The contributions of the alpha 2 beta 1 integrin to vascular thrombosis in vivo

The alpha 2 beta 1 integrin serves as a receptor for collagens, laminin, and several other nonmatrix ligands. Many studies have suggested that the alpha 2 beta 1 integrin is a critical mediator of platelet adhesion to collagen within the vessel wall after vascular injury and that the interactions of the platelet alpha 2 beta 1 integrin with subendothelial collagen after vascular injury are required for proper hemostasis. We have used the alpha 2 beta 1 integrin-deficient mouse to evaluate the contributions of the alpha 2 beta 1 integrin in 2 in vivo models of thrombosis. Studies using a model of endothelial injury to the carotid artery reveal that the alpha 2 beta 1 integrin plays a critical role in vascular thrombosis at the blood-vessel wall interface under flow conditions. In contrast, the alpha 2 beta 1 integrin is not required for the formation of thrombi and pulmonary emboli following intravascular injection of collagen. Our results are the first to document a critical in vivo role for the alpha 2 beta 1 integrin in thrombus formation at the vessel wall under conditions of shear following vascular injury.     

Detection of SARS coronavirus in patients with suspected SARS

Cases of severe acute respiratory syndrome (SARS) were investigated for SARS coronavirus (SARS-CoV) through RNA tests, serologic response, and viral culture. Of 537 specimens from patients in whom SARS was clinically diagnosed, 332 (60%) had SARS-CoV RNA in one or more clinical specimens, compared with 1 (0.3%) of 332 samples from controls. Of 417 patients with clinical SARS from whom paired serum samples were available, 92% had an antibody response. Rates of viral RNA positivity increased progressively and peaked at day 11 after onset of illness. Although viral RNA remained detectable in respiratory secretions and stool and urine specimens for >30 days in some patients, virus could not be cultured after week 3 of illness. Nasopharyngeal aspirates, throat swabs, or sputum samples were the most useful clinical specimens in the first 5 days of illness, but later in the illness viral RNA could be detected more readily in stool specimens.     

Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype

Rationale: Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma. Objectives: We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and, furthermore, that leptin would alter the response of alveolar macrophages to bacterial LPS. Methods: Forty-two subjects with asthma and 46 healthy control subjects underwent research bronchoscopy. Bronchoalveolar lavage fluid from 66 was analyzed for the level of cellular inflammation, cytokines, and soluble leptin. Cultured primary macrophages from 22 subjects were exposed to LPS, leptin, or leptin plus LPS. Cytokines were measured in the supernatants. Measurements and Main Results: Leptin levels were increased in overweight/obese subjects, regardless of asthma status (P = 0.013), but were significantly higher in overweight/obese subjects with asthma. Observed levels of tumor necrosis factor-α were highest in overweight/obese subjects with asthma. Ex vivo studies of primary alveolar macrophages indicated that the response to LPS was most robust in alveolar macrophages from overweight/obese subjects with asthma and that preexposure to high-dose leptin enhanced the proinflammatory response. Leptin alone was sufficient to induce production of proinflammatory cytokines from macrophages derived from overweight/obese subjects with asthma. Conclusions: Ex vivo studies indicate that alveolar macrophages derived from overweight/obese subjects with asthma are uniquely sensitive to leptin. This macrophage phenotype, in the context of higher levels of soluble leptin, may contribute to the pathogenesis of airway disease associated with obesity.     

Influence of vertical growth pattern on faciolingual inclinations and treatment mechanics

Control of faciolingual tooth inclinations is obtained by using rectangular wire with third-order bends and standard edgewise brackets or by using a straight wire in a preadjusted appliance system. Ideal faciolingual inclinations have been determined previously by measuring facial surface contours relative to coronal long axes. This study evaluates faciolingual inclinations based on occlusal table inclinations relative to occlusal planes. The samples compared include untreated ideal occlusions and malocclusions in three different vertical skeletal growth patterns. Faciolingual inclinations of first molars and central incisors were measured relative to the occlusal plane and to selected cephalometric angular measurements. Statistical comparisons between groups revealed significant differences in the inclinations of the upper incisor relative to the occlusal plane (U1-OP) and the inclination of the occlusal plane relative to sella nasion (OP-SN). No statistically significant intergroup differences were found in the inclination of the lower incisor relative to the occlusal plane (L1-OP) or in the faciolingual inclinations of the maxillary and mandibular first molars. On the basis of the large intergroup differences in the mean angle between the occlusal plane and sella nasion (OP-SN), the use of straight-wire appliance therapy is discussed in terms of the potential for creating differential moments. Because differential moments may facilitate or hinder treatment goals, the practitioner must know the biomechanical sequelae resulting from occlusal plane-sella nasion variations, which differ from normative values when preadjusted brackets are used.