In vitro infection of human primary adipose cells with HIV-1: a reassessment

We reassessed the infection ability of human primary preadipocytes. The use of X4, R5 or VSV-G-pseudotyped viral particles indicated that viral entry is the limiting step. However, transfection with HIV-1 receptors restored efficient infection. Analyses of CD4, CXCR4 and CCR5 expression on preadipocytes and adipocytes revealed that receptor co-expression levels did not permit HIV-1 entry into adipose cells from all biopsies tested. We concluded that adipose tissue cannot be infected with HIV-1 in vivo.     

Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (uña de gato)

Two extracts of different collections of the traditional medicine u?a de gato (Uncaria tomentosa) from Peru were characterized by High Pressure Liquid Chromatography as containing approximately 6 mg/g total oxindole content prior to studies with alveolar macrophages. The plant preparations greatly stimulated IL-1 and IL-6 production by rat macrophages in a dose dependent manner in the range of 0.025-0.1 mg/ml. They were also able to enhance IL-1 and -6 in lipopolysaccharide-stimulated macrophages. The results suggest a strong immunostimulant action of this plant.     

Early lung events following low-dose asbestos exposure

A conscious sheep model recently developed to study sequentially the bronchoalveolar milieu was applied to the investigation of the early lung events following very low dose asbestos exposure. UICC Canadian chrysotile fibers were administered in three monthly intratracheal injections of a suspension of 0 (controls), 1, 2, 4, 8, and 16 mg of asbestos in 50 ml saline. Three sheep per dose were repeatedly exposed to the same monthly doses and all were studied by serial pulmonary function (PF) tests, transbronchial lung biopsies (LB), and bronchoalveolar lavages (BAL). These low-dose exposures did not change the PF tests; routine lung histopathology was not altered except for the observation of occasional fibers in the alveoli, but there was a significantly higher yield in the total BAL cellular due to a marked increase in the macrophage and a small rise in the lymphocyte populations. These changes in the BAL cells occurred without significant changes in the biochemical analyses of the BAL supernatant. These data establish that very low dose asbestos exposure induces migration of macrophages and lymphocytes into the bronchoalveolar milieu. These cells have a major role in the lung defense and have been implicated in the development of asbestos-related diseases.     

Blood loss and replacement in total hip arthroplasty: a multicenter study. The Preoperative Autologous Blood Donation Study Group

To determine blood loss, the number of transfusions, and the hemoglobin levels achieved in patients via transfusion in the course of total hip arthroplasty, 324 patient records from 1987 through 1989 were reviewed at three university and three community hospitals. Calculated blood loss was 3.2 +/- 1.3 units in primary procedures and 4.0 +/- 2.1 units in revision procedures (mean +/- SD). Of 777 red cell units transfused, 455 (59%) were autologous units. Transfused patients received 2.0 +/- 1.8 units for primary procedures and 2.9 +/- 2.3 units for revision procedures (mean +/- SD). The maximum number of units given to 95 percent of the transfused patients was 4 for primary procedures and 6 for revision procedures. The mean postoperative hemoglobin level after all transfusions was 103 to 110 g per L, regardless of patient age group of physical status, autologous donor status, or hospital. No difference in length of hospital stay was observed for patients less than 65 years old with hemoglobin concentrations of 80 to 139 g per L at discharge.     

IL-9 exerts biological function on antigen-experienced murine T cells and exacerbates colitis induced by adoptive transfer

IL-9 is involved in various T cell-dependent inflammatory models including colitis, encepahlitis, and asthma. However, the regulation and specificity of IL-9 responsiveness by T cells during immune responses remains poorly understood. Here, we addressed this question using two different models: experimental colitis induced by transfer of naive CD4⁺CD45RB^high T cells into immunodeficient mice, and OVA-specific T cell activation. In the colitis model, constitutive IL-9 expression exacerbated inflammation upon transfer of CD4⁺CD45RB^high T cells from WT but not from Il9r^−/− mice, indicating that IL-9 acts directly on T cells. Suprisingly, such naïve CD4⁺CD45RB^high T cells failed to express the Il9r or respond to IL-9 in vitro, in contrast with CD4⁺CD45RB^low T cells. By using OVA-specific T cells, we observed that T cells acquired the capacity to respond to IL-9 along with CD44 upregulation, after long-lasting (5 to 12 days) in vivo antigenic stimulation. Il9r expression was associated with Th2 and Th17 phenotypes. Interestingly, in contrast to the IL-2 response, antigen restimulation downregulated IL-9 responsiveness. Taken together, our results demonstrate that IL-9 does not act on naïve T cells but that IL-9 responsiveness is acquired by CD4⁺ T cells after in vivo activation and acquisition of memory markers such as CD44.     

Risk factors for early bronchiolitis at asthma during childhood: case-control study of asthmatics aged 4 to 12 years]

The group of general paediatrics of the French Paediatrics Society conducted a case-control study in order to verify the link between the occurrence of an acute bronchiolitis early during the first year of life, more specifically during the first trimester, and asthma during later childhood. METHODS: Parents of 4-to-12-year-old children answered a questionnaire during a general paediatrics visit. Exposition was attested by a diagnosis of bronchiolitis mentioned on the personal health record of the child. Environmental factors and medical history, obtained from the parents and by checking the health record of the child, were studied using multivariate analysis. RESULTS: Nineteen paediatricians included 80 children with asthma and 160 controls. Fifty-four per cent of asthmatic children had a medical history of bronchiolitis during the first year of life versus 17% of control children (P < 0.001). Mean age of bronchiolitis occurrence was 6.6 months in both groups (P = 0.98). Multivariate analysis showed that occurrence of bronchiolitis during the first year of life was significantly more frequent in asthmatic children (P < 0.001, OR = 5.6, IC95 = [2.6-11.6]) but this effect was not observed during the first trimester of life. CONCLUSION: Bronchiolitis during the first year of life was significantly related to later asthma in 4-to-12-year-old children treated by general paediatricians. On the other hand, a very early bronchiolitis during the first trimester of life did not appear, in our set of data, as a contributive factor to explain asthma in later childhood.     

Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo

This report describes the discovery of the first centrally active allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5). Appropriately substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides (e.g., 8) have been identified as a novel class of potent positive allosteric modulators of mGluR5 that potentiate the response to glutamate. An iterative analogue library synthesis approach provided potentiators with excellent potency and selectivity for mGluR5 (vs mGluRs 1-4, 7, 8). Compound 8q demonstrated in vivo proof of concept in an animal behavior model where known antipsychotics are active, supporting the development of new antipsychotics based on the NMDA hypofunction model for schizophrenia.