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T Moran

Publications and source records attributed to T Moran.

At least 109 records · Page 6Linked to original sources
PubMed1989

Origin of the autoreactive anti-type II collagen response. II. Specificities, antibody isotypes and usage of V gene families of anti-type II collagen B cells.

Autoantibodies play an important role in the pathogenesis of type II collagen-induced arthritis in mice. We have earlier reported a high frequency of cells producing anti-CII autoantibodies and a low frequency of cells producing multispecific antibodies, in regional lymph nodes 9 to 11 days after primary immunization with CII. It is shown here that anti-CII antibodies produced during primary immune response are IgG-antibodies mainly of IgG2a, IgG1 and IgG2b subclasses while IgM antibodies dominate primary responses elicited by OVA and denatured CII as analyzed with a large panel of hybridomas. Anti-CII antibodies generated during the primary response recognize at least five different epitopes on the CII molecule. The specificities of these antibodies for various epitopes result from combinational association of products encoded by genes derived from various VH and VK families and/or by the occurrence of somatic mutations. It is suggested that the primary anti-CII autoantibody response involves activation of memory B cells and is in this aspect different from the origin of "natural" autoantibodies.

Animals↗
PubMed1989

Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors.

To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas. Esophagus bound both tracers, whereas pancreas bound only 125I-[Tyr4]bombesin. In each tissue binding was saturable, dependent on pH, on time, and on temperature, reversible, and specific. Autoradiography demonstrated binding of both tracers only to the muscularis mucosae of the esophagus and binding of 125I-[Tyr4]bombesin diffusely over pancreatic acini. In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae. In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B. Similar relative potencies were found for stimulation of enzyme secretion from dispersed pancreatic acini. Computer analysis in both tissues demonstrated only a single binding site. The present study demonstrates that rat esophagus muscle possesses specific receptors for bombesin-related peptides. Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin. In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B.

Animals↗
PubMed1988

Sexual abuse in young children: its clinical presentation and characteristic patterns.

A retrospective record survey was performed using all child clients aged less than 7 years seen at a community mental health center during the period 1982-1984. The total number of 202 children fell into three groups: sexually abused (n = 37), physically abused (n = 35), and nonabused clinical children (n = 130). These groups were compared in order to learn more about sexual abuse in young children. Family background of both abused groups were similar to each other but differed from the nonabused group in having more factors related to family stress than the nonabused group. Clinical presentations of all the children overlapped a great deal symptomatically; however, the sexually abused children had a statistically significant higher frequency of inappropriate sexual behavior than the other two groups. Several characteristics of the abusive patterns suffered by the two abuse groups differed at or near statistical significance: sexually abused children were more often victimized in single acts by nonrelated child perpetrators than were physically abused children.

Adaptation, Psychological↗
PubMed1987

The human and murine influenza-specific B cell repertoires share a common idiotope.

We have dissected the human influenza-specific B cell repertoire by performing Epstein-Barr virus (EBV) limiting dilution analysis of lymphocytes obtained from donors before and after immunization with a commercially available influenza vaccine. In addition to an analysis of precursor frequency and light chain diversity, we studied sera and culture supernatants containing human anti-influenza antibodies with a panel of murine monoclonal antibodies specific for idiotopes identified on murine anti-PR8 and anti-X-31 antibodies. An idiotypic specificity present on the X-31-specific murine monoclonal PY206 has previously been shown to be shared by murine antibodies specific for PR8, X-31, and other influenza viruses. We observed little correlation among the following parameters: anti-viral titer, serum idiotope content, precursor frequency and immune status. More interestingly, there was a striking predominance of human influenza-specific antibodies that utilized lambda light chains. In addition, 12 of 26 human anti-influenza monoclonals strongly inhibited the binding of one of the murine anti-idiotopes to the labeled murine antibody, PY206. This is the same idiotope that is shared among murine antiinfluenza antibodies and all six individuals studied contained clones reactive with this anti-idiotope. Seven of these 12 idiotope-positive human antibodies gave partial cross-reactivity in a second anti-idiotypic system. These observations imply that a significant level of homology exists between the binding sites of human and murine influenza-specific antibodies and suggest that idiotypic manipulation of the human immune response to influenza virus may have important therapeutic implications.

Adult↗
PubMed1987

Effect of syngeneic anti-idiotypic antibody on influenza virus neuraminidase antibody response.

Influenza viruses possess two major surface glycoproteins - hemagglutinin (HA) and neuraminidase (NA). Py203, a monoclonal antibody (Ab) specific for the neuraminidase of the PR8 (H1N1) influenza virus, was used to prepare syngeneic monoclonal anti-idiotypic (anti-Id) Abs. From a BALB/c mouse immunized with Py203 (anti-N1), we obtained RM1, a monoclonal anti-Id Ab. The Py203-Id was detected in a significant fraction of immunoglobulins (Igs) in the primary and secondary responses elicited by PR8 (H1N1) and X31 (H3N2) viruses. In animals injected with minute amounts of RM1 and subsequently boosted with an identical dose of RM1, no detectable anti-NA activity was noted, but a significant increase in Py203-Id-bearing Igs was observed. In the sera of animals injected with minute amounts of RM1 and subsequently boosted with PR8 (H1N1) or X31 (H3N2) viruses, an increase in anti-NA activity and in the level of Py203-Id was noted. Animals injected with large amounts of RM1 and boosted with PR8 and X31 showed a marked suppression of the Py203-Id but no alteration in the anti-NA response. The anti-Id recognizes an idiotope (the Py203 idiotope) shared by antibodies specific for the N1 and N2 neuraminidase variants.

Animals↗
PubMed1987

High frequency of autoantibodies bearing cross-reactive idiotopes among hybridomas using VH7183 genes prepared from normal and autoimmune murine strains.

Hybridomas obtained by in vitro stimulation with lipopolysaccharides (LPS) of BALB/c, MRL/lpr, and NZB splenocytes were selected for expression of VH7183 by hybridization using slot blotting. Northern blot analysis showed that the majority of hybrids produce a full length message complementary to the VH7183 probe. The frequency of VH7183 hybridomas was significantly higher in NZB mice as compared with BALB/c mice. Using multiple binding assays, 60% of the total antibodies encoded by VH7183 were specific for self-epitopes. Finally, the vast majority express cross-reactive idiotypes borne by autoantibodies of various specificities.

Animals↗
PubMed1985

A rapid and efficient immunization protocol for production of monoclonal antibodies reactive with autoantigens.

A simple, time-saving and efficient immunization method suitable for the production of mouse monoclonal antibody secreting hybridomas is described. Draining lymph nodes isolated 9 days after a primary immunization were used as the source of antibody producing cells. No systemic spread of antibody producing cells or specific antibodies could be detected. The present protocol was employed to generate a panel of collagen type II reactive monoclonal antibodies. Most of the monoclonals so generated were found to be of the IgG class.

Animals↗
PubMed1985

In vivo treatment of rats with monoclonal anti-T-cell antibodies. Immunohistochemical and functional analysis in normal rats and in experimental allergic neuritis.

The effects of intraperitoneal injection of monoclonal anti-rat T-lymphocyte antibodies were evaluated immunohistochemically and functionally in normal rats and in rats with experimental allergic neuritis. In the normal animals a single injection of OX8 antibodies, reactive with suppressor/cytotoxic T cells, completely eliminated OX8-reactive cells from peripheral lymphoid organs and from circulation, whereas the 'pan' T-cell-reactive W3/13 antibodies and the helper T-cell-reactive W3/25 antibodies only caused a partial elimination of their respective target cells. Injection of the W3/13 and W3/25 antibodies but not of OX8 antibodies led to a diminished responsiveness to allogeneic stimulation in vitro for spleen cells obtained from the treated rats, whereas the OX8 injection caused a complete elimination of the in vitro cytotoxic response to allogeneic cells in the mixed lymphocyte reaction-activated spleen cell population. When Lewis rats were injected with peripheral nerve myelin and Freund's adjuvant for the induction of EAN, treatment with W3/13 antibodies completely prevented the onset of disease, whereas treatment with the OX8 antibodies exaggerated the disease symptoms.

Animals↗
PubMed1984

Shared idiotopes among monoclonal antibodies specific for A/PR/8/34 (H1N1) and X-31(H3N2) influenza viruses.

A monoclonal antibody specific for the hemagglutinin (HA) of influenza A X-31 (H3N2) virus (X-31) was obtained during a fusion of spleen cells from a BALB/c mouse immunized with influenza A/PR/8/34 (H1N1) virus (PR8). This monoclonal antibody (Py206) shares crossreactive idiotopes expressed on several monoclonal antibodies specific for PR8 HA and X-31 HA as well as an individual idiotope shared with one monoclonal antibody specific for X-31 HA. The presence of shared idiotypy among antibodies of such diverse binding specificities may result from regulation by idiotype-specific T cells. In addition, the results suggest that, in contrast to the diversity of paratypes expressed, relatively few germ-line variable region genes may be used in the antibody response to influenza A virus antigens.

Animals↗
PubMed1979

Liver cells.

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Animals↗