Lymphotoxin but not tumor necrosis factor functions to maintain splenic architecture and humoral responsiveness in adult mice

To compare the function of the tumor necrosis factor (TNF) and lymphotoxin (LT)α/β systems in the mature immune system, these two pathways were blocked with soluble receptor-immunoglobulin (R-Ig) fusion proteins in normal adult mice. Inhibition of LTα/β signaling using LTβR-Ig or a blocking monoclonal antibody against murine LTβ had profound effects. The spleen lacked discrete B cell follicles and the marginal zone was altered. Less marked changes were detected in lymph nodes. LTα/β inhibition also prevented germinal center formation in the spleen and impaired Ig production in response to sheep red blood cells (SRBC) immunization. These results show that the LTα/β system is required for the maintenance of splenic architecture and normal immune responses, and not simply for the development of peripheral immune organs during ontogeny. In contrast, inhibition of the TNF/LTα pathway with TNF-R55-Ig did not affect the splenic architecture or the anti-SRBC response. Splenic defects and impaired antibody responses are seen in TNF-deficient mice, suggesting that TNF is important during development. Therefore relative to TNF, the LT system has the dominant influence on splenic organization and anti-SRBC Ig formation in the adult mouse.     

Prevalence and correlates of HIV infection among young injection drug users in San Francisco

OBJECTIVE: We assessed the prevalence of HIV infection and associated risk behaviors among street-recruited young injection drug users (IDUs) in San Francisco. METHODS: In a cross-sectional study, 304 young (age <30 years) IDUs with a history of injecting in the previous 30 days were interviewed and tested for antibodies to HIV. Analyses assessing independent associations with HIV infection were limited to males only, due to the low number of infections in women. RESULTS: The prevalence of HIV infection was 5.3% overall but was highly stratified by gender and sexual preference (15.6% among homosexual/bisexual men vs. heterosexual men) and recruitment neighborhood (18% in the Polk Street area). Of 16 HIV infections, 14 (88%) were in males. Factors independently associated with HIV infection in males included sexual preference (homosexual/bisexual vs. heterosexual: adjusted odds ratio [AOR], 7.5; 95% confidence interval [CI], 1.5-36.6), recruitment neighborhood (Polk Street neighborhood vs. other neighborhoods: AOR, 4.8; 95% CI, 1.4-16.7), and duration of residence in San Francisco (>or=1 year vs. <1 year: AOR, 11.8; 95% CI, 1.4-95.8). CONCLUSIONS: The prevalence of HIV infection was highest among male IDUs who have sex with men. The strong associations between HIV infection and sexual orientation and HIV infection and recruitment locale suggest that risk may be attributable largely to sexual risk. In addition to successful prevention efforts aimed at reducing needle-associated risk, current intervention models aimed at young IDUs should target high-risk neighborhoods and emphasize sexual risk reduction measures, in particular among men who have sex with men.     

Enhanced Phagocytosis and Bactericidal Activity of Hepatic Reticuloendothelial System During Endotoxin Tolerance

The effects of tolerance to Escherichia coli endotoxin on the phagocytic and bactericidal activity of the hepatic reticuloendothelial system against viable E. coli were examined using ex vivo perfused rat livers. Livers were isolated from control and endotoxin-tolerant rats and perfused with a medium containing 5% homologous serum from either control or tolerant rats. After the addition of the E. coli (2 × 10⁷ cells per ml) to the perfusate, the hepatic clearance of the bacteria was followed for 30 min. The highest activation of the hepatic reticuloendothelial system was observed when serum from tolerant animals was added to the perfusate. Under these conditions phagocytosis was 47% (12% in controls), and 37 to 38% of the bacteria were killed (5% in controls). This activation was less when livers obtained from tolerant rats were perfused with serum from controls or with saline only. The data suggests that, during endotoxin tolerance, humoral factors play an important role in the activation of the hepatic reticulendothelial system, although a direct stimulation of Kupffer cells also occurs. The enhancement of phagocytosis by tolerant serum did not require the presence of homologous antibodies and involved the activation of the alternative complement pathway, since it was lost after removal of factor B activity. On the other hand, stimulation of intracellular killing required both complement and specific antibodies. The data suggest a role of endotoxin in the activation of humoral and cellular mechanisms involved in the host resistance to gram-negative bacterial infection.     

Emergence of nonencapsulated and encapsulated non-b-type invasive Haemophilus influenzae isolates in Portugal (1989-2001)

Phenotypes and genetic relatedness of invasive Haemophilus influenzae strains were evaluated from 1989 through 2001. Among 119 isolates, multidrug resistance decreased (from 50 to 0%), the level of H. influenzae serotype b (Hib) strains declined (from 81 to 16%), the level of noncapsulated strains rose (from 19 to 80%), and the first invasive H. influenzae serotype f strain was described. This study documents changes in invasive H. influenzae infections in Portugal, i.e., the emergence of non-type-b strains that are genetically diverse and unrelated to Hib.     

The effect of calpain 3 deficiency on the pattern of muscle degeneration in the earliest stages of LGMD2A

Limb girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the calpain 3 gene. In a large family affected by LGMD2A with four severely affected members, three additional asymptomatic relatives had very high serum creatine kinase concentrations. All were homozygous for the R110X mutation and showed a total absence of calpain 3 in the muscle. Histological analysis of muscle in these three rare preclinical cases showed a consistent but unusual pattern, with isolated fascicles of degenerating fibres in an almost normal muscle. This pattern was also seen in one patient with early stage LGMD2A who had a P82L missense mutation and a partial deficiency of calpain 3 in the muscle, but was not seen in early stage patients affected by other forms of LGMD. These findings suggest that a peculiar pattern of focal degeneration occurs in calpainopathy, independently of the type of mutation or the amount of calpain 3 in the muscle.     

A longitudinal study of mental health consumer/survivor initiatives: Part V–Outcomes at 3‐year follow‐up

The objective of this study was to evaluate the impacts of participation in mental health Consumer/Survivor Initiatives (CSIs), organizations run by and for people with mental illness. A nonequivalent comparison group design was used to compare three groups of participants: (a) those who were continually active in CSIs over a 36‐month period (n = 25); (b) those who had been active in CSIs at 9‐ and 18‐month follow‐up periods, but who were no longer active at 36 months (n = 35); and (c) a comparison group of participants who were never active in CSIs (n = 42). Data were gathered at baseline, 9‐, 18‐, and 36‐month follow‐ups. The three groups were comparable at baseline on a wide range of demographic variables, self‐reported psychiatric diagnosis, service use, and outcome measures. At 36 months, the continually active participants scored significantly higher than the other two groups of participants on community integration, quality of life (daily living activities), and instrumental role involvement, and significantly lower on symptom distress. No differences between the groups were found on other outcome measures. Improvements in 36‐month outcomes for people with mental illness who participated in CSIs suggest the potential value of these peer support organizations. Further research is needed to determine the replicability of these positive findings. © 2007 Wiley Periodicals, Inc. J Comm Psychol 35: 655–665, 2007.     

Molecular pathology of well-differentiated thyroid carcinomas

The newly discovered molecular features of well-differentiated thyroid carcinomas derived from follicular cells are reviewed, within the frame of the 2004 WHO classification of thyroid tumours, under the following headings: “Follicular carcinoma”, “Papillary carcinoma”, “Follicular variant of papillary carcinoma” and “Hürthle cell tumours”. A particular emphasis is put on the meaning of PAX8–PPARγ rearrangements, RAS and BRAF mutations, and deletions and mutations of mitochondrial genes and of nuclear genes encoding for mitochondrial enzymes, for thyroid tumorigenesis.