tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: Role of interferon-á2b and ribavirin in MERS-CoV infection as treatment and prophylaxis
Authors: Mohammed Khalid, Basha Khan, Khaliq Agha Rehan, Quaid Nadri, Abdullah Al Mobeireek, Ruwaida AlIsmaili, Mehar Rehman, Taimur Butt, Mohammed Zeitouni, Abdullah Al Dalaan, Sarfraz Saleemi, Khalid Maghrabi, Eid Al Mutairy
Journal: European Respiratory Journal (2014)

Introduction: 

Middle East Respiratory Syndrome Coronavirus ( MERS-CoV) in the Kingdom with 60% mortality is alarming. We report 6 patients with MERS-CoV infection treated with Interferon-a2b and Ribavirin. 

Results: 

All MERS-CoV positive PCR. Active disease 1-4 (Table 1), 2 asymptomatic contacts 5-6 (table 1) out of 53contacts tested for virus. Active patient progressed to respiratory and multisystem failure. Patient 1-3 (table 1) were older age/comorbid condition, died. Patient #4 (Table 1) was diagnosed early with treatment recovered. 2 contact cases with early lung infiltrates which resolved after treatment.

Discussion: 

MERS-CoV is associated with high mortality. It attaches to DPP4 receptors in the lower respiratory tract, kidneys, liver and prostate leading to respiratory and multi-organ failure. Older patients with comorbid condition and delay in treatment associated in high mortality. Treatment in proven and asymptomatic contacts may prevent mortality and morbidity.

Conclusion: 

MERS-CoV infection is associated with high mortality in older patients with comorbid condition and in whom diagnosis and the treatment is delayed. Early intervention for confirmed cases with disease manifestation and confirmed MERS CoV asymptomatic cases may respond to the treatment. Human to human transmission is quite low.

View this table:

Table1:Patients Overview
Intensive Single-Agent Mitoxantrone for Metastatic Breast Cancer
Authors: E. J. Shpall, R. B. Jones, J. F. Holland, S. Bhardwaj, P. A. Paciucci, C. L. Wilfinger, A. Strashum
Journal: JNCI Journal of the National Cancer Institute (1988)

Twenty-seven women with metastatic breast cancer were treated with mitoxantrone as a single agent, with the use of an intensive dose-escalating schedule. Doses were given at 0.5 mg/m2/day as an iv injection for 3 consecutive days and then were escalated each month by 2.5 mg/m2/day until maximal tolerance was reached on the basis of hematologic or cardiac toxicity. No complete responses were demonstrated. Six patients (22%) had partial responses of 5.5 months' median duration. Four of 12 patients who had not received prior doxorubicin responded (33%), whereas two of 15 patients with previous doxorubicin exposure responded (13%). Cardiotoxicity, determined by serial radionuclide ventriculography, occurred in 10 patients (37%) at a mean total mitoxantrone dose of 83.0 mg/m2. Three of these 10 patients had no predisposing risk factors, four had received thoracic radiotherapy that might have involved the heart, and three had received prior doxorubicin without clinical toxicity. The failure of dose intensification to augment the response rate when compared to the response rates reported for less myelotoxic doses of the drug, in addition to the extent of cardiotoxicity noted, calls into question the value of dose intensification of mitoxantrone in the treatment of metastatic breast cancer.
Health inequalities target will be met, claims health secretary
Authors: A. O'Dowd
Journal: BMJ (2008)

The UK government is on track to meet its targets to reduce health inequalities by 10% in 2010, according to the health secretary, Alan Johnson.

Mr Johnson, giving evidence to the parliamentary health select committee this week as part of its inquiry into health inequities, said that he was confident that the government would meet its targets set out in the Tackling Inequalities: A Programme for Action strategy, published in 2003.

The strategy set specific targets, such as a 10% reduction in inequities by 2010, measured by infant mortality and life expectancy at birth.

“I think we are going to make the target,” Mr Johnson told the committee’s …
Renal Ischemia-Reperfusion Injury Amplifies the Humoral Immune Response
Authors: Richard Fuquay, Brandon Renner, Liudmila Kulik, James W. McCullough, Claudia Amura, Derek Strassheim, Roberta Pelanda, Raul Torres, Joshua M. Thurman
Journal: Journal of the American Society of Nephrology (2013)

Renal transplant recipients who experience delayed graft function have increased risks of rejection and long-term graft failure. Ischemic damage is the most common cause of delayed graft function, and although it is known that tissue inflammation accompanies renal ischemia, it is unknown whether renal ischemia affects the production of antibodies by B lymphocytes, which may lead to chronic humoral rejection and allograft failure. Here, mice immunized with a foreign antigen 24–96 hours after renal ischemia-reperfusion injury developed increased levels of antigen-specific IgG1 compared with sham-treated controls. This amplified IgG1 response did not follow unilateral ischemia, and it did not occur in response to a T-independent antigen. To test whether innate immune activation in the kidney after ischemia affects the systemic immune response to antigen, we repeated the immunization experiment using mice deficient in factor B that lack a functional alternative pathway of complement. Renal ischemia-reperfusion injury did not cause amplification of the antigen-specific antibodies in these mice, suggesting that the increased immune response requires a functional alternative pathway of complement. Taken together, these data suggest that ischemic renal injury leads to a rise in antibody production, which may be harmful to renal allografts, possibly explaining a mechanism underlying the link between delayed graft function and long-term allograft failure.
Mosaic Tumor Vessels: Cellular Basis and Ultrastructure of Focal Regions Lacking Endothelial Cell Markers
Authors: Emmanuelle di Tomaso, Diane Capen, Amy Haskell, Janet Hart, James J. Logie, Rakesh K. Jain, Donald M. McDonald, Rosemary Jones, Lance L. Munn
Journal: Cancer Research (2005)

Abstract Endothelial cells of blood vessels in tumors may be thin, fragile, and defective in barrier function. We found previously that the endothelium of vessels in human colon carcinoma xenografts in mice is a mosaic structure. Approximately 85% of tumor vessels have uniform CD31 and/or CD105 immunoreactivity, but the remainder have focal regions that lack these common endothelial markers. The present study assessed the ultrastructure of the vessel lining and the integrity of the basement membrane in these regions. Using immunolabeling and confocal microscopy, we identified blood vessels that lacked CD31 and CD105 immunoreactivity and then analyzed the ultrastructure of these vessels by transmission electron microscopy. Eleven percent of vessels in orthotopic tumors and 24% of vessels in ectopic tumors had defects in CD31 and CD105 staining measuring on average 10.8 μm (range, 1-41.2 μm). Ultrastructural studies identified endothelial cells at 92% of CD31- and CD105-negative sites in orthotopic tumors and 70% of the sites in ectopic tumors. Thus, most regions of tumor vessels that lack CD31 and CD105 immunoreactivity represent attenuated endothelial cells with abnormal expression of endothelial cell markers, but some are gaps between endothelial cells. More than 80% of the defects lacked immunoreactivity for multiple basement membrane proteins.
FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells
Authors: Qiuhong Zhang, Fengtian He, Ramalinga Kuruba, Xiang Gao, Annette Wilson, Jiang Li, Timothy R. Billiar, Bruce R. Pitt, Wen Xie, Song Li
Journal: Cardiovascular Research (2007)

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and plays an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. We and others have recently shown that FXR is also expressed in the vasculature, including endothelial cells and smooth muscle cells (SMC). However, the biological significance of FXR activation in SMC is still poorly understood. In this study, we examine the effect of FXR ligands on the angiotensin system in rat aortic SMC (RASMC), as angiotensin II (Ang II) signalling contributes to various types of vascular lesions by promoting cell growth of vascular SMC. Treatment of RASMC with a FXR ligand showed no obvious effect on the expression of angiotensinogen, Ang II type 1 receptor (AT1R) or type 4 receptor (AT4R) but led to a significant increase in the expression of type 2 receptor (AT2R). FXR ligand treatment also resulted in an inhibition of Ang II-mediated extracellular signal-regulated kinase (ERK) activation and growth proliferation. Promoter reporter gene and electrophoretic mobility-shift assays suggest that FXR upregulates AT2R expression at a transcriptional level. Upregulation of AT2R appears to play a role in the FXR-mediated inhibition of ERK activation via upregulation of Rous sarcoma oncogene (Src) homology domain-containing tyrosine phosphatase 1 (SHP-1) because FXR-mediated upregulation of SHP-1 can be blocked by an AT2R antagonist and FXR-mediated ERK inactivation was significantly attenuated via treatment with either an AT2R antagonist or a SHP-1 inhibitor. FXR in SMC may serve as a novel molecular target for modulating Ang II signalling in the vasculature.
Cysteinyl leukotrienes induce nuclear factor κb activation and rantes production in a murine model of asthma
Authors: Tetsuya Kawano, Hiroto Matsuse, Yuki Kondo, Ikuko Machida, Sachiko Saeki, Shinya Tomari, Kazuko Mitsuta, Yasushi Obase, Chizu Fukushima, Terufumi Shimoda, Shigeru Kohno
Journal: Journal of Allergy and Clinical Immunology (2003)
Venous Thromboembolism Prophylaxis and Treatment in Cancer: A Consensus Statement of Major Guidelines Panels and Call to Action
Authors: Alok A. Khorana, Michael B. Streiff, Dominique Farge, Mario Mandala, Philippe Debourdeau, Francis Cajfinger, Michel Marty, Anna Falanga, Gary H. Lyman
Journal: Journal of Clinical Oncology (2009)

Venous thromboembolism (VTE) is an increasingly frequent complication of cancer and its treatments, and is associated with worsened mortality and morbidity in patients with cancer.
Cognitive Behavior Therapy and Paroxetine in the Treatment of Hypochondriasis: A Randomized Controlled Trial
Authors: Anja Greeven, Anton J.L.M. van Balkom, Sako Visser, Jille W. Merkelbach, Yanda R. van Rood, Richard van Dyck, A.J. Willem Van der Does, Frans G. Zitman, Philip Spinhoven
Journal: American Journal of Psychiatry (2007)

This study, to the authors' knowledge, is the first randomized controlled trial comparing the efficacy of cognitive behavior therapy (CBT), paroxetine, and a placebo (administered in a double blind fashion) in the treatment of hypochondriasis.The authors randomly assigned 112 subjects with hypochondriasis according to DSM-IV criteria to 16 weeks of outpatient treatment with CBT, paroxetine, or a placebo. The main outcome measure was the Whiteley Index. The authors made pretest and posttest assessments and analyzed all outcome measures using a General Linear Model 3x2 repeated measures analysis of variance with Helmert contrasts. The authors considered subjects who scored at least one standard deviation below the mean pretest score on the Whiteley Index as responders. All analyses were conducted on intent-to-treat and completer bases.On the Whiteley Index, Helmert contrasts on the intent-to-treat and completer cohorts revealed that pooled CBT and paroxetine were significantly superior to placebo, but did not differ significantly from each other. The responder analysis on the intent-to-treat cohort and completer cohort, respectively, revealed the following percentages of responders per group: CBT group, 45% and 54%; paroxetine group, 30% and 38%; and placebo group, 14% and 12%. In the intent-to-treat analysis, only CBT differed significantly from the placebo. In the completer analysis, both paroxetine and CBT differed significantly from the placebo.CBT or paroxetine are effective short-term treatment options for subjects with hypochondriasis.
Uniform Scale-Independent Gene Transfer to Striated Muscle After Transvenular Extravasation of Vector
Authors: Leonard T. Su, Kapil Gopal, Zhonglin Wang, Xiaoqing Yin, Anthony Nelson, Benjamin W. Kozyak, James M. Burkman, Marilyn A. Mitchell, David W. Low, Charles R. Bridges, Hansell H. Stedman
Journal: Circulation (2005)

The muscular dystrophies exemplify a class of systemic disorders for which widespread protein replacement in situ is essential for treatment of the underlying genetic disorder. Somatic gene therapy will require efficient, scale-independent transport of DNA-containing macromolecular complexes too large to cross the continuous endothelia under physiological conditions. Previous studies in large-animal models have revealed a trade-off between the efficiency of gene transfer and the inherent safety of the required surgical and pharmacological interventions to achieve this.Rats and dogs underwent limb or hemibody isolation via atraumatic tourniquet placement or myocardial isolation via heterotopic transplantation. Recombinant adenovirus (10(13) particles per kilogram) or recombinant adeno-associated virus (10(14) genome copies/kg) encoding the lacZ transgene was delivered through pressurized venous infusion without pharmacological mediators. Muscle exhibited almost 100% myofiber transduction in rats and dogs by X-galactosidase staining and significantly higher beta-galactosidase levels compared with nonpressurized delivery. No significant difference was seen in beta-galactosidase levels between 100- or 400-mm Hg groups. The <50-mm Hg group yielded inhomogeneous and significantly lower transgene expression.Uniform scale- and vector-independent skeletal and cardiac myofiber transduction is facilitated by pressurized venous infusion in anatomic domains isolated from the central circulation without pharmacological interference with cardiovascular homeostasis. We provide the first demonstration of uniform gene transfer to muscle fibers of an entire extremity in the dog, providing a firm foundation for further translational studies of efficacy in canine models for human diseases.
Lifelong Cancer Incidence in 47 697 Patients Treated for Childhood Cancer in the Nordic Countries
Authors: Jørgen H. Olsen, Torgil Möller, Harald Anderson, Frøydis Langmark, Risto Sankila, Laufey Tryggvadóttír, Jeanette Falck Winther, Catherine Rechnitzer, Gudmundur Jonmundsson, Jane Christensen, Stanislaw Garwicz
Journal: JNCI Journal of the National Cancer Institute (2009)

The pattern of cancer in long-term survivors from childhood cancer has not been investigated comprehensively.We obtained a cohort of 47,697 children and adolescents aged 0-19 years with cancer as defined by the country-wide cancer registries of Denmark, Finland, Iceland, Norway, and Sweden during 1943-2005. Cohort members were followed through age 79 years for subsequent primary cancers notified to the registries, and the age-specific risk pattern of the survivors was compared with that of the national populations using country and sex standardized incidence ratios (SIRs). We used a multiplicative Poisson regression model to estimate relative risk of cancer for attained age, with adjustment for calendar period and age at diagnosis of primary cancer. We also calculated excess absolute risk (EAR) attributable to status as childhood cancer survivor and determined the cumulative incidence of second primary cancer as a function of attained age for three subcohorts defined by period of treatment for childhood cancer.A total of 1180 asynchronous second primary cancers were observed in 1088 persons, yielding an overall SIR of 3.3 (95% confidence interval = 3.1 to 3.5). The relative risk was statistically significantly increased in all age groups, even for cohort members approaching 70 years of age. The EAR for second primary cancer among survivors increased gradually from one additional case per 1000 person-years of observation in early life to six additional cases per 1000 person-years in the age group 60-69 years. For children treated in the prechemotherapy era (1943-1959), the cumulative risk for a second primary cancer reached 18%, 34%, and 48% at ages 60, 70, and 80 years, respectively. The age-specific incidence rates were highest for cohort members treated in the era of intensive, multiple-agent chemotherapy (1975-2005).Survivors of childhood cancer have a persistent excess risk for a second primary cancer throughout their lives, accompanied by continuous changes in the risk of cancers at specific sites.
Integrated PET/CT in the staging of nonsmall cell lung cancer: technical aspects and clinical integration
Authors: W. De Wever, S. Stroobants, J. Coolen, J. A. Verschakelen
Journal: European Respiratory Journal (2008)

Lung cancer is a common disease and is a leading cause of death in many countries. The management of lung cancer is directed by an optimal staging of the tumour. Integrated positron emission tomography (PET)/computed tomography (CT) is an anatomo-metabolic imaging modality that has recently been introduced to clinical practice and combines two different techniques: CT, which provides very detailed anatomic information; and PET, which provides metabolic information. One of the advantages of PET/CT is the improved image interpretation. This improvement can result in the detection of lesions initially not seen on CT or PET, a more precise location of lesions, a better characterisation of the lesion as benign or malignant and a better differentiation between tumour and surrounding structures. Initial studies demonstrate better results for PET/CT in the staging of lung cancer in comparison with PET alone, CT alone or visual correlation of PET and CT. The purpose of the present article is to discuss technical aspects of integrated PET/CT and to attempt to outline how to introduce integrated PET/CT in clinical and daily practice.
An Address on Operative and Expectant Treatment in Ectopic Pregnancy: Delivered before the Colchester Medical Society
Authors: G. E. Herman
Journal: BMJ (1904)

Alcohol is among the most widely consumed dietary substances. Excessive alcohol consumption damages the liver, heart and brain. Alcohol also has strong immunoregulatory properties. Here we report how alcohol impairs T cell function via acetylation of cortactin, a protein that binds filamentous actin and facilitates branching. Upon alcohol consumption, acetate, the metabolite of alcohol, accumulates in lymphoid organs. T cells exposed to acetate, exhibit increased acetylation of cortactin. Acetylation of cortactin inhibits filamentous actin binding and hence reduces T cell migration, immune synapse formation and activation. While mutated, acetylation-resistant cortactin rescued the acetate-induced inhibition of T cell migration, primary mouse cortactin knock-out T cells exhibited impaired migration. Furthermore, acetate-induced cytoskeletal changes effectively inhibited activation, proliferation, and immune synapse formation in T cells in vitro and in vivo in an influenza infection model in mice. Together these findings reveal cortactin as a possible target for mitigation of T cell driven autoimmune diseases.
Estrogen Modulates AT <sub>1</sub> Receptor Gene Expression In Vitro and In Vivo
Authors: Georg Nickenig, Anselm T. Bäumer, Christian Grohè, Stefan Kahlert, Kerstin Strehlow, Stephan Rosenkranz, Alexander Stäblein, Frank Beckers, Jos F. M. Smits, Mat J. A. P. Daemen, Hans Vetter, Michael Böhm
Journal: Circulation (1998)

Background —The AT 1 receptor has been implicated in the pathogenesis of hypertension and atherosclerosis. Estrogen deficiency is also associated with cardiovascular diseases. Therefore, we examined the AT 1 receptor gene expression in ovariectomized rats with and without estrogen replacement therapy and the influence of estrogen on AT 1 receptor expression in cultured vascular smooth muscle cells. Methods and Results —Rat aortic tissue was examined 5 weeks after ovariectomy. In one group, estrogen (1.7 mg estradiol) was administered during the 5-week period. Functional experiments assessed angiotensin II–induced contraction of aortic rings. AT 1 receptor mRNA levels were measured by quantitative polymerase chain reaction and Northern blotting. AT 1 receptor density was assessed by radioligand binding assays. These techniques were also applied in cultured vascular smooth muscle cells. The efficacy of angiotensin II on vasoconstriction was significantly increased in aortas from ovariectomized rats. As assessed by radioligand binding assays, AT 1 receptor density was increased to 160% without changes in receptor affinity during estrogen deficiency. AT 1 receptor mRNA levels were consistently increased to 187% in ovariectomized rats compared with sham-operated animals. Estrogen substitution therapy in ovariectomized rats reversed this AT 1 receptor overexpression. To explore the underlying mechanisms, the direct influence of estradiol on AT 1 receptor expression was investigated in VSMCs. Estradiol (1 μmol/L) led to a time-dependent downregulation of AT 1 receptor mRNA, with a maximum of 33.3% at 12 hours. There was a correlative decrease in AT 1 receptor density. Conclusions —This novel observation of estrogen-induced downregulation of AT 1 receptor expression could explain the association of estrogen deficiency with hypertension and atherosclerosis, because activation of the AT 1 receptor plays a key role in the regulation of blood pressure, fluid homeostasis, and vascular cell growth.
Evolutionary History of Chromosome 20
Authors: D. Misceo
Journal: Molecular Biology and Evolution (2004)

The evolutionary history of human chromosome 20 in primates was investigated using a panel of human BAC/PAC probes spaced along the chromosome. Oligonucleotide primers derived from the sequence of each human clone were used to screen horse, cat, pig, and black lemur BAC libraries to assemble, for each species, a panel of probes mapping to chromosomal loci orthologous to the loci encompassed by the human BACs. This approach facilitated marker-order comparison aimed at defining marker arrangement in primate ancestor. To this goal, we also took advantage of the mouse and rat draft sequences. The almost perfect colinearity of chromosome 20 sequence in humans and mouse could be interpreted as evidence that their form was ancestral to primates. Contrary to this view, we found that horse, macaque, and two New World monkeys share the same marker-order arrangement from which the human and mouse forms can be derived, assuming similar but distinct inversions that fully account for the small difference in marker arrangement between humans and mouse. The evolutionary history of this chromosome unveiled also two centromere repositioning events in New World monkey species.
Increase in Interleukin-1β in Late-Life Depression
Authors: Alan J. Thomas, Sue Davis, Christopher Morris, Elizabeth Jackson, Richard Harrison, John T. O’Brien
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Depression has been associated with increases in circulating cytokines in younger adults, and there is evidence for prefrontal inflammation in late-life depression. The authors tested the hypothesis that levels of cytokine interleukin-1β (IL-1β) would be higher in subjects with late-life major depression. METHOD: Serum levels of IL-1β were measured in three groups of subjects who were older than 60: 19 subjects with major depression, 20 subjects with subsyndromal depression, and 21 healthy comparison subjects. The Montgomery-Åsberg Depression Rating Scale and the Geriatric Depression Scale were used to assess severity of depression. RESULTS: Compared with healthy subjects, those with major depression had significantly higher levels of IL-1β (170%); the higher levels of IL-1β strongly correlated with current depression severity. There were no significant differences between subjects with subsyndromal depression and the other two groups. CONCLUSIONS: These findings support the existence of an inflammatory response, which may be state dependent, in late-life depression.