Role of endogenous IFN-gamma in macrophage programming induced by IL-12 and IL-18.

Besides the established role of interleukin-12 (IL-12) and IL-18 on interferon-gamma (IFN-gamma) production by natural killer (NK), T, and B cells, the effects of these cytokines on macrophages are largely unknown. Here, we investigated the role of IL-12/IL-18 on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production by CD11b(+) adherent peritoneal cells, focusing on the involvement of endogenously produced IFN-gamma. C57BL/6 cells released substantial amounts of NO when stimulated with IFN-gamma or lipopolysaccharide (LPS), but failed to respond to IL-12 or IL-18 or both. However, IL-12/IL-18 pretreatment was able to program these cells to release 6-8-fold more NO and TNF-alpha in response to LPS or Trypanosoma cruzi stimulation, with NO levels directly correlating with macrophage resistance to intracellular parasite growth. Analysis of IL-12/IL-18-primed cells from mice deficient in IFN-gamma, IFNGR, and IFN regulatory factor-1 (IRF-1) revealed that these molecules were essential for LPS-induced NO release, but TNF-alpha production was IFN-gamma independent. Conversely, the myeloid differentiation factor 88 (MyD88)-dependent pathway was indispensable for IL-12/IL-18-programmed LPS-induced TNF-alpha production, but not for NO release. Contaminant T and NK cells largely modulated the IL-12/IL-18 programming of LPS-induced NO response through IFN-gamma secretion. Nevertheless, a small population of IFN-gamma(+) cells with a macrophage phenotype was also identified, particularly in the peritoneum of chronically T. cruzi-infected mice, reinforcing the notion that macrophages can be an alternative source of IFN-gamma. Taken together, our data contribute to elucidate the molecular basis of the IL-12/IL-18 autocrine pathway of macrophage activation, showing that endogenous IFN-gamma plays an important role in programming the NO response, whereas the TNF-alpha response occurs through an IFN-gamma-independent pathway.     

Human gene for proliferating cell nuclear antigen has pseudogenes and localizes to chromosome 20

We have isolated from a human genomic library a pseudogene of the proliferating cell nuclear antigen (PCNA)gene. Its sequence shows a 78% similarity with the human PCNA/cDNA. The PCNAgene is located on human chromosome 20, while the pseudogene maps to chromosome region XpterXq13. An additional locus detected by the full-length PCNA cDNA, but not by intron probes, segregates concordantly with chromosome region 6p126pter and probably represents a second pseudogene.     

Mast cell populations in the chick embryo lung and their response to compound 48/80 and dexamethasone

Summary Two mast cell populations, connective tissue mast cells (CTMCs) and mucosal mast cells, (MMCs) containing different proteoglycans in their granules, can be distinguished in several animal species by means of histochemical methods. In this study we documented the presence of these two types of mast cell in the chick embryo lung, from the 15th incubation day for the MMCs, and from the 18th incubation day for the CTMCs. Lungs of embryos treated with compound 48/ 80, which produces degranulation of the CTMCs, showed a decrease in the number of this type of mast cell and an unchanged number of MMCs. In the lungs of embryos treated with dexamethasone, which degranulates MMCs, a reduction in the number of these cells and an unchanged number of the CTMs were found.     

Physiological and Psychological Effects of Delivering Medical News Using a Simulated Physician–Patient Scenario

We examined the acute stress response associated with having to deliver either bad or good medical news using a simulated physician–patient scenario. Twenty-five healthy medical students were randomly assigned to a bad medical news (BN), a good medical news (GN), or a control group that read magazines during the session. Self-report measures were obtained before and after the task. Blood pressure and heart rate were measured throughout the task period. Four blood samples were obtained across the task period. The BN and GN tasks produced significant increases in self-reported distress and cardiovascular responses compared with the control group. There was also a significant increase in natural killer cell function 10 min into the task in the BN group compared with the control group. The BN task was also somewhat more stressful than the GN task, as shown by the self-report and cardiovascular data. These findings suggest that a simulated physician–patient scenario produces an acute stress response in the physician, with the delivery of bad medical news more stressful than the delivery of good medical news.     

Identification of dermatophyte species by 28S ribosomal DNA sequencing with a commercial kit

We have shown that dermatophyte species can be easily identified on the basis of a DNA sequence encoding a part of the large-subunit (LSU) rRNA (28S rRNA) by using the MicroSeq D2 LSU rRNA Fungal Sequencing Kit. Two taxa causing distinct dermatophytoses were clearly distinguished among isolates of the Trichophyton mentagrophytes species complex.     

Primary Immunodeficiency Diseases in Latin America: First Report from Eight Countries Participating in the LAGID

The Latin American Group for Primary Immunodeficiencies, formed in 1993, presently includes 12 countries. One goal was to study the frequency of primary immunodeficiencies in various regions of the American continent and to enhance knowledge about these diseases among primary-care physicians, as well as allergist–immunologists. Important for this purpose was the development of a registry of primary immunodeficiencies using a uniform questionnaire and computerized database. To date, eight countries have collected information on a total of 1428 patients. Predominantly antibody deficiencies were reported in 58% of patients, followed by cellular and antibody immunodeficiencies associated with other abnormalities in 18%, immunodeficiency syndromes associated with granulocyte dysfunction in 8%, phagocytic disorders in 9%, combined cellular and antibody immunodeficiencies in 5%, and complement deficiencies in 2% of patients. The information gathered from this initial analysis of data will serve to expand the patient database to more areas within participating countries and to new countries and to increase collaboration toward better diagnosis and treatment of these diseases.