Background: Even though commercial nucleic acid amplification tests (NAATs) have become the most frequently used molecular tests for laboratory diagnosis of pulmonary tuberculosis (TB), published studies report variable estimates of their diagnostic accuracy. We analysed the accuracy of commercial NAATs for the diagnosis of pulmonary TB in smear positive and smear negative respiratory samples using culture as a reference standard. Methods: English language studies reporting data sufficient for calculating sensitivity and specificity of commercial NAATs on smear positive and/or smear negative respiratory samples were included. Metaregression was used to analyse associations with reference test quality, the prevalence of TB, sample and test type. Predictive values for different levels of pre-test probability were quantified using Bayes' approach. Results: Sixty three journal articles published between 1995 and 2004 met the inclusion criteria. Pooled sensitivity and specificity were 0.96 and 0.85 among smear positive samples and 0.66 and 0.98 among smear negative samples. The number of culture media used as reference test, the inclusion of bronchial samples, and the TB prevalence were found to influence the reported accuracy. The test type had no effect on the diagnostic odds ratio but seemed to be correlated with sensitivity or specificity, probably via a threshold effect. Conclusions: Commercial NAATs can be confidently used to exclude TB in patients with smear positive samples in which environmental mycobacteria infection is suspected and to confirm TB in a proportion of smear negative cases. The methodological characteristics of primary studies have a considerable effect on the reported diagnostic accuracy.

The expression of neurotrophins (NTs) and related high- and low-affinity receptors was studied in surgical samples of histologically diagnosed human tumors of the lower respiratory tract. The experiment was conducted with 30 non-small cell lung cancer specimens and in eight small cell lung cancer specimens by Western blot analysis and immunohistochemistry to assess expression and distribution of NT and NT receptor proteins in tissues examined. Immunoblots of homogenates from human tumors displayed binding of anti-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3 antibodies as well as of anti-tyrosine-specific protein kinase (Trk) A, TrkB, and TrkC receptor antibodies, with similar migration characteristics than those displayed by human beta-NGF and proteins from rat brain. A specific immunoreactivity for NTs and NT receptors was demonstrated in vessel walls, stromal fibroblasts, immune cells, and sometimes within neoplastic cell bodies. Approximately 33% of bronchioloalveolar carcinomas exhibited a strong membrane NGF and TrkA immunoreactivity, whereas 46% adenocarcinomas expressed an intense TrkA immunoreactivity but a weak immunostaining for NGF within tumor cells. Moreover, squamous cell carcinomas developed an intense TrkA immunoreactivity only within stroma surrounding neoplastic cells. A faint BDNF and TrkB immunoreactivity was documented in adenocarcinomas, squamous cell carcinomas, and small cell lung cancers. NT-3 and its corresponding TrkC receptor were found in a small number of squamous cell carcinomas within large-size tumor cells. No expression of low-affinity p75 receptor protein was found in tumor cells. The detection of NTs and NT receptor proteins in tumors of the lower respiratory tract suggests that NTs may be involved in controlling growth and differentiation of human lung cancer and/or influencing tumor behavior.

The growth factor activin A belongs to the transforming growth factor-β superfamily and was initially isolated as an inducer of follicle-stimulating hormone secretion. Activin A was later found to play roles in cell proliferation, differentiation, apoptosis, and metabolism. More recently, activin A has also been recognized as a novel player in mediating inflammation, immunity, wound repair, and fibrosis. Elevated levels of activin A during inflammation are responsible for the increased production of extracellular matrix in different pathological conditions, including fibroids. Our group has demonstrated a profibrotic role of activin A in leiomyoma growth. Uterine leiomyoma can be considered as a fibrotic disorder that initiates from myometrial smooth muscle layer of uterus in reproductive-age women and that is driven by a strong inflammatory component. In fertile women, transient inflammation is a physiological and essential process during menstruation, ovulation, and parturition. However, tissue injury from extravasated menstrual blood and/or an altered response to harmful stimuli, such as pathogens, damaged cells, or irritants, can establish chronic inflammation in the uterus, ultimately leading to dysregulated tissue repair. Myofibroblasts are key cells in normal repair and the chronic tissue remodeling characteristic for fibrosis and uterine leiomyoma. In this review, we discuss the role of activin A in inflammation, tissue repair, and fibrosis and we elaborate the hypothesis that it plays a central role in myofibroblast activation and leiomyoma development and growth.

The localization of neurotrophins (NTs) and NT receptors was analyzed in sections of human extra- and intrapulmonary arteries by Western blot analysis and immunohistochemistry. In extrapulmonary branches of human pulmonary artery, NT and NT receptor immunoreactivity was located in the tunica intima, within endothelium, in the tunica media, within smooth muscle and in the tunica adventitia. In different sized intrapulmonary arteries, NT and NT receptor immunoreactivity was observed primarily in the tunica adventitia. A faint NT and NT receptor immunoreactivity was observed in the tunica media of large-sized branches of intrapulmonary arteries, but not within medium- or small-sized intrapulmonary vessels or in tunica intima of different sized intrapulmonary arteries. These findings suggest that NTs may have a role in the control of vascular responses in the pulmonary system acting as local paracrine or autocrine mediators. The possible relevance of the NT system in human pulmonary vasculature identified in this study is discussed.

Abstract-We investigated the expression of ␣ 1 -adrenergic receptor subtypes in intact human peripheral blood lymphocytes using reverse transcription-polymerase chain reaction (RT-PCR) and radioligand binding assay techniques combined with antibodies against the three subtypes of ␣ 1 -adrenergic receptors (␣ 1A , ␣ 1B , and ␣ 1D 3 H]prazosin binding to a different extent. This indicates that human peripheral blood lymphocytes express the three ␣ 1 -adrenergic receptor subtypes. Of the three different ␣ 1 -adrenergic receptor subtypes, the ␣ 1B is the most represented and the ␣ 1D , the least. Future studies should clarify the functional relevance of ␣ 1 -adrenergic receptors expressed by peripheral blood lymphocytes. The identification of these sites may represent a step for evaluating whether they represent a marker of ␣ 1 -adrenergic receptors in cardiovascular disorders or for assessing responses to drug treatment on these receptors. (Hypertension. 1999;33:708-712.) Key Words: lymphocytes Ⅲ receptors, adrenergic, alpha Ⅲ receptor subtypes Ⅲ receptor antibodies I n the past few years, ␣-and ␤-adrenergic receptors have been demonstrated in peripheral blood lymphocytes with the use of radioligand binding assay techniques. The majority of information is available on ␤-adrenergic receptors, which were investigated primarily in essential hypertension, impaired left ventricular function, and acute stress. 1-5 Data on the expression of ␣-adrenergic receptors in peripheral blood lymphocytes are less extensive, with the ␣ 2 -receptor subtype being the most extensively investigated. 6,7 Some studies on the ␣ 1 -adrenergic receptor have not found its expression in human peripheral blood lymphocytes 8,9 and some studies have. 10 ␣ 1 -Adrenergic receptors mediate some cardiovascular sympathetic responses, such as arteriolar smooth muscle constriction 11 and cardiac contractility, 12 and are involved in a variety of cardiovascular disorders, including hypertension, heart failure, and cardiac hypertrophy. 13 ␣ 1 -Adrenergic receptors represent a class of heterogeneous receptors. 14 Cloning studies have identified three distinct ␣ 1 -adrenergic receptor subtypes, named ␣ 1a -, ␣ 1b -, and ␣ 1d -adrenergic receptors. 14 -17 At present, ␣ 1 -adrenergic receptor subtypes are defined as ␣ 1A (␣ 1a ), ␣ 1B (␣ 1b ), and ␣ 1D (␣ 1d ), with uppercase and lowercase subscripts being used to designate native or recombinant receptor, respectively. 14,18 In view of the difficulty of investigating ␣ 1 -adrenergic receptors in vivo or in vitro using human samples of cardiovascular system, circulating blood cells may represent a model for the study of the cardiovascular ␣ 1 -adrenergic receptor system.In this article we have characterized ␣ 1 -adrenergic receptor subtypes expressed by human peripheral blood lymphocytes by reverse transcription-polymerase chain reaction (RT-PCR) to detect mRNA expression and by radioligand binding assay techniques combined with antibodies against different subtypes of ␣ 1 -adrenergic receptors. Methods Subjec...