tbuckley/cabot-search huggingface dataset:
Efficacy and safety of interferon alfa therapy in chronic hepatitis C with autoantibodies to liver-kidney microsomes
Authors: Luca Todros, Giorgio Saracco, Marilena Durazzo, Maria Lorena Abate, Giovanni Touscoz, Luca Scaglione, Giorgio Verme, Mario Rizzetto
Journal: Hepatology (1995)

Interferon alfa (IFN) therapy is efficacious in chronic viral hepatitides. It may, however, cause adverse immunologic reactions in patients with concomitant autoimmune phenomena. A minority of patients with chronic type C hepatitis have antibodies against liver and kidney microsomes (anti-LKM) in serum. We therefore carried out this study to find out whether IFN is safe and efficacious also in this subgroup. We treated 92 consecutive cases of chronic hepatitis C with IFN. Twelve patients had anti-LKM< and the remaining 80 tested negative to the anti-LKM. The hepatitis C virus (HCV) infection was diagnosed on the basis of positive anti-HCV and HCV-RNA tests. We compared the clinical and virological virological results of the therapy and the side effects found in the two groups. We found that the response to therapy and the outcome after 1 year of follow-up were similar. Treatment was discontinued in one anti-LKM-positive patient because of a drastic increase in ALT levels at the fourth month of therapy. No untoward effect was observed in the other cases. Hepatitis C patients with anti-LKM may be exposed to an increased risk of an adverse hepatitic reaction while being treated with IFN. However, we found that the extent of the risk was minimal compared with the expected benefits of the therapy. IFN is therefore recommended as the first therapy to choose in these patients. They must, however, be monitored more closely for possible liver dysfunction than the ordinary hepatitis C patient.
Gastric antral dysrhythmias in children with chronic idiopathic intestinal pseudoobstruction.
Authors: S P Devane, A M Ravelli, W M Bisset, V V Smith, B D Lake, P J Milla
Journal: Gut (1992)

Chronic idiopathic intestinal pseudoobstruction is a serious disorder of intestinal neuromuscular function resulting in recurrent episodes of intestinal obstruction, and is caused by primary disease of the enteric nerves or enteric smooth muscle. Gastric electrical control activity detected by the non-invasive technique of surface electrogastrography was investigated in 11 children (0.1-16 years) with proven chronic idiopathic intestinal pseudoobstruction (four with known disease of the enteric nerves, three with disease of smooth muscle cells, and four without defined pathology), to determine whether abnormalities were present and whether these were useful in detecting the underlying pathology. Abnormalities were present in eight of 11 patients. Persistent tachygastria (electrical control activity frequency &gt; 5 cycles/minute) was found in three patients, all with a proven neuropathy. A continuously irregular frequency was found in five patients, three with a proven myopathy and two with undefined pathology. A normal electrical control activity frequency was present in three patients, one with a proven neuropathy and two with undefined pathology. It is suggested that this non-invasive technique may provide a useful screening test of the pathophysiological basis of the functional obstruction in children with chronic idiopathic intestinal pseudoobstruction.
Lumbar disc disease shows linkage to chromosome 19 overlapping with a QTL for hand OA
Authors: F M K Williams, B S Kato, G Livshits, P N Sambrook, T D Spector, A J MacGregor
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> Cervical and lumbar degenerative disc disease (CDD and LDD, respectively) form part of the spine osteoarthritis (OA) phenotype and are known to be influenced by genetic factors. A genome-wide linkage analysis was performed to identify new chromosomal regions of interest. <h3>Methods:</h3> Dizygotic healthy female twin volunteers (n = 348) from the TwinsUK register who had magnetic resonance imaging scans 10 years ago coded for degenerative disease, were identified. Multipoint genome-wide linkage analysis was conducted using 737 highly polymorphic markers of approximate spacing 10 cM. <h3>Results:</h3> The mean age of the twins was 52 years. Significant linkage peaks (log of the odds (LOD) &gt;3) were identified for LDD at three chromosomal regions. These included chromosome 1 (position 285 cM), chromosome 5 (position 175 cM) and chromosome 19 (position 80 cM). The peak on chromosome 19 had LOD = 4.06, and the empirical p = 6.7×10<sup>-4</sup> confirmed reliability of the linkage signal. It lies close to a linkage peak previously obtained by our group for hand OA. <h3>Conclusions:</h3> This genome-wide linkage study of CDD and LDD shows evidence of linkage for LDD on chromosome 19. The region of interest is likely to harbour genes that are common to LDD and hand OA.
Physiological Response to Pressure Support Ventilation Delivered before and after Extubation in Patients Not Capable of Totally Spontaneous Autonomous Breathing
Authors: MICHELE VITACCA, NICOLINO AMBROSINO, ENRICO CLINI, ROBERTO PORTA, CIRO RAMPULLA, BARBARA LANINI, STEFANO NAVA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We designed a prospective, physiological study in 12 patients affected by chronic respiratory disorders. The study was aimed at assessing the diaphragm energy expenditure (PTPdi), lung resistance (Rl) and elastance (El), arterial blood gases (ABG), breathing pattern, and dyspnea measured by a visual analog scale during invasive pressure support ventilation (i-PSV) and noninvasive PSV (n-PSV). The ventilator settings were kept the same. Both i-PSV and n-PSV significantly reduced the PTPdi per minute, compared with that during a T-piece trial (204.4 ± 93.8 cm H2O × s/min [i-PSV]; 197.5 ± 119.8 [n-PSV]; 393.8 ± 129.0 [T-piece]). Expired tidal volume (Vte) was significantly higher (p < 0.05) during n-PSV (615 ± 166 ml) than during i-PSV (519 ± 140 ml). The respiratory pump (PTPdi/Vte) was more effective (p < 0.05) with noninvasive ventilation (22.3 ± 2.3 cm H2O × s/L for i-PSV versus 17.2 ± 3.3 for n-PSV). Rl and El were similar with the two modes of ventilation. Overall dyspnea was significantly (p < 0.05) better during n-PSV than i-PSV, whereas ABG were similar. We have shown, in patients affected by stable chronic respiratory disorders not ready to sustain totally spontaneous breathing, that i-PSV and n-PSV are equally effective in reducing the PTPdi and in improving ABG, but that n-PSV seems to be better tolerated.Keywords: noninvasive ventilation; weaning; respiratory mechanics; diaphragm function
Biological Aspects and Binding Strategies of Vascular Endothelial Growth Factor in Renal Cell Carcinoma
Authors: Brian I. Rini, W.Kimryn Rathmell
Journal: Clinical Cancer Research (2007)

Abstract Vascular endothelial growth factor (VEGF) is a key mediator in the pathogenesis of renal cell carcinoma (RCC). VEGF is up-regulated in clear cell RCC as a result of loss of the von Hippel-Lindau tumor suppressor gene and subsequent activation of the hypoxia response pathway. VEGF expression drives the migration and proliferation of endothelial cells to support the extensive angiogenesis in RCC. Strategies have been developed to bind and neutralize VEGF and have been investigated in RCC with promising results. Bevacizumab, a VEGF ligand-binding antibody, has shown prolonged time-to-progression versus placebo in treatment-refractory RCC patients and is being investigated currently in multiple RCC settings. VEGF-Trap is also a VEGF binding molecule with ongoing investigation in RCC.
Final 5-Year Results of the TAXUS II Trial
Authors: Sigmund Silber, Antonio Colombo, Adrian P. Banning, Karl Hauptmann, Janusz Drzewiecki, Eberhard Grube, Dariusz Dudek, Donald S. Baim
Journal: Circulation (2009)

Background— The TAXUS II trial was designed to evaluate the safety and efficacy of the commercialized slow-release (SR) and an investigation-only moderate-release (MR) polymer-based TAXUS paclitaxel-eluting stent compared with a bare-metal stent for the treatment of de novo coronary lesions. Methods and Results— This prospective, randomized, double-blind, controlled trial enrolled 536 patients in 2 consecutive cohorts to compare TAXUS SR (n=131) and TAXUS MR (n=135) with an identical but uncoated bare-metal stent control (n=270). The present analysis reports final 5-year clinical outcomes of TAXUS II. At 5 years, both TAXUS SR and MR showed superior outcomes compared with control. The 5-year rates of major adverse cardiac events were 27.6%, 20.4%, and 15.1% ( P =0.01); rates of target-vessel revascularization were 22.5%, 16.6%, and 9.0% ( P =0.004); and rates of target-lesion revascularization were 18.4%, 10.3%, and 4.5% ( P &lt;0.001) for the control, TAXUS SR, and TAXUS MR groups, respectively. The rates of all-cause death and myocardial infarction were low and similar between groups, with 2 stent thromboses with bare-metal stents compared with no event beyond 2 years with either of the TAXUS stents. Conclusions— TAXUS II is the first large TAXUS trial to have reached 5-year follow-up. Both the SR and MR stents lowered the rates of target-vessel and target-lesion revascularization, which indicates their sustained efficacy. Furthermore, the low overall rates of all death, myocardial infarction, and stent thrombosis support the long-term safety of the TAXUS stent system.
Satisfaction and Quality of Life With Premeal Inhaled Versus Injected Insulin in Adolescents and Adults With Type 1 Diabetes
Authors: Marcia A. Testa, Donald C. Simonson
Journal: Diabetes Care (2007)

OBJECTIVE—We sought to compare and evaluate the impact of inhaled versus injected insulin on potential mediators of patient acceptance of insulin therapy while maintaining comparable A1C levels. RESEARCH DESIGN AND METHODS—During a noninferiority efficacy trial conducted in 40 centers in the U.S., we surveyed treatment satisfaction, quality of life, and adherence barriers at weeks −4, −1, 6, 12, 20, and 24 in adolescents aged 12–17 years and adults with type 1 diabetes who received premeal regular plus twice-daily NPH insulin during a 4-week run-in; then, subjects were randomized to premeal inhaled human insulin plus twice-daily NPH (adults, n = 102; adolescents, n = 60) (inhaled) or remaining on run-in therapy (n = 105 and 60, respectively) (subcutaneous injection). RESULTS—Overall treatment satisfaction (0–100) increased by 13.2 ± 1.1 units for inhaled insulin (baseline = 63.3 ± 1.2) compared with 1.7 ± 0.8 for subcutaneous insulin injection (baseline = 64.1 ± 1.2, P &amp;lt; 0.0001). All 12 satisfaction subscales favored inhaled insulin (all P &amp;lt; 0.01), and effects did not vary by age or sex. Despite similar baseline-adjusted end point A1C for inhaled (7.7 ± 0.1%) and subcutaneous (7.9 ± 0.1%) regimens, quality-of-life scales of mental health, symptoms, health status, cognitive functioning, and adherence barriers during treatment were more favorable for inhaled insulin (all P &amp;lt; 0.05). Greater satisfaction was associated with fewer barriers to insulin adherence (rho = −0.78, P &amp;lt; 0.0001) and a greater reduction in A1C (rho = −0.18, P &amp;lt; 0.001). CONCLUSIONS—Treatment satisfaction was substantially more favorable, adherence barriers moderately lower, and quality of life moderately higher for inhaled compared with subcutaneous regimen. It remains to be demonstrated whether these patient-reported outcomes will translate into improved adherence and glycemic control.
The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications
Authors: J Satsangi
Journal: Gut (2006)

In recent years, investigators have readdressed the complex issues involved in the classification of inflammatory bowel diseases. In 2003, a Working Party of investigators with an interest in the issues involved in disease subclassification was formed with the aim of summarising recent developments in disease classification and establishing an integrated clinical, molecular, and serological classification of inflammatory bowel disease. The results of the Working Party were reported at the 2005 Montreal World Congress of Gastroenterology. Here we highlight the key issues that have emerged from discussions of the Montreal Working Party and the relevance to clinical practice and research activities.
Uveitis as a presenting feature of chronic sarcoidosis
Authors: G Rizzato, M Angi, P Fraioli, L Montemurro, E Pilotto, A Tommasini
Journal: European Respiratory Journal (1996)

Uveitis is often a manifestation of sarcoidosis. Less well-recognized, however, is the development of uveitis several years before the diagnosis of systemic sarcoidosis. The possibility that presentation of uveitis is a marker for the chronicity of sarcoidosis has never been investigated. The aim of this work was to evaluate, in a Caucasian population, the epidemiology of uveitis as the primary manifestation of sarcoidosis with long-term follow-up, and the relationship of uveitis to the chronicity of sarcoidosis. The records of 1,156 Caucasian patients with histologically proven sarcoidosis, first seen in the period 1976-1992, were reviewed. In patients in whom uveitis was the primary feature of sarcoidosis, the following parameters were identified: systemic manifestations; time interval between the diagnosis of uveitis and sarcoidosis; therapy; the evolution of chest radiographic image over time; chronicity; the relationship between sarcoidosis and uveitis; and, finally, status in October 1994. In nine patients, uveitis was the reason for seeking medical treatment, resulting in the discovery of systemic sarcoidosis, which was then found to be chronic in 7 out of 9 cases. In an additional eight patients, uveitis preceded the diagnosis of systemic sarcoidosis by 1-11 yrs, and yet most subjects had systemic manifestations that went unrecognized during this time period, with chest radiograph at the time of diagnosis suggesting a long-standing chronic disease. Thus, uveitis appeared to be the primary manifestation of sarcoidosis in 17 of the 1,156 patients studied (1.5%). In conclusion, any uveitis of unknown origin may be due to sarcoidosis, although its systemic manifestations may not occur for up to 11 yrs. Uveitis patients need a very long-term follow-up, including periodic diagnostic tests for systemic sarcoidosis. Furthermore, when uveitis precedes the systemic symptoms and diagnosis of sarcoidosis by more than one year, it may be regarded as a marker of the chronicity of sarcoidosis.
Regulated vesicle fusion generates signaling nanoterritories that control T cell activation at the immunological synapse
Authors: Helena Soares, Ricardo Henriques, Martin Sachse, Leandro Ventimiglia, Miguel A. Alonso, Christophe Zimmer, Maria-Isabel Thoulouze, Andrés Alcover
Journal: The Journal of Experimental Medicine (2013)

How the vesicular traffic of signaling molecules contributes to T cell receptor (TCR) signal transduction at the immunological synapse remains poorly understood. In this study, we show that the protein tyrosine kinase Lck, the TCRζ subunit, and the adapter LAT traffic through distinct exocytic compartments, which are released at the immunological synapse in a differentially regulated manner. Lck vesicular release depends on MAL protein. Synaptic Lck, in turn, conditions the calcium- and synaptotagmin-7-dependent fusion of LAT and TCRζ containing vesicles. Fusion of vesicles containing TCRζ and LAT at the synaptic membrane determines not only the nanoscale organization of phosphorylated TCRζ, ZAP70, LAT, and SLP76 clusters but also the presence of phosphorylated LAT and SLP76 in interacting signaling nanoterritories. This mechanism is required for priming IL-2 and IFN-γ production and may contribute to fine-tuning T cell activation breadth in response to different stimulatory conditions.
Angiotensin II Stimulates p21-Activated Kinase in Vascular Smooth Muscle Cells
Authors: Udo Schmitz, Takafumi Ishida, Mari Ishida, James Surapisitchat, Mohammed I. Hasham, Steven Pelech, Bradford C. Berk
Journal: Circulation Research (1998)

Angiotensin II (Ang II) has been previously shown to stimulate the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinase family members. Little is known regarding the upstream signaling molecules involved in Ang II-mediated JNK activation. Ang II has been shown to activate the Janus kinase/signal transducer(s) and activator(s) of transcription (JAK/STAT) pathway, suggesting similarities to cytokine signaling. In response to cytokines such as interleukin-1 and tumor necrosis factor-alpha, the p21-activated kinase (PAK) has been identified as an upstream component in JNK activation. Therefore, we hypothesized that PAK may be involved in JNK activation by Ang II in vascular smooth muscle cells (VSMCs). AlphaPAK activity was measured by myelin basic protein phosphorylation in rat aortic VSMCs. In response to Ang II, alphaPAK was rapidly stimulated within 1 minute, with a peak (5-fold increase) at 30 minutes. AlphaPAK stimulation preceded activation of JNK in VSMCs. Ang II-mediated activation of both alphaPAK and JNK was Ca2+ dependent and inhibited by downregulation of phorbol ester-sensitive protein kinase C isoforms (by pretreatment with phorbol 12,13-dibutyrate) but not by pretreatment with GF109203X. Activation of both PAK and JNK was partially inhibited by tyrosine kinase inhibitors but not by specific Src inhibitors, suggesting regulation by a tyrosine kinase other than c-Src. Finally, introduction of dominant negative PAK markedly reduced the JNK activation by Ang II in both Chinese hamster ovary and COS cells stably expressing the Ang II type 1 receptor (AT1R). Our data provide evidence for alphaPAK as an upstream mediator of JNK in Ang II signaling and extend the role of Ang II as a proinflammatory mediator for VSMCs.
Are hepatitis C virus antibodies involved in chronic liver diseases other than non-A, non-B hepatitis?
Authors: Luis Viola, Eduardo Pimentel, Pedro Morgante, José Luis Fernández, Albert Parés, Josep Marí Barrera, Joan Caballería, Guadalupe Ercilla, Miquel Bruguera, Llorencl Caballería, Ricardo Castillo, Joan Rodés
Journal: Hepatology (1991)
Granulocyte colony-stimulating factor impairs liver regeneration in mice through the up-regulation of interleukin-1β
Authors: Tomio Ogiso, Masahito Nagaki, Shinji Takai, Yoshihiko Tsukada, Tsuyoshi Mukai, Kiminori Kimura, Hisataka Moriwaki
Journal: Journal of Hepatology (2007)
Combined reduction of intercellular coupling and membrane excitability differentially affects transverse and longitudinal cardiac conduction
Authors: M. Stein, T. A.B. van Veen, C. A. Remme, M. Boulaksil, M. Noorman, L. van Stuijvenberg, R. van der Nagel, C. R. Bezzina, R. N.W. Hauer, J. M.T. de Bakker, H. V.M. van Rijen
Journal: Cardiovascular Research (2009)

AimsReduced excitability and gap junction expression are commonly found in electrically remodelled diseased hearts, but their contribution to slow conduction and arrhythmias is unclear. In this study, we have investigated the effect of isolated and combined reductions in membrane excitability and intercellular coupling on impulse propagation and arrhythmogeneity in genetically modified mice.
Patients' preferences for the management of non-metastatic prostate cancer: discrete choice experiment
Authors: Mark Sculpher, Stirling Bryan, Pat Fry, Patricia de Winter, Heather Payne, Mark Emberton
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To establish which attributes of conservative treatments for prostate cancer are most important to men. <b>Design</b> Discrete choice experiment. <b>Setting</b> Two London hospitals. <b>Participants</b> 129 men with non-metastatic prostate cancer, mean age 70 years; 69 of 118 (58%) with T stage 1 or 2 cancer at diagnosis. <b>Main outcome measures</b> Men9s preferences for, and trade-offs between, the attributes of diarrhoea, hot flushes, ability to maintain an erection, breast swelling or tenderness, physical energy, sex drive, life expectancy, and out of pocket expenses. <b>Results</b> The men9s responses to changes in attributes were all statistically significant. When asked to assume a starting life expectancy of five years, the men were willing to make trade-offs between life expectancy and side effects. On average, they were most willing to give up life expectancy to avoid limitations in physical energy (mean three months) and least willing to trade life expectancy to avoid hot flushes (mean 0.6 months to move from a moderate to mild level or from mild to none). <b>Conclusions</b> Men with prostate cancer are willing to participate in a relatively complex exercise that weighs up the advantages and disadvantages of various conservative treatments for their condition. They were willing to trade off some life expectancy to be relieved of the burden of troublesome side effects such as limitations in physical energy.
Trophic Effect of Norepinephrine on Arterial Intima-Media and Adventitia Is Augmented by Injury and Mediated by Different α1-Adrenoceptor Subtypes
Authors: Hua Zhang, James E. Faber
Journal: Circulation Research (2001)

In vivo studies have suggested that norepinephrine (NE) directly contributes to normal vascular wall growth and worsening of hypertrophy, atherosclerosis, and restenosis. However, it is unknown whether these effects are secondary to hemodynamic changes caused by systemic NE or α-adrenoceptor (AR) antagonists. Herein, we determined if NE directly stimulates growth of medial smooth muscle cells (SMCs) and adventitial fibroblasts (AFBs) that we have shown express α1-ARs in similar abundance. The rat aorta was isolated before injury, 4 days after, or 12 days after balloon injury, and maintained under circumferential tension in organ culture for 48 hours with 1 μmol/L NE. Intima-media and adventitia were separated and DNA content, protein synthesis, and protein content measured. In uninjured aorta, NE increased DNA and protein content similarly in adventitia, and increased only protein content in intima-media, suggesting AFB proliferation and SMC hypertrophy. In vessels isolated 4 or 12 days after injury, NE increased all 3 endpoints in both layers by up to 20-fold greater than in uninjured vessels. These effects were dose-dependent and were unaffected by α2- or β-AR blockade (except increased DNA content in adventitia that was also inhibited by α2-AR blockade). Intima-media growth was blocked by KMD3213 (α1A-AR antagonist) and adventitial growth by AH11110A (α1B-AR antagonist), whereas BMY7378 (α1D-AR antagonist) had no effect. NE decreased SMC marker proteins (eg, α-smooth muscle actin and desmin) and augmented the changes induced by injury. These data suggest that prolonged stimulation of α1A- and α1B-ARs induces growth of SMCs and AFBs, respectively, that is significantly augmented by injury.
Heparan sulfate proteoglycans in glomerular inflammation
Authors: Angelique L.W.M.M. Rops, Johan van der Vlag, Joost F.M. Lensen, Tessa J.M. Wijnhoven, Lambert P.W.J. van den Heuvel, Toin H. van Kuppevelt, Jo H.M. Berden
Journal: Kidney International (2004)
Systemic delivery of an adenoviral vector encoding canine factor VIII results in short-term phenotypic correction, inhibitor development, and biphasic liver toxicity in hemophilia A dogs
Authors: Angela M. Gallo-Penn, Pamela S. Shirley, Julie L. Andrews, Shawn Tinlin, Sandy Webster, Cherie Cameron, Christine Hough, Colleen Notley, David Lillicrap, Michael Kaleko, Sheila Connelly
Journal: Blood (2001)