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Biomedical subjects

C Hale

Publications and source records attributed to C Hale.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1981

Induction and persistence of B-cell tolerance to the thymus-dependent component of the alpha(1 leads to 6) glucosyl determinant of dextran. Recovery induced by treatment with dextranase in vivo.

A direct comparison was made between thymus-dependent (TD) and thymus-independent (TI) responses in mice tolerized for (1 leads to 6) glycosyl determinants by the injection of dextran B512. Long-lasting B-cell tolerance by dextran was reversed when mice were treated with dextranase in vivo. Complete or partial reversion of tolerance with the enzyme was invariably obtained for the TI response but the TD component proved to be more resistant and dependent on the immunogen used to test the reversion. The uniformity of the spectrotype in BALB/c mice, even under conditions of partial tolerance, permitted the analysis by isoelectric focussing of serum from tolerant mice treated with dextranase and immunized with TD dextran-ovalbumin. Results showed that, with one single exception, mice thus treated produced spectrotypes no different from the pattern normally found in immune animals. The results presented suggest that at least some alpha(1 leads to 6) specific B cells, both TD and TI, persist in tolerized mice for at least 2 weeks after tolerance induction and they do not support the concept of clonal elimination for either TI or TD responses in adult mice.

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

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↗
PubMed1979

Characteristics of the T-dependent alpha(1 leads to 6) glucosyl (dextran) antibody response induced in mice with isomaltohexaose coupled to chicken gamma-globulin.

Isomaltohexaose flavazole coupled to chicken gamma-globulin (IM6-CGG) induced T cell-dependent anti-alpha(1 leads to 6) dextran-specific IgM and IgG responses in CBA, BALB/c and A strain mice. The IgG responses were of restricted heterogeneity as judged by isoelectric focusing, and belonged mostly to the IgG1 subclass with a minor IgG3 component in the case of BALB/c and CBA mice. All four subclasses of IgG were produced in A strain mice. In contrast, native dextran B 512 induces exclusively T cell-independent IgM responses of the same specificity for all 3 strains. All BALB/c mice immunized with different doses of IM6-CGG either in Freund's adjuvant or with Al(OH)3 plus Bordetella pertussis showed the same spectrotypes by isoelectric focusing. Sera obtained at different times after immunization of BALB/c mice failed to show spectrotype variations. Late, but not early, bleedings from CBA mice showed a tendency towards more uniform isoelectric focusing patterns.

Animals↗
PubMed1978

Tardive dyskinesia and antihistamines.

A case of tardive dyskinesia due to the prolonged administration of antihistamines is reported. Clinical features are discussed, as well as the alleviation of these by haloperidol.

Dyskinesia, Drug-Induced↗
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

Blockade of specific antibody-forming cells in vivo by dextrans and levans.

Fractions of dextrian (DE) B512, DE B1355 and levan (LE) have been shown to induce a specific blockade of antibody-forming cells (AFC) when injected into previously immunized mice. Whereas specific blockade with DE B512 (450 000 daltons) was easily induced by as little as 10 mug, blockade to LE and DE B1355 was more resistant and required 1 and 10 mg, respectively. AFC blockade and tolerance are dissociable phenomena, as the former effect could be achieved with nontolerogenic low mol. wt DE B512 (10 000 daltons). Conversely, perennial rye grass fructosan (7600 daltons), which is tolerogenic for LE, did not induce a blockade. Furthermore, blockade of anti-DE response specific for alpha (1 leads to 3)-linked glucosyl determinants was achieved in BALB/c mice, whereas attempts to induce stable tolerance have been unsuccessful.

Animals↗
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↗