PubMed Health⌕ Search

Biomedical subjects

L N Martin

Publications and source records attributed to L N Martin.

At least 73 records · Page 4Linked to original sources
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

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↗
PubMed1985

Experimental leprosy in the mangabey (Cercocebus atys): necropsy findings.

A mangabey monkey (Cercocebus atys) was inoculated intravenously and intracutaneously with acid-fast bacilli (AFB) from a mangabey with spontaneously acquired leprosy. It developed generalized lepromatous leprosy and died 46 months after inoculation. Necropsy revealed severe lepromatous infiltrates in the skin, nasal mucosa, peripheral nerves, and testicles. Internal organs were only minimally involved. The lesions seen at necropsy were very similar to those seen in untreated cases of human lepromatous leprosy. These findings further substantiate the mangabey monkey as a suitable animal model for the study of lepromatous leprosy.

Animals↗
PubMed1984

Electron microscopic study of leprosy in a mangabey monkey (natural infection).

Ultrastructural features of the leproma of a) a naturally infected mangabey monkey, and lepromas and liver of b) a passage mangabey monkey, c) a rhesus monkey, d) an African green monkey, and e) a nine-banded armadillo inoculated with leprosy bacilli isolated from the leproma of a naturally infected mangabey monkey were studied by the freeze-etching technique. The size, shape, and ultrastructural features of leprosy bacilli in the phagolysosomes of macrophages in all of these samples were essentially the same as those in humans, nude mice, and armadillos inoculated with human Mycobacterium leprae. Distinct accumulations of small spherical droplets were observed around leprosy bacilli inside lepra cells of all the samples but were scarce in the specimen from the green monkey. The bacilli in all samples were long and slender, and had band structures on the smooth cell wall surfaces. The bacilli were indistinguishable from M. leprae.

Animals↗
PubMed1983

Functional analysis of monkey lymphocyte subsets defined by OKT4 and OKT8 Monoclonal Antibodies.

The percentages of rhesus monkey blood lymphocytes (PBL) reactive with OKT4 and OKT8 antibodies and the OKT4/OKT8 ratio showed significant correlations with the log of the immunoglobulin plaque-forming cell (PFC) response after stimulation with pokeweed mitogen (PWM). These correlations suggested that monkey OKT4+ cells function as "helper" cells and OKT8+ cells function as "suppressor" cells for the PFC response. This was confirmed by separation and study of enriched T- and B-cell subpopulations. OKT8-depleted (OKT4+) and OKT4-depleted (OKT8+) cells were obtained by treatment of purified T cells with antibody and complement. OKT4+ cells augmented the PWM-induced B-cell differentiation into PFC but OKT8+ cells did not. OKT8+ cells suppressed the PFC response by mixtures of B cells and OKT4+ cells. OKT8 antibodies also detected a suppressive cell subset in African green monkeys since the percentage of OKT8+ cells showed a negative correlation with the log PFC response. OKT4 antibodies failed to bind to African green monkey PBL.

Animals↗
PubMed1982

Separation of guinea pig IgG subclasses by affinity chromatography on protein A-sepharose.

Guinea pig serum was chromatographed on a column of protein A-Sepharose equilibrated in citrate-phosphate buffer at pH 7.3. The bulk of serum proteins eluted in the starting buffer. Two peaks of protein A-bound serum proteins were eluted by a decreasing pH gradient, a smaller peak centered at pH 4.7 and a larger peak centered at pH 4.3. IgG contained in the peak eluted at pH 4.7 had fast gamma immunoelectrophoretic mobility and IgG in the peak eluted at pH 4.3 had slow gamma mobility. Antiserum to guinea pig IgG, when absorbed with the pH 4.7 peak, reacted only with the pH 4.3 peak. Antiserum to guinea pig IgG1, when absorbed with the pH 4.3 peak, reacted only with the pH 4.7 peak. The IgG in the pH 4.7 peak had the immunoelectrophoretic and antigenic characteristics of IgG1 and the IgG in the pH 4.3 peak had the characteristics of IgG2. The two subclasses were efficiently separated by pH-dependent affinity chromatography on protein A-Sepharose. The IgG1 in the pH 4.7 peak was contaminated with 10.8% IgG2, and the IgG2 in the pH 4.3 peak was contaminated with 2.7% IgG1.

Animals↗
PubMed1982

Chromatographic fractionation of rhesus monkey (Macaca mulatta) IgG subclasses using deae cellulose and protein A-sepharose.

Rhesus monkey serum was applied to a protein A-Sepharose column at pH 7.3. IgG was not detectable in the unbound effluent. Bound protein was eluted with a pH gradient of citrate-phosphate buffer. Two major elution peaks reproducibly resulted at pH 4.85-4.9 and pH 4.35-4.43, respectively, with only slight variability among individuals. Since the immunoelectrophoretic mobility of IgG in the peak at pH 4.85-4.9 was slower than that of the peak at pH 4.35-4.43, serum was first fractionated by ion exchange chromatography into 2 fractions: the first did not bind to DEAE cellulose in 0.01 M phosphate buffer pH 7.8, the second did bind and was eluted by an NaCl gradient. Each DEAE fraction was then further fractionated on protein A-Sepharose. IgG in the first DEAE fraction bound to protein A at pH 7.3 and eluted in a single peak at pH 4.72-5.0. IgG in the second DEAE fraction also bound to protein A, but eluted in 2 peaks at pH 4.65-5.1, and 4.25-4.6, respectively. All 3 IgG fractions eluted in the same position from an A5m column, had immunodiffusion reactions of identity with anti-human gamma chain and were composed of similar heavy and light chains judged by SDS polyacrylamide gel electrophoresis. However, IgG eluting from protein A at the low pH (4.25-4.6) had a reaction of partial identity with other IgG fractions when tested by immunodiffusion against rabbit anti-rhesus gamma chain, suggestive of an antigenically different subclass. Analysis of rabbit antisera prepared against the 3 IgG fractions confirmed the occurrence of at least 3 antigenically distinct rhesus monkey IgG subclasses. These 3 subclasses have been provisionally designated IgG I, IgG II and IgG III.

Animals↗
PubMed1982

Heterogeneity of human lymphocyte Fc receptors: studies using heat-aggregated and antigen-complexed IgG from human, rabbit, guinea pig, horse and goat.

We have studied the ability of human peripheral blood lymphocytes (HuPBL)4 to interact with IgG from several animal species. Three functions or activities that are reported to depend on an interaction between complexed IgG and HuPBL receptors (R) for the Fc piece of IgG (Fc gamma R) were compared: (1) antibody-dependent cell-mediated cytotoxicity (ADCC); (2) binding of heat-aggregated IgG (aggG); and (3) rosette formation with IgG-sensitized erythrocytes [RBC-A(gamma)]. IgG (and IgM) antibodies to chicken erythrocytes (CRBC) were purified from the sera of the following species after injection with CRBC stroma: (1) horse (Ho); (2) goat (Go); (3) rabbit (Ra); and (4) guinea pig (Gp). Good IgG-agglutinating antibody titers were obtained from each injected species. Using 51Cr-labeled CRBC targets and HuPBL effector cells, only Ra anti-CRBC IgG gave good ADCC at high dilutions. Ho and Go anti-CRBC (IgG) failed to give ADCC, and Gp anti-CRBC (IgG) gave approx. 30% of the level of kill as Ra. Ra Fab2 fragments of IgG antibody failed to produce ADCC. Treatment of HuPBL with Ra anti-lymphocyte serum (ALS) almost totally ablated ADCC, whereas HoALS failed to alter ADCC. Pretreatment of HuPBL with aggG showed that Ra or Hu aggG gave essentially equal inhibition of ADCC, Gp gave approx. 30% of the degree of inhibition as Hu and Ra, and Ho or Go aggG had essentially no effect of ADCC. These results confirmed the following order of ability of IgG to interact with HuPBL ADCC killer (K) cells: (Hu greater than or equal to)Ra greater than Gp much greater than Ho, Go. The data suggest that Gp IgG interacts with only a subpopulation (approximately 30%) of HuPBL K cells. The binding of aggG to total HuPBL failed to strictly correlate with the ADCC results or with the results of rosette formation between total HuPBL and CRBC-A(gamma). The observations suggest that there is a heterogeneity of Fc gamma R between K and non-K cell subpopulations of HuPBL both in terms of the type of complexed IgG they are able to bind, and in terms of species of origin of the IgG. The data also support contentions that Fc gamma R that bind RBC-A (gamma) complexes differ from those that bind aggG.

Animals↗
PubMed1982

Genetically determined antigens of squirrel monkey (Saimiri sciureus) IgG.

Alloantigens of squirrel monkey (Saimiri sciureus) IgG were studied using alloantisera prepared by cross-immunizations among four subspecies. The results demonstrated the occurrence of IgG antigenic polymorphism. Three distinct Fd fragment allotypes were detected. Greater alloantigenic complexity occurred among Colombian and Peruvian squirrel monkeys, which occupy the more central regions of the geographic range; Bolivian and Guyanan monkeys, which occupy the extremes of the range, expressed less alloantigenic complexity.

Animals↗
PubMed1981

Immunology of pyelonephritis in the primate model: live versus heat-killed bacteria.

We produced nonobstructive pyelonephritis in the rhesus monkey (Macaca mulatta) by means of a retrograde inoculation of Escherichia coli to the point of pyelotubular backflow. To evaluate the immune response separate from the effects of infection, we introduced heat-killed bacteria in the same fashion. The disease from live bacteria is self-limited and associated with both a local and generalized immune response. The most marked cellular response is in the regional lymph nodes and is more specific to the bacterial antigen than is generalized stimulation of the immune system. Dead bacteria, while eliciting the formation of serum antibody to the O antigen, appear to ablate the cellular response seen with live bacteria. Loss of renal tubules with attended scarring and loss of renal function does occur from live bacteria. This does not appear to be due to the antigen alone (unless a heat labile antigen is responsible), because heat-killed bacteria do not cause renal scarring. Thus, renal damage seems dependent on an active infection and not on the immune response.

Animals↗
PubMed1981

Immunology of pyelonephritis in the primate model. II. Effect on immunosuppression.

Nonobstructive pyelonephritis was produced in the rhesus monkey (Macaca mulatta) by means of retrograde inoculation of Escherichia coli to the point of pyelotubular backflow. The effects of treatment with cyclophosphamide or azathioprine were determined. Commensal renal viruses were not activated by the immunosuppression, and thus did not complicate our results. Both cyclophosphamide and azathioprine prolonged the bacteriuria and produced more severe pathology. Cyclophosphamide decreased the leukocytic response and partically suppressed the antibody response. The increased amount of acute pyelonecytic response and partially suppressed the antibody response. The increased amount of acute pyelonephritic lesions after treatment with this drug suggest that the antibody and inflammatory responses may be important protective mechanisms, particularly regarding prevention of abscesses. In contrast, azathioprine did not decrease the leukocytosis nor the antibody responses, but resulted in decreased in vitro responsiveness of lymphocytes to mitogens. The increased severity of chronic pyelonephritic lesions after azathioprine treatment suggests that the cellular immune response also may be an important protective mechanism during late stages of the disease. The results thus indicate that the immune response is protective and is not directly responsible for the chronic scarring of pyelonephritis.

Animals↗
PubMed1979

In vivo effects of antiserum to IgD on surface immunoglobulins, serum immunoglobulins and lymphocyte blastogenesis in rhesus monkeys.

The effects of injecting monkeys with goat antiserum to IgD, the IgG fraction of that antiserum or normal goat serum (NGS) were compared. The subcutaneous injection of 4 ml/kg of the whole antiserum resulted in decreased percentages of lymphocytes with surface IgD or IgM lasting from day 1 through day 7 post-injection followed by substantial recovery on day 10. Lymphocytes from these animals were stimulated as indicated by the increased incorporation of 3H-TdR by cells placed in culture on days 7-21 post-injection. The increased blastogenesis occurred in rosette-depleted (B cell) populations and did not occur in rosette-enriched (T cell) preparations. Hypergammaglobulinaemia and increased concentration of serum IgG were first detected on day 10 postinjection, maximal on day 14 and were in decline by day 18. Injection of 4 ml/kg NGS did not alter the percentages of lymphocytes with surface immunoglobulins, result in hypergammaglobulinaemia, or stimulate the degree of blastogenesis observed after anti-IgD. Injection of the IgG fraction of the antiserum resulted in decreased lymphocytes with surface immunoglobulins but did not stimulate hypergammaglobulinaemia or increase blastogenesis. Injection of one monkey with the IgG fraction of anti-IgD combined with NGS resulted in increased serum IgG and increased blastogenesis. Both antibody to IgD and multiple antigenic challenge appear to be required for these responses.

Animals↗