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C Betts

Publications and source records attributed to C Betts.

13 recordsLinked to original sources
PubMed1998

Nitric oxide produced in the lungs of mice immunized with the radiation-attenuated schistosome vaccine is not the major agent causing challenge parasite elimination.

Mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni exhibit high levels of protection against a challenge with normal larvae. The immune effector mechanism, which operates against schistosomula in the lungs, requires CD4+ T cells capable of producing interferon-gamma (IFN-gamma). This cytokine can stimulate production of nitric oxide (NO), via its ability to up-regulate inducible nitric oxide synthase (iNOS). We have therefore evaluated the potential role of NO in the effector mechanism operating in vaccinated mice. Evidence for the production of NO in the lungs of such animals was obtained from assays on antigen-stimulated airway cell cultures. Enhanced levels of NO, compared with those in cultures from control mice, were detected both after vaccination and after challenge; elevated levels of iNOS mRNA were also present in whole lung after challenge. However, administration of an iNOS inhibitor to vaccinated mice after percutaneous challenge did not significantly increase the worm burden. Furthermore, when mice with a disrupted iNOS gene were vaccinated they showed a highly significant level of protection. Although NO from activated macrophages can mediate cytotoxic killing of newly transformed schistosomula in vitro, we have demonstrated that the addition of erythrocytes to these larvicidal assays abolishes its effects. We interpret this to mean that once migrating schistosomula enter the bloodstream they will be protected against the cytotoxic actions of NO. Our data thus provide little evidence to implicate NO as a major component of the pulmonary effector response to S. mansoni in vaccinated mice.

Animals↗
PubMed1996

Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-gamma receptor gene exposed to the irradiated Schistosoma mansoni vaccine.

A high level of protection against Schistosoma mansoni is elicited in mice by the irradiated cercaria vaccine and interferon-gamma (IFN-gamma) is a key cytokine in the pulmonary effector response. The role of this cytokine has been investigated in mice with a targeted disruption of the IFN-gamma receptor gene (IFN-gamma R-/- mice). The level of protection was impaired relative to that elicited in C57BL/6 and 129 wild-type (WT) animals. These two groups developed compact effector foci, of largely mononuclear cell composition, around individual challenge parasites migrating through the lungs. In contrast the IFN-gamma R-/- mice showed a massive and generalized leucocytic infiltration of the airways and interstitium in which eosinophils were a prominent feature. Cultures of airway leucocytes from C57BL/6 mice produced abundant IFN-gamma whilst those from IFN-gamma R-/- mice produced interleukin-4 (IL-4), IL-5 and IL-10, indicating default to the Th2 pathway; the WT animals showed an intermediate response. The pattern of cytokine gene transcripts in whole lung tissue agreed remarkably well with the level of cytokine protein detected in leucocyte cultures, with the exception of substantial IL-4 mRNA but negligible protein in C57BL/6 mice. The loose but intense infiltrate of leucocytes in the lungs of IFN-gamma R-/- mice was clearly ineffective in eliminating challenge parasites, whereas the level of IFN-gamma protein and mRNA in the lungs of C57BL/6 and WT mice correlated with the size and compactness of effector foci. On the basis of these and earlier observations, we suggest that a primary role for IFN-gamma is to promote intercellular adhesion between the leucocytes in an effector focus, promoting its ability to block parasite migration.

Animals↗
PubMed1996

Kinetics and mechanism of effector focus formation in the lungs of mice vaccinated with irradiated cercariae of Schistosoma mansoni.

The sequence of events involved in effector focus formation around challenge schistosomula in the lungs of mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni has been characterized following intravenous administration of lung stage larvae. Histopathological analysis of the lungs of vaccinated animals revealed that infiltrating cells were present around larvae within 24 h. The main increment in cell recruitment occurred between 2 and 4 days, with foci reaching maximal diameter on day 8. No additional infiltration of the airways was detected by bronchoalveolar sampling before day 4 when the maximum number of cells, predominantly lymphocytes, was recovered. In contrast, responses in challenge control animals were relatively slight prior to day 12. IFN gamma was the major cytokine in airway cultures from vaccinated mice, the greatest increment in production coinciding with peak cell recruitment. A similar pattern of IFN gamma mRNA expression was observed in whole lung extracts, highlighting the dominance of Th1 responses in the effector mechanism. The slow start to focus formation may be due to the need for antigen, released by the intravascular parasite, to be translocated across the endothelium, processed by accessory cells and presented to the helper T cells which orchestrate the effector mechanism. The delay is of the same order as the period of development which the parasite must undergo in the lung, to facilitate further migration. This similarity in the timing may explain why some larvae are able to avoid the consequences of the pulmonary effector response.

Animals↗
PubMed1994

The behaviour of nuclear domains in the course of apoptosis.

Programmed cell death is activated, by different stimuli and in many cell types, to regulate cell population balance during tissue proliferation and embryogenesis. Its initial event seems to be, in most cases, the activation of a Ca(2+)-dependent endonuclease, causing DNA cleavage into nucleosomic fragments. Its morphological expression is characterized by deep nuclear changes, consisting of typical cap-shaped chromatin marginations, followed by nuclear fragmentation and final formation of numerous micronuclei. Cytoplasmic damage appears in a very late stage of the process and the greatest part of the phenomenon appears to take place despite good preservation of the plasma membrane and organellar component. In the present study we analyzed apoptosis in camptothecin-treated HL60 leukaemia cells, and in freshly isolated mouse thymocytes treated with dexamethasone. The process was first quantified and time monitored by flow cytometry. Subsequently the specimens were processed for morphological examination in order to investigate the behaviour of the different nuclear domains. To follow DNA and RNA localization, we utilized osmium ammine and DNase-colloidal gold cytochemical reactions. The concentration of most DNA in the cap-shaped structures was demonstrated by these reactions. Confocal microscopy of cells processed by in situ nick-translation suggested that DNA was firstly cleaved and subsequently condensed in cup-shaped structures. Despite the strong nuclear modifications, nucleoli could be clearly recognized until the late apoptotic stages.

Animals↗
PubMed1994

HIV/AIDS and its interaction with tuberculosis in Latin America and the Caribbean.

At present, human immunodeficiency virus (HIV) is thought to have infected over 17 million people worldwide, over 1 million in North America and roughly 2 million in Latin America and the Caribbean. By comparison, infection with the tuberculosis (TB) agent Mycobacterium tuberculosis is far more common, current estimates indicating that roughly one-third of the world's population is infected. These two infections tend to aggravate each other. That is, HIV leads to a progressive immune system depression that favors reactivation of TB in people with latent tuberculous infections; it promotes progression of TB primary infections or reinfections to full-blown tuberculous disease; and it fosters TB transmission, because those simultaneously infected with HIV and M. tuberculosis tend to develop a bacilliferous and contagious TB that can be transmitted to other susceptible individuals, even though the latter are HIV-negative. In addition, this coinfection tends to promote circulation of drug-resistant M. tuberculosis and to produce peculiar manifestations that complicate TB diagnosis, treatment, and control. Overall, it seems clear that the growing threat posed by these associated agents demands effective action in the form of well-coordinated measures involving throughgoing participation by all countries.

AIDS-Related Opportunistic Infections↗
PubMed1984

Apocrine differentiation in lobular carcinoma of the breast: a morphologic, immunologic, and ultrastructural study.

The frequency of apocrine differentiation in breast carcinomas, assessed on purely morphologic grounds, is controversial. Apocrine differentiation in two cases of lobular carcinoma in situ (lobular neoplasia; LCIS) is reported for the first time. Using an immunohistochemical method for the detection of GCDFP-15, a protein present in apocrine epithelium and in the fluid of tension cysts of the breast, the apocrine differentiation in LCIS is confirmed. The histiocytoid variant of invasive lobular carcinoma is shown to be "apocrine" in nature, antigenically at least. The ultrastructural findings in one case of histiocytoid carcinoma are discussed in the context of an apparent discrepancy between the morphologic features of this tumor and the presence of an apocrine antigenic marker.

Adult↗