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Biomedical subjects

L Hudson

Publications and source records attributed to L Hudson.

At least 91 records · Page 5Linked to original sources
PubMed1983

Immunopathogenesis of experimental Chagas' disease in mice: damage to the autonomic nervous system.

Infection of mice with Trypanosoma cruzi produces pathological change which in many ways parallels the evolution of Chagas' disease in human patients. An essential element in this experimental pathology is the intense denervation observed during the resolution of acute-stage parasitaemia. Host cells, from a variety of tissues, have been shown to absorb parasite antigens and thus to become targets for the hosts' own anti-parasite immune response. The definition of common antigenic determinants, shared by T. cruzi and human neuronal cells, might explain why the electrical conduction systems and the autonomic nervous system are especially vulnerable to the postulated autoimmune process. We have the models, the tools and the hypotheses, and now we await the proof.

Animals↗
PubMed1983

Trypanosoma cruzi: the immunological consequences of infection.

Trypanosoma cruzi, the causative agent of Chagas' disease, infects an estimated 12 million people in Latin America and may induce cardiopathy and megaformation of the oesophagus and colon. During the early, acute stage of the infection, parasite-induced inflammatory infiltrates may cause transitory disease which terminates with the emergence of an immune response sufficient to reduce the parasite to insignificant levels. Even so, severe disease may develop many years after the original infection. It has been suggested that this might result from an autoimmune process triggered by the parasite and mediated either 1) by the adsorption of parasite antigens to host cells, thus rendering these cells susceptible to the host's own antiparasite immune response, or 2) via cross-reactive antigens shared by the host and parasite. In common with many parasitic diseases, there is an urgent need for studies on the T-cell response to T cruzi infection, as this might not only hold the key to the immunopathology but also serve as a means of clearing this lifelong infection which survives by sequestering into an intracellular site.

Animals↗
PubMed1982

A monoclonal antibody defining antigenic determinants on subpopulations of mammalian neurones and Trypanosoma cruzi parasites.

An IgM lambda class monoclonal antibody raised against membranes from rat dorsal root ganglia defines a novel antigenic determinant expressed by subpopulations of mammalian central and peripheral neurones. In the presence of complement the antibody is cytotoxic to mammalian neurones in vitro. The same antibody labels Trypanosoma cruzi, the protozoan responsible for Chagas' disease. Classes of mammalian neurones and cardiac muscle that are labelled by the antibody are known to degenerate in Chagas' disease. The common neuronal and trypanosomal antigens recognized by the antibody may therefore be important in pathogenic events underlying this disorder.

Animals↗
PubMed1982

Growth of Trypanosoma cruzi in vitro: development and application of a continuous-flow culture system.

The design and operation of a modular, bacteriological continuous-flow culture system have been adapted for the growth of Trypanosoma cruzi epimastigotes in simple monophasic media. The system was designed to achieve a minimum of 200 days of continuous culture and provision was made for the continuous supply of medium and collection of parasites under sterile conditions. The system provides large quantities of epimastigotes with homogeneous morphology and uniform viability. The system also lends itself to the analysis of the factors which affect parasite growth. We examined the effects of changes in environmental parameters on epimastigote growth rate. Optimal growth was observed at 27 degrees C. The rate of stirring of the culture had a small but definable effect on the growth rate, which was greatest at 80 rp.m. Growth was only slightly affected by the level of dissolved oxygen between 10 and 50% saturation, but was inhibited at higher concentrations. Growth was slower at extreme values of pH but showed a broad optimum around pH 7.4.

Animals↗
PubMed1982

Influence of long-term infusions on lidocaine kinetics.

Lidocaine kinetics were examined during continuous infusions in five healthy subjects using stable isotope lidocaine labeled with two deuterium atoms. During phase 1, lidocaine and stable isotope lidocaine (50 mg IV each) were given as a bolus to confirm that the two species were kinetically identical. Phase 2 consisted of a long-term (30 hr) lidocaine infusion designed to produce a steady-state concentration equal to 1.5 microgram/ml. Twenty-four hours into the infusion, stable isotope lidocaine (50 mg) was given as an intravenous bolus and kinetic parameters were calculated. Phase 3 differed from phase 2 in that target steady-state lidocaine concentration was 4 microgram/ml and the stable isotope lidocaine dose was reduced to 40 mg. A gas chromatograph-mass spectrometer was used to determine lidocaine and stable isotope lidocaine serum concentrations. Compared to phase 1, clearance decreased (P less than 0.05) and half-life increased (P less than 0.025) during phases 2 and 3. The volume of distribution at steady-state remained constant during all three phases. Lidocaine cumulated in serum during long-term infusions in all five patients; repeated decreases in infusion rate were necessary to avoid exceeding desired target concentrations in phases 2 and 3.

Adult↗
PubMed1982

Mitogen-stimulated immunoglobulin production by chronic lymphocytic leukaemic lymphocytes.

The capacity of B cells from patients with chronic lymphocytic leukaemia (CLL) to produce and secrete immunoglobulin following mitogen stimulation was investigated using sensitive radioimmunoassays for mu, gamma, alpha, kappa, and lambda immunoglobulin chains. Lymphocytes from seven of the 11 patients studied secreted immunoglobulin in response to pokeweed mitogen (PWM). IgM was always the major immunoglobulin and in five of the seven responders it was the only class detected; only one type of light chain was observed in most cases. This was in contrast to normal lymphocytes which secreted all classes of immunoglobulin (IgM was invariably the lowest) containing both types of light chain. Lipopolysaccharide induced immunoglobulin secretion in only one of four CLL cases. This was again IgM with only one type of light chain. The assays are therefore most probably measuring a response by the leukaemic cells. In most CLL cases, immunoglobulin secretion by the residual normal cells, which proliferate in response to mitogen, was not observed. This inability of the normal lymphocytes to differentiate fully into immunoglobulin secreting cells and the block in switching from IgM production to other classes in the leukaemic cells may both be attributable to a defect in the regulatory system of the immune response in CLL patients.

Aged↗
PubMed1982

The roles of leukaemic and residual normal cells in the proliferative response of chronic lymphocytic leukaemic lymphocytes to mitogens.

The proliferative response of lymphocytes from patients with chronic lymphocytic leukaemia (CLL) to the polyclonal activators, phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) correlates inversely with the logarithm of the circulating lymphocyte concentration in vivo (P less than 0.001). This suggests that the response is due primarily to residual normal cells in the circulation. In support of this postulate, dilution of normal cells reproduced the effect and also induced a delayed response to PHA, which is found frequently with CLL lymphocytes. A combination of autoradiography and immunofluorescence microscopy identified both B and T cells in the responding population in similar proportions from both normal and CLL donors. These data demonstrate that the 3H-thymidine assay used in most mitogenic studies is not suitable alone for investigating the functional capacity of leukaemic lymphocytes in CLL and other diseases involving a gross perturbation of lymphocyte populations.

Aged↗
PubMed1981

The tyrT locus: termination and processing of a complex transcript.

The tyrT locus of E. coli contains a 208 bp spacer region that separates two copies of sequence encoding tRNATyr1. The spacer includes a 120 bp sequence that is homologous to a sequence that is repeated three times in the distal portion of the tyrT locus. The tyrT locus possesses a graded set of transcription termination sites that are spaced at 180 base intervals, corresponding to the distal repeated gene structure. The major termination site occurs within the second repeat unit, 225 bases beyond the mature tRNA sequences. In the presence of a temperature-sensitive rho protein there is increased read-through at this site to a termination site located 180 bases downstream in the third repeat and to several termination sites even further downstream. The primary native transcript, in the region distal to the second tRNA, carries the information for a low molecular weight, extremely basic protein. Although analogous coding sequences are present in the spacer and other repeat units, because of single base substitutions these sequences are pseudogenes. The parallel between the tyrT and TyrU gene clusters is discussed in relation to dual function transcripts that specify both tRNA and protein.

Bacterial Proteins↗
PubMed1981

Denervation and the immune response in mice infected with Trypanosoma cruzi.

C57B1 mice were infected with Trypanosoma cruzi Y strain trypomastigotes and showed a peak of parasitaemia 9 days after infection. Virtually all mice survived the acute stage of infection and were aparasitaemic thereafter. Coincident with the peak of parasitaemia, there was a progressive loss of cardiac neurones (up to the 20th day after infection) and an appearance of T. cruzi antigen on myofibres. Anti-parasite immunity, evidenced by a significant inhibition of macrophage migration in the presence of T. cruzi antigens (MIF test) and the deposition of complement and immunoglobulin in vivo around the nests of parasites, developed between days 7-10 after infection. Immunity to "self' components (MIF) test using neurone and heart antigens) was not detected until 15-20 days after infection. Although the MIF test detected a progressive increase in anti-neurone immunity between 20-90 days after infection, there was no additional loss of cardiac neurones during this period. In contrast to current hypotheses, these data suggest that the immunity to heart and neuronal antigens commonly detected in animals infected with T. cruzi is the result rather than the cause, of host cell destruction.

Animals↗
PubMed1980

Trypanosoma cruzi: immunological consequences of parasite modification of host cells.

Parasite antigens released from Trypanosoma cruzi-infected cells were adsorbed to infected and uninfected mammalian cells thus rendering them susceptible to immune lysis by antibody and cell-mediated immunity directed against the parasite. BALB/c mice infected with T. cruzi for 15 days developed cytotoxic T lymphocytes specific for parasite antigens. At 60 days post infection, however, the mice developed an additional population of cytotoxic T lymphocytes that were able to kill normal syngeneic muscle or neuronederived cell lines in vitro. These '60-day" T lymphocytes did not kill HeLa cells unless they were coated with T. cruzi antigens suggesting that the population of atuoaggressive T lymphocytes was not an artefact due to an increase in natural killer cells.

Animals↗
PubMed1978

Allelic exclusion of M1 (IgM) allotype on the surface of chicken B cells.

The membrane expression of M1 (IgM) and G1 (IgG) allotype markers on peripheral blood lymphocytes was examined by immunofluorescence. In homozygous chickens 15% lymphocytes stained with either anti-M1 or with polyspecific rabbit anti-Ig serum, suggesting that M1 is expressed on the surface of probably all B lymphocytes. In heterozygous M1a/M1b individuals antisera against either allelic antigens reacted with 50% of the total surface Ig positive cells as evidence for the allelic exclusion of surface M1 expression. Donor allotype synthesis was determined from serum allotype levels in congenic cyclophosphamide-treated recipients of lymphoid cells. Treatment of cells with anti-M1 serum prior to transfer inhibited both M1 and G1 allotype synthesis. The treatment of heterozygous (M1a/M1b, G1a/G1e) cells with anti-M1b serum inhibited specifically the synthesis of M1b and G1e allotypes controlled by linked genes from the same parental chromosome. Thus, B cells which had been the targets for anti-M1 antibody mediated suppression are also subject to allelic exclusion.

Animals↗
PubMed1977

Effect of bronkosol and its components on cardiopulmonary parameters in asthmatic patients.

Bronkosol and its components, isoetharine hydrochloride and phenylephrine hydrochloride, were compared in a double-blind randomized fashion for their effect on pulmonary and cardiovascular parameters in patients with reversible bronchospasm. Bronkosol and isoetharine produced significant bronchodilatation as measured by forced expiratory volume in one second (FEV), forced vital capacity (FVC), and mean forced expiratory flow during the middle half of the FVC (isovolume FEF 25% to 75%), and phenylephrine did not. There was no difference between Bronkosol and isoetharine in the degree or duration of bronchodilatation. Significantly more patients had to "discontinue" after 15 min on the day of testing with phenylephrine than with Bronkosol or isoetharine. Heart rate was not increased after Bronkosol or isoetharine, confirming its selective beta-2 action. The addition of phenylephrine to isoetharine had no beneficial effect on oxygen saturation. There was no significant difference between these drugs in systolic and diastolic blood pressure, pulse, or respiration. The results of this study cast doubt on the useful contribution of phenylephrine in Bronkosol.

Adolescent↗
PubMed1976

Specific adsorption of IgM antibody onto H-2-activated mouse T lymphocytes.

Evidence is presented to support the contention that IgM demonstrable by surface immunofluorescent staining on H-2-activated T cells represents specifically adsorbed B-cell-derived alloantibody. T cells activated to H-2 determinants expressed surface IgM only when the progenitor cell populations contained B lymphocytes. IgM was not detected on T cells activated to determinants which fail to stimulate alloantibody production (e.g., M-locus determinants). In addition, IgM-negative H-2 activated T cells (derived from B-cell-depleted lymphoid cells), unlike M-locus-activated T cells, adsorbed IgM in a specific manner when incubated in vitro with "early bleed" antisera raised against the activating H-2 determinants.

Adsorption↗