% T cells, 34% T4 cells, 16% T8 cells, 24% B cells, and 11% monocyte/macrophages. Cerebrospinal fluid from 8 of 10 patients had increased IgG concentrations. Mononuclear cells in the cerebrospinal fluid of 6 patients with active disease were, on average, 61% T cells, 40% T4 cells, 16% T8 cells, 3% B cells, and 18% monocyte/macrophages. This distribution of cells is similar to that found in the central nervous system during a cellular immune response and suggests the possibility that one component of this disease is immunologically mediated.

Adolescent↗
PubMed1985

A double labeling technique for performing immunocytochemistry and in situ hybridization in virus infected cell cultures and tissues.

This report describes a combined immunocytochemical and in situ hybridization procedure which allows visualization of cellular or viral antigens and viral RNA in the same cell. Cultures infected with visna or measles virus were fixed in periodate-lysine-paraformaldehyde-glutaraldehyde, stained by the avidin-biotin-peroxidase technique using antibodies to viral or cellular proteins and then incubated with radiolabeled specific DNA probes (in situ hybridization). The immunoperoxidase stain was preserved through the hybridization procedure. Nonspecific 'sticking' of probes over peroxidase stained cells was prevented by incorporation of 0.1% Triton X-100 into the hybridization solution and the post-hybridization washes. The in situ hybridization signal (silver grains/cell) on peroxidase-stained cells was reduced relative to hybridization with unstained cells. The double labeling technique was also applied to sections of paraffin-embedded tissues from a sheep infected with visna virus and mice infected with the HNT strain of measles virus. Visna virus RNA was detected in immunocytochemically identified macrophages in the synovium. A greater number of these cells had viral RNA than had viral protein. In measles virus-infected brains viral RNA was detected only in cells with viral protein. This technique provides a new approach to the study of viral pathogenesis by: identifying the types of cells which are infected in the host and identifying points of blockade in the virus life cycle during persistent infections.

Animals↗
PubMed1985

Efficiency of in situ hybridization as a function of probe size and fixation technique.

In an attempt to improve fixation technique for viral RNA detection by in situ hybridization, we have quantitatively compared the hybridization signal obtained when measles virus or visna virus infected cell cultures were fixed with eight different fixatives and hybridized with 35S-labeled virus-complementary DNA probes of several size ranges. Small probes (mean length, 70 bases) gave higher signals than larger probes (mean lengths 140, 350, and 780 bases) with all fixatives. This increase in signal was minimal with acetic ethanol or formalin, but was dramatic with fixatives containing glutaraldehyde; with these fixatives the signals with small probes were 6.5- to 22-fold greater than with large probes. The highest signals were obtained with periodate-lysine-paraformaldehyde-glutaraldehyde (PLPG) fixed cells hybridized with small probes, and were 1.5- to 6.7-fold greater than those obtained with the commonly used fixative acetic ethanol. PLPG and other glutaraldehyde based fixatives also greatly improved the preservation of cellular morphology compared to acetic ethanol.

Acetates↗
PubMed1984

Immunocytochemical identification and quantitation of the mononuclear cells in the cerebrospinal fluid, meninges, and brain during acute viral meningoencephalitis.

The mononuclear cells of the central nervous system (CNS) inflammatory response were characterized in cerebrospinal fluid (CSF), meningeal exudate, and brain parenchyma of mice 3-14 d after infection with Sindbis virus. The inflammatory infiltrate in CSF peaked and resolved before that of the parenchyma or meningeal exudate. Immunoperoxidase staining with monoclonal antibodies identified CSF inflammatory cells to be almost exclusively T cells, while inflammatory cells in the brain parenchymal perivascular cuffs and the meninges were a mixture of T cells, B cells, and macrophages. The percentage of B cells and macrophages increased at the later time points. Approximately 20% of CSF and 50% of the cells present early in the perivascular cuffs were not identified, suggesting that another subset of inflammatory cells may be present. We concluded that significant differences exist in the time course and cellular composition of the inflammatory responses in different compartments of the CNS during an acute viral infection.

Acute Disease↗
PubMed1983

Selection of a fixative for identifying T cell subsets, B cells, and macrophages in paraffin-embedded mouse spleen.

Fixation techniques were investigated for their ability to preserve morphology, esterase activity and cell surface antigens in paraffin-embedded mouse lymphoid tissue. The avidin-biotin-peroxidase system was used to stain antigens Thy-1.2, Lyt-1, Lyt-2, RA32C2 and F4/80. Conventional fixatives were compared with fixatives containing periodate and lysine plus paraformaldehyde and/or glutaraldehyde. Conventional fixatives preserved esterase activity but not many cell surface antigens. Periodate-lysine fixatives allowed better preservation of membrane antigens, but esterase activity was often lost at antigen-preserving concentrations of paraformaldehyde or glutaraldehyde. However, a periodate-lysine fixative containing both paraformaldehyde and glutaraldehyde preserved esterase and showed good to excellent staining of Lyt-1, Thy-1.2, RA32C2, and F4/80. Lyt-2 could not be stained with any fixative, but was well preserved in frozen material post-fixed with periodate-lysine based fixatives. We conclude that with proper fixation immune cell surface markers can be identified in paraffin-embedded tissue.

Animals↗
PubMed1982

Septic arthritis caused by Propionibacterium acnes.

The traditional view that Propionibacterium acnes is nonpathogenic for man, except as an agent associated with acne vulgaris, has been refuted. Propionibacterium acnes has been shown to cause endocarditis, meningitis, and other serious infections. We report a case of P acnes infection causing septic arthritis and contributing to a concurrent soft-tissue infection. This case supports and extends previous observations of the clinical importance of P acnes as a pathogen. A positive culture for P acnes cannot be uncritically dismissed as a bothersome contaminant without considering the clinical circumstances.

Abscess↗