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Biomedical subjects

J G Howard

Publications and source records attributed to J G Howard.

At least 73 records · Page 4Linked to original sources
PubMed1981

Comparison of various extenders for freeze-preservation of semen from selective captive wild ungulates.

Semen collected by electroejaculation from selected captive wild ungulates was used to evaluate the cryoprotective ability of 4 semen diluents. Three species of ungulates were used: blesbok (Damaliscus dorcas phillipsi), dorcas gazelle (Gazella dorcas), and onager (Equus hemionus onager). Fresh semen was immediately evaluated for the percentage of motility and the progressive motility, and an aliquot was fixed for evaluation of the acrosomal integrity of spermatozoa. The remaining volume of ejaculate was divided into equal aliquots and either frozen raw on dry ice or extended with each of the 4 diluents. Samples were concurrently equilibrated at 5 C, frozen on dry ice, and stored in liquid nitrogen. Aliquots were thawed for evaluation of motility traits and spermatozoal acrosomes. Each diluent provided cryoprotection in each species. However, spermatozoa varied in ability to survive cryopreservation, and postthaw viability was influenced by the semen diluent used. Although ineffective in the onager, the study of morphologic forms of spermatozoal acrosomes proved useful for assessing the cryoprotective property of semen diluents in the blesbok and dorcas gazelle.

Acrosome↗
PubMed1981

Immunological regulation of experimental cutaneous leishmaniasis. IV. Prophylactic effect of sublethal irradiation as a result of abrogation of suppressor T cell generation in mice genetically susceptible to Leishmania tropica.

The overwhelming susceptibility of BALB/c mice to infection with Leishmania tropica can be substantially reversed by immediately prior sub-lethal irradiation. This is related to radiation dosage, and at 550 rad, causes 60 percent complete cures and only 19 percent (instead of 100 percent) incidence of progressive disease. Irradiation 10 d before infection is only weakly prophylactic, whereas 10 d after is without effect. Control of lesion development is only apparent after the first 30 d, coincident with the analogous onset previously found in resistant strains and adult thymectomized, x-irradiated, bone marrow-reconstituted BALB/c mice. Instead of the specific suppression of DTH characteristic of L. tropica infection in the BALB/c strain, healed irradiated mice express strong anti-leishmanial DTH reactivity and resistance to reinfection. T cells from these mice transfer DTH reactivity which is suppressed by admixture with cells from nonhealed, nonreactive donors. Irradiated BALB/c mice again develop inexorable disease progression, after its transient arrest, when they are reconstituted with normal T cells. When the T cells are derived from uncontrollably-infected donors, the susceptibility regained is indistinguishable from that of normal mice. B cells do not modify the prophylactic effect of 550 rad, whereas T cells from healed mice confer strong protective immunity throughout the initial phase. Regression or progression of disease correlates completely with DTH reactivity in all these groups. Although BALB/c mice express an extreme level of genetic susceptibility to L. tropica infection, they are nevertheless capable of mounting a curative cell mediated immune response. That this is ineffective during pathogenesis of the disease was previously associated correlatively with potent specific suppressor T cell generation, which is now shown to be preventable by prior irradiation. Most important, however, a causal role for these cells in vivo has been demonstrated directly by reconstitution.

Animals↗
PubMed1981

Immunological regulation of experimental cutaneous leishmaniasis. 2. Studies with Biozzi high and low responder lines of mice.

Susceptibility to Leishmania tropica was studied in Biozzi 'high' (Ab/H) and 'low' (Ab/L) responder mice of Selections I and III which, although originally selected with heterologous erythrocytes and Salmonella flagellar antigens respectively, both show non-specific separation of antibody responses. Ab/H Sel I produce only small lesions, even with the largest infecting dose, which heal after 2 months with minimal antibody responses. Specific delayed-type hypersensitivity (DTH) levels found in both are normal and equivalent. (Ab/H x Ab/L)F1 mice behave intermediately. A smaller inter-line difference is only detectable in Sel III with lower infecting doses. Both Ab/L and Ab/H mice given high doses develop chronic non-healing disease. These results imply that spontaneous resolution of cutaneous L. tropica lesions during the immune phase is independent of humoral antibody. While the great resistance and slower development of lesions found in Ab/L Sel I are entirely consistent with the macrophage 'hyperactivity' characteristic of the line, attempts to demonstrate this in vitro with comparisons of infected peritoneal exudate have been inconclusive so far.

Animals↗
PubMed1980

Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica.

BALB/c mice have been an exceptional susceptibility to Leishmania tropica infection such that cutaneous lesions grow without restraint in all cases leading to fatal metastasis and visceralization in normal and x-irradiated, bone-marrow reconstituted (XBM) animals. Adult thymectomized, x-irradiated, bone marrow-reconstituted (ATxXBM) BALB/c mice, however, show pronounced retardation of lesion growth leading to some survival and even cures. A similar trend was also found in moderately susceptible (BALB/c X C57BL/6)F1 mice, in contrast with the "resistant" CBA strain, in which, as previously known, ATxXBM animals showed impairment of normal, spontaneous self-healing. These convere effects are paralleled by respective leishmania-specific delayed-type hypersensitivity (DTH) reactivities, prior thymectomy leading to diminution in CBA and augmentation in BALB/c and (BALB/c X C57BL/6)F1. Anti-leishmanial DTH responses, amplfiable by cyclophosphamide pretreatment, can be detected in BALB/c mice within 10 d of infection with 2 X 10(7) promastigotes, but becomes near-totally suppressed by day 25-35. No such suppressin is found in CBA, C57BL/6, or (BALB/c X C57BL/6)F1 mice together with varying degrees of immune control of lesion development or regression. Suppression of DTH in BALB/c mice is leishmania specific and does not extent to 2,4-dinitrofluorobenzene (DNFB) or sheep erythrocytes specificities. Spleen cells from suppressed L. tropica-infected mice when transferred to normal BALB/c mice impaired the induction of DTH to leishmanial antigen. This property resided in the T cell-enriched fraction and not in the T cell-depleted fraction. It is concluded that a major component of the striking inability of BALB/c mice to control L. tropica infection involves profound impairment of a potentially curative cell-mediated immune response by suppressor T cell generation. The possibility is discussed that this may be secondary to rapid amastigote (antigen) accumulation in macrophages expressing the primary genetic "defect."

Animals↗
PubMed1980

Regulation of delayed-type hypersensitivity. V. Suppressor cell memory in antigen-specific suppression of delayed-type hypersensitivity to sheep erythrocytes.

Mice printed i.v. wit 10(9) sheep red blood cells (SRBC) produce antigen-specific T suppressor (Ts) cells which inhibit both the induction and the expression of delayed-type hypersensitivity (DTH). These Ts cells are detectable in the spleen and lymph nodes 3-5 days after priming but are largely absent by 6 days. The transient detectability of the Ts cells contrasts sharply with the profound antigen-specific suppression which persists in primed donor mice for at least a year. Evidence is presented that this long-term impairment of DTH is maintained, at least in part, by memory Ts cells which are Thy-1+, cyclophosphamide-resistant and antigen-specific. Although they appear to be co-induced with the short-lived primary Ts cells and localize initially in the lymphoid organs, they are present in the long-lived circulating pool of T cells and can be adoptively transferred by celomic parabiosis. Memory Ts cells are readily reactivated by lower doses of SRBC which would induce T effector cells rather than Ts cells in naive animals. Reactivated memory Ts cells seem to generate a population of antigen-specific secondary Ts cells which again localizes in the lymphoid organs and can adoptively suppress the induction and expression of DTH to SRBC.

Animals↗
PubMed1980

Immunological regulation of experimental cutaneous leishmaniasis. 1. Immunogenetic aspects of susceptibility to Leishmania tropica in mice.

Models of the different disease patterns of cutaneous leishmaniasis can be induced by the same dose of L. tropica promastigotes in various inbred strains of mice. The susceptibility of BALB/c is exceptional, essentially dosage independent (being demonstratable with as few as 20 parasites) and leads to huge progressive lesions with fatal visceral and cutaneous metastasis. Lesions also extend progressively but more slowly in BDA/1 and BDA/2 mice. Strains A C57BL/6 and CBA are relatively resistant to even 2 X 10(7) promastigotes, with arrest of lesion growth within 3 weeks and subsequent gradual healing. Similar resistance of A.SW to 2 X 10(5) is overcome by a larger dose. The major inter-strain differences are H-2 independent, for C57BL/10 congenic mice possessing six different H-2 antigen complexes all show early arrest of lesion growth leading to healing (H-2s, H-2a, H-2k) or mild residual disease (H-2b, H-2d, H-2q). Inter-line differences within the latter group varied between experiments such that no clear rank order emerged. Inexorable disease progression was found in congenic BALB/B, BALB/c, and BALB/K alike, although it was significantly slower in the latter line when infected with smaller doses. Genetic control of BALB/c susceptibility is thus predominantly in the non-H-2 background with only a minor H-2 linked regulatory influence in the later stage. C57BL/6, BALB/c and their F1 hybrid characteristically display "healing", "fatal progressive" and "non-healing" lesions respectively over a wide dose range. "BALB/c-like" susceptibility segregates strictly in the F2 and backcross progeny according to a one predominant gene prediction. A comparison of the present data with those concerning genetic regulation of acute and chronic stages of systemic. L. donovani infection in mice (Bradley, 1977, Blackwell, Freeman & Bradley 1980) reveals differing control for the outcome of cutaneous L. tropica infection, in which other important genetic influences must be involved.

Animals↗
PubMed1976

Lack of neonatal susceptibility to induction of tolerance by polysaccharide antigens.

Susceptibility to tolerance induction by polysaccharides during the neonatal period has been studied with the alpha-1.3 and alpha-1.6 glucosyl epitopes of dextran B1355 in BALB/c mice and the beta-2.6 fructosyl epitope of levan in CBA mice. Acquisition of responsiveness, as measured by plaque-forming cell (PFC) assays, is relatively late - taking more than 14 days to appear and 2 - 3 months to attain maturity in the case of alpha-1.6 glucosyl and beta-2.6 fructosy. The mice responded well to sheep red blood cells and 2,4-dinitrophenylated (DNP) keyhole limpet hemocyanin (KLH) by 14 days, but were refractory to another thymus-independent antigen DNP-Ficoll. Nonresponsiveness of 2-week-old spleen cells to the polysaccharides was stable on transfer and could not be attributed to suppressor cells. Despite this long post-natal phase of immaturity, no evidence was obtained of concomitant susceptibility to tolerance induction by textran and levan. Response curves in mice injected at birth with weight-adjusted doses revealed similar or even higher "high-zone" thresholds to those tolerized at 3 months. Only partial alpha-1.3 glucosyl tolerance is inducible in adults but this was no greater after neonatal exposure, which led also to short-lived alpha-1.6 tolerance. Repeated injections of B1355 and levan during the first 10 days was no more tolerogenic and PFC appeared spontaneously with maturity in mice given these antigens neonatally. Thus, the recognized neonatal susceptibility to thymus-dependent antigens does not extend to these thymus-independent antigens. It is therefore considered that tolerance studied with polysaccharides has little relevance to the mechanism of self-tolerance acquired in the embryo and, in vivo, is determined by interaction with a relatively mature B cell rather than by "clonal abortion" of a tolerance-sensitive precursor stage.

Age Factors↗
PubMed1976

Lack of effect of thymectomy on spontaneous recovery from tolerance to levan.

Adult CBA mice were made tolerant with 1 mg levan and tested subsequently for sponteneous recovery by plaque-forming cell assay in response to immunizing challenge. Weakening of tolerance was first detectable only after 100 days, while return to full normal responsiveness required 400 days. Thymectomy 2 weeks prior to tolerization neither retarded nor diminished the recovery process. Loss of tolerance which had been induced by 1 mg dextran B512 was much slower in onset (greater than 250 days), yet not delayed by thymectomy (full recovery was not followed). These findings in relation to other considerations imply that associative recognition by T cells is not required for B cell responses to these "thymus-independent" antigens.

Animals↗
PubMed1976

Influence of reticuloendothelial blockade on the induction of tolerance and immunity by polysaccharides.

The intensity of reticuloendothelial blockade by carrageenan, silica and ethyl stearate was measured and its effect studied on the susceptibility to tolerance induction by polysaccharide antigens in mice. The most intense RE depression reduced the tolerance threshold dose of levan only by 3-fold and that of dextran B512 not at all. The genetic resistance of BALB/c mice to tolerization with the alpha1-3 glucose epitope of dextran B1355 was not overcome by carrageenan blockade which did however, render them normally susceptible to tolerance induction by human gamma-globulin. PFC responses to immunization by the polysaccharides were diminished by blockade, relative to its intensity and to the antigen itself. These and other data suggest that severe RE blockade (a) can promote tolerance by suppressing the active role(s) of the macrophages in immune induction rather than by sustaining circulating antigen, and (b) depresses responses to thymus-independent antigens, probably by an immunosuppressive influence mediated by damaged macrophages.

Animals↗