tbuckley/cabot-search huggingface dataset:
CC Chemokine Receptors and Chronic Inflammation—Therapeutic Opportunities and Pharmacological Challenges
Authors: Gemma E. White, Asif J. Iqbal, David R. Greaves
Journal: Pharmacological Reviews (2013)

Chemokines are a family of low molecular weight proteins with an essential role in leukocyte trafficking during both homeostasis and inflammation. The CC class of chemokines consists of at least 28 members (CCL1-28) that signal through 10 known chemokine receptors (CCR1-10). CC chemokine receptors are expressed predominantly by T cells and monocyte-macrophages, cell types associated predominantly with chronic inflammation occurring over weeks or years. Chronic inflammatory diseases including rheumatoid arthritis, atherosclerosis, and metabolic syndrome are characterized by continued leukocyte infiltration into the inflammatory site, driven in large part by excessive chemokine production. Over years or decades, persistent inflammation may lead to loss of tissue architecture and function, causing severe disability or, in the case of atherosclerosis, fatal outcomes such as myocardial infarction or stroke. Despite the existence of several clinical strategies for targeting chronic inflammation, these diseases remain significant causes of morbidity and mortality globally, with a concomitant economic impact. Thus, the development of novel therapeutic agents for the treatment of chronic inflammatory disease continues to be a priority. In this review we introduce CC chemokine receptors as critical mediators of chronic inflammatory responses and explore their potential role as pharmacological targets. We discuss functions of individual CC chemokine receptors based on in vitro pharmacological data as well as transgenic animal studies. Focusing on three key forms of chronic inflammation—rheumatoid arthritis, atherosclerosis, and metabolic syndrome—we describe the pathologic function of CC chemokine receptors and their possible relevance as therapeutic targets.
Varicella-Zoster Virus Infections in Patients Treated With Fingolimod
Authors: Ann M. Arvin, Jerry S. Wolinsky, Ludwig Kappos, Michele I. Morris, Anthony T. Reder, Carlo Tornatore, Anne Gershon, Michael Gershon, Myron J. Levin, Mauritz Bezuidenhoudt, Norman Putzki
Journal: JAMA Neurology (2014)

Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity. To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management. Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated. In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-years at the time of analysis). Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting. Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical Bayes geometric mean, 1.88 [90% CI, 0.87-3.70]). Corticosteroid treatment for relapses might be a risk factor for VZV reactivation. Rates of VZV infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipients. Rates reported in the postmarketing setting are comparable. We found no sign of risk accumulation with longer exposure. Serious or complicated cases of herpes zoster were uncommon. We recommend establishing the patient's VZV immune status before initiating fingolimod therapy and immunization for patients susceptible to primary VZV infection. Routine antiviral prophylaxis is not needed, but using concomitant pulsed corticosteroid therapy beyond 3 to 5 days requires an individual risk-benefit assessment. Vigilance to identify early VZV symptoms is important to allow timely antiviral treatment.
Nutritional status in chronic obstructive pulmonary disease
Authors: Sonia Habibech, Hamida Kwas, Ines Zendah, Ayari Aymen, Amel Khattab, Ibtihel Khouaja, Habib Ghedira
Journal: European Respiratory Journal (2014)

Introduction: Changes in nutritional status, such as weight loss and malnutrition, are a common complication in patients with chronic obstructive pulmonary disease (COPD). Malnutrition in these patients is mainly due to increases in resting energy expenditure and a high systemic inflammatory response.

Aim: To evaluate nutritional status in COPD by measuring the body mass index (BMI) and to determine consequences of malnutrition on disease severity and its exacerbation.

Patients and methods: Retrospective study including 53 patients (50 men and 3 women) hospitalized in our department for exacerbation of COPD.

Results: The mean age was 64.3 years. Smoking was noted in 95% of the patients. Patients weight varied from 40 to 99 kg (mean 76 kg). The mean BMI was 32 Kg/m2 (14.3 to 35.8 Kg/ m2). The malnutrition was found in 80 % cases. It was severe in 15% cases (BMI < 16 Kg/ m2). Biologic finding revealed microcytic hypochromic anemia in 20% of cases and a plyglobulia in 17% of cases. The COPD was classified according to the GOLD classification :stage I (15%), stage II (30%), stage III (23%) and stage IV (32%). Treatment was based on fractioned hypercaloric feeding in malnourished patients. Mean hospitalization duration was 15 days (5-32 days). Ten patients with low BMI have necessitated noninvasive ventilation. Five patients with severe malnutrition were transferred to intensive care unit due to the deterioration of their respiratory status.

Conclusion: This study underlines the correlation of the severity of the COPD and the nutritional status. In fact, over the BMI is low and therefore the nutritional status is poor more prognosis of COPD is severe and the treatment of exacerbations is more delicate.
Screening for α<sub>1</sub>‐Pi deficiency in patients with lung diseases
Authors: M. Wencker, A. Marx, N. Konietzko, B. Schaefer, E.J. Campbell
Journal: European Respiratory Journal (2002)

In patients with pulmonary emphysema, studies have reported 2–3% of individuals with severe α 1 ‐Pi deficiency. The aims of this study were to evaluate the accuracy of a new method for quantifying α 1 ‐Pi through phenotyping from dried blood spots (DBS) and to test the hypothesis that the screening of a population at risk increases the detection rate for severe α 1 ‐Pi deficiency. The accuracy of phenotyping results from DBS was compared to conventional methods in a total of 555 individuals. In a prospective study 1,060 patients with chronic lung disease were screened for α 1 ‐Pi deficiency using DBS. The validation of the phenotyping method from DBS showed an accuracy of 100%. Out of 1,060 tested patients, none had a severe PiZ deficiency and only 3 had PiSZ, whilst 36 (3.34%) individuals were identified as heterozygous for PiMS and 39 (3.68%) for PiMZ. No patients with severe α 1 ‐Pi deficiency could be detected in this population and the frequency of PiMS or PiMZ detected was similar to that of the normal population. Thus, the screening of an unselected population of chronic obstructive pulmonary disease and asthma patients may not detect a large number of individuals with severe α 1 ‐Pi deficiency.
Sexual dimorphism of the fifth component of mouse complement.
Authors: A Baba, T Fujita, N Tamura
Journal: The Journal of Experimental Medicine (1984)

Sexual dimorphism of mouse complement component 5 (C5) was detected by isoelectric focusing of desialated ethylenediamine tetraacetic acid (EDTA)-plasma on agarose gel, followed by immunofixation with anti-mouse C5. Male plasma displayed two C5 bands, basic and acidic, while female plasma had only a basic C5 band. In all mouse strains tested except C5-deficient strains, the identical patterns of the dimorphism were obtained. The basic and acidic C5 were antigenically and hemolytically indistinguishable from each other. In the neonatal mice of both sexes, the basic C5 was observed at the same levels, but the acidic C5 was only slightly detected. Injection of testosterone into mice resulted in an appearance of the acidic C5 in females and its increase in males. By contrast, injection of estradiol decreased the acidic C5. These results indicate that the expression of the acidic C5 is under the control of testosterone.
Beneficial effects of combination of ACE inhibitor and angiotensin II type 1 receptor blocker on cardiac remodeling in rat myocardial infarction
Authors: Y Nakamura
Journal: Cardiovascular Research (2002)

Angiotensin-converting enzyme (ACE) inhibitor and angiotensin II type I receptor blockers (ARB) prevent cardiac remodeling after myocardial infarction (MI). However, it is controversial whether combination therapy of ACE inhibitor and ARB is more effective on cardiac remodeling than each agent alone. In this study, we compared the effects of an ACE inhibitor (temocapril), an ARB (CS-866), and their combination on cardiac remodeling after MI.Temocapril at 3 or 30 mg/kg/day, CS-866 at 1 or 10 mg/kg/day, or combined temocapril and CS-866 at 1.5 and 0.5 mg/kg/day or at 15 and 5 mg/kg/day, respectively, were administered to rats after MI. At 4 weeks after MI, we assessed hemodynamics, cardiac function by Doppler echocardiography and non-infarcted myocardial mRNA expression.Animals treated with a combination of the two drugs had hemodynamics, heart weights and dimensions similar to the other treated animals. However, the combination of the two drugs suppressed ANP, BNP and other gene expressions related to contractile proteins of fetal type and collagens more effectively than ACE inhibitor or ARB alone.These data suggest that combination of the two drugs, independent of the hemodynamic effect, may improve left ventricular phenotypic change, collagen accumulation and diastolic function.
Wip1 Directly Dephosphorylates γ-H2AX and Attenuates the DNA Damage Response
Authors: Hyukjin Cha, Julie M. Lowe, Henghong Li, Ji-Seon Lee, Galina I. Belova, Dmitry V. Bulavin, Albert J. Fornace
Journal: Cancer Research (2010)

Abstract The integrity of DNA is constantly challenged throughout the life of a cell by both endogenous and exogenous stresses. A well-organized rapid damage response and proficient DNA repair, therefore, become critically important for maintaining genomic stability and cell survival. When DNA is damaged, the DNA damage response (DDR) can be initiated by alterations in chromosomal structure and histone modifications, such as the phosphorylation of the histone H2AX (the phosphorylated form is referred to as γ-H2AX). γ-H2AX plays a crucial role in recruiting DDR factors to damage sites for accurate DNA repair. On repair completion, γ-H2AX must then be reverted to H2AX by dephosphorylation for attenuation of the DDR. Here, we report that the wild-type p53–induced phosphatase 1 (Wip1) phosphatase, which is often overexpressed in a variety of tumors, effectively dephosphorylates γ-H2AX in vitro and in vivo. Ectopic expression of Wip1 significantly reduces the level of γ-H2AX after ionizing as well as UV radiation. Forced premature dephosphorylation of γ-H2AX by Wip1 disrupts recruitment of important DNA repair factors to damaged sites and delays DNA damage repair. Additionally, deletion of Wip1 enhances γ-H2AX levels in cells undergoing constitutive oncogenic stress. Taken together, our studies show that Wip1 is an important mammalian phosphatase for γ-H2AX and shows an additional mechanism for Wip1 in the tumor surveillance network. Cancer Res; 70(10); 4112–22. ©2010 AACR.
Cartilage repair in transplanted scaffold-free chondrocyte sheets using a minipig model
Authors: Goro Ebihara, Masato Sato, Masayuki Yamato, Genya Mitani, Toshiharu Kutsuna, Toshihiro Nagai, Satoshi Ito, Taku Ukai, Miyuki Kobayashi, Mami Kokubo, Teruo Okano, Joji Mochida
Journal: Biomaterials (2012)
Cardiovascular risk factors in patients with obstructive sleep apnoea syndrome
Authors: J.L. Kiely, W.T. McNicholas
Journal: European Respiratory Journal (2000)

Cardiovascular disorders are common in patients with obstructive sleep apnoea syndrome (OSAS) but there is debate as to whether OSAS is an independent risk factor for their development, since OSAS may be associated with other disorders and risk factors that predispose to cardiovascular disease. In an effort to quantify the risk of OSAS patients for cardiovascular disease arising from these other factors, the authors assessed the future risk for cardiovascular disease among a group of 114 consecutive patients with established OSAS prior to nasal continuous positive airway pressure therapy, using an established method of risk prediction employed in the Framingham studies. Patients were 100 males, aged (mean+/-SD) 52+/-9.0 yrs, and 14 females, aged 51+/-10.4 yrs, with an apnoea/hypopnoea index of 45+/-22 x h(-1). Based on either a prior diagnosis, or a mean of three resting blood pressure recordings >140 mmHg systolic and/or 90 diastolic, 68% of patients were hypertensive. Only 18% were current smokers, while 16% had either diabetes mellitus or impaired glucose tolerance, and 63% had elevated fasting cholesterol and/or triglyceride levels. The estimated 10-yr risk of a coronary heart disease (CHD) event in males was (mean+/-SEM) 13.9+/-0.9%, 95% confidence interval (95% CI) 12.1-16.0, and for a stroke was 12.3+/-1.4%; 95% CI 9.4-15.1, with a combined 10 yr risk for stroke and CHD events of 32.9+/-2.7%; 95% CI 27.8-38.5 in males aged >53 yrs. These findings indicate that obstructive sleep apnoea syndrome patients are at high risk of future cardiovascular disease from factors other than obstructive sleep apnoea syndrome, and may help explain the difficulties in identifying a potential independent risk from obstructive sleep apnoea syndrome.
Treatment options for autoimmune hepatitis: A systematic review of randomized controlled trials
Authors: Mieke M.H. Lamers, Martijn G.H. van Oijen, Martine Pronk, Joost P.H. Drenth
Journal: Journal of Hepatology (2010)

<h3>Background & Aims</h3> Predniso(lo)ne with or without azathioprine is considered the mainstay in the treatment of autoimmune hepatitis (AIH), but many therapeutic options are available. The primary objective of this review was to explore the published literature on the optimal induction and subsequent maintenance therapy for AIH. <h3>Methods</h3> We performed a systematic search on electronic databases MEDLINE (1950-07.2009), Web of Science, Cochrane, and the website www.clinicaltrials.gov. Randomized controlled trials (RCTs) on apparent beneficial treatment regimens as induction or maintenance treatment in AIH were included. Pediatric studies were excluded. We calculated relative risks (RR) for comparison of treatment options on the primary outcome measure, which was defined as clinical, biochemical and histological remission. <h3>Results</h3> Eleven RCTs were included, of which 7 studies evaluated the induction therapy in AIH patients: 3 treatment naive (<i>n</i>=253), 2 relapse (<i>n</i>=53), 2 combination of naive and relapse (<i>n</i>=110). The remaining 4 studies (<i>n</i>=162) assessed maintenance therapy. All but one maintenance study (thymostimulin versus no therapy) studied predniso(lo)ne (PRED), azathioprine (AZA) or combination PRED+AZA. We found no differences in primary outcome between induction therapy with PRED and PRED+AZA in treatment naive patients (RR=0.98; 95% CI 0.65–1.47). AZA monotherapy as induction was considered as not viable because of a high mortality rate (30%). This was similar in AIH patients who relapsed: RR for PRED versus PRED+AZA for inducing remission was not different: 0.71 (95% CI 0.37–1.39). PRED+AZA maintained remission more often than PRED (RR=1.40; 95% CI 1.13–1.73). Also AZA maintained a higher remission rate than PRED (RR=1.35; 95% CI 1.07–1.70). Maintenance of remission was not different between PRED+AZA and AZA (RR=1.06; 95% CI 0.94–1.20). <h3>Conclusions</h3> Based on available RCTs, PRED monotherapy and PRED+AZA combination therapy are both viable induction therapies for AIH treatment naives and relapsers, while for maintenance therapy PRED+AZA and AZA therapy are superior to PRED monotherapy.
THE CONSTITUTION OF MITOCHONDRIA AND MICROSOMES, AND THE DISTRIBUTION OF NUCLEIC ACID IN THE CYTOPLASM OF A LEUKEMIC CELL
Authors: Albert Claude
Journal: The Journal of Experimental Medicine (1944)

1. Rat tumor extracts, containing chiefly the cytoplasmic constituents of leukemic cells, were fractionated into three main portions, the different components separating in the centrifuge according to size. 2. Mitochondria were isolated by centrifugation at relatively low speed. Elementary composition of purified mitochondria was found to correspond to about 11.5 per cent nitrogen, 1.6 per cent phosphorus, and 27 per cent lipids. Phosphorus and nitrogen content of the lipid portion suggests that as much as 75 to 80 per cent of the lipids of mitochondria is represented by phospholipids. Tests for ribose nucleic acid were positive. 3. Microsomes were separated by means of centrifugation at 18,000 x g. A relation between the high phosphorus content of the microsomes and the marked basophilia of the cytoplasm of leukemic cells is suggested. 4. Phosphorus distribution in the tumor extract, and light absorption analysis of the third fraction, seem to demonstrate that nucleic acid was not present either in a free condition, or in the form of nucleoprotein of relatively low molecular weight. The nature of the results suggests that ribose nucleic acid occurs in the cytoplasm of leukemic cells only in association with formed elements of relatively large size, namely microsomes, and mitochondria.
O92 HEPATITIS C VIRUS INCIDENCE IN THE AMSTERDAM COHORT STUDY AMONG MEN WHO HAVE SEX WITH MEN; 1984–2011
Authors: J.W. Vanhommerig, I.G. Stolte, F.A.E. Lambers, R.B. Geskus, T.J.W. van de Laar, S.M. Bruisten, J. Schinkel, M. Prins
Journal: Journal of Hepatology (2014)
Regulation of protease-activated receptor-1 by vasodilatory prostaglandins via NFAT
Authors: A. C. Rosenkranz, B. H. Rauch, K. Freidel, K. Schror
Journal: Cardiovascular Research (2009)

AimsWe recently reported that prostacyclin suppresses protease-activated receptor-1 (PAR-1) in human vascular smooth muscle cells (VSMC) via cyclic AMP and protein kinase A. This study examines the downstream mechanisms, particularly the role of nuclear factor of activated T-cells (NFAT).
Prevalence, Clinical Profile, and Significance of Left Ventricular Remodeling in the End-Stage Phase of Hypertrophic Cardiomyopathy
Authors: Kevin M. Harris, Paolo Spirito, Martin S. Maron, Andrey G. Zenovich, Francesco Formisano, John R. Lesser, Shannon Mackey-Bojack, Warren J. Manning, James E. Udelson, Barry J. Maron
Journal: Circulation (2006)

End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined.Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction <50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients < or = 40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3+/-3 years. Duration from onset of HCM symptoms to ES identification was considerable (14+/-10 years), but ES onset to death/transplantation was brief (2.7+/-2 years). ES occurred with similar frequency in patients with or without prior myectomy (P=0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients.ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation.
Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT
Authors: Charles Crawley, Marc Lalancette, Richard Szydlo, Maria H Gilleece, Karl S Peggs, Stephen Mackinnon, Gunnar Juliusson, Lucia Ahlberg, Arnon Nagler, Avichai Shimoni, Anna Sureda, Jean-Michel Boiron, Herman Einsele, Rajesh Chopra, Angelo Carella, Jamie Cavenagh, Alois Gratwohl, Frederic Garban, Axel Zander, Bo Björkstrand, Dietger Niederwieser, Gösta Gahrton, Jane F Apperley
Journal: Blood (2005)
Professor X. Vilanova
Authors: H. J. Wallace
Journal: British Journal of Dermatology (1966)

Journal Article Professor X. Vilanova Get access H. J. Wallace H. J. Wallace Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 78, Issue 1, 1 January 1966, Page 52, https://doi.org/10.1111/j.1365-2133.1966.tb12133.x Published: 01 January 1966