Search PubMed⌕ Search

Biomedical subjects

K Connolly

Publications and source records attributed to K Connolly.

At least 37 records · Page 2Linked to original sources

School breakfast improves verbal fluency in undernourished Jamaican children.

School feeding programs exist in many countries, but few have been properly evaluated. In this study, the short-term effects of breakfast on children's cognitive functions were examined. The subjects were 97 undernourished (weight-for-age < or = -1 SD of reference) and 100 adequately nourished (weight-for-age > -1 SD) children in four primary schools in rural Jamaica. The children were randomly assigned to a group provided with breakfast or a group given a quarter of an orange as a placebo, and then given a battery of four cognitive function tests. After a few weeks the treatments were reversed and the tests repeated. Undernourished children's performance improved significantly on a test of verbal fluency when they received breakfast, whereas that of the adequately nourished children did not change (breakfast x group interaction, P < 0.05). There were no other effects of breakfast on test scores. The findings extend those of a previous Jamaican study conducted under more controlled conditions, and support the targeting of school meals to undernourished children.

Child↗

Behavioural correlates of selection for oviposition by Drosophila melanogaster females in a patchy environment.

The behaviour of females from lines selected for high (H) and low (L) aggregated oviposition was compared in an environment consisting of discrete patches of resource available for larval development. Oviposition behaviour was influenced by the conformation and by the texture of the substrate, but this does not account for the selective differences in levels of aggregation which are under genetic control. The distribution of males of both selected populations tends to be overdispersed across resource patches. This observation is consistent with male territorial behaviour. The dispersal patterns of females of the two selected populations differ significantly. H females show a contagious distribution whereas the distribution for L females is more nearly random. Differences in adult female dispersion are likely to be a significant factor contributing to aggregated oviposition. The level of aggregated oviposition affects the pattern of progeny survival when the unit of resource in each patch is small.

Animals↗

Disruption of the structure of larval foraging behaviour in interspecific hybrids in Drosophila.

Larval foraging behaviour in two sibling species, Drosophila pavani and Drosophila gaucha belonging to the mesophragmatica species group, is described. Interspecific hybrid larvae derived from both reciprocal crosses of the parent species show disruption in the organization of their behaviour, leading to lower mean feeding rates. This, together with interactions involving biotic residues, described elsewhere, is likely under competitive conditions to contribute to reduced fitness of the hybrids relative to the parent species.

Animals↗

Development of murine lupus in CD4-depleted NZB/NZW mice. Sustained inhibition of residual CD4+ T cells is required to suppress autoimmunity.

Chronic administration of anti-CD4 mAb prevents autoimmune disease in NZB/NZW F1 (B/W) mice. This may be due either to CD4 cell depletion or to inhibition of CD4 cell function. To evaluate the relative importance of these mechanisms, we devised a system in which the consequences of cell depletion could be analyzed independent of the inhibitory effects of chronic mAb therapy. This was accomplished by performing adult thymectomy before mAb administration. Specifically, female B/W mice underwent thymectomy or sham thymectomy at age 6 wk, followed at age 3 mo by a short course of either anti-CD4 (2 mg/wk for 3 wk) or saline. Treatment with anti-CD4 depleted 90% of circulating CD4 cells, but a small subpopulation (10%) of CD4 cells was refractory to depletion. In non-thymectomized mice, the CD4 population gradually reconstituted after cessation of therapy. In contrast, in thymectomized mice, recovery of CD4 cells was prevented by the absence of the thymus. Despite the striking reduction in CD4 cells in thymectomized mice, severe autoimmune disease developed, with autoantibody levels, proteinuria, and mortality comparable with non-thymectomized, nondepleted controls. The unexpected development of lupus nephritis in thymectomized, CD4-depleted B/W mice suggested that the thymus might be required to achieve the benefits of therapy with anti-CD4. To exclude this possibility, we demonstrated that chronic therapy with anti-CD4 prevents autoimmunity in thymectomized B/W mice. These findings imply that: 1) substantial depletion of CD4 T cells is not sufficient to suppress autoimmunity; 2) suppression of autoimmunity requires sustained functional inhibition of CD4 T cells; and 3) a small subpopulation of CD4 cells that is refractory to depletion by anti-CD4 is sufficient to promote the full expression of murine lupus in B/W mice.

Age Factors↗

Effect of successful treatment with amphotericin B on Histoplasma capsulatum variety capsulatum polysaccharide antigen levels in patients with AIDS and histoplasmosis.

PURPOSE: The purpose of this study was to establish the effect of induction and maintenance treatment with amphotericin B on levels of Histoplasma capsulatum var. capsulatum polysaccharide antigen (HPA) in the urine and blood of patients with acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. PATIENTS AND METHODS: This was a retrospective study of the effect of amphotericin B treatment on levels of HPA in the urine or serum from 70 patients with AIDS and disseminated histoplasmosis. All patients received initial intensive induction treatment with amphotericin B, and a subset continued to receive amphotericin B at less frequent intervals for maintenance therapy to prevent relapse. Treatment regimens varied in intensity and duration and specimens were obtained at irregular intervals. Urine and serum specimens were stored and retested for HPA in the same radioimmunoassay. RESULTS: HPA levels in serum decreased by at least 2 units during induction therapy in all 19 (100%) patients with initial levels of greater than or equal to 2.6 units and reverted to negative in 40.9% of those with initial levels of greater than or equal to 1.0 unit. HPA in urine decreased by at least 2 units in 84.8% and reverted to negative in 17.3% of patients. During induction treatment, HPA cleared more rapidly from serum than from urine. During maintenance treatment, HPA levels in serum decreased by at least 2 units in 100% and became negative in 66.7%. HPA in urine decreased by at least 2 units in 54.5% and reverted to negative in 20.0%. Rates of clearance of HPA from the serum and urine were similar, 0.01 unit/week compared with -0.04 unit/week, respectively, but less than rates during induction treatment. CONCLUSIONS: Successful therapy of histoplasmosis with amphotericin B is associated with reduction of HPA in body fluids. Periodic measurement of HPA levels offers a method for monitoring the response to therapy and for comparing new treatments for histoplasmosis.

Acquired Immunodeficiency Syndrome↗

Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid.

Diagnosis of histoplasmosis in patients with Acquired Immunodeficiency Syndrome (AIDS) may be established by detection of the organism in lung tissue or bronchoalveolar lavage fluid. In this report we have evaluated the utility of Histoplasma capsulatum polysaccharide antigen (HPA) detection in bronchoalveolar lavage fluid for diagnosis of histoplasmosis. HPA was detected in bronchoalveolar lavage fluid of 19 of 27 cases (70.3%). Of 122 controls with a variety of underlying diseases, HPA was detected in none. Eight of the negative specimens from patients with histoplasmosis were retested after fivefold concentration, and HPA was detected in five. Fivefold concentration of 10 control samples had no effect on HPA level. H. capsulatum was seen by methenamine silver or Giemsa stain in 19 of the 27 (70.3%) and isolated by culture in 24 of 27 (88.9%) cases. Twenty-four of 26 (92.3%) cases had positive cultures from extrapulmonary sites as well. HPA was detected in the urine of 25 (92.6%) and the serum of 23 (88.5%) of the 26 cases. We conclude that HPA detection offers a rapid method for identification of pulmonary histoplasmosis in patients with AIDS and could be a helpful addition to the battery of tests performed on bronchoalveolar lavage fluids in areas where histoplasmosis is endemic.

Acquired Immunodeficiency Syndrome↗

Histoplasmosis relapse in patients with AIDS: detection using Histoplasma capsulatum variety capsulatum antigen levels.

OBJECTIVE: To assess the accuracy of Histoplasma capsulatum variety capsulatum polysaccharide antigen testing for the identification of histoplasmosis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective study using stored specimens. SETTING: A referral center and several private hospitals. PATIENTS: Twenty episodes of histoplasmosis relapse were evaluated in 17 patients with AIDS from November 1987 to August 1990. Controls included 30 patients with AIDS and histoplasmosis who did not have a relapse during maintenance therapy and who were initially tested during the same week as the patients with relapse. A second control group included seven patients with AIDS and histoplasmosis who were evaluated for relapse on 23 occasions; relapse, however, was excluded on each occasion. MEASUREMENTS: To avoid interassay variability, specimens were tested for H.c. var. capsulatum polysaccharide antigen with the same radioimmunoassay. MAIN OUTCOME MEASURE: The change in the H.c. var. capsulatum polysaccharide antigen level during successful as opposed to unsuccessful maintenance therapy for the prevention of histoplasmosis relapse. MAIN RESULTS: For the 20 episodes of relapse (17 patients), H.c. var. capsulatum antigen levels increased by at least 2 radioimmunoassay units in 12 of 14 serum specimens tested (85.7%; 95% Cl, 57.2% to 98.2%) and in 17 of 18 urine specimens tested (94.4%; Cl, 72.7% to 99.9%). Antigen levels increased in the urine or serum in 1 of 83 specimens (1.2%; CI, 0.03% to 6.6%) obtained on 56 occasions (1.8%; CI, 0.04% to 9.6%) from controls (specificity, 98.2%; CI, 90.4% to 99.96%). In three cases of relapse, antigen levels increased before clinical relapse, antigen levels increased before clinical relapse was suspected. Complement fixation titers increased by at least 2 dilutions in 4 of 11 cases (36.4%; CI, 10.9% to 69.2%) but in 0 of 9 control patients (CI, 0% to 28.3%). CONCLUSION: An increase in H.c. var. capsulatum polysaccharide antigen levels of 2 units or more strongly suggests histoplasmosis relapse. The presence of increasing titers of anti-H.c. var. capsulatum antibodies by complement fixation is less accurate for the diagnosis of relapse.

Acquired Immunodeficiency Syndrome↗

Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis.

We sought to determine if Histoplasma capsulatum polysaccharide antigen (HPA) levels correlate with the extent of infection in murine of histoplasmosis. Separate groups of mice were inoculated intratracheally with varying numbers of H. capsulatum yeast cells. After 1 week, HPA levels and fungal burden (quantitative culture of lung and spleen and histopathologic stain of lung) were determined in lung and spleen, and HPA levels in serum. HPA levels, cultures and histopathological stain results of lung and spleen tissue showed a direct correlation with increasing inoculum size. HPA levels in serum also correlated with the size of inoculum. H. capsulatum antigen in lung correlated with silver stain scores of lung tissue, (R = 0.948, P less than 0.001) and with quantitative culture scores of lung, (R = 0.929, P less than 0.001). HPA levels in spleen tissue also correlated with spleen culture scores, (R = 0.724, P less than 0.001). These results indicate that determination of HPA level in serum and tissue may be a useful test in evaluating the severity of diseases as well as efficacy of antifungal therapy in histoplasmosis.

Animals↗

Mutants of staphylococcal toxic shock syndrome toxin 1: mitogenicity and recognition by a neutralizing monoclonal antibody.

Toxic shock syndrome toxin 1 (TSST-1), a 22-kilodalton protein made by strains of Staphylococcus aureus harboring the chromosomal toxin gene, may elicit toxic shock syndrome in humans. In vitro, TSST-1 induces T cells to proliferate and macrophages to secrete interleukin-1. To conduct a structure-function analysis, point mutations on the TSST-1 gene were generated by site-directed mutagenesis to identify amino acids critical for activity of the toxin. Specific tyrosine and histidine residues were replaced by alanines. Wild-type and mutant TSST-1 gene constructs were expressed in Escherichia coli, and the products were tested for their mitogenic potential and reactivity with a TSST-1 neutralizing monoclonal antibody (MAb 8-5-7). Four of the mutants were similar to the wild type; i.e., the mutant toxins stimulated murine T cells and reacted with MAb 8-5-7 equally as well as the wild type. Two mutants exhibited a decrease in mitogenic activity, but one of these retained the capacity to bind with MAb 8-5-7 while the other was no longer recognized by the same antibody. One double mutant demonstrated minimal mitogenic activity and did not react in enzyme-linked immunosorbent and immunoblot assays with MAb 8-5-7. The data show that specific residues near the carboxy terminus of TSST-1 are essential for mitogenic activity and in forming the epitope recognized by neutralizing MAb 8-5-7.

Animals↗

Neural tube defects in rural Ireland.

The incidence of neural tube defects in a rural area of the west of Ireland from 1974 to 1985 was 2.96 per 1000. The prevalence was unchanged during the 11 years. When compared with a control group there was no increased incidence of anaemia in mothers of affected infants.

Female↗

Fibronectin in acute and chronic inflammation.

Recent evidence suggests that fibronectin (Fn), a high molecular weight glycoprotein, may be used as an indicator protein in rats with adjuvant-induced arthritis. Rocket immunoelectrophoresis, using purified goat anti-rat Fn, provided a specific and sensitive means of measuring plasma Fn in rats during the development of various inflammatory disease states. It was shown that normal rat plasma Fn levels of approximately 400 micrograms/ml double within 24 hours after injection of adjuvant. Plasma Fn levels in this model of chronic systemic inflammatory joint disease were tracked for more than 4 months and remained significantly higher than normal. On the other hand, a carrageenan-induced inflammatory response in the pleural cavity of rats resulted in a large local accumulation of leukocytes, but no change in plasma Fn levels. A carrageenan-induced model of acute inflammation resulted in increased paw swelling within 6 hours and enhanced plasma Fn levels within 24 hours; plasma Fn levels returned to normal within 1 week. Quantitation of plasma Fn levels in the rat may provide a useful biochemical parameter for the study of chronic systemic inflammatory diseases.

Acute Disease↗