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N Gengozian

Publications and source records attributed to N Gengozian.

At least 55 records · Page 3Linked to original sources
PubMed1978

Spontaneous colonic adenocarcinoma in marmosets.

We find that colonic adenocarcinoma, which is an extremely rare neoplasm of all animals except man and carcinogen-treated rodents, occurs spontaneously in some marmosets. The cotton-topped Saguinus oedipus oedipus is particularly prone to develop it, but we have found it also at necropsy in Callimico goeldii (Goeldi's marmoset). Numerous metastases to regional lymph nodes develop. The cancers arise de novo in the mucosa and early invade the submucosa and lymphatic apparatus and paracolonic lymph nodes. These findings and the continuing occurrence of this cancer in our colony suggests that the marmoset may be the long-sought primate model for experimental intestinal carcinogenesis.

Adenocarcinoma↗
PubMed1977

T-and B-lymphocyte chimerism in the marmoset.

Marmosets are natural blood chimeras, this condition resulting from the high frequency of fraternal twinning and the consistent development of placental vasular anastomoses between the two embryos. Identification of chimerism by sex-chromosome analysis of cultured blood lymphocytes provided a means of determining the proportion of chimerism among T and B lymphocytes. Peripheral blood lymphocytes were enriched for T or B cells by filtration through a nylon column (yields greater than 95 per cent T-cells) or inactivation of T lymphocytes by treatment with a goat anti-marmoset thymocyte antiserum in the presence of complement (yeilds greater than 95 per cent B cells). Mitogenic stimulation of these separated, enriched cell populations yielded metaphase plates which could be scored for percentage male and female cells. Tests on five different blood chimeras showed the T- and B-lymphocyte chimerism to be the same. Stimulation of blood lymphocytes with cells from another species of marmoset in a mixed lymphocyte culture test revealed the chimeric T-cell response (i.e., host and co-twin cells) to be similar to that obtained with a mitogenic lectin. The demonstration of equivalent T- and B-cell chimerism in these animals suggests derivation of these cells from a common stem cell pool and the response of both T-cell populations to an antigenic stimulus in proportions similar to their percentage chimerism suggests complete immunologic tolerance exists in this species for co-twin histocompatibility antigens.

Animals↗
PubMed1977

Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras.

The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production.

Animals↗
PubMed1977

In vitro stimulation of primate hemoglobin synthesis by L-thyroxine.

Bone marrow cells from adult and abortus primates (marmosets) were incubated in vitro to determine their responsiveness to L-thyroxine. 3H-leucine incorporation into purified globin chains was the parameter assayed to determine responsiveness. Bone marrow from spontaneously aborted animals consistently was stimulated by the presence of physiologic levels of L-thyroxine. Bone marrow cells from adult animals were unaffected by the hormone.

Animals↗
PubMed1976

Characterization of the antibody response of the marmoset to sheep red blood cells.

The immune competence of two species of marmosets, S. fusciollis and S. oedipus, was evaluated by the intravenous (i.v.) and intramuscular (i.m.) injection of sheep red blood cells (SRBC). In S. fusciollis marmosets, 1 ml of a 50% suspension yielded titres of haemolysin and agglutinating antibodies equal to or greater than 1 ml of a 10% dose of antigen. In both species, the i.v. route, while resulting in formation of 19S and 7S agglutinins, yielded only 19S haemolysins, even after multiple antigen injections. Repeated i.v. injections resulted in a progressive decrease in peak titres, in contrast to the i.m. route, where booster inoculations gave a typical anamnestic response. Jerne plaque-forming cells (PFC) in the spleens of S. oedipus marmosets showed predominately 19S plaques after a primary i.v. challenge; only 19S PFC were detected in the spleen of an animal that had been given multiple inoculations, the type of antibody produced reflecting that found in the serum. 19S but not 7S haemolysins of both species were sensitive to heating at 56 degrees C for 1/2 hr. The serum titres and splenic PFC data from the marmosets suggest these animals, particularly S. oedipus, respond poorly to SRBC when a comparison is made to similar studies in mice and rats.

Agglutinins↗
PubMed1976

T and B lymphocytes in the marmoset: a natural haemopoietic chimera.

The thymus-derived (T) lymphocyte and bone marrow-derived (B) lymphocyte populations of the marmoset were characterized using specific cell surface markers Approximately 85% of the thymocyates formed rosettes with neuraminidase-treated sheep erythrocytes (En). The percentage (approximately 69%) of peripheral blood lymphocytes (PBL) forming rosettes with En was the same as that which stained with fluorescently labelled goat anti-marmoset thymocyte serum (ATS). These two assays identified the same cell population since treatment of cells with ATS and complement resulted in a concomitant decrease in En rosette formation. Marmoset PBL also formed rosettes with human erythrocytes sensitized with antibody and complement (HEAC); since the percentage (approximately 20%) HEAC rosette was the same as that of cells stained with fluorescently labelled goat anti-marmoset IgG, these cells were considered to be B cells. A small percentage of cells (approximately 1-5%) possessed both types of receptors. The mean percentages of T and B cells present in PBL of single-born, presumably non-chimeric animals, were the same as that of iso-sexual and heterosexual chimeras.

Animals↗
PubMed1975

Suppression and recovery of the immune response and CFU potential of mice during and after chronic low-dose-rate gamma-irradiation.

Chronic exposure of mice to 60Co gamma-rays at rates of 1-6 R/hr and 6 R/hr leads to profound immunosuppression, as demonstrated with the Jerne haemolysis-in-agar technique. The immunosuppressive effect is dose-rate dependent. Thus, significant reduction of the number of splenic antibody plaque-forming cells (PFC) to sheep red blood cells is seen after exposure to 1005 R at 1-6 R/hr; at the higher exposure rate of 6 R/hr, PFC suppression is seen after a total dose on only 468 R. Although recovery of the PFC response is possible after accumulated doses of 1005, 1579, and 2138 R at 6 R/hr and 5256 R at 1-6 R/hr, normal immunological capacity had not returned 120 days after irradiation. In contrast the recovery of splenic colony-forming units (CFU), as an expression of the haematological potential of chronically irradiated mice, is found to be much more rapid than the repair of the immune system. Thus, 10 days after irradiation, at a time when little or no recovery in immune competence is apparent, the spleen of the chronically irradiatee animal has a CFU capacity about 50 times greater than has that of a normal, unirradiated mouse. The CFU's in the chronically irradiated spleens were also shown to be functional by virtue of their ability to protect lethally irradiated animals from haemopoietic death.

Animals↗
PubMed1975

Effect of antithymocyte globulin pretreatment on immunological reconstitution of lethally irradiated animals.

Clinical and experimental studies have shown that antithymocyte globulin pretreatment will reduce the severity of the graft-versus-host reaction after allogeneic bone marrow transplantation. To determine whether this was attributable to a persisting cytotoxic factor in the recipients' sera or a result of the "masking" of foreign antigens by the antihymocyte globulin, an experimental schema utilizing a syngeneic transfer of immunocompetent cells was devised. Lethally irradiated mice that had been pretreated with rabbit antimouse thymocyte globulin (RAMTG) were injected with syngeneic spleen or bone marrow cells and their immunological competence was measured by the response to a test antigen, sheep red blood cells. It was found that such pretreatment had an adverse effect on the immunological potential of the infused cells. Thus, the plaque-forming cell response to sheep red blood cell antigen in RAMTG-pretreated recipients injected with spleen cells was reduced when compared to the saline or normal rabbit globulin-treated controls. The immunological recovery of lethally irradiated animals protected with syngeneic bone marrow was also delayed, but not permanently impaired, when the recipients had been pretreated with RAMTG. These effects were evident although the spleen or bone marrow cells had been injected into the RAMTG-pretreated recipients at a time when their sera were devoid of any cytotoxic antibodies. It is speculated that two mechanisms may contribute to this alteration in immune function of the infused cells: (1) that RAMTG exists in the serum in amounts sufficient to attach to receptor sites on lymphocytes or their precursors but insufficient to kill the cells, interfering with the antigen recognition mechanism or migration and homing patterns, or (2) that the RAMTG treatment creates a temporary defect in the microenvironment of the spleen and other hemopoietic tissues, thereby affecting the transplantation and proliferation kinetics of the infused cells.

Animals↗
PubMed1975

An evaluation of the mixed lymphocyte culture reaction in marmosets.

Marmosets are unique in that all members may be considered to be natural blood chimeras because of the high frequency of fraternal twinning and placental vascular anastomoses between the fetuses. The mixed lymphocyte culture (MLC) reaction utilizing blood lymphocytes was evaluated to determine whether this in vitro test could detect histocompatibility differences among related and unrelated marmosets. It was found that the responses could be correlated with the probable immunogenetic relationships of these animals. Thus, an allogeneic MLC reaction in which the responding (R) and stimulating (S) cells were obtained from unrelated animals within one subspecies of marmosets (Saquinus fuscicollis illigeri) yielded a lower response than a semi-xenogeneic reaction involving R and S cells from two different subspecies of marmosets (S.f. illigeri (R) versus S.f. lagonotus (S). In contrast, MLC reactions between cells from chimeric marmoset co-twins were essentially negative, indicating specific immune tolerance. Under certain experimental conditions, however, it was suggested that the dual lymphocyte cell population from a chimeric marmoset could undergo "autostimulation" as measured by label incorporation studies. The necessity of further experiments was recognized before the data could be truly accepted as reflecting an in vitro manifestation of incompatibility between the two different genetic populations of blood lymphocytes from a chimera.

Animals↗
PubMed1975

Single-born marmosets without hemopoietic chimerism: naturally occurring and induced.

Marmosets have a high frequency of fraternal twinning, and placental vascular anastomoses between the twin fetuses invariably lead to hemopoietic chimerism. The occasional finding of chimerism in single-born marmosets suggested that in a twin pregnancy one fetus had undergone resorption after contributing hemopoietic stem cells to its twin. In this study non-chimeric single-born marmosets were produced by fallopian tube ligation or surgical relocation of one ovary in breeding females. Further, in an examination of hemopoietic cells from over 50 single-born young from nonoperated females, chimerism occurred less frequently than what one would expect if resorption of a co-twin had occurred after a functional anastomosis had been established.

Age Factors↗
PubMed1975

Rat-mouse radiation chimeras: characterization of an antibody-mediated graft-vs-host reaction.

A modification of the Jerne hemolysis-in-agar technique was used to demonstrate antibody-mediated graft-vs-host (GvH) hemolytic activity in lymphoid tissues of rat-mouse radiation chimeras. Initial foci of hemolytic activity were detected on the 3rd day in spleens of lethally x-irradiated mice infused with rat spleen cells (950 R-RSp chimeras). The peak of GvH foci response occurred near the end of the 1st week when 70% of 950 R-RSp chimera spleens examined contained an average of 18 to 21 foci per spleen. GvH hemolytic activity was also detected in mice reconstituted with rat bone marrow (950 R-RBM chimeras); however, only 40% of these chimeras contained splenic foci (nine foci per spleen) on day 8, the peak day of response. Mesenteric lymph nodes from 950 R-RSp chimeras, but not 950 R-RBM chimeras, also contained GvH hemolytic foci. Specificity experiments demonstrated that the GvH hemolytic reaction could be inhibited with rabbit anti-rat IgM serum and host (C3BF) antigenic cell fragments. Indirect (IgG) hemolytic activity was also observed in spleens of 950 R-RSp chimeras 6 to 10 days after treatment. At least 90% of indirect foci appeared coincident with direct foci. Rat IgM and IgG containing cells beneath hemolytic foci were observed by combining the fluorescent antibody and foci techniques. To determine whether the foci response reflects and in vivo sensitization of donor cells, spleen cell transfer experiments were done. The results indicate that spleen cells from 950 R-RSp chimeras were more effective in acelerating mortality and anemia and induced a higher incidence of Coomb's positive red cells in lethally irradiated isogeneic recipients than spleen cells from 950 R-RBM chimeras; spleen cells from either chimera were more effective in accelerating GvH indices than spleen and marrow cells from normal rats.

Animals↗
PubMed1975

Actively induced thrombocytopenia in the marmoset. A possible autoimmune model.

Inoculation of S. oedipus marmosets with white blood cells and platelets from another species of marmosets, S. fuscicollis, led to an acute and fatal thrombocytopenia. Antibody in the recipients to the immunizing platelets was found by agglutination and indirect immunofluorescence; also, serum from the afflicted animals passively induced thrombocytopenia in S. fuscicollis marmosets. Similar inoculations of S. oedipus marmosets with platelet-free white blood cell preparations from the same donors were without any clinical effect; also, immunization with autologous, allogeneic (unrelated S. oedipus) or human platelets, did not cause the disease, even though antibody to the latter species of platelets, human, was formed in the recipients. Failure to detect antibody to autologous (or allogeneic) platelets in the afflicted animals suggests induction of a disease process similar to that of post-transfusion purpura,where it has been speculated that the thrombocytopenia results from the adherence of antigen (donor) antibody complexes to host platelets, leading to their destruction by the reticuloendothelial system. The severity and consistency of inducing the disease in the marmoset by an active immunization process suggests this system may serve as an excellent animal model for autoimmune diseases falling within the syndrome of idiopathic thrombocytopenic purpura in man.

Animals↗