Genetic control of eosinophilia in parasitic infections: responses of mouse strains to treatment with cyclophosphamide and parasite antigen.
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Animals↗
Biomedical subjects
L A Mitchell
Publications and source records attributed to L A Mitchell.
Adoptive transfer of enhanced eosinophilia and resistance to infection in mice by an in vitro generated T-cell line specific for Mesocestoides corti larval antigen.
A T-cell line specific for tetrathyridial antigens of the cestode parasite Mesocestoides corti was generated in vitro. The T-cells expressed the L3T4+ Ly2- phenotype and secreted the lymphokines: interleukin-1 (IL-1), interleukin-2 (IL-2), gamma interferon (IFN-gamma), colony stimulating factor (CSF), mast cell growth factor (MCGF) and eosinophil differentiation factor (EDF) in response to antigen stimulation. The line was stable for up to 16 weeks and produced an enhanced peripheral eosinophil response and a reduced parasite burden (40-50%) when adoptively transferred into naive recipients undergoing a primary infection.
Animals↗
Genetic control of immunity to Trichinella spiralis in mice. Response of rapid- and slow-responder strains to immunization with parasite antigens.
Slow-responder C57BL/10 (B10) mice responded poorly to immunization with muscle larval antigen of Trichinella spiralis showing no accelerated loss of worms from a subsequent challenge infection. In contrast, rapid-responder NIH mice and (B10 X NIH) F1 mice developed high levels of immunity after immunization. Lymphocyte proliferation studies showed that immunized B10 mice did respond to in vitro restimulation with antigen, though less well than NIH mice. Failure of B10 mice to respond to immunization did not therefore reflect a failure to recognize larval antigen, a view confirmed by the fact that immunization was achieved using abbreviated enteral infections and, to a smaller extent, by parenterally administered muscle larvae.
Animals↗
Interleukin-1 and interleukin-2 production in resistant and susceptible inbred mice infected with Trypanosoma congolense.
In vitro production of interleukin-1 (IL-1) by LPS-stimulated adherent peritoneal exudate and spleen cells and alveolar macrophages, and interleukin-2 (IL-2) by concanavalin A-stimulated splenocytes were measured in resistant (C57BL/6J) and susceptible (A/J) inbred mice during the early stages of subacute infections with the African trypanosome, Trypanosoma congolense. Production of IL-1 was severely depressed in both mouse strains as early as 24 hr after intraperitoneal injection of bloodstream trypanosomes. Similarly, in both mouse strains, an early decline in IL-2 activity was observed, followed by partial recovery then depression to subnormal levels. These changes in measurable IL-1 and IL-2 activity in infected mice concurred with progressive depression in the spleen cell proliferative response to the mitogen concanavalin A.
Animals↗
Antibody responses in resistant and susceptible inbred mice infected with Trypanosoma congolense.
Antibody responses were evaluated in inbred mice previously shown to be susceptible (A/J) or resistant (C57BL/6J and B6AF1 hybrid) to infections with relatively avirulent Trypanosoma congolense. Titres and the isotype distribution antibodies specific for the trypanosome variant surface glycoprotein (VSG) were determined by indirect immunofluorescence in sera of mice after primary infections with Trypanosoma congolense and after challenge infections with the same variant following drug cure. The results of these investigations showed that, during active infection, resistant mice made relatively strong VSG-specific IgM antibodies. This isotype also predominated in challenge infections with the homologous variant following drug cure. In contrast, A/J mice made little or no VSG-specific antibody on first exposure to T. congolense. However, these animals were able to produce substantial amounts of protective VSG-specific IgG antibody after multiple-challenge infections with the homologous variant. Substantial titres of VSG-specific antibodies in resistant mice did not influence the numbers of trypanosomes in the first parasitaemic peak as initial parastiaemias were similar in both C57BL/6J and A/J mice. However, C57BL/6J mice cleared parasites in this peak, whereas A/J mice did not. Mice of both strains immunized by infection cure were equally effective in clearing parasites when challenged with homologous trypanosomes. It is clear from the results of this study that antibody is not the sole factor contributing to murine resistance to African trypanosomes.
Animals↗
Kinetics of expulsion of the nematode, Nippostrongylus brasiliensis, in mast-cell deficient W/WV mice.
Mucosal mast-cell hyperplasia is frequently observed in intestinal nematode infections and it has been suggested that mast-cell responses to parasite antigens are involved in worm expulsion (self cure). To evaluate the importance of this mechanism, the course of infection and expulsion of Nippostrongylus brasiliensis was compared in mast-cell deficient W/WV and normal (+/+) mice. Initial infectivity rates were similar, but the subsequent kinetics of expulsion of adult worms differed principally in that the onset of expulsion in mast-cell deficient mice appeared to occur 24-36 h later than that in normal mice. Expulsion was complete by the 14th day post infection in both W/WV and normal mice. Worm fertility (as estimated by faecal egg output) also differed in W/WV and normal mice, with maximal egg output in W/WV mice occurring 24 h later than that in normal mice. Although a few mast cells were present in the intestinal mucosa and tongue of W/WV mice, their numbers did not change during the course of infection with N. brasiliensis. In contrast, worm expulsion in normal mice was associated with a moderate increase in numbers of intestinal mast cells, commencing at the onset of expulsion and peaking several days after expulsion was completed.
Animals↗
Antibody responses induced by immunization of inbred mice susceptible and resistant to African trypanosomes.
We tested the ability of inbred mice that were either susceptible (strain A/J) or resistant (strain C57BL/6 and A/J X C57BL/6 hybrids) to African trypanosomes to produce specific antibodies to trypanosome antigens in the absence of living parasites. This experiment was carried out to eliminate the influence of trypanosome growth or metabolism on immune responsiveness. Mice were immunized with keyhole limpet hemocyanin or solubilized Trypanosoma brucei gambiense, and serum antibodies were measured in solid-phase radioimmunometric assays after primary and challenge injections. Both susceptible and resistant mice showed increases in keyhole limpet hemocyanin-specific or trypanosome-specific immunoglobulin M and immunoglobulin G after immunization. When immunized with trypanosome antigens, resistant mice made qualitatively and quantitatively superior specific immunoglobulin M responses, particularly to the trypanosome major variable surface glycoprotein. Susceptible A/J mice produced good specific antibody responses, although these were predominantly of the immunoglobulin G isotypes. These results show that A/J and C57BL/6 mice respond differentially in terms of immunoglobulin isotype and repertoire in response to injected antigens. The possibility that this differential antibody response influences susceptibility to African trypanosomes is discussed.
Animals↗
Extrapulmonary influences on A-aD021.0 following cardiopulmonary bypass.
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Blood Gas Analysis↗
Recognition of contiguous allele-specific peptide elements in the rubella virus E1 envelope protein.
Peptides which bind to human HLA-DRB1 class II molecules in an allele-specific fashion were derived from the immunodominant E1 envelope protein of rubella virus. Two nonoverlapping E1 peptide epitopes were recognized by rubella virus-specific T cells in the context of independent HLA alleles when presented either separately or as a contiguous polypeptide containing both epitopes. Direct binding analysis of potential peptide epitopes to distinct HLA molecules provides a direct approach for selecting antigenic peptides useful for epitope-based vaccine targeted to multiple HLA types.
Alleles↗
Thermodilution and Fick cardiac index determinations following cardiac surgery.
With the thermodilution technique, repeated determination of cardiac index (CI) has become a rapid, easily accomplished, safe procedure. We paired 77 CI determinations measured by direct Fick and thermodilution techniques in 21 patients who underwent myocardial revascularization. Commercially available thermistor-tipped catheters and a cardiac output computer were used to determine CI according to the manufacturer's instructions. Oxygen consumption and arterial-venous oxygen content differences were measured directly to determine CI by the Fick method. Comparisons were made during mechanical ventilation with and without positive end-expiratory pressure (PEEP) and during spontaneous ventilation with and without PEEP. Cardiac indices measured by the two techniques were within +/- 0.5 L/min/m2 of each other only 76% of the time and within +/- 1.0 L/min/m2 96% of the time, if CI greater than or equal to 4.0 L/min/m2 were omitted. Ventilatory pattern had no apparent effect on results.
Cardiac Output↗
Pulmonary effects of ventilatory pattern following cardiopulmonary bypass.
Twenty-one patients who underwent cardiopulmonary bypass for myocardial revascularization received postoperatively controlled mechanical ventilation (CMV) or intermittent mandatory ventilation (IMV), with or without positive end-expiratory pressure (PEEP). Functional residual capacity (FRC), right-to-left intrapulmonary shunt, dynamic compliance, physiological dead space, and arterial and mixed venous blood gases were measured during mechanical ventilation and spontaneous ventilation following weaning. Controlled ventilation increased physiological dead space and arterial pH. FRC correlated positively with dynamic compliance, but not with right-to-left intrapulmonary shunt. Postoperatively, FRC was significantly lower than normal when patients were ventilated without PEEP, but was normal when patients received PEEP. Arterial oxygen tension (PaO2), intrapulmonary shunt, and dead space were unaffected in spite of higher FRC, suggesting that patients who received PEEP had fewer atelectatic and fewer unperfused "silent" lung units than those who had not received PEEP.
Cardiopulmonary Bypass↗
Experience with diffusion-weighted imaging in an acute stroke unit.
We performed diffusion-weighted MRI (DWI) on a standard 1.5-tesla MRI scanner using a high-speed stimulated echo pulse sequence (turboSTEAM) in 9 stroke patients and 9 control subjects to investigate whether this technique can be used clinically to assist in ischaemic stroke diagnosis within the time frame for potential therapy. Stroke patients underwent DWI between 3.75 h and 3 days after stroke onset. Three patients were studied on more than one occasion. DWI was normal in the 9 controls. Seven of 9 stroke patients showed areas of increased signal on DWI. DWI detected cerebral ischaemia 3.75 h after stroke onset when both CT and T2-weighted MRI were normal. In 6 DWI-positive patients studied at later times, increased signal on T2-weighted images was present at the same time. Two patients had normal CT, T2-weighted and DWI images; both made good neurological recoveries. For the routine assessment of stroke patients, DWI implemented on a standard MRI system can provide additional information of clinical value to that obtained with conventional pulse sequences. In particular it facilitates early detection of cerebral ischaemia during the first few hours after stroke.
Adult↗
Cancer plasma effects on skeletal muscle metabolism.
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Animals↗
Serologic responses to measles, mumps, and rubella (MMR) vaccine in healthy infants: failure to respond to measles and mumps components may influence decisions on timing of the second dose of MMR.
Measles, mumps, and rubella-specific IgG antibodies were evaluated in 134 healthy infants routinely immunized with trivalent live attenuated measles-mumps-rubella (MMR) vaccine at one year of age. Blood samples were collected just before, and at 1, 3, and 12 months after MMR. Specific IgG was measured by commercial enzyme immunoassays. Before vaccination, 98.5%, 99.2%, and 98.5% of the infants tested were seronegative for measles, mumps, and rubella, respectively. One year after MMR, 16.4% and 22.4% of vaccinees lacked demonstrable antibody to measles and mumps while none were found to be seronegative for rubella. Response profile analysis revealed primary failure rates of 12.1% (measles) and 8.6% (mumps) while 4% (measles) and 13.8% (mumps) of the infants responded initially but became seronegative within one year. These observations suggest that earlier administration (at age 18 months) of the second dose of MMR may be more desirable than revaccination at school entry.
British Columbia↗