Biomedical subjects

B J Gormus

Publications and source records attributed to B J Gormus.

At least 37 records · Page 2Linked to original sources

PubMed1990

Intraocular pressure changes and postural changes of intraocular pressure in experimentally induced Hansen's disease of rhesus, mangabey, and African green monkeys.

In our long term evaluation of patients with Hansen's disease we have frequently found reduction of their intraocular pressure. Furthermore, we noted changes in their intraocular pressure on change of posture. To determine if these changes have any significance we measured the intraocular pressures of 24 experimentally infected and 39 control monkeys in both sitting and reclining positions. We found significant reduction of intraocular pressure in 66.7% compared with controls in the sitting position, and a significant increase in intraocular pressure in 79% when checked first in the sitting then in the reclining position. We offer a possible pathophysiological explanation as to why the changes occur.

Animals↗

PubMed1990

Pathology of dual Mycobacterium leprae and simian immunodeficiency virus infection in rhesus monkeys.

Three rhesus monkeys were experimentally inoculated with sooty-mangabey-derived Mycobacterium leprae and were inadvertently infected with the simian immunodeficiency virus (SIV) as well. They died of an immunodeficiency syndrome, and at autopsy all had lesions caused by M. leprae. One monkey was inoculated twice with M. leprae, initially with an inoculum from a sooty mangabey that was not infected with SIV and, subsequently, with an inoculum from a mangabey that was SIV infected. The monkey did not develop clinical lesions and became strongly lepromin skin test (LST) positive after the first inoculation, but became infected with both agents and LST negative following the second inoculation. These observations suggest that SIV-infected rhesus monkeys have an increased susceptibility to M. leprae infection and, by analogy, imply that HIV-infected human beings may have an increased susceptibility as well.

Animals↗

PubMed1990

Antibodies to lipoarabinomannan antigen in sooty mangabey monkeys experimentally inoculated with Mycobacterium leprae.

IgG and IgM antibody levels to mycobacterial lipoarabinomannan (LAM) antigen were determined by ELISA in eight sooty mangabey monkeys (Cercocebus atys) prior to and at intervals after experimental inoculation with Mycobacterium leprae. High levels of anti-LAM IgG were present before inoculation and increased thereafter in the five mangabeys that developed lepromatous (LL) forms of leprosy; lower levels of anti-LAM IgG were observed in two mangabeys that developed indeterminate leprosy and tuberculoid/neuritic leprosy, respectively, and in a mangabey that was leprosy resistant. IgM anti-LAM levels were near zero before M. leprae inoculation in all eight animals, rose significantly in only three LL-leprosy-susceptible animals after inoculation, and returned to near zero in all animals within 3 years. Anti-LAM antibody levels appear to be potentially valuable as an indicator of leprosy susceptibility, and when measured longitudinally together with antibody levels to M. leprae-specific phenolic glycolipid-I antigen, as a means to detect preclinical M. leprae infections in high-risk individuals.

Animals↗

PubMed1989

Interactions between simian immunodeficiency virus and Mycobacterium leprae in experimentally inoculated rhesus monkeys.

Thirty-four rhesus monkeys were inoculated with Mycobacterium leprae inoculum isolated from sooty mangabey monkeys with leprosy. Later it was learned that one of the M. leprae-donor mangabeys was asymptomatically infected with simian immunodeficiency virus (SIV). Thus, five of the rhesus monkey were coinoculated with M. leprae and SIV. Three of the five became SIV-positive and developed signs of leprosy and an AIDS-like illness. Two animals remained healthy. The coinoculated leprosy-positive rhesus monkeys developed leprosy despite serologic response patterns to M. leprae antigens that usually indicate leprosy resistance. Three (60%) of the five SIV-positive rhesus monkeys developed leprosy compared with 21% of the animals who received SIV-free M. leprae inocula. Diminished lepromin skin test responses and decreasing T-helper cell percentages were observed in SIV-coinoculated rhesus monkeys with leprosy. These observations suggest that SIV increases the susceptibility of rhesus monkeys to leprosy, possibly related to loss of T-helper cell function.

Animals↗

PubMed1988

Serologic responses to Mycobacterium leprae-specific phenolic glycolipid-I antigen in sooty mangabey monkeys with experimental leprosy.

Four pairs of sooty mangabey monkeys (Cercocebus atys) were inoculated with serial, 10-fold dilutions of Mycobacterium leprae. The highest-dose pair received 4.8 X 10(10) M. leprae. Serum samples were obtained and clinical signs of leprosy were recorded at intervals of 35 months. Longitudinal serum samples were assayed by an ELISA method for the presence of IgG and IgM antibodies to the M. Leprae-specific phenolic glycolipid-I (PGL-I) antigen. In general, the onset of disease symptoms paralleled the number of M. leprae inoculated, but the ultimate course of disease depended upon individual animal susceptibility. Both IgG and IgM anti-PGL-I isotypes were observed in variable levels and patterns, related to the disease stage, among the eight mangabeys. The data suggest that high IgG and low IgM anti-PGL-I levels correlated with less severe disease; whereas initial high IgM titers and/or rising or sustained high IgM titers, especially together with low IgG anti-PGL-I titers, preceded or corresponded to periods of progressive leprosy. The results show that IgG and IgM anti-PGL-I antibodies can be present in significant titers among mangabeys early after infection with M. leprae. It appears likely that the relative levels of these anti-PGL-I isotypes may be correlated with the susceptibility of individual animals to the development of lepromatous leprosy.

Animals↗

PubMed1988

Histopathological changes in the eyes of mangabey monkeys with lepromatous leprosy.

Leprosy is the third leading cause of preventable blindness; however, little is known about the spread of infection to the eye. We have studied the eyes of three sooty managabey monkeys. Two were experimentally infected with Mycobacterium leprae; the third was not infected. In one of the infected animals there was histopathological evidence of lepromatous leprosy as evidenced by a chronic inflammatory infiltrate at the limbus, and detection of acid-fast bacilli in the corneal stroma, blood vessel walls, and corneal nerves. The latter were damaged as a result of the bacillary invasion. Electron microscopy revealed involvement and distortion of keratocytes with M. leprae and invasion of the corneal stroma by macrophages containing bacilli. Both infected animals showed focal collections of lymphocytes in the superficial stroma of the conjunctiva and in the ciliary body. This is the first report of the ocular manifestations of leprosy in any primate, including man, in which the duration of infection is known.

Animals↗

PubMed1988

A second sooty mangabey monkey with naturally acquired leprosy: first reported possible monkey-to-monkey transmission.

The existence of naturally acquired leprosy in a second sooty mangabey monkey has been documented. The disease has the clinical and histopathological characteristics of subpolar lepromatous leprosy (LLs), and microbiological studies thus far confirm the etiologic agent as Mycobacterium leprae. This mangabey had been housed in direct contact with the first mangabey in which naturally acquired leprosy was diagnosed in 1979. Clinical symptoms appeared in the second mangabey in 1986, almost 7 years after the appearance of skin lesions in the first monkey. It is likely that the second mangabey contracted leprosy from the first mangabey or that both animals contracted the disease by contact with an unknown common third source. This is the only known possible natural transmission of leprosy from monkey to monkey, and suggests that a potential zoonosis exists in wild monkeys that may serve as a reservoir for the disease in areas where human leprosy is endemic.

Animals↗

PubMed1987

Lepromin-induced lymphoproliferative response of experimental leprosy monkeys: regulatory role of monocyte and lymphocyte subsets.

We investigated the immunological status of seven normal, control Mangabey monkeys and 23 Mangabey monkeys experimentally inoculated with Mangabey-origin Mycobacterium leprae. Clinically, these monkeys were divided into three broad groups: a recently inoculated group, a resistant group, and a susceptible group. The resistant group included 11 monkeys, seven of which showed no clinical sign of disease to date and four of which had shown local disease that partially regressed spontaneously. The susceptible group included eight monkeys, five of which have disseminated disease and three with local but stable disease. When peripheral blood mononuclear cells of these monkeys were cultured with Dharmendra-type human lepromin, one of seven normal monkeys, four of four of the recently inoculated group, seven of 10 resistant monkeys, and three of eight susceptible monkeys showed significant responses. In this experimental monkey model, we studied possible regulatory mechanisms by using OKT4- and OKT8-enriched lymphocytes, and Fc receptor-positive (FcR+) and FcR- monocyte (M phi) subsets. The OKT4+ subset was the main lepromin-responsive cell type. High percentages of OKT8+ cells showed a good negative correlation with the lymphoproliferative responses of T-enriched cells supplemented with unfractionated M phi. But the depletion of OKT8+ cells could not increase the response of nonresponding monkeys' lymphocytes. The resistant group and susceptible group did not differ in their percentages of OKT8+ cells. Because OKT8+ cells negatively regulate the response of lymphocytes and OKT4+ cells are the main responding cells, OKT8+ cells are phenotypically and functionally suppressor cells and OKT4+ cells are the helper/inducer cell population in this system. The FcR- M phi population mainly includes antigen-presenting activity, but high percentages of FcR- M phi showed a significant negative correlation with lymphoproliferative responses in the resistant group. A weak but significant lymphocyte response to Dharmendra lepromin was obtained by depleting FcR+ M phi from cultures of some susceptible monkeys, whereas lymphocytes of other susceptible monkeys remained unresponsive to lepromin. By these criteria, we could find an array of immunological defects in monkeys with experimental leprosy. The data suggest that some immunological defects may exist in the OKT4+ lymphocytes or FcR- M phi of leprosy monkeys.

Animals↗

PubMed1987

Experimental leprosy in African green monkeys (Cercopithecus aethiops): a model for polyneuritic leprosy.

Three African green monkeys (Cercopithecus aethiops) were inoculated intravenously and intracutaneously with Mycobacterium leprae derived from a naturally infected mangabey monkey. All developed cutaneous lesions at inoculation sites. One developed disseminated cutaneous lesions, while the cutaneous lesions in the other two regressed and eventually disappeared. The animals were examined at necropsy five years after inoculation. All three had active leprosy infection in peripheral nerves with extensive inflammation and fibrosis. The disease histologically resembled borderline-lepromatous leprosy. These findings add a new dimension to animal models of leprosy.

Animals↗

PubMed1987

Regulatory role of FcR+ and FcR- monocyte subsets in Mycobacterium leprae-induced lymphoproliferative response in vitro.

We investigated nine rhesus monkeys (Macaca mulatta) inoculated with Mycobacterium leprae and three normal human contacts. Peripheral blood monocytes were separated into Fc receptor positive (FcR+) and Fc receptor negative (FcR-) fractions, and their regulatory role in the lymphoproliferative response in vitro to M. leprae was studied. FcR- monocytes had strong antigen presentation activity and produced no suppressor effect while FcR+ monocytes had weak antigen presentation activity and produced a non-specific suppressor factor spontaneously. With this assay system we determined that M. leprae-inoculated rhesus monkeys could be divided into three groups: good responders, very weak responders, and non-responders.

Animals↗

PubMed1987

Experimental leprosy in a rhesus monkey: necropsy findings.

A 6-month-old male rhesus monkey (Macaca mulatta) was inoculated intravenously and intracutaneously with Mycobacterium leprae obtained from a naturally infected mangabey monkey. The animal developed generalized lepromatous leprosy, and was killed for pathological examination 56 months after inoculation. Lesions were observed in the skin, nasal mucosa, peripheral nerves, and peripheral lymph nodes, with relative sparing of viscera. The monkey was carefully evaluated for the retrovirus STLV-III infection and was found negative. The rhesus monkey thus provides another animal model for the study of leprosy.

Animals↗

PubMed1986

Epstein-Barr virus-related herpesvirus from a rhesus monkey (Macaca mulatta) with malignant lymphoma.

A herpesvirus (RhEBV) was isolated from a lymphoblastoid cell line (LCL) that became established from a malignant lymphoma in a rhesus monkey. The predominant cell marker in the LCL was that of B lymphocytes. RhEBV-induced viral capsid (VCA) and nuclear antigens (NA) in the LCL were serologically related to similar antigens known to be induced by human Epstein-Barr virus (EBV). RhEBV was of nonhuman primate origin and was clearly differentiated from EBV in the anti-complement immunofluorescence reaction using human and non-human primate sera with antibodies to the NA induced by the respective viruses. While human sera reacted with NA induced by both EBV and RhEBV, monkey sera failed to recognize the NA induced by EBV. RhEBV-induced NA was present in nearly all the cells of a suspension prepared from the tumor tissue mass, but not in the monolayer fibroblasts derived from the tumor tissue or in the blood and lymph-node lymphocytes of clinically healthy animals. RhEBV induced in vitro transformation and establishment of LCLs from peripheral blood lymphocytes of normal rhesus and cynomolgus monkeys but not from those of 6 other non-human primate species tested. The LCLs, with predominant B-lymphocyte markers, established after treatment with RhEBV, all had evidence of the virus infection since nearly all cells in the culture expressed the virus-induced NA.

Animals↗

PubMed1986

Transmissible lymphoma and simian acquired immunodeficiency syndrome in rhesus monkeys.

Four rhesus monkeys (Macaca mulatta) were inoculated with a homogenate of a cutaneous lepromatous leprosy lesion from a mangabey monkey (Cercocebus atys). One died of B-cell lymphoma, and another died of an immunodeficiency syndrome. Cell suspensions prepared from the tumor and spleen of the monkey with lymphoma induced lymphoma or an immunodeficiency syndrome when inoculated into additional young rhesus monkeys. The immunodeficiency syndrome was similar to simian acquired immunodeficiency syndrome and consisted of opportunistic infections, lymphoid hyperplasia or atrophy, wasting, and syncytial cell formation. Mitogen responses and percentages of T4- and T8-positive lymphocytes were normal until the animals were moribund. Lymphoblastoid cell lines became established in vitro from tumor cell suspensions. These cells were infected with a herpesvirus related to Epstein-Barr virus. In addition, a retrovirus morphologically similar to human T-cell lymphotrophic virus type III (HTLV-III) and simian T-lymphotrophic virus type III (STLV-III) was isolated from one of the lymphoblastoid cell lines (LCL). Type D retroviruses could not be demonstrated in the monkeys in the transmission study; however, a retrovirus similar to that in the LCL was isolated from 4 animals by coculture of peripheral blood lymphocytes with the human cell line H9. These results suggest that this retrovirus, STLV-III/Delta, may be associated with the immunodeficiency syndrome in these macaques and may be of mangabey origin.

Acquired Immunodeficiency Syndrome↗

PubMed1986

In situ characterization of T lymphocyte subpopulations in leprosy in the mangabey monkey.

Leprosy in the mangabey monkey is an experimental model which is similar both clinically and histologically to human lepromatous leprosy. The immunopathology of these diseases was compared using monoclonal antibodies against T lymphocyte subpopulations in frozen tissue sections with an immunoperoxidase technique. In both mangabey and human lepromatous granulomas OKT4 (or Leu 3a) and Leu 2a cells were scattered among macrophages with greater numbers of Leu 2a as compared with OKT4 (or Leu 3a) cells. The results suggest that from an immunopathological standpoint experimental leprosy in mangabeys will provide a suitable model for the investigation of the pathogenesis of human lepromatous leprosy and for the evaluation of new antileprosy vaccines.

Animals↗

PubMed1986

The lepromin test in rhesus monkeys.

The lepromin test was studied in rhesus monkeys. Six control monkeys which had not been inoculated with Mycobacterium leprae, six monkeys with experimentally induced leprosy, and nine monkeys which had been inoculated with M. leprae but had not developed leprosy were evaluated with 1X, 10X, and 15X lepromin A, with 1X and 10X lepromin M (mangabey monkey derived), with 1X and 25X purified inactivated M. leprae, and with an armadillo mock lepromin. We found that the lepromin test is useful in rhesus monkeys, but that a higher concentration of antigen than is used in humans is required to induce a response in monkeys. Control monkeys appear to be lepromin negative. Animals which have been inoculated and which develop lepromatous leprosy are also negative. Monkeys which are experimentally inoculated with M. leprae and do not develop leprosy become lepromin positive. Monkeys with indeterminate leprosy have reactions intermediate between lepromatous and resistant animals. No monkeys reacted to armadillo tissue. Our results indicate that 10X lepromin A is a useful preparation for the lepromin testing of rhesus monkeys.

Animals↗

PubMed1985

Comparison of peripheral blood lymphocyte C3 receptor capping properties in patients with chronic lymphocytic leukemia and lymphoma.

Bacteria-antibody complexes were used to study capping of receptors for the activated third component of complement on peripheral blood lymphocytes. The impairment of C3d receptor capping improves in patients with chronic lymphocytic leukemia responding to therapy, but this does not necessarily correspond to the fall in peripheral lymphocytosis. Following lymphapheresis, increased capping appears to be due to selective removal of noncapping cells, but the mechanisms of improvement remain unexplained following other therapeutic measures. Lymphoma capping at 37 degrees C was normal in untreated patients but impaired after treatment, suggesting that this is related to the therapy itself. A high proportion of lymphocytes had receptors in the capped configuration in the basal state before incubation. In non-Hodgkin's lymphoma this was unrelated to treatment status, but it occurred only in untreated patients with Hodgkin's lymphoma with no further increment in capping after incubation. These receptors may exist in the aggregated state without the addition of exogenous ligand.

Complement C3↗

PubMed1985

Experimental leprosy in three species of monkeys.

Eleven mangabey monkeys inoculated with Mycobacterium leprae developed lepromatous-type leprosy. Nine of the mangabeys were inoculated with M. leprae isolated from a mangabey with naturally acquired lepromatous leprosy. Immune function was depressed in some of these animals after dissemination of the disease. Two mangabeys developed lepromatous leprosy after inoculation with human M. leprae passaged in an armadillo. Three rhesus and three African green monkeys inoculated with mangabey-derived M. leprae also developed lepromatous leprosy. Mangabeys may be the first reported nonhuman primate model for the study of leprosy. Rhesus and African green monkeys may also prove to be reproducibly susceptible to the disease.

Animals↗

PubMed1985

Depression of lymphocyte responses to mitogens in mangabeys with disseminated experimental leprosy.

Mononuclear cells from mangabey monkeys with disseminated experimental leprosy had increasingly severe depression of blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen as the disease progressed. Blastogenic responses were not depressed in cells from mangabeys with more localized disease. Blastogenic responses of cells from normal mangabeys appeared to vary with a circannual rhythm. The demonstration of significant negative correlations between the blastogenic responses to mitogens and the percentages of OKT8+ cells suggested that the mangabey OKT8+ subset may contain cells with suppressor function. The depressed responses to mitogens by cells from monkeys with disseminated experimental leprosy were associated with relatively high percentages of OKT8+ cells. Polyclonal immunoglobulin plaque-forming cell responses to pokeweed mitogen were depressed in cells from experimentally infected mangabeys. The results indicated that defects in immune regulation may occur in experimental leprosy in mangabeys, similar in some respects to the defects that have been reported in human leprosy.

Animals↗