Reduced bronchial CD4+ T-cell density in smokers with occupational asthma.

Cigarette smoking may alter bronchial inflammation in asthma. Multicolour immunohistofluorescent examination on bronchial cryosections was used to examine bronchial inflammatory cell infiltrate in patients with occupational asthma. Monoclonal antibodies to CD3, CD4, CD8, T-cell receptor-delta1, CD68 and human leukocyte antigen-DR were combined to identify T-cell subsets and macrophages in bronchial biopsies from 20 workers with occupational asthma (12 smokers and eight nonsmokers), 15 healthy workers (seven smokers and eight nonsmokers) and 10 nonsmoking, nonexposed controls. The increased subepithelial CD4+ T-cell density in nonsmoking asthmatics was not present in smoking asthmatics, who had the lowest CD4+ T-cell density of all groups. The decreased subepithelial CD4+ and CD8+ T-cell density correlated with a reduction in lung function, as measured by percentage predicted forced expiratory volume in one second, in smoking asthmatics only. Although smoking asthmatics had a significantly increased number of intraepithelial CD8+ T-cells and macrophages compared with nonsmoking asthmatics, the proportion of gammadelta-T-cells was significantly decreased in both asthmatic groups. Smoking asthmatics had a distinctly different distribution of T-cell subsets compared with nonsmoking asthmatics. The accumulation of subepithelial CD4+ T-cells, which was observed in nonsmoking asthmatics, appeared to be inhibited in smoking asthmatics, suggesting a smoking-induced bronchial immune modulation, at least in occupational asthma in the aluminium industry.     

Long-term survival in children under 3 years of age with low-grade astrocytoma

Objective The purpose of this study is to analyze clinical aspects and disease-free survival (DFS) in children less than 3 years of age diagnosed with low-grade astrocytoma. Methods In a period of 24 years (1980–2004), a total of 43 (5.4%) children were registered with these characteristics. Twenty-three patients had pilocytic astrocytoma, 18 diffused, and 2 mixed. Thirty-one (72.1%) children had incomplete surgical tumor resection and 12 (27.9%) had a complete tumor resection. Twelve (27.9%) patients had cranial radiotherapy and 17 (39.5%) received chemotherapy. Overall survival was recorded in 23 (53%). DFS was 50% at 250 months of follow-up for the whole group. DFS for the supratentorial group was 60% at 250 months, whereas, for the infratentorial, it was 22% at 120 months (p = 0.008). Conclusion The only favorable prognostic pattern was the supratentorial presentation. Radiotherapy and chemotherapy did not alter the outcome.     

Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter’s Syndrome (KS)

Objects Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter’s Syndrome (KS) as co-morbid condition. Materials and methods The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. Conclusion In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.     

Interferon for non-A, non-B chronic hepatitis. A meta-analysis of randomised clinical trials

We reviewed randomised clinical trials evaluating the effect of lymphoblastoid or recombinant alpha-interferon in non-A, non-B chronic hepatitis. The outcomes assessed were the rates of serum alanine aminotransferase normalization and relapse during and after stopping interferon. Data were pooled by meta-analysis and a 50% overall rate difference, favouring treated patients, was found. Results showed homogeneity in direction of treatment effect both after short-term (2-6 months, greater than or equal to 2 mega-units thrice weekly) and long-term (9-18 months, variable dose) interferon course. Moreover, results did not change when type of publication (abstracts vs. full reports) and treatment duration or schedule were accounted for. About 50% of patients originally responding to treatment relapsed within 6 months of either dose reduction or stopping interferon, thus suggesting that only in about one out of four patients is benefit from treatment sustained up to 1 year. We conclude that larger trials are needed to identify an optimal schedule of treatment and to evaluate predictors of interferon effectiveness in patients with non-A, non-B chronic hepatitis.     

The effects of literacy and education on the quantitative and qualitative aspects of semantic verbal fluency.

Semantic verbal fluency tasks are commonly used in neuropsychological assessment. Investigations of the influence of level of literacy have not yielded consistent results in the literature. This prompted us to investigate the ecological relevance of task specifics, in particular, the choice of semantic criteria used. Two groups of literate and illiterate subjects were compared on two verbal fluency tasks using different semantic criteria. The performance on a food criterion (supermarket fluency task), considered more ecologically relevant for the two literacy groups, and an animal criterion (animal fluency task) were compared. The data were analysed using both quantitative and qualitative measures. The quantitative analysis indicated that the two literacy groups performed equally well on the supermarket fluency task. In contrast, results differed significantly during the animal fluency task. The qualitative analyses indicated differences between groups related to the strategies used, especially with respect to the animal fluency task. The overall results suggest that there is not a substantial difference between literate and illiterate subjects related to the fundamental workings of semantic memory. However, there is indication that the content of semantic memory reflects differences in shared cultural background--in other words, formal education--, as indicated by the significant interaction between level of literacy and semantic criterion.     

The mitochondrial K(ATP) channel opener BMS-191095 reduces neuronal damage after transient focal cerebral ischemia in rats.

Activation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels protects the brain against ischemic or chemical challenge. Unfortunately, the prototype mitoK(ATP) channel opener, diazoxide, has mitoK(ATP) channel-independent actions. We examined the effects of BMS-191095, a novel selective mitoK(ATP) channel opener, on transient ischemia induced by middle cerebral artery occlusion (MCAO) in rats. Male Wister rats were subjected to 90 mins of MCAO. BMS-191095 (25 microg; estimated brain concentration of 40 micromol/L) or vehicle was infused intraventricularly before the onset of ischemia. In addition, the effects of BMS-191095 on plasma and mitochondrial membrane potentials and reactive oxygen species (ROS) production in cultured neurons were examined. Finally, we determined the effects of BMS-191095 on cerebral blood flow (CBF) and potassium currents in cerebrovascular myocytes. Treatment with BMS-191095 24 h before the onset of ischemia reduced total infarct volume by 32% and cortical infarct volume by 38%. However, BMS-191095 administered 30 or 60 mins before MCAO had no effect. The protective effects of BMS-191095 were prevented by co-treatment with 5-hydroxydecanoate (5-HD), a mitoK(ATP) channel antagonist. In cultured neurons, BMS-191095 (40 micromol/L) depolarized the mitochondria without affecting ROS levels, and this effect was inhibited by 5-HD. BMS-191095, similar to the vehicle, caused an unexplained but modest reduction in the CBF. Importantly, BMS-191095 did not affect either the potassium currents in cerebrovascular myocytes or the plasma membrane potential of neurons. Thus, BMS-191095 afforded protection against cerebral ischemia by delayed preconditioning via selective opening of mitoK(ATP) channels and without ROS generation.     

Phenotype traits associated with different alleles at the RPS5 locus in Saccharomyces cerevisiae

Summary The RPS5 gene has been characterised through its ability to reduce invertase production by the SUC5 gene. In this paper we show that RPS5 acts by maintaining low levels of SUC5 mRNA. We also show that RPS5 acts on the SUC1 and SUC4 genes but not on SUC2 and SUC3, which are members of the SUC family. RPS5 also shows a pleiotropic effect on the amount of mitochondrial cytochromes.