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Biomedical subjects

J D Watson

Publications and source records attributed to J D Watson.

At least 217 records · Page 12Linked to original sources
PubMed1985

Immunity to leprosy. 1. The proliferative response of murine T lymphocytes to Mycobacterium leprae.

A microculture assay is described for measuring the response of murine T lymphocytes to Mycobacterium leprae antigens. Mice were immunized with M. leprae in Freund's incomplete adjuvant at the base of the tail, and after five days lymphocytes from draining lymph nodes were harvested and cultured with M. leprae antigens. Radioactive thymidine uptake was used to quantitate the antigen-induced proliferation of the lymphocytes. The effects of cell density and antigen concentration on the kinetics of the proliferative response were determined. We present evidence that it is the T lymphocytes that proliferate in response to antigen in microcultures, and that the lymphocyte response varies with the mouse strain used. This assay system can be used to identify the antigens of M. leprae that elicit T cell responses and the effector function of the M. leprae-specific T cell involved.

Animals↗
PubMed1985

Induction of antibody responses to influenza virus in human lymphocyte cultures. I. Role of interleukin 2.

The in vitro T cell-dependent antibody response of human lymphocytes to influenza virus X31 was used to study the role of T cell-derived lymphokines in antigen-specific responses. Supernatant from cultures of phytohaemagglutinin-stimulated, pooled human tonsil cells (PHA-MLR) was capable of replacing T cells and inducing T-depleted tonsil cells to secrete influenza-specific antibody. The T cell-replacing activity of PHA-MLR supernatant co-purified with interleukin 2 (IL 2) on Ultrogel AcA54 gel filtration and reversed phase-high performance liquid chromatography. PHA-MLR supernatant and IL 2 also enhanced B cell proliferation induced by anti-mu or Staphylococcal aureus strain Cowan I (SAC). A murine monoclonal antibody directed against the human IL 2 receptor (Mab 2A3) was used to completely block the enhancement of influenza-specific antibody production mediated by PHA-MLR supernatant, purified IL 2, and recombinant human IL 2. Mab 2A3 did not affect the T-independent B cell proliferation induced by anti-mu or SAC, but abrogated the enhancing effect of the PHA-MLR supernatant and IL 2 in this culture system. Immunofluorescence studies failed to demonstrate binding of Mab 2A3 to B cells activated by the X31 influenza virus and IL 2, or by SAC. By using Mab 2A3 to mask out IL 2 effects in the influenza-specific culture system, no other B cell differentiating activities were revealed in supernatants from lymphocytic cultures stimulated with a variety of mitogens. Thus, our results indicate that the production of influenza-specific antibodies by T-depleted human lymphocyte cultures is absolutely dependent on the presence of both antigen and IL 2.

Antibodies, Monoclonal↗
PubMed1985

Immunity to leprosy. II. Genetic control of murine T cell proliferative responses to Mycobacterium leprae.

T cell proliferative responses to Mycobacterium leprae were measured after immunization of mice at the base of the tail with antigen and challenging lymphocytes from draining lymph nodes in culture with M. leprae. This T cell response to M. leprae has been compared in 18 inbred strains of mice. C57BL/10J mice were identified as low responder mice. The congenic strains B10.M and B10.Q were found to be high responders, whereas B10.BR and B10.P were low responders. F1 (B10.M X C57BL/10J) and F1 (B10.Q X C57BL/10J) hybrid mice were found to be low responders, similar to the C57BL/10J parent, indicating that the low responsive trait is dominant. Whereas B10.BR mice were shown to be low responders to M. leprae, B10.AKM and B10.A(2R) were clearly high responders, indicating that the H-2D region influences the magnitude of the T cell proliferative response. Gene complementation within the H-2 region was evident. Genes outside the H-2 region were also shown to influence the response to M. leprae. C3H/HeN were shown to be high responder mice, whereas other H-2k strains, BALB.K, CBA/N, and B10.BR, were low responders. Gene loci that influence the T cell proliferation assay have been discussed and were compared to known background genes which may be important for the growth of intracellular parasites. Because mycobacteria are intracellular parasites for antigen-presenting cells, genes that affect bacterial growth in these cells will also influence subsequent immune responses of the host.

Animals↗
PubMed1985

The effects of sodium butyrate on lymphokine production.

The effect of sodium butyrate on lymphokine production in WEHI-3, LBRM-33, and JURKAT cells, as well as an IL-2-dependent T cell line (I) was studied. Constitutive production of IL-3 by WEHI-3 cells was enhanced by sodium butyrate and was accompanied by the growth arrest of WEHI-3 cells in the G1 phase of the cell cycle. Treatment of I cells with ConA and sodium butyrate led to an increase in IL-3 production and the initiation of IL-2 production. In contrast, the synthesis of IL-2 and IL-3 by the ConA-activated T lymphoma line LBRM-33 was coordinately inhibited by sodium butyrate. Similarly, the synthesis of IL-2 by the human T cell lymphoma JURKAT was inhibited by sodium butyrate. No cell cycle-specific effects of sodium butyrate were observed in LBRM-33 or JURKAT cells.

Animals↗
PubMed1985

Induction of IL 2 responsiveness in a murine IL 3-dependent cell line.

A mouse IL 3-dependent cell line, FD.C/1, can be induced to IL 2 growth responsiveness by culture in IL 2-conditioned culture medium. The IL 2-dependent cell lines derived by this procedure have been designated FD.C/2 cells. Once established, the FD.C/2 cells respond to human, rat, and mouse IL 2. When cultured with murine IL 3, FD.C/2 cells did not proliferate, appearing to accumulate in the G1 phase of the cell cycle. Other human and mouse lymphokines failed to stimulate FD.C/2 cell growth. The growth dependence of FD.C/2 cells on IL 2 could not be reversed to IL 3. Cell lines derived by these procedures could provide in vitro models for hemopoietic differentiative events.

Absorption↗
PubMed1984

Fasciotomy and Z-plasty in the management of Dupuytren's contracture.

The technique of fasciotomy and Z-plasty for the management of Dupuytren's contracture is described. The results of its use in a series of nine patients is presented. It is suggested that this method is applicable to the patient whose disease is confined to a single ray in the palm. None of the patients studied required re-operation during the period of follow-up which ranged from 2 years 4 months to 5 years 6 months.

Adult↗
PubMed1984

Successful prophylaxis with tinidazole of infection after major head and neck surgery for malignant disease.

A prospective double-blind trial of tinidazole was carried out in a group of 8 patients, each undergoing radical surgery for the removal of a large squamous cell carcinoma (SCC) of the oropharynx. In the 4 patients given tinidazole there was no wound infection, wound healing was more rapid and the foul odour associated with infection in such patients was eliminated. Post-operatively, 3 of the 4 patients given the placebo developed wound infections. Mixed cultures of gram-negative anaerobic bacilli, predominantly bacteroides, were grown from the upper drain fluids of the infected patients. Anaerobes were not isolated from the drain fluids of patients receiving tinidazole. The efficacy of tinidazole was demonstrated in these patients who are at high risk of acquiring infection because of the extensive surgery required for tumour removal and the inevitable contamination of the tissues with the diverse, resident oral flora.

Aged↗
PubMed1984

Effects of externally imposed elastic loads on the ability to estimate position and force.

Normal adult subjects attempted, with vision excluded, to match the position of the left index finger by pointing to it with the right one, using only flexion-extension movements at the right elbow. An elastic load applied at the right wrist was altered from trial to trial. When instructed to align the fingers, subjects were found to select the position of the right forearm by taking into account both a position signal and some measure of the force exerted by the elbow flexors. When instructed to match a target force, instead of position, the subjects were able to give greater weighting to signals of force than in the position matching task.

Adult↗
PubMed1984

Ranitidine and single-dose antacid therapy as prophylaxis against acid aspiration syndrome in obstetric practice.

The efficacy of the non-particulate antacid 0.3 M sodium citrate in single and multiple dose regimes was investigated in 156 obstetric patients, both emergency and elective, who required operative delivery under general anaesthesia. Failure of either of these regimes to elevate the intragastric pH consistently to an acceptable level (greater than 3) led to investigation of a regime combining the histamine H2-receptor antagonist, ranitidine, and a single pre-anaesthetic dose of 0.3 M sodium citrate in a further 170 patients. Satisfactory pH values (greater than 3) were achieved in all patients studied. The results from the first 99 cases were analysed statistically by comparison with the multiple dose sodium citrate regime and showed a very significant improvement in the ranitidine group for intragastric pH and volume. No untoward side-effects were discovered in either mother or baby and the 6-hourly administration of ranitidine, which was easily complied with, had no effect on the progress of labour or operative delivery rate.

Anesthesia, General↗
PubMed1984

Role of the H-2s haplotype in survival of mice after infection with Trypanosoma cruzi.

In studies of the resistance of inbred mice to infection with Trypanosoma cruzi Peru, mouse strain B10.S was the only strain which survived the infection resulting from the inoculation of 10(3) trypomastigotes. This is the only inbred mouse strain studied to survive infection. To investigate the effect of the H-2 haplotype on survival, C57BL/10 congenic mouse strains bearing H-2S recombinant haplotypes and mouse strains A.SWSn/J and SJL/J were tested for their ability to overcome the T. cruzi infection. None of the recombinant strains tested, including B10.S(7R), B10.S(8R), B10.S(9R), and B10.HTT, survived the infection, indicating that at least two or more regions of the H-2 locus must be H-2S to ensure survival. Strains A.SWSn/J and SJL/J with the H-2S haplotype did not survive, indicating that the genetic background outside the H-2 complex also influences survival. The congenic F1 hybrid (C57BL/10 X B10.S) F1 exhibited intermediate survival levels when compared with the parental strains, indicating that H-2S survival is affected by gene dosage. The F1 hybrid strain [B10.S(7R) X B10.S(8R)]F1, which possesses the complete H-2S haplotype in the trans configuration, did not survive T. cruzi infection, suggesting that H-2S-mediated survival does not operate by trans complementation.

Animals↗
PubMed1984

Interleukin 1 induces proliferation in two distinct B cell subpopulations responsive to two different murine B cell growth factors.

Two distinct classes of B cell growth factor (BCGF) have been described. BCGF I induces proliferation of anti-IgM-activated B cells, whereas BCGF II acts on a subpopulation activated by dextran sulfate. We examined the effect on both these B cell subsets of a B cell growth and differentiation factor that copurifies with interleukin 1 (BGDF/IL 1) produced by the WEHI-3 cell line. Proliferation was induced by BGDF/IL 1 in cultures of normal spleen cells depleted of T cells and adherent cells and activated by anti-IgM or dextran sulfate. Little effect was observed in cultures of spleen cells from B cell-deficient CBA/N mice. In cultures of normal B cells activated with anti-IgM and dextran sulfate together, BGDF/IL 1 induced a proliferative response comparable with the sum of the responses to the factor and either stimulus alone. These results suggest that anti-IgM and dextran sulfate activate distinct and independent B cell subpopulations, both of which are responsive to BGDF/IL 1.

Animals↗
PubMed1984

Interleukin-2 is required for the induction of erythrocyte--specific antibody responses in human lymphocyte cultures.

The involvement of interleukin-2 (IL-2) in the generation of human antibody responses was studied using the pokeweed mitogen (PWM)-induced sheep erythrocyte-specific plaque-forming cell (SE-PFC) response of cultured tonsilar lymphocytes. IL-2-containing supernatants from phytohemagglutinin-stimulated human spleen or tonsil cells or the cloned human T cell line JURKAT were capable of replacing the requirement for PWM in the generation of SE-PFC and resulted in a more prolonged response than that observed with PWM. This effect of IL-2-containing medium was dependent on the presence of SE-derived antigens and was not due to the induction of polyclonal antibody synthesis. When purified by gel filtration the SE-PFC-inducing activity co-eluted with IL-2 with an apparent molecular weight of approximately 15,000 (range, 8,000-20,000). Selective removal of IL-2 from crude or partially purified IL-2 preparations by extensive adsorption with activated murine thymocytes or an IL-2-dependent T cell line completely eliminated SE-PFC-inducing activity, indicating that IL-2 itself was necessary for the effect. The question of whether or not this effect was mediated through T cells is discussed.

Animals↗
PubMed1984

In vivo modulation of thymus-derived lymphocytes with monoclonal antibodies in mice. II. Separation of natural killer cells and cytotoxic T cells.

Treatment of mice with ascitic fluid containing high titres of T24-31.7 monoclonal antibody (rat anti-mouse Thy-1) lead to a rapid loss of T cells from peripheral lymphoid organs. Spleen and lymph node tissue lost all detectable Thy-1+ and mitogen-responsive T cells within 72 hr. These tissues were completely T cell-depleted for more than a week before repopulation with T cells began. Lectin-induced splenic T cell cytoxicity in culture was lost within 72 hr after treatment of mice in vivo. In contrast, treatment of mice with T24-31.7 ascitic fluid was followed by an immediate increase in natural killer (NK) cell-mediated cytolytic activity. After 96 hr, NK activity began to decrease and did not reappear in the T cell-depleted spleens. While purified T24-31.7 antibody was responsible for T cell depletion in vivo, a non-immunoglobulin component of the ascitic fluid stimulated splenic NK cell activity. The presence of phytohaemagglutinin (PHA) on target cells in the lytic assay was shown to inhibit NK activity but enhance T cell-mediated cytotoxicity. The relationship of NK cells and cytotoxic T lymphocytes (CTL) to the T cell lineage is discussed.

Animals↗
PubMed1984

In vivo modulation of thymus-derived lymphocytes with monoclonal antibodies in mice. III. Spontaneous and natural cytotoxic effector cells.

Cytotoxic effector cell populations in murine spleen can be characterized by the phenotype of the cytotoxic cells or the nature of target cells. Lytic events can be antigen-specific, MHC-restricted and clonal, or target cell-specific but apparently non-MHC-restricted. Two cytotoxic effectors of this latter category are spontaneous and natural killers. Normal spleen cells from (BALB/c X DBA/2J)F1 mice (CDF1) cultured without added antigen develop a population of Thy-1+ spontaneous cytotoxic lymphocytes (SCTL) that lyse the DBA/2J mastocytoma P815, as well as the BALB/c-derived plasmacytomas MOPC-11 and SP2/0. Cold target competition experiments reveal the BALB/c-derived plasmacytomas MOPC-11, SP2/0, J558 and the A strain-derived T cell lymphoma YAC-1, but not normal lymphoblasts, block the lysis of P815 target cells. Thus, while these tumour cells appear to express common antigens which are recognized by SCTL cells, plasmacytomas such as J558 are not susceptible to lysis by SCTL. The relationship of SCTL to natural killer (NK) cells was examined. In-vivo treatment of mice with monoclonal anti-Thy-1 antibody leads to a rapid loss of SCTL and precursors from the spleen, but there is a concomitant increase in NK cell activity.

Animals↗
PubMed1984

Biochemical comparison of murine colony-stimulating factors secreted by a T cell lymphoma and a myelomonocytic leukemia.

Factors that stimulate the proliferation and differentiation of murine bone marrow cells have been purified from a cloned T cell lymphoma, LBRM-33, and a cloned myelomonocytic leukemia cell line, WEHI-3. These colony-stimulating factors (CSF) have been purified by sequential fractionation by using salt precipitation, gel filtration, anion and cation exchange chromatography, and high pressure liquid chromatography. Both LBRM-33 and WEHI-3 cells secrete a CSF species with similar chemical and biologic properties. This CSF species appears to exist in two forms, termed CSF-2 alpha and CSF-2 beta, both of which stimulate the growth of bone marrow cells in the granulocyte, macrophage, megakaryocyte, mast cell, and erythrocyte lineages, as well as the growth of a CSF-dependent cell line, FDC-P2. These properties of CSF-2 alpha and -2 beta are similar to those reported for interleukin 3, hematopoietic cell growth factor, mast cell growth factor, and persisting cell growth factor. However, LBRM-33 cells secrete another CSF species, not produced by WEHI-3 cells. This CSF species, unique to LBRM cells, is termed here CSF-2 gamma and it stimulates the proliferation of granulocytes and macrophages from bone marrow but does not support the growth of FDC-P2 cells.

Animals↗
PubMed1983

Controlled dispersion analysis: flow-injection analysis without injection.

Flow-injection analysis is a precise, elegant, and economical technique, but its most troublesome feature is the mode of injection of the sample slug. We describe an alternative approach in which the sample is aspirated by the sample probe. In the simplest version the probe normally rests in reagent; when sampling is to take place, the pump is stopped and the probe is transferred to the sample container. The pump makes a predetermined angular movement, the probe is returned to reagent, and the pump is restarted. In more advanced versions the same approach is combined with the merging zone technique. The system is economical, precise, and capable of full automation in a multichannel discretionary analyzer.

Autoanalysis↗