Haemophilus influenzae in respiratory pathology in adults

Fifty patients were diagnosed bronchopulmonary Haemophilus infections, because of the production of a purulent sputum, containing at least 10(8) Haemophilus influenzae per ml. Among them were 36 males (average 52 years old) and 14 females (average 58 years old). There was a high percentage (64%) of smokers (over 30 packs/year) within this population, which also included heavy drinkers. The top incidence occurred in winter and spring. Most cases were related to an acute infection in a chronic bronchitis (26 cases). The other cases included 6 cancers, 6 sequelae of tuberculosis, 4 bronchiectasis, 4 asthma, and only 3 pulmonary consolidations. There usually was a low grade fever (only 8 cases reached or went beyond 38 degrees, while in 29 cases the body temperature kept below 38 degrees). The return to a normal temperature was obtained after 4 to 10 days of ampicillin therapy, with no fatal case within this series. The 50 strains were studied by the microbiology laboratory. The minimum inhibitory concentrations showed a peculiar response to ampicillin and erythromycin, and a less dramatic response to chloramphenicol and tetracyclin. Some strains were proved resistant (MIC over 4 micrograms per ml) to cefoxitine and cefamandole.     

Stability of phenotypic and genotypic traits during the establishment of a human neuroblastoma cell line, IGR-N-835

A prerequisite for the study of biological characteristics in neuroblastoma is the establishment of cell lines from tumors of patients. For our study a neuroblastoma cell line, IGR-N-835, was established from a primary tumor. During in vitro establishment of this line morphological changes were observed. IGR-N-835 exhibited both anchored cells and floating clusters. When cultured on bovine endothelial corneal cellular matrix, all tumor cells anchored to the matrix and proliferated, giving a continuous cell line. IGR-N-835 was studied in vitro and in vivo. Treatment with retinoic acid resulted in cell growth arrest and morphological differentiation. IGR-N-835 was highly tumorigenic in nude mice, exhibited a doubling time of 65 hr and was able to form colonies in methyl-cellulose with a cloning efficiency of 0.46%. Immunocytochemical studies showed reactivity of this line and its primary passages with CE7 monoclonal antibody (MAb). Cytogenetic analyses revealed stable mode and markers resulting from structural changes in chromosomes 10, 11 and 21 with no homogeneously staining regions or double minute chromosomes. Genomic amplification and overexpression of the N-myc oncogene exhibited by the patient's tumor remained unchanged in nude mouse xenografts and the IGR-N-835 cell line. These phenotypic and genotypic traits were unchanged during establishment of this neuroblastoma line. IGR-N-835 could therefore constitute a suitable material for the study of the biology or therapeutics of human neuroblastoma.     

The role of interleukin-10 in the differential expression of interleukin-12p70 and its beta2 receptor on patients with active or treated paracoccidioidomycosis and healthy infected subjects

Paracoccidioidomycosis patients present an antigen-specific Th1 immunosuppression. To better understand this phenomenon, we evaluated the interleukin (IL)-12 pathway by measuring IL-12p70 production and CD3+ T cell expression of the IL-12 receptor (IL-12R)beta1/beta2 chains, induced with the main fungus antigen (gp43) and a control antigen, from Candida albicans (CMA). We showed that gp43-induced IL-12p70 production and IL-12Rbeta2 expression were significantly decreased in acute and chronic patients as compared to healthy subjects cured from PCM or healthy infected subjects from endemic areas. Interestingly, the healthy infected subjects had higher gp43-induced IL-12p70 production and beta2 expression than the cured subjects. The addition of a neutralizing anti-IL-10 antibody to the cultures increased IL-12p70 levels and beta2 expression in acute and chronic patients to levels observed in cured subjects. Conversely, addition of the cytokine IL-10 strongly inhibited both parameters in the latter group. In conclusion, we have shown that paracoccidioidomycosis-related Th1 immunosuppression is associated with down-modulation of the IL-12 pathway, that IL-10 may participate in this process, and that patients cured from paracoccidioidomycosis may not fully recover their immune responsiveness.     

Fatal septic shock due to a disseminated chronic form of paracoccidioidomycosis in an aged woman

Once rare, septic shock (SS) due to disseminated fungal infections has been increasingly reported due to a growing number of immunocompromised patients, but remains rare in non-immune-compromised individuals. In paracoccidioidomycosis, it has been described in only three patients with the severe, acute form of the disease. We describe the development of a refractory, fatal septic shock due to a severe disseminated chronic form of paracoccidioidomycosis in an older woman without any other microbial insults. A striking event in the evolution of her case was the severe depletion of lymphocytes from the peripheral blood and lymphoid organs. Lymphocyte depletion due to apoptosis is described in the late phase of sepsis and can contribute both to immunosuppression and the progression of SS. The possible mechanisms involved in the induction of SS in the chronic form of paracoccidioidomycosis are discussed.     

The Trypanosoma brucei CCCH zinc finger proteins ZC3H12 and ZC3H13

CCCH-type zinc finger proteins have various roles in RNA metabolism. We here analysed the functional relevance of two such proteins from Trypanosoma brucei, TbZC3H12 and TbZC3H13. Each protein has a single CCCH motif very similar to those seen in metazoan proteins that regulate mRNA degradation. TbZC3H12 is expressed in bloodstream form parasites at low levels. It is phosphorylated, cytosolic and not required for normal growth of cultured bloodstream trypanosomes. RNA interference targeting TbZC3H13, on a TbZC3H12 null background, also had no effect on bloodstream trypanosome growth, but over-expression of tagged TbZC3H13 inhibited procyclic trypanosome growth. Tandem affinity purification of both proteins revealed various interesting potential interactions; specificity was assessed against a list of proteins that were found in 24 other pull-down experiments, which is provided. The conservation of TbZC3H12 in all kinetoplastids, and TbZC3H13 in Salivaria, suggests that the two proteins may be required for optimal growth at some stage of the parasite life-cycle.     

A patient with erythema nodosus leprosum and Chagas cardiopathy: challenges in patient management and review of the literature

We report a patient with severe multi-bacillary leprosy complicated by recurrent episodes of erythema nodosum necrotisans that required thalidomide and/or corticosteroids during follow-up. Although the patient was from an area to which Chagas disease is endemic, this diagnosis was initially missed and was only investigated when heart failure developed in the patient. The difficulties of managing erythema nodosum necrotisans and heart failure concomitantly and those involved in excluding the diagnosis of acute myocarditis caused by reactivation of Chagas disease secondary to the immunosuppressive regimen are discussed. Other potential causes for the heart failure and possible interactions between the two diseases and their treatments are discussed. We also reviewed the literature for the association between leprosy and Chagas disease, both of which are highly endemic in Brazil. This case emphasizes the importance of searching for subclinical co-infections in leprosy patients because reactions frequently develop during specific treatment in these patients, and these reactions require prolonged therapy with immunosuppressive drugs.