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Biomedical subjects

D W Thomas

Publications and source records attributed to D W Thomas.

At least 253 records · Page 14Linked to original sources
PubMed1978

An instrument for routine measurements with x-ray therapy equipment operating between 10 and 250 kv.

X-ray equipment, used for radiation therapy at low voltages, is frequently operated in small hospitals which do not have full-time physics staff. Most of the X-ray units involved are not fitted with dose-rate monitors which would allow continuous control dose so that the output must be checked at frequent intervals by the radiographer using a suitable instrument. The design criteria for such an instrument are discussed and its construction described in detail together with the tests and field trials carried out. The instrument is designed to measure dose rates from 2500 rad min-1 at 10 kV to 50 rad min-1 at 250 kV. It has been possible by use of the instrument to determine the 'normal' behaviour of each X-ray unit and to establish criteria by which 'abnormal' behaviour can be determined.

Radiation Monitoring↗
PubMed1978

Nature of the antigenic complex recognized by T lymphocytes. V. Genetic predisposition of independent F1 T cell subpopulations responsive to antigen-pulsed parental macrophages.

Nonimmune (2 x 13)F1 guinea pig T lymphocytes initially stimulated with trinitrophenyl- (TNP) modified macrophages from one parental strain and then treated with bromodeoxyuridrine (BUdR) and light are unable to be primed subsequently with TNP-modified macrophages of the same parental strain. In contrast, these BUdR and light treated F1 T cells can be primed with TNP-modified macrophages of the other parental strain. These results demonstrate that in a nonimmune F1 animal two T cell subpopulations exist before priming that are genetically predisposed to respond to antigen associated with macrophages derived from one or the other parent.

Animals↗
PubMed1978

The expression of Ia antigens on immunocompetent cells in the guinea pig. III. Functional selection of Ia-negative T cells by in vitro culture.

In the present study we examined the expression of I-region-associated (Ia) antigens by guinea pig T lymphocytes stimulated in vitro with antigen-pulsed macrophages. Treatment of lymph node (LNL) or peritoneal exudate (PEL) T cells taken directly from immune animals with anti-Ia serum and complement (C) dramatically reduced their proliferative response to antigen-pulsed macrophages when determined on the 4th day of culture. In contrast, the response of immune T cells that had been selected by culture for a week with antigen-pulsed macrophages and restimulated in a second culture was not affected by anti-Ia and C treatment. This same result occurred with selected LNL or PEL that were initially treated before the selection culture with either normal serum or anti-Ia serum and C. LNL became resistant to anti-Ia serum and C treatment by 3 days of culture whereas antigen-specific PEL were still sensitive at that time. These results indicate that in an immune animal two antigen-specific T cell subpopulations are generated based on their sensitivity to anti-Ia serum and C treatment, but that only the resistant population is selected by in vitro culture. In addition, we demonstrated that the Ig-negative T cell population can only be activated by histocompatible antigen-pulsed macrophages.

Animals↗
PubMed1978

Hapten-specific T lymphocyte activation by glutaraldehyde-treated macrophages: an argument against antigen processing by macrophages.

In this communication the effects of glutaraldehyde treatment of trinitrophenyl-(TNP) modified macrophages on their ability to stimulate TNP-specific guinea pig T lymphocyte proliferation were studied. TNP-modified macrophages briefly treated with glutaraldehyde retained much of their ability to stimulate TNP-primed T cells. In contrast, similar treatment of allogeneic macrophages or soluble protein antigen-pulsed syngeneic macrophages completely eliminated their ability to stimulate a mixed leukocyte reaction or protein antigen-specific proliferation, respectively. TNP-modification did not appear to interfere with glutaraldehyde reactivity since macrophages treated with glutaraldehyde before or after TNP-modification stimulated equivalent T cell responses. However, glutaraldehyde treatment of TNP-modified macrophages that had been cultured overnight dramatically reduced their ability to stimulate TNP-specific T cells. Glutaraldehyde-treated TNP-modified macrophages also expressed the same genetic restrictions of T cell activation as untreated stimulators. Thus, T cells primed with syngeneic TNP-modified macrophages were restimulated only by glutaraldehyde-treated TNP-modified syngeneic, but not by allogeneic, macrophages. These results are discussed with respect to the nature of the TNP-specific immunogen recognized by T cells.

Aldehydes↗
PubMed1978

Nature of the antigenic complex recognized by T lymphocytes. VI. The effect of anti-TNP antibody on T cell responses to TNP-conjugated macrophages.

In this paper we examined the effect of anti-TNP antibody on guinea pig T cell proliferation in response to TNP-modified macrophages in vitro. The addition of anti-TNP to TNP-modified macrophages immediately after conjugation inhibited their ability to stimulate TNP-specific T cell proliferation. This inhibition appeared to be specific for the TNP response since anti-TNP had no effect on the ability of TNP-modified macrophages pulsed with either PPD or TNP-Ova to stimulate efficient PPD or Ova T cell responses. On the other hand, anti-TNP had no effect on the TNP-specific response to TNP-modified macrophages that had been cultured overnight before addition to primed T cells or to macrophages which had been pulsed with TNP-Ova. We also demonstrated that the same TNP-specific T cell subpopulation responds to both freshly TNP-modified macrophages and overnight cultured TNP-modified macrophages. These results suggest that the relevant TNP-determinants recognized by T cells are not exposed on the macrophage surface and raise the possibility that macrophages must process membrane-conjugated TNP to create the immunogen recognized by T cells.

Animals↗
PubMed1978

Nature of the antigenic complex recognized by T lymphocytes. VII. Evidence for an association between TNP-conjugated macrophage membrane components and Ia antigens.

In the present study we examined the effects of anti-sera directed against guinea pig Ia antigens on the ability of TNP-conjugated macrophages to stimulate TNP-specific T lymphocyte proliferation. Treatment of macrophages with anti-Ia sera for 1 hr before, 1 hr immediately after, or as late as 24 hr after TNP-modification resulted in a reduced ability to stimulate the TNP-specific T cell. The inhibition produced by anti-Ia sera was specific and did not result from interference with the ability of macrophages to process TNP-conjugated membrane antigens in a nonspecific manner. Brief treatment with anti-Ia serum did not result in inhibition of Ia-antigen synthesis nor could evidence of carry-over of anti-Ia antibody into the lymphocyte cultures be obtained. These results demonstrate that anti-Ia sera interfere with the development of a TNP-specific immunogen on the macrophage surface and strongly suggest that an association exists between TNP-modified membrane proteins and Ia antigens on the macrophage surface.

Animals↗
PubMed1977

Nature of the antigenic complex recognized by T lymphocytes II. T-cell activation by direct modification of macrophage histocompatibility antigens.

In order to analyze the molecular structures involved in T-cell recognition we developed an in vitro primary response against alloantisera bound to histocompatibility antigens in which nonimmune guinea pig T cells can be sensitized and subsequently challenged in tissue culture with antisera-treated macrophages. If macrophages were incubated with alloantisera directed against the I-region-associated (Ia) antigens of the guinea pig major histocompatibility complex (MHC) T cells could be sensitized to the antisera bound to macrophage Ia determinants. Anti-Ia-treated syngeneic macrophages in the first and second cultures elicited specific T-cell activation, as measured by increased DNA synthesis, to the antisera-induced immunogenic determinants. Similarly, antiIa-treated allogeneic macrophages also specifically stimulated T cells to antisera bound to allogeneic Ia determinants while reducing the mixed leukocyte reaction. Antisera to the B.1 antigens of the guinea pig MHC, the homologue of the mouse H-2K or H-2D antigens, also elicited specific T-cell activation that did not cross-react with that produced by the anti-Ia alloantisera. Furthermore, the anti-B.1-induced stimulation appeared to be associated with the Ia antigens of the macrophage used for priming since (2 x 13)F1 T cells sensitized with anti-B.1-treated parental macrophages could be restimulated only with the parental macrophage used for initial sensitization, and not with those of the other parent. Since the parental strain 2 and strain 13 guinea pigs express serologically identical B.1 antigens and differ only by Ia antigens of the MHC, this observation suggests that both B.1 and Ia antigens may be included in the immunogenic complex recognized by T cells. However, we cannot rule out the possibility that this restriction is due to other genetic differences between strain 2 and strain 13 guinea pigs that is unrelated to the I-region. We interpret these findings as showing that macrophage Ia antigens may serve to directly present antigens bound to the Ia molecule, and possibly indirectly aid in the presentation of antigens bound to other membrane components, such as the B.1 antigens.

Animals↗
PubMed1977

Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells.

Thymus-dependent (T) lymphocytes from (2 x 13)F1 hybrid guinea pigs immunized to ovalbumin (OVA) in complete Freund's adjuvant can be stimulated to proliferate in vitro by antigen-pulsed peritoneal exudate cells (PECs) derived from either strain 2 or strain 13 donors. In this communication, we show that the population of primed F1 T lymphocytes which can be activated by antigen-pulsed strain 2 PECs is largely independent of the population of cells that can be activated by antigen-pulsed strain 13 PECs. This was demonstrated by both positive and negative selection procedures. In the former, T lymphocytes from OVA-primed (2 x 13)F1 donors were enriched by initial culture with OVA-pulsed strain 2 or strain 13 PECs for 1 wk. Cells selected by culture with OVA-pulsed strain 2 PECs responded well to OVA-pulsed strain 2 PECs and poorly to OVA-pulsed strain 13 PECs. If positive selection had been carried out with OVA-pulsed strain 13 PECs, the selected F1 T cells responded well to OVA-pulsed 13 PECs and poorly to OVA-pulsed 2 PECs. Negative selection was achieved by short term culture with antigen-pulsed PECs and by eliminating proliferating cells by treatment with bromodeoxyuridine and light. This procedure demonstrated that the population of primed F1 T lymphocytes which are responsive to OVA or to purified protein derivative of tuberculin can be divided into subpopulations uniquely responsive to antigen on either strain 2 or strain 13 PECs. Evidence was presented to indicate that this selective responsiveness was not the result of the action of alloantigen-specific suppressor cells. The results are considered in terms of current concepts of the genetic and molecular regulation of the interaction of PECs and T lymphocytes.

Animals↗
PubMed1977

Application of 13C-NMR spectroscopy to in vitro analysis of enzyme kinetics.

The conversion of D,L-alpha-13C-histidine to similarly labeled alpha-13C histamine by bacterial and mammalian histidine decarboxylase was studied by 13C-NMR spectroscopy and GLC-mass spectrometry. The results obtained with the partially purified bacterial enzyme were in essentially perfect agreement with results obtained simultaneously with a standard radioisotopic method using carboxyl-labeled-14C-L-histidine. For a crude tissue preparation of the mammalian enzyme, the radioisotopic method indicated an activity three times that based on 13C-NMR measurement of alpha-13C-histamine. The difference in results was accountable in terms of additional 13C-NMR signals attributable to products other than histamine due in part to enzymatic degradation of the latter.

Animals↗
PubMed1977

Nature of the antigenic complex recognized by T lymphocytes: specific sensitization by antigens associated with allogeneic macrophages.

Alloreactive guinea pig thymus-derived (T) cells generated in vitro were rendered unresponsive to allogeneic macrophages by treatment with bromodeoxyuridine and light. The remaining T cells were subsequently primed and rechallenged in tissue culture with trinitrophenyl (Tnp)-modified syngeneic or allogeneic macrophages. By this procedure we found that the remaining T cells primed with Tnp-modified allogeneic macrophages could be restimulated only with Tnp-modified allogeneic, not syngeneic, macrophages. Similarily, if the remaining T cells were primed with Tnp-modified syngeneic macrophages, they could be restimulated only by Tnp-modified syngeneic, and not by allogeneic, macrophages. In contrast, no T cell sensitization with Tnp-modified syngeneic or allogeneic macrophages occurred if the alloreactive T cells were treated with light alone, suggesting that an uninhibited mixed leukocyte reaction causes nonspecific suppression of antigen-specific T cell priming. These results indicate that the genetic restriction of T cell-macrophage interactions is imposed by the type of macrophage used for initial sensitization rather than by a requirement for self-recognition through cellular interaction structures.

Animals↗