Immunological and pharmacological analysis of the primary and secondary reagin response to Nippostrongylus brasiliensis in the rat

When systemic anaphylaxis has been induced in rats infected once with the nematode, Nippostrongylus brasiliensis, the gross pathological lesions are found in the small intestine (`early' anaphylaxis). When systemic anaphylaxis is induced in rats infected four times, these lesions appear predominantly in the lungs (`late' anaphylaxis). The reasons for the change in localization of the lesions have been studied.

Reaginic antibodies are involved in both `early' and `late' anaphylaxis but there was no difference in the physicochemical and biological properties of circulating reagins taken after one or after four infections. In particular, no differences in their preference for a distinct tissue structure was detected because, in rats given either `early' or `late' reaginic antibody, passive systemic anaphylaxis resulted in lesions restricted to the small intestine. The amount of `blocking' antibody increased after several successive infections and did not explain the decrease in sensitivity to systemic anaphylaxis which occurred in rats infected twice or three times.

Differences in the degree of anaphylactic sensitization of a given tissue were assessed by measuring titres of local reaginic antibody and concentrations of tissue histamine. Following an initial infection, anaphylactic sensitization is highest along the small intestine; following several successive infections, anaphylactic sensitization is especially high in lung tissue. It is suggested that the changes in the local site and degree of anaphylactic sensitization are due to the increase in immunity of the host which allows the parasite to migrate to the lungs but not to reach the intestine.

     

The morphology of immune reactions in normal, thymectomized and reconstituted mice: I. The response to sheep erythrocytes

The response to sheep red blood cells has been studied in the lymph nodes draining their site of injection in normal mice, and in thymectomized, irradiated, bone-marrow injected mice with and without a reconstituting thymus graft. By using a chromosome marker to differentiate between cells derived from the bone-marrow and thymus graft it has proved possible to show that the immune response should be thought of in terms of at least two cell populations. Cells of thymic origin are stimulated to mitotic activity in the interfollicular cortex, and their activity precedes both antibody production and morphological signs of activity in the follicular regions. Mitotic divisions of cells of bone-marrow origin reached a peak a day later than did the thymic cells and their activity was sustained. Follicular enlargement and germinal centre production were coincident in time both with antibody production and bone-marrow cell mitotic activity. Lymph nodes of animals lacking a thymic influence showed only minor changes after antigenic stimulation and these were restricted to the follicular regions. There appeared to be only a small quantitative difference between the responses of normal and of reconstituted animals.     

Prospective evaluation of the new chromogenic medium Candida ID, in comparison with Candiselect, for isolation of molds and isolation and presumptive identification of yeast species

We conducted a prospective evaluation of Candida ID chromogenic medium (bioMérieux, Marcy l'Etoile, France) with 786 clinical specimens in comparison with Candiselect medium (Bio-Rad, Marnes la Coquette, France). Candida ID chromogenic medium identified 97.7% of Candida albicans strains; enabled presumptive identification of C. tropicalis, C. lusitaniae, C. guillermondii, and C. kefyr and better detection of yeast combinations (11.4% more often); and was more sensitive for the isolation of filamentous fungi (17.7% more often). However, Candida ID chromogenic medium appeared to be less selective vis-à-vis bacteria, with bacterial colonies sometimes pigmented blue.     

Human natural killer cells mediate killing of intracellular Mycobacterium tuberculosis H37Rv via granule-independent mechanisms

Despite the continued importance of tuberculosis as a world-wide threat to public health, little is known about the mechanisms used by human lymphocytes to contain and kill the intracellular pathogen Mycobacterium tuberculosis. We previously described an in vitro model of infection of human monocytes (MN) with virulent M. tuberculosis strain H37Rv in which the ability of peripheral blood lymphocytes to limit intracellular growth of the organism could be measured. In the current study, we determined that lymphocyte-mediated killing of intracellular M. tuberculosis occurs within the first 24 h of coculture with infected MN. Natural killer (NK) cells isolated from both purified protein derivative (PPD)-positive and PPD-negative subjects were capable of mediating this early killing of intracellular H37Rv. NK cell-mediated killing of intracellular M. tuberculosis was not associated with the production of gamma interferon. Transferred supernatants of cocultured NK cells and M. tuberculosis-infected MN could not mediate the killing of intracellular M. tuberculosis, and Transwell studies indicated that direct cell-to-cell contact was required for NK cells to mediate the killing of the organism. Killing was not dependent upon exocytosis of NK cell cytotoxic granules. NK cells induced apoptosis of mycobacterium-infected MN, but neither killing of intracellular M. tuberculosis by NK cells nor NK cell-induced apoptosis of infected MN was inhibited by blocking the interaction of FasL and Fas. Thus, human NK cells may mediate killing of intracellular M. tuberculosis via alternative apoptotic pathways.     

A 1463 gene cattle-human comparative map with anchor points defined by human genome sequence coordinates

A second-generation 5000 rad radiation hybrid (RH) map of the cattle genome was constructed primarily using cattle ESTs that were targeted to gaps in the existing cattle-human comparative map, as well as to sparsely populated map intervals. A total of 870 targeted markers were added, bringing the number of markers mapped on the RH(5000) panel to 1913. Of these, 1463 have significant BLASTN hits (E < e(-5)) against the human genome sequence. A cattle-human comparative map was created using human genome sequence coordinates of the paired orthologs. One-hundred and ninety-five conserved segments (defined by two or more genes) were identified between the cattle and human genomes, of which 31 are newly discovered and 34 were extended singletons on the first-generation map. The new map represents an improvement of 20% genome-wide comparative coverage compared with the first-generation map. Analysis of gene content within human genome regions where there are gaps in the comparative map revealed gaps with both significantly greater and significantly lower gene content. The new, more detailed cattle-human comparative map provides an improved resource for the analysis of mammalian chromosome evolution, the identification of candidate genes for economically important traits, and for proper alignment of sequence contigs on cattle chromosomes.     

Factors associated with BMI, weight perceptions and trying to lose weight in African-American smokers

This study examined sociodemographic, behavioral and psychosocial factors associated with BMI, weight perceptions and trying to lose weight among African-American smokers (N=600, M=44.2 years, 70% female). Sixty-eight percent of the sample were overweight or obese (sample BMI M=28.0, SD=6.7). Three separate, simultaneous multivariable regression models were used to determine which factors were associated with BMI, weight perceptions and trying to lose weight. Poorer health, female gender and high-school education or higher were significantly associated with higher BMIs (p<0.05). Being female (OR=5.8, 95% CI=3.6-9.3) and having a higher BMI (OR=0.6, 95% CI=0.5-0.6) was associated with perception of overweight and smoking more cigarettes per day (OR=1.0, 95% CI=1.0-1.1), and perceiving oneself as overweight (OR=14.1, 95% CI=8.2-24.2) was associated with trying to lose weight. Participants somewhat underestimated their BMI in their weight perceptions. Those who perceived themselves as overweight were more likely to be trying to lose weight; therefore, increasing participant awareness of actual BMI status may lead to improved weight-control efforts in African-American smokers. Several expected associations with outcomes were not found, suggesting that BMI and weight constructs are not well-understood in this population.     

Anger Cognitions and Cardiovascular Recovery Following Provocation

The current study describes the creation and validation of the Anger Cognitions Inventory (ACI) to assess the cognitive appraisals associated with resentful and reflective anger. The ACI was created based on a content analysis of self-reports of participants' thoughts and feelings following anger provocation in the laboratory. Exploratory and confirmatory factor analyses on two separate college student samples (N = 267 and N = 276, respectively) revealed five subscales which could validly be grouped into resentful and reflective anger. Convergent and divergent validity data showed that resentful anger correlated positively with anger-out/trait anger and reflective anger correlated positively with anger-in/brooding. A second study showed positive correlations between rumination and delayed cardiovascular recovery following anger provocation. Limitations of both studies include restricted samples which limit generalizability of results and cardiovascular recovery data collected in Study II which does not include assessment of autonomic balance between vagal and sympathetic responsivity.