Altered expression of the Salmonella typhimurium-specific B-cell repertoire in mice chronically treated with antibodies to immunoglobulin D

Using a modification of the splenic focus assay, we analyzed the Salmonella typhimurium-specific B-cell repertoire in salmonella-susceptible BALB/c mice. Although these mice normally succumbed to salmonella infection before antibody was produced, they appeared to have splenic S. typhimurium-specific B-cell precursors that could be activated to differentiate and secrete antibody in a manner which was quantitatively and qualitatively identical to that of salmonella-resistant mouse strains. We also analyzed the primary S. typhimurium-specific B-cell repertoire in BALB/c mice that had been chronically treated with antibodies to immunoglobulin D (IgD) and therefore had no surface IgD-positive B cells. Although the frequency of S. typhimurium-specific precursors in these mice was similar to that of control mice, there was an apparent alteration in the isotype distribution pattern in anti-IgD-treated mice. Control mice generated a significantly greater proportion of IgG-secreting clones than did anti-IgD-treated mice. In addition, a greater proportion of S. typhimurium-specific clones from control mice secreted IgG2 than secreted IgG1, and those clones that secreted IgG2 but not IgM, IgG3, or IgG1 were greater than 20-fold more common in control than in anti-IgD-treated mice. Finally, we analyzed the immune response of control and anti-IgD-treated mice to a live avirulent vaccine, S. typhimurium SL3235. Although both groups were protected after challenge with a live virulent S. typhimurium strain, only the control mice made serum antibodies to this vaccine. Taken together, these results show that (i) salmonella-susceptible BALB/c mice have S. typhimurium-specific B cells, (ii) the S. typhimurium-specific B cells in anti-IgD-treated mice may have a restricted capacity to switch heavy-chain classes, (iii) the similarity observed in the frequency of the S. typhimurium-specific precursors for these two groups of BALB/c mice is not reflected in the serum, and (iv) the failure of anti-IgD-treated mice to generate a serum antibody response to SL3235 in the face of complete protection suggests that this model may be used to study cell-mediated immune mechanisms in the apparent absence of humoral immunity.     

"Covert toxocariasis" in a child treated with low-dose diethylcarbamazine

A girl aged 2.5 years with "covert toxocariasis" was treated with low-dose diethylcarbamazine because of supposed noticeable disseminated Toxocara canis infection without ocular or visceral manifestations. There was marked blood and bone marrow eosinophilia, significant increased Toxocara canis antibody (ELISA) and immunoglobulins E, G and M, leucocytosis and an increased sedimentation rate. She had no geophagia, but often sucked small stones, probably contaminated with faeces from puppies. Symptoms were fever, inactivity, weakness, tiredness and loss of appetite. She was followed clinically and with blood samples throughout a period of three years and four months.     

Cognitive rehabilitation with patients having persistent,severe psychiatric disabilities

The effectiveness of cognitive rehabilitation in ameliorating the symptomatic, cognitive, and functional deficits associated with schizophrenia and schizoaffective disorders was assessed in this prospective study. Thirty-eight participants who met DSM-IV criteria were assigned to cognitive rehabilitation treatment or treatment as usual (TAU) groups, using the method of minimization to equalize groups on prognostic variables believed to affect outcome (i.e., duration and severity of illness, Clozapine). Participants were assessed at baseline, treatment end, and 3-month follow-up. Improvement across time was found for both groups in delayed visuospatial memory and visual information processing speed, and the participant's status on the prognostic variables was found to be related to level of performance on measures of delayed visuospatial memory, negative symptoms, and speech disturbance. However, the findings did not provide evidence that cognitive rehabilitation is associated with greater improvement than TAU. Nor did the findings indicate that prognosis interacted with treatment to produce differential treatment outcomes.     

PKC-alpha shows variable patterns of translocation in response to different stimulatory agents

Reports from numerous laboratories suggest that protein kinase C (PKC) translocation to substrate target sites may vary depending on cell type and experimental conditions. We have proposed that acutely variable targeting of PKC to different substrate sites could greatly expand the functional properties of individual isoforms in individual cell types (Li et al., 2001). Confocal microscopy and PKC alpha-enhanced green fluorescent protein (PKC alpha-EGFP) fusion protein expression were utilized to investigate the spatial and temporal pattern of PKC alpha translocation to different stimulating agents in A7r5 smooth muscle cells. Phorbol 12, 13 dibutyrate (PDBu 10(-8) M) caused a slow but irreversible relocation of the fusion protein from the cytosol to the plasmalemma. By comparison, thapsigargin (10(-5) M) and A23 187 (2 x 10(-5) M) induced a rapidly transient translocation to the cell membrane which was completed within 4 min. In contrast to these agents, angiotensin II (Ang II, 10(-6) M) caused only partial relocalization of cytosolic PKC alpha-EGFP to brightly fluorescing patches at the cell periphery. Localization at peripheral patches was completed within seconds and the fusion protein returned to the cytosol within 2 min. The PKC inhibitor staurosporine blocked cellular contraction to PDBu but not A(23 187) and had no effect on PKC alpha-EGFP translocation. By comparison, the calcium chelators EDTA and BAPTA-AM blocked the contraction to A(23 187), attenuated the contraction to PDBu, and abolished the translocation of PKC alpha-EGFP by both agents. The results show that in a single cell type the spatial and temporal characteristics of individual PKC isoform translocation may differ markedly. This further suggests the existence of potentially complex mechanisms which regulate the rate and location of target site availability.     

The natural history of infection with the lymphadenopathy-associated virus/human T-lymphotropic virus type III

Over half of the persons infected with the lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III), the retrovirus that causes the acquired immunodeficiency syndrome (AIDS), become persistently infected with the virus. These "carriers" serve as the major reservoir of infection for others. Virus from their vascular and lymphatic spaces infects others through direct blood or mucous membrane exposure. After months to years, a high proportion of those infected will develop clinical manifestations of infection. For infected homosexual men, approximately 25% have developed AIDS-related conditions, mainly lymphadenopathy, and approximately 10% have developed AIDS. Because of the large number of infected persons in the United States, increasing rates of disease can be expected.     

PGD15 Veterans'' Satisfaction with H2-Receptor Antagonist (H2RA) Drug Conversion

OBJECTIVES: To determine the relative cost-effectiveness of the inhaled corticosteroids beclomethasone dipropionate (BDP), budesonide (BUD), and fluticasone propionate (FP), for managing moderate to severe asthma in adults over a one-year time horizon from the perspective of the Ministry of Health (MOH) in Canada.
METHODS: A single-arm meta-analysis of randomized control trials containing at least one of FP, BUD, and BDP was performed in order to derive estimates of effectiveness and tolerance. A decision tree analysis was then used to model the cost-effectiveness analysis. Only direct medical costs were included in the analysis (i.e., inpatient care, emergency visits, physician services, nursing services, drugs, diagnostic tests). The time horizon of the study was 52 weeks, precluding discounting. All costs are presented in 1996 Canadian dollars (CDN$). The cost-effectiveness was the cost per additional symptom-free day ($/SFD).
RESULTS: 69 of 398 articles were included in the metaanalysis. The Monte Carlo base case analysis showed that FP and BUD resulted in an annual cost of $1,383 and $1,147 respectively (p > 0.01). FP produced 216 SFDs while BUD resulted in 214 SFDs, which were not significantly different at p = 0.01 (corrected for multiple comparisons). BDP cost $1,343/year and yielded 213 SFD/year (BDP was excluded from the final analysis, dominated by BUD). With no difference in effectiveness, a cost-minimization analysis showed that BUD was the cost-effective alternative, costing $236 CDN less than the FP strategy.
CONCLUSIONS: Of the inhaled corticosteroids available on the MOH Formulary in Canada, BUD is a costeffective alternative for the treatment of adults with moderate to severe asthma.