PubMed Health⌕ Search

Biomedical subjects

T R Moench

Publications and source records attributed to T R Moench.

At least 19 recordsLinked to original sources
PubMed1997

Contraceptive effect of sperm-agglutinating monoclonal antibodies in rabbits.

Immune infertility in humans correlates clinically with the presence of anti-sperm antibodies that trap (agglutinate) sperm in semen and cervical mucus. To test whether sperm-agglutinating antibodies can be effective contraceptive agents, several mouse anti-rabbit sperm (MARS) sperm-agglutinating monoclonal antibodies (mAbs) were developed that rapidly and completely agglutinate sperm: MARS-M3 (IgM), MARS-G16 (IgG3), and MARS-G17 (IgG3). Contraceptive efficacy of these mAbs was tested by mixing the mAb with 0.1 ml semen (approximately 1/5 of a whole ejaculate) immediately before artificially inseminating rabbits paracervically. This paracervical dose of semen provided a rigorous test since it delivered several thousand times more fertilizing doses than does a human ejaculate. All of the mAbs were contraceptively effective, and MARS-G16 reduced the number of fetuses per animal by 88% and 95% with doses of 150 microg and 2 mg, respectively. The contraceptive efficacy of the MARS mAbs in the rabbit suggests that human sperm-agglutinating mAbs may be effective agents for vaginal contraception in humans.

Animals↗
PubMed1996

Genes for chemokines MuMig and Crg-2 are induced in protozoan and viral infections in response to IFN-gamma with patterns of tissue expression that suggest nonredundant roles in vivo.

MuMig and Crg-2 are IFN-inducible murine chemokines whose human homologues, HuMig and IP-10, respectively, share activity in vitro as T cell chemoattractants. We analyzed the expression of the genes Mumig, crg-2, and IFN-gamma during experimental infections with Plasmodium yoelii, Toxoplasma gondii, and vaccinia virus. Mumig, crg-2, and IFN-gamma were induced in multiple organs. During the acute phase of each infection as well as after i.p. injection of rIFN-gamma, levels of Mumig mRNA in the liver were as high or higher than levels in any of the other organs. In contrast, the organs showing the highest expression of crg-2 and IFN-gamma varied among the experimental models, with induction of these latter two genes colocalizing. Differences in relative levels of expression of Mumig and crg-2 in liver and spleen were not demonstrably due to expression of the genes in different cell types within these organs. We showed that both Mumig and crg-2 are induced in the liver in hepatocytes and in the spleen in CD11b+ cells. IFN-gamma was necessary for induction of Mumig during infections with T. gondii or vaccinia virus. In contrast, induction of crg-2 was not completely dependent on IFN-gamma. These data demonstrate that despite the overlap in activities within chemokine subsets, chemokine genes show differences in their patterns of expression and in their responses to inducers that suggest nonredundant roles in vivo. Moreover, the pattern of induction of crg-2 is consistent with Crg-2 acting primarily locally, while the pattern for Mumig induction suggests that MuMig may have a systemic role during infection.

Animals↗
PubMed1996

Topically applied human recombinant monoclonal IgG1 antibody and its Fab and F(ab')2 fragments protect mice from vaginal transmission of HSV-2.

A recombinant human anti-herpes simplex virus monoclonal IgG1, antibody and the corresponding Fab and F(ab')2 fragments were tested for efficacy in preventing vaginal transmission of HSV-2 infection in a well-established mouse model for genital herpes. IgG1, Fab, and F(ab')2 were approximately equally protective; vaginal delivery of 1-5 ng provided approximately 50% protection, and vaginal delivery of 400 ng completely protected mice from genital herpes infection (P < 0.001). These results suggest that topical applications of human monoclonal antibodies may be useful in developing new methods for preventing sexually transmitted disease.

Administration, Intravaginal↗
PubMed1995

Brain endothelial cell infection in children with acute fatal measles.

Neurologic diseases are important complications of measles. The role of virus infection of the central nervous system as well as the route of virus entry has been unclear. Five autopsied cases of individuals who died with severe acute measles 3-10 d after the onset of the rash were studied for evidence of viral involvement of the central nervous system. In all cases, in situ hybridization and RT-PCR in situ hybridization techniques showed endothelial cell infection. Immunoperoxidase staining with an anti-ferritin antibody revealed a reactive microgliosis. These data suggest that endothelial cells in the brain are frequently infected during acute fatal measles. This site of infection may provide a portal of entry for virus in individuals who subsequently develop subacute sclerosing panencephalitis or measles inclusion body encephalitis and a target for immunologic reactions in post-measles encephalomyelitis.

Base Sequence↗
PubMed1993

Infection of monocytes during measles.

Immune suppression has long been recognized to be a consequence of measles and a likely contributor to the secondary complications of this infection. Since measles virus can be isolated from peripheral blood leukocytes during the early phases of infection, it has been widely assumed that measles virus suppresses the immune system by replicating in and damaging T lymphocytes. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay able to detect wild-type strains of measles virus was applied to the study of peripheral blood mononuclear cells (PBMC) during natural measles virus infection. Measles virus RNA was detected by RT-PCR in monocyte-enriched adherent cells up to 6 days after the appearance of the rash. No viral RNA was detected in the lymphocyte-enriched nonadherent cell fraction. The numbers of virus-infected PBMC detected by in situ hybridization ranged from 1 in 125 to 1 in 2500. Dual staining identified infected cells as monocytes. It is concluded that the primary leukocytes infected during measles are monocytes, not lymphocytes. This cellular tropism has implications for understanding the immune suppression associated with measles.

Adolescent↗
PubMed1993

The cat/feline immunodeficiency virus model for transmucosal transmission of AIDS: nonoxynol-9 contraceptive jelly blocks transmission by an infected cell inoculum.

OBJECTIVES: To develop an animal model to study transmucosal lentivirus transmission, and to determine whether topical application of contraceptive jelly can block transmission by an infected cell incoulum. DESIGN: Feline immunodeficiency virus (FIV), a lentivirus similar to HIV, causes an AIDS-like disease in domestic cats. HIV is transmitted primarily across mucosal surfaces, and infected cells may be important in this transmission. We tested the ability of FIV-infected cells to transmit infection across the vaginal, rectal and oral mucosa of the cat, and whether a vaginal contraceptive jelly could prevent such transmission. METHODS: An inoculum consisting of 2 million FIV-infected primary cat T cells was administered vaginally, rectally or orally to female cats that had received either no pretreatment or pretreatment with a contraceptive jelly containing the detergent nonoxynol-9 as spermicide. Transmission was detected by monitoring recipient animals for viral antibodies and by viral cultures of blood leukocytes. RESULTS: A single dose of the infected cell inoculum efficiently transmitted FIV infection when delivered into the vagina or rectum (10 out of 11 animals became infected). Pretreatment of the vagina (five animals) or rectum (four animals) with contraceptive jelly protected all animals from transmission by the highly infectious inoculum. CONCLUSIONS: The cat/FIV model provides an efficient means to study transmucosal transmission of lentivirus infections, and for assessing vaginal barrier methods that could block transmission. One such method, nonoxynol-9 contraceptive jelly, effectively prevents transmucosal transmission by an FIV-infected cell inoculum.

Animals↗
PubMed1991

Borna disease virus replicates in astrocytes, Schwann cells and ependymal cells in persistently infected rats: location of viral genomic and messenger RNAs by in situ hybridization.

Borna disease (BD) is an immune-mediated neurological disease caused by infection of the nervous system with a negative strand RNA virus, Borna disease virus (BDV). The host range for BDV is broad and extends from birds to primates. A BDV-like agent may cause disease in humans. Until recently, BDV-infected neural cells could only be identified immunocytochemically using serum from BDV-infected animals. The advent of BDV cDNA clones allowed definition of the relationship between viral nucleic acids and viral proteins in vivo. In situ hybridization with strand-specific RNA probes from a BDV cDNA clone, pAF4, identified BDV genomic RNA and BDV mRNAs in neurons, astrocytes, Schwann cells and ependymal cells in an anatomic distribution consistent with that of BDV proteins. Genomic RNA was contained primarily within the nucleus, whereas mRNAs were found in both the nuclear and cytoplasmic compartments. Viral RNAs were demonstrated in neurons expressing BDV proteins and in glial cells by combined techniques of immunocytochemistry and in situ hybridization.

Animals↗
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↗