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Biomedical subjects

M C Watkins

Publications and source records attributed to M C Watkins.

At least 19 recordsLinked to original sources
PubMed1993

Characteristics of services and educational programs in libraries serving problem-based curricula: a group self-study.

A group of librarians from institutions with formal problem-based learning (PBL) curricula tracks began meeting informally in 1989 to explore the common elements among libraries serving PBL curricula. In 1991, a self-study was undertaken to delineate library services in these schools and also to identify the mechanisms that enable libraries to respond directly to the PBL curriculum. This paper reports results of this self-study, including findings regarding services, collection access, library access, and, particularly, areas that facilitate the PBL process, such as availability of on-demand and tailored user education, end-user literature searching, and electronic mail. Formal and informal library instruction, both optional and required, is described. The self-study also identified structured and unstructured methods of student access to PBL curriculum resources, including bibliographies, formally defined reserve collections, and student and faculty resources. The many roles of the professional librarian within the PBL curriculum are described; librarians may serve as traditional service providers, as resource persons, as faculty, or as tutors or facilitators in PBL curriculum sessions.

Curriculum↗
PubMed1986

Nonspecific inhibitor of DNA synthesis elaborated by T-acceptor cells. II. Requirements for its production and action.

The production of a nonspecific inhibitor of DNA synthesis (nsINH) appears to be one of the final events in the T-suppressor cell circuit in mice exposed to contact sensitizers. We report here that: The nsINH suppresses the proliferative response to a polyclonal T-cell mitogen, concanavalin A (Con A), regardless of the dose of Con A used. It also suppresses DNA synthesis in lymphoid cells stimulated with alloantigens. This suppression can be completely eliminated by adding exogenous interleukin 2 (IL-2). DNA synthesis in lymphoid cells exposed to nsINH before the proliferative stimulus is uninfluenced so that activation of the lymphoid cells at the same time as exposure to nsINH seems to be a requirement for its action. Since the activity of nsINH can be absorbed by activated Lyt-1+ or Lyt-2+ lymphocytes, the early activated T cell appears to be a target of the action of nsINH. The production of nsINH is abolished or severely reduced by adult thymectomy. Natural killer (NK) cells are resistant to nsINH action and no interferon (IFN)-like activity can be demonstrated in nsINH preparation using a conventional assay for IFN.

Animals↗
PubMed1984

Nonspecific inhibitor of contact sensitivity made by T-acceptor cells: triggering of T cells armed with antigen-specific T-suppressor factor (TsF) requires both occupancy of the major histocompatibility complex recognition site by soluble I-J product and cross-linking of the antigen recognition sites of the TsF.

The phenomenon of associative recognition, i.e., the recognition of antigen together with major histocompatibility complex products (MHC) was studied in a model system. T-acceptor cells armed with antigen-specific T-suppressor factor (TsF) released a nonspecific inhibitor of the transfer of contact sensitivity when exposed to antigen together with MHC. The MHC product occurred in a KCl extract of cells and behaved genetically and serologically as I-J. Cells armed with anti-picryl or anti-"oxazolone" TsF could be triggered by the corresponding "bis-picryl-L-lysine" and "bis-oxazolone-L-lysine" together with MHC. This suggested that cross-linking of antigen recognition sites on separate molecules of TsF might be required. To investigate this possibility the bifunctional "mixed" hapten "N alpha-picryl-N epsilon-oxazolone-L-lysine," which is univalent with respect to the picryl and oxazolone haptenic groups, was synthesized. This triggered cells armed with a mixture of anti-picryl and anti-oxazolone TsF but not cells armed with either TsF alone. It was concluded that both occupancy of the I-J recognition site and the cross-linking of separate molecules of TsF was required for triggering. Moreover the hapten and the KCl extract could be given sequentially and in either order. This finding suggested that the triggering of the release of nonspecific inhibitor was due to the separate recognition of I-J and antigen and not to new antigenic determinants produced by their interaction.

Animals↗
PubMed1984

Two-chain structure of T-suppressor factor: antigen-specific T-suppressor factor occurs as a single molecule and as separate antigen-binding and I-J+ parts, both of which are required for biological activity.

Antigen-specific T-suppressor factor (TsF), which acts at the expression stage of the contract sensitivity reaction, was produced by culturing the lymphoid cells of mice injected with picryl-sulphonic (trinitrobenzenesulphonic) acid and then painted with picryl chloride. Supernatant activity was found around 50-60 and 90 kDa on Sephadex gel filtration. The activity at 50-60 kDa was due to two separate (or readily separable) molecules, one antigen binding and the other bearing I-J determinants as shown by affinity chromatography on insolubilized antigen and anti-I-J. These two separate molecules were inactive alone but complemented each other and may be designated as the variable chain of TsF (TsFv) and the I-J+ chain. The use of gel filtration and sequential absorption of individual pools on anti-I-J antibody followed by antigen, together with a complementation assay, also showed a TSFv chain at 30-40 kDa and an I-J+ chain at 20-30 kDa. The higher-molecular-weight activity around 90 kDa was due to a single molecule which was both antigen binding and I-J+. This molecule dissociated on treatment with the reducing agent dithioerythritol followed by alkylation into two separate chains, one antigen binding and the other I-J+, both of which were required for activity. There was a requirement for genetic matching between the antigen-binding chain (TsFv) and the I-J+ chain for biological activity. These data support a two-chain model of TsF in which TsFv and the I-J+ chain occur as a single disulphide-bonded molecule around 90 kDa, or as two separate (or readily separable) chains of lower molecular weight which were inactive alone but complemented each other.

Animals↗
PubMed1984

Non-specific inhibitor made by T acceptor cells inhibits both the afferent and efferent stage of the contact sensitivity reaction.

In the T suppressor circuit which affects contact sensitivity, the T acceptor cell (Tacc) armed with T suppressor factor (TsF) and then triggered by antigen and major histocompatibility complex products (I-J) releases non-specific inhibitor (nsINH). These non-specific inhibitor(s) affect both the efferent and afferent stage of the contact sensitivity reaction and were originally detected by the inhibition of the passive transfer of contact sensitivity. The nsINH also blocks the induction of contact sensitivity when given intravenously at the time of immunization but has no effect when given at the time of challenge. Similarly, it blocks proliferation in the regional lymph nodes induced by contact sensitizer in a dose-dependent fashion; it acts when given at the time of immunization but not 1 day later. This effect is antigen non-specific and H-2 unrestricted. The nsINH bears I-J determinants as shown by affinity chromatography on monoclonal antibody. The nsINH comes from the Tacc and is not a breakdown product of the TsF. This is shown by the fact that, when the Tacc and TsF have I-J of different genotypes, the genotype of the nsINH corresponds to that of the Tacc. Parallel measurements of inhibition of lymphoproliferation and of passive transfer show that the nsINH has a molecular weight of 50-60 Kd and a pI around 6.8 and suggest that similar or identical molecules block both the afferent and efferent stage of the contact sensitivity reaction.

Animals↗
PubMed1983

Nonspecific inhibitor of DNA synthesis elaborated by T acceptor cells. I. Specific hapten- and I-J-driven liberation of an inhibitor of cell proliferation by Lyt-1-2+ cyclophosphamide-sensitive T acceptor cells armed with a product of Lyt-1+2+-specific suppressor cells.

Lyt-1+2+ hapten-specific T suppressor cells (Ts) from mice injected and then painted with picryl or oxazolone derivatives produce hapten-specific T suppressor factors (TsF) in vitro. Stimulation by painting with contact sensitizer (which need not be specific) gives rise to Lyt-1-2+, I-J+, cyclophosphamide-sensitive T acceptor cells (Tacc). When the Tacc population is armed with TsF and then is exposed to specific antigen in the context of I-J-controlled determinants (antigen-presenting, haptenized spleen cells and Ts sharing the same I-J subregion), a nonspecific inhibitor of DNA synthesis (nsINH) appears in the supernatant. This inhibitor suppresses the primary DNA synthetic response to concanavalin A, lipopolysaccharide, and alloantigens in both syngeneic and allogeneic lymphocytes. The nsINH is only effective when added to lymphocyte cultures less than 8 hr after the stimulation with concanavalin A. The nsINH, however, affects neither primary nor secondary cytotoxicity in vitro. These data suggest the mouse immune system is capable of selective regulation of the response to specific antigen by the production of nonspecific soluble suppressor factor(s).

Animals↗
PubMed1981

Suppression of antibody responses by cells from mice treated with picryl sulfonic acid: T cells that suppress IgG antibody without inhibiting concomitant IgE responses.

T cells from mice injected with picryl sulfonic acid (PSA) can inhibit the anti-trinitrophenyl (TNP) antibody responses of mice produced after skin painting with picryl chloride (PCl). This had unusual specificity because the cells could inhibit IgG PFC responses in draining lymph nodes by 90% without affecting anti-TNP IgE responses as measured by heterologous adoptive cutaneous anaphylaxis. Although showing specificity for the class of antibody, the suppressors did inhibit IgG antibody responses to another sensitizer, oxazolone, although to a lesser degree. Responses to TNP-KLH, however, were unaffected.

Anaphylaxis↗
PubMed1981

Differences in the ability of T cells to suppress the induction and expression of contact sensitivity.

T cells from mice injected with picryl sulphonic acid (PSA) inhibit the expression of contact sensitivity to picryl chloride. Adult thymectomy (aTx) prevents the production of cells which inhibit the effector stage but cells from aTx mice are, however, still able to suppress the induction of contact sensitivity. These cells are antigen-specific T cells but unlike suppressor cells for the effector phase, they cannot be produced in cyclophosphamide (Cy)-treated mice. Similar properties have been reported for cells inhibiting the DNA synthesis in lymph nodes of mice painted with picryl chloride. It was also shown that cells from Cy-treated but non-thymectomized mice could not inhibit sensitivity when injected at the time of sensitization, i.e. suppressors of the effector phase, which are induced in Cy-treated mice cannot inhibit sensitivity when injected at the induction phase. These results show there are distinct mechanisms and probably distinct cells which inhibit the induction and expression of contact sensitivity.

Animals↗
PubMed1980

Antigen-specific mast cell degranulation in contact sensitivity to picryl chloride. An early event.

Mast cells from the peritoneum of mice painted with the contact sensitizing agent picryl chloride degranulate when exposed to antigen (TNP) in vitro. Degranulation was consistently demonstrated 4 days after painting which associated with the ability of mice to produce contact sensitivity reactions as measured by ear swelling and radiometric assays. Serum reagin or reagin-producing cells could not be detected until 6 days after painting but TNP-phage neutralizing activity was detected after 2 days. Mast cell degranulation could be elicited by TNP or DNP derivatives indicating the involvement of antibody.

Animals↗
PubMed1980

Experimental erythrocyte autoimmunity. I. Mice congenic for immunoglobulin allotypes vary in production of autoantibodies but produce suppressor cells not restricted by allotypes.

Erythrocyte autoantibodies can be elicited in mnce by injections of rat RBC which are cross-reactive with mouse RBC. This report shows that induction of autoantibodies is dependent, in part, on gene(s) outside the H-2 complex. Using CBA mice congenic for Ig allotype and the F1 and F2 hybrids, a higher incidence of autoantibody production was observed in mice bearing the Ig allotype 1b (1b/b or 1a/b) in contrast to mice homozygous for the allotype Ig-1a. Serum haemagglutination titres against rat RBC were not reduced in the groups of mice with the lower incidence of autoantibody production. A probable explanation for these observations is that the change in Ig allotype is associated with some change in the variable region determining autoimmune specificity that is governed by VH genes linked to allotype genes. The transfer of 30 x 10(6) spleen cells from Coombs' positive mice to syngeneic recipients before starting the immunization regime with rat RBC suppressed autoantibody production and enhanced antibody production against rat RBC. These suppressor cells were effective in congenic mice and in F1 hybrids, which suggest that the Ig allotype is not a crucial site for the effector stage of suppression of this autoimmune response.

Animals↗
PubMed1980

Distribution of immunogenic cells after painting with the contact sensitizers fluorescein isothiocyanate and oxazolone. Different sensitizers form immunogenic complexes with different cell populations.

The distribution of fluorescent cells in the draining lymph nodes of mice painted with the contact sensitizing agent fluorescein isothiocyanate (FITC) was investigated using a fluorescence-activated cell sorter. Up to 30% of the cells were fluorescent after 18 h and this decreased thereafter becoming undetectable after 4-5 days. Most of the fluorescent cells were morphologically lymphocytes, theta - ve and adherent to nylon wool. Immunogenicity of these cells was tested by injecting them into the footpads of normal mice and measuring contact sensitivity after 6 days. This was restricted to large cells which represented less than 5% of the white cell population and nearly all of which became fluorescent after skin painting. The large fluorescent cells were a mixture of monocytes and lymphocytes. Most of the lymphocytes had surface immunoglobulin. The immunogenicity was reduced by nylon filtration but was not affected by silica and anti-theta. These results showed that the immunogenicity is not associated with T cells. In contrast, similar immunogenic activity in the draining lymph nodes of mice painted with oxazolone is associated with T cells. The results therefore showed that different sensitizers form immunogenic complexes with different cell populations, perhaps in this case becuase of the different water solubilities of FITC and oxazolone. They also suggested that this may cause important differences in antigen presentation, for example in their association with different MHC products.

Animals↗