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Biomedical subjects

R G Lynch

Publications and source records attributed to R G Lynch.

At least 91 records · Page 5Linked to original sources

No adaptogen response of mice to ginseng and Eleutherococcus infusions.

There was no significant difference in mortality, weight gain, liquid consumed, or pathogenesis between mice ingesting four different ginseng infusions for up to 96 days, and control mice drinking distilled water. These results suggest no toxicity or tea selectivity of mice subjected to such regimens. Mice that drank concentrated Siberian ginseng wuchaseng extract with sugar showed significantly more aggressive behavior than those drinking other infusions or distilled water. However, there was no significant difference in stamina or longevity between mice drinking infusions of two preparations of Siberian ginseng, Oriental ginseng, or American ginseng, and control mice when subjected to swimming trials in cold water 38, 46 and 96 days after treatment began. Consequently, ingestion of adaptogenic glycosides did not significantly affect the survival of mice under major environmental stress.

Adaptation, Physiological↗

Enhancement of B lymphocyte secretory differentiation by a Ly 1+,2-,Qa-1+ helper T cell subset that sees both antigen and determinants on immunoglobulin.

The question of how many helper T cells are required for producing optimal antibody responses and what function each of the candidate helper cells performs are subjects of intense interest (and controversy) to the majority of immunologists. Our manuscript directly demonstrates for the first time that B cell clone growth and secretory differentiation are controlled by two distinct classes of helper T cells which can be discriminated from one another by profiles of their expressed cell surface alloantigens. There is a significant amount of inferential evidence that two types of helper T cells are required to interact with B cells and antigen in order to induce maximal antibody responses. In all reports, classical MHC-restricted, carrier-specific helper T cells (TH 1) had to interact with hapten-specific B cells via carrier-hapten bridges before the second helper cell (TH 2) could act. In contrast to the TH 1 cells, TH 2 cells have been reported neither to be MHC-restricted nor to require carrier-hapten bridges in their interaction with hapten-specific B cells. That certain isotype-, allotype-, or idiotype-expressing portions of the antigen-induced antibody response are preferentially enhanced in the presence of and depleted in the absence of the appropriate TH 2 cells has led to the suggestion that such TH 2 cells interact with B cells through receptors specific for determinants expressed on B cell surface immunoglobulin molecules. That TH 2 cells recognize autologous immunoglobulin determinants is also indirectly supported by their reported absence in appropriately immunized mice which were deficient in the relevant immunoglobulin during ontogeny [e.g. all TH 2 cells in anti-mu-treated mice; T15-specific TH 2 cells in (CBA/N X BALB/c)F1 male Xid mice which lack T15+ B cells]. It has been suggested that TH 2 cells recognize not only autologous immunoglobulin determinants but also "nominal" antigen since they have been reported to be dependent on antigen priming and reexposure to the priming antigen. However, to establish firmly that a TH 2 cell expresses receptors for both antigen and Ig determinants, one must isolate that helper cell by virtue of its receptor for one of these two moieties and show that the isolated cell has receptors for the other. We have done this, as well as showing that the Ig-recognizing, carrier-immune T cell selectively enhanced B cell secretory differentiation while having no effect on clonal expansion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Immunoregulation of murine myeloma in vitro. II. Suppression of MOPC-315 immunoglobulin secretion and synthesis by idiotype-specific suppressor T cells.

In previous studies, BALB/c mice immunized with trinitrophenyl-specific IgA protein (M315) produced by MOPC-315 developed idiotype (Id315)-specific T cells that suppressed M315 secretion in vivo. In the present in vitro studies, we show that inhibition of M315 secretion is mediated by a theta,Lyt-1-2+ cell that expresses a surface membrane receptor for Id315. The suppressor signal is a diffusable product that acts directly on M315-secreting myeloma cells. Inhibition of M315 secretion is T cell dose-dependent, Id315-specific, reversible, and occurs without any effect on MOPC-315 growth, viability, or surface membrane expression of M315. Inhibition of M315 secretion results from a selective inhibition of M315 synthesis in the myeloma cell. These studies provide new insight into the mechanisms of direct B cell regulation by idiotype-specific T cells.

Animals↗

Cytochemistry of brain amyloid in adult dementia.

A cytochemical study of 14 cases of adult dementia revealed the presence of gamma globulin in the amyloid of three cases of congophilic angiopathy by means of immunofluorescence microscopy. In these cases, the additional identification of human albumin is regarded to indicate a non-specific macromolecular leak in the blood-brain barrier. Both reactions are inhibited by prior absorption with the appropriate serum protein. Twelve of the 14 cases had congophilic amyloid deposits which were not affected by permanganate pre-treatment, so that immunoglobulin content remains a possibility, despite the negative immune reaction. Alcianophilia was studied at a varying pH and electrolyte concentration, but these findings do not appear to have nosologic significance. The three positive cases are characterized by a rapid terminal decline. The heterogeneity of amyloid and the significance of immunoamyloid in the pathogenesis of adult dementia is discussed.

Aged↗

Expansion of Fc receptor-bearing T lymphocytes in patients with immunoglobulin G and immunoglobulin A myeloma.

Lymphocytes obtained from the blood of normal individuals and six patients with newly diagnosed multiple myeloma were separated into T and non-T cell populations by rosette-formation with sheep erythrocytes, and were then assayed for the presence of surface membrane Fc receptors. When compared with normal individuals, four patients with IgG myeloma had a three- to fourfold increase in T cells with IgG receptors (T gamma cells) and two patients with IgA myeloma had a two- to threefold increase in T cells with IgA receptors (T alpha cells). Patients with IgG or IgA myeloma had normal numbers of non-T lymphocytes with surface receptors for IgG and IgA, respectively. The finding that human myeloma is accompanied by elevated numbers of T cells with Fc receptors for the heavy chain class of the myeloma protein: (1) may account for the apparent "monoclonal" lymphocyte population in patients with myeloma; (b) extends to humans similar observations made in mice with secretory plasmacytomas; and (c) is of interest because T cells with Fc receptors are immunoregulatory lymphocytes.

Cell Count↗

T cells with Fc receptors for IgA: induction of T alpha cells in vivo and in vitro by purified IgA.

Previous studies demonstrated that BALB/c mice with the IgA-secreting plasmacytomas MOPC-315 (alpha lambda 2), MOPC-167 (alpha kappa), McPC-603 (alpha kappa) and TEPC-15 (alpha kappa) developed large numbers of T cells with surface membrane receptors for IgA (T alpha cells). The lack of T alpha cell expansion in mice with variant plasmacytomas that were nonsecretors or low secretors of IgA implied that elevated serum IgA contributed to the increase in T alpha cells. The present studies show that normal BALB/c mice that were given daily injections of 30 mg of IgA (M315 protein) develop a marked increase in the number of T alpha cells. These studies also show that the T alpha cells induced by injection of IgA are Lyt1-2+ T cells. In addition, the data presented demonstrate that nylon wool nonadherent T cells, treated with purified polymeric IgA (M315 protein) in vitro, develop a marked increase in the number of T alpha cells. The in vitro induction of T alpha cells by IgA requires DNA and protein synthesis. These findings indicate that the T alpha cell expansion observed in mice with IgA myeloma is related to the high serum level of IgA and not to the myeloma tumor per se. In addition, these observations have a more general relevance to the issue of B cell regulation because they demonstrate that secreted immunoglobulin can directly induce expansion of immunoregulatory T cells.

Animals↗

Lymphocyte surface membrane immunoglobulin in myeloma. II. T cells with IgA-Fc receptors are markedly increased in mice with IgA plasmacytomas.

BALB/c mice with established subcutaneous IgA plasmacytomas (MOPC-315, MOPC-167, McPC-603, or TEPC-15) develop large numbers of circulating theta-bearing lymphocytes that have surface membrane receptors for IgA. The extraordinary expansion of T alpha cells in mice with IgA plasmacytomas accounts for the large number of lymphocytes with surface membrane myeloma protein that are found in these mice. The IgA myeloma protein that was originally bound to the T cell receptor in vivo was competitively displaced in vitro by other purified IgA myeloma proteins but not by their F(ab)' fragments. After overnight incubation in vitro, or brief exposure to pronase, IgA was released from the T cell surface, rendering available a surface membrane receptor for IgA. In vitro binding of purified IgA to the T alpha cell receptor was not inhibited by purified IgG1 or IgM myeloma proteins. T alpha cells were not increased in mice with three variant plasmacytomas that did not secrete large amounts of IgA. These observations: i) establish the generality of T alpha cell expansion in mice with IgA plasmacytomas, ii) establish an association between elevated serum IgA levels and T alpha cell expansion, and iii) identify a source of large numbers of T alpha cells that can be specifically purified for structural and functional studies.

Animals↗

Immunoregulation of localized and disseminated murine myeloma: antigen-specific regulation of MOPC-315 stem cell proliferation and secretory cell differentiation.

Tumor development, MOPC-315 stem cells, and M315-secretory cells were quantitated in carrier-primed BALB/c mice that had been challenged subcutaneously or i.v. with mixtures of TNP-carrier and TNP-binding MOPC-315 cells. We observed that tumor incidence, myeloma stem cells, and secretory myeloma cells were: i) suppressed in mice in whom carrier-specific suppressor T cells had previously been induced and ii) initially ehnahced in mice with carrier-specific helper T cells. The early enhancement in mice with carrier-specific helper T cells was followed by progressively declining myeloma stem cell frequencies and regression of established tumors. These studies demonstrate that T cell-derived immunoregulators of host origin can be focused onto localized and disseminated malignant B cells and specifically regulate the expansion and differentiation of the neoplastic clone.

Animals↗