Citations

Activation of complement on endothelium triggers physiological changes that promote coagulation, thrombosis, and inflammation. Unlike agonists such as cytokines and endotoxin that induce these changes through transcription of many genes, complement, particularly the membrane attack complex, primarily induces release of IL-1α by the endothelial cells; the cytokine may then be removed by normal blood flow or may promote activation of the full range of endothelial cell responses in an autocrine or paracrine manner. We studied the intracellular signaling pathways used by complement to activate interleukin (IL)-1α transcription in cultured endothelial cells. The membrane attack complex and other pore-forming proteins stimulated calcineurin and activated selective transcription of the IL-1α gene. In contrast, the action of cytokines such as IL-1α was not selective and not dependent on calcineurin activity. Transcription of IL-1α, whether stimulated by complement and calcineurin or by “conventional agonists,” such as IL-1α independent of calcineurin, proceeded via binding of nuclear factor κB transcriptional activators to the IL-1α gene promoter. These findings define a molecular mechanism through which complement regulates IL-1α production by endothelial cells and explain how blood flow may determine the extent of complement-stimulated inflammation.

Abstract The term “bronchiolitis” refers to a broad morphologic spectrum of inflammatory events that are centered on small conducting airways. Bronchiolitis may be an isolated pathologic finding, although it is often a secondary consequence of diseases affecting other parts of the conducting apparatus or pulmonary acinus. Divergent causes of bronchiolitis may have similar microscopic findings. Hence, a pathologic diagnosis is nonspecific and not clinically meaningful unless placed in the context of relevant clinical and radiographic findings. Etiologically, most cases of bronchiolitis are infectious in nature or related to smoking. Increasingly, other causes of bronchiolitis have been recognized, including collagen vascular disease, idiopathic inflammatory bowel disease, or toxins/drugs. Many cases are idiopathic. Histologically, most examples of bronchiolitis demonstrate acute inflammation, usually corresponding to viral infection. Other well-defined histologic categories of bronchiolitis include bronchiolitis obliterans, in which there is fibroblast proliferation within airspaces, and follicular bronchiolitis, corresponding to lymphoid hyperplasia with formation of germinal centers. In recent years, several new forms of bronchiolitis have been recognized, including constrictive bronchiolitis, diffuse panbronchiolitis, and airway-centered fibrosis. This article highlights the clinical and pathologic features of these more recently described entities.

ABSTRACT The Invader 1.0 assay (Invader HCV Genotyping Assay, version 1.0; Third Wave Technologies, Inc., Madison, WI) has been developed for the rapid differentiation of hepatitis C virus (HCV) genotypes 1 to 6 based on sequence variation within the HCV 5′ noncoding (NC) region. In the present study, we evaluated the compatibility of Invader 1.0 with the COBAS MONITOR (COBAS AMPLICOR HCV MONITOR Test, version 2.0; Roche Molecular Systems, Inc., Branchburg, NJ), COBAS AMPLICOR (COBAS AMPLICOR Hepatitis C Virus Test, version 2.0; Roche Molecular Systems, Inc.), and COBAS TaqMan (COBAS TaqMan HCV Test; Roche Molecular Systems, Inc.) assays. The minimum HCV RNA titers required for successful HCV genotyping (≥90% success rate) were 1,000 IU/ml for COBAS MONITOR, 100 IU/ml for COBAS AMPLICOR, and 10 IU/ml for COBAS TaqMan. Invader 1.0 results obtained from unpurified COBAS TaqMan amplification products of 111 retrospectively selected clinical serum specimens (genotypes 1 to 6, with virus titers ranging from 15.1 to 2.1 × 10 7 IU/ml) showed 98% concordance with results obtained from the TRUGENE HCV 5 ′ NC Genotyping Kit (Bayer HealthCare LLC, Tarrytown, NY), used in conjunction with COBAS AMPLICOR. Although the assay is sensitive, accurate, and easy to perform, additional optimization of the Invader 1.0 interpretive software (Invader Data Analysis Worksheet) may be necessary to reduce potential misidentification of HCV genotypes in low-titer specimens. In summary, Invader 1.0 is compatible with a variety of commercially available PCR-based HCV 5′ NC region amplification assays and is suitable for routine HCV genotyping in clinical laboratories.

Dieser zweiteilige Artikel stützt sich auf ein vergleichendes und beschreibendes Modell, anhand dessen sich die Wahrnehmungen der Symptombelastung von Lungenkrebspatientinnen und -patienten und die Einschätzungen der sie hauptsächlich pflegenden Angehörigen im familiären Rahmen untersuchen lassen. Der zweite Teil beschreibt die Resultate der qualitativen Komponente dieser Untersuchung. Eine Auswahl von 37 Paaren, die aus Patient/in und pflegendem Familienmitglied bestanden, füllte die McCorkle and Young Symptom Distress Scale (SDS) aus. Die Gesamtresultate der pflegenden Angehörigen korrelierten mäßig1 mit jenen der Patienten (r = 0.71; P < 0.001). Bei 10 der 13 Symptome fanden sich keine bedeutsamen Unterschiede in der Einstufung. Pflegende sollten sich daher bewußt sein, daß die pflegenden Angehörigen die Symptombelastung von Lungenkrebspatienten bei mindestens 10 der 13 auf der SDS aufgeführten Symptome zuverlässig einschätzen. Dies ist vor allem dann von großer Bedeutung, wenn der Patient oder die Patientin selbst nicht in der Lage ist, über seine/ihre Symptombelastung zu sprechen.