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In an effort to identify a clinical biomarker for lung cancer, we used cDNA microarray and 2D protein analyses to demonstrate that increased Fas-associated death domain (

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Background Sympathetic nerve activity is important to cardiac arrhythmogenesis. Objectives (1) To develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. (2) This method (neuECG) can be used to adequately estimate the sympathetic tone. Methods We recorded neuECG signals from the skin in 56 human subjects. The signals were low pass filtered to show the ECG and high pass filtered to show nerve activity. Protocol (P)-1 included 12 healthy volunteers who underwent cold water pressor test (CPT) and Valsalva maneuver. P-2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. P-3 included 22 patients admitted with electrical storm and monitored for 39.0±28.2 hours. P-4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection. Results In patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. The SKNA recorded from chest leads (V1–V6) during CPT and Valsalva maneuver (P-1) was invariably higher than during baseline and recovery periods (p<0.001). In P-2, the average SKNA correlated with the heart rate acceleration (r=0.73±0.14, p<0.05) and shortening of the QT interval (p<0.001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of P-3, 106 episodes (73%) were preceded by SKNA within 30 s of onset. P4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA. Conclusions SKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating the sympathetic tone.

Background and objectives: Renal function and imaging findings have not been comprehensively and prospectively characterized in a broad age range of patients with molecularly confirmed autosomal recessive polycystic kidney disease (ARPKD).Design, setting, participants, & measurements: Ninety potential ARPKD patients were examined at the National Institutes of Health Clinical Center. Seventy-three fulfilled clinical diagnostic criteria, had at least one PKHD1 mutation, and were prospectively evaluated using magnetic resonance imaging (MRI), high-resolution ultrasonography (HR-USG), and measures of glomerular and tubular function.Results: Among 31 perinatally symptomatic patients, 25% required renal replacement therapy by age 11 years; among 42 patients who became symptomatic beyond 1 month (nonperinatal), 25% required kidney transplantation by age 32 years. Creatinine clearance (CrCl) for nonperinatal patients (103 ؎ 54 ml/min/1.73 m 2 ) was greater than for perinatal patients (62 ؎ 33) (P ‫؍‬ 0.002). Corticomedullary involvement on HR-USG was associated with a significantly worse mean CrCl (61 ؎ 32) in comparison with medullary involvement only (131 ؎ 46) (P < 0.0001). Among children with enlarged kidneys, volume correlated inversely with function, although with wide variability. Severity of PKHD1 mutations did not determine kidney size or function. In 35% of patients with medullary-only abnormalities, standard ultrasound was normal and the pathology was detectable with HR-USG.Conclusions: In ARPKD, perinatal presentation and corticomedullary involvement are associated with faster progression of kidney disease. Mild ARPKD is best detected by HR-USG. Considerable variability occurs that is not explained by the type of PKHD1 mutation.Clin J Am Soc Nephrol 5: 972-984, 2010.

Since type 2 cytokines are known to promote lupus glomerulosclerosis, decreased IL-4 and IL-10 production in captopril-treated mice may be related to this agent's renoprotective effects. We argue here that ACE inhibitors not only act as selective TGF-beta inhibitors, but also as selective immunomodulators, to improve lupus nephritis.

Acute graft-versus-host disease (GVHD) and leukemic relapse are serious complications of allogeneic stem-cell transplantation (SCT). Recruitment of activated T cells to host target tissues or sites of leukemic infiltration (graft-versusleukemia [GVL]) is likely mediated by chemokine receptor-ligand interactions.We examined the contribution of donor cell CCR1 expression to the development of GVHD and GVL using a well-established murine SCT model (B6 3 B6D2F1) and CCR1-deficient mice (CCR1 ؊/؊ ). Allo-SCT with CCR1 ؊/؊ donor cells significantly reduced systemic and target organ GVHD severity, and CCR1 expression on both T cells and accessory cells contributed to GVHD mortality. Significant GVL activity was preserved following CCR1 ؊/؊ SCT, but the survival advantage diminished with increasing tumor burden. We then explored the effects of CCR1 expression on allo-specific T-cell responses. Although cytolytic effector function was maintained on a per-cell basis, T-cell proliferation and IFN␥ secretion were significantly reduced both in vivo and in vitro. T-cell function was partially dependent on interactions between CCR1 and CCL5.Collectively, these data demonstrate that CCR1 expression on donor cells contributes to the development of both GVHD and GVL, and suggest that CCR1/CCL5 receptorligand interactions modulate allo-specific T-cell responses occurring in this context. IntroductionAllogeneic stem-cell transplantation (allo-SCT) is an important therapeutic option for a variety of malignant and nonmalignant disorders. 1 Acute graft-versus-host disease (GVHD) is the most frequent and serious complication following allo-SCT and continues to limit the broader application of this therapy. 2 In the context of hematologic malignancies, a delicate balance exists between the harmful consequences of GVHD and the beneficial effects incurred when donor T cells attack recipient malignant cells, a process referred to as the graft-versus-leukemia (GVL) effect. 3,4 A better understanding of the mechanisms responsible for these graft-versushost reactions may ultimately allow for directed therapies that promote GVL while reducing GVHD. 5 The pathophysiology of acute GVHD is complex. Experimental and clinical data suggest that host antigen-presenting cells (APCs) present alloantigen to donor T cells and initiate a cascade of events resulting in the development of cytotoxic effectors and the release of inflammatory proteins including cytokines and chemokines. 6 Activated donor leukocytes subsequently traffic to specific host tissues, where they, along with soluble effectors, cause end organ damage and dysfunction.Leukocyte migration is characterized by an orchestrated process involving interactions between white blood cells (WBCs) and endothelial cells that are mediated by adhesion molecules, chemoattractants, and their receptors. Chemokines are a large family of chemotactic cytokines that interact with specific G-proteincoupled chemokine receptors. 7 Chemokines are involved in both the innate and adaptive immune responses, 8 and h...