tbuckley/cabot-search huggingface dataset:
Computerized Image Analysis of Sirius Red–Stained Renal Allograft Biopsies as a Surrogate Marker to Predict Long-Term Allograft Function
Authors: Paul C. Grimm, Peter Nickerson, Jim Gough, Rachel McKenna, Elzbieta Stern, John Jeffery, David N. Rush
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Chronic allograft nephropathy (CAN) is a major problem in posttransplant management. The lack of a reliable and early surrogate marker of CAN has hampered patient care and research. In this study, the Cortical Fractional Interstitial Fibrosis Volume (VIntFib), quantitated with computerized image analysis of Sirius Red–stained protocol biopsies, was examined as a potential surrogate for time to graft failure (TTGF) in 68 renal allograft recipients. At 6 mo posttransplant, VIntFib was highly correlated with TTGF (r = 0.64, P < 0.001). Both the Banff Chronic Sum and the Acute Sum Scores were also correlated with TTGF, but less strongly (r = 0.28, P < 0.02; r = 0.35, P < 0.003, respectively). As VIntFib was not correlated with the Banff Chronic Score, a multivariate model was created that incorporated VIntFib and both Acute and Chronic Banff pathology. This model was highly correlated with TTGF (r = 0.7, P < 0.0001). These findings suggest that VIntFib determined by computerized image analysis of Sirius Red–stained protocol biopsies at 6 mo posttransplant, with or without incorporation of Banff acute and chronic scoring, may provide an early surrogate for time to graft failure in renal allograft recipients. E-mail: [email protected]
Inhibition of allergic responses by CD40 gene silencing
Authors: M. Suzuki, X. Zheng, X. Zhang, T. E. Ichim, H. Sun, N. Kubo, M. Beduhn, A. Shunnar, B. Garcia, W.‐P. Min
Journal: Allergy (2009)

Background: Gene silencing using small interfering RNA (siRNA) is a potent method of specifically knocking down molecular targets. Small interfering RNA is therapeutically promising, however, treatment of allergic diseases with siRNA has not been explored in vivo . The aim of this study was to evaluate therapeutic effects of CD40 siRNA on inhibition of allergic responses. Methods: Mice sensitized with ovalbumin (OVA) and alum were treated with CD40 siRNA, scrambled siRNA, or phosphate buffer saline (PBS) alone, and then challenged intranasally with OVA. Results: A significant reduction in nasal allergic symptoms was observed in the CD40 siRNA treated OVA‐allergic mice compared to the controls of scrambled siRNA and PBS alone, which is correlated with the decrease of local eosinophil accumulation. CD40 siRNA treatment knocked down CD40 expression on dendritic cells (DCs) in vivo and impaired their antigen presenting function. Treatment with CD40 siRNA resulted in inhibition of OVA‐specific T cell response and decrease of interleukin‐4 (IL‐4), IL‐5, and interferon‐γ production from T cells stimulated with OVA. Administration of CD40 siRNA also suppressed CD40 expression on B cells, resulting in down‐regulation of OVA‐specific immunoglobulin E (IgE), IgG1, and IgG2a levels. Additionally, increased regulatory T cells were observed in the CD40 siRNA treated mice. Conclusions: The present study demonstrates a novel therapeutic use for siRNA in allergy. CD40 siRNA attenuated allergy through inhibition of DC and B cell functions and generation of regulatory T (Treg) cells.
Long-Term Cardiac Follow-Up in Relapse-Free Patients After Six Courses of Fluorouracil, Epirubicin, and Cyclophosphamide, With Either 50 or 100 mg of Epirubicin, As Adjuvant Therapy for Node-Positive Breast Cancer: French Adjuvant Study Group
Authors: Jacques Bonneterre, Henri Roché, Pierre Kerbrat, Pierre Fumoleau, Marie-Josèphe Goudier, Pierre Fargeot, Philippe Montcuquet, Pierre Clavère, Jean-Claude Barats, Alain Monnier, Corinne Veyret, Jean Datchary, Isabelle Van Praagh, Isabelle Chapelle-Marcillac
Journal: Journal of Clinical Oncology (2004)

PURPOSE To evaluate long-term cardiac function in patients without disease who had received six cycles of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 50) or the same regimen with epirubicin 100 mg/m(2) (FEC 100) as adjuvant chemotherapy for node-positive breast cancer in the French Adjuvant Study Group-05 trial. PATIENTS AND METHODS One hundred fifty patients (FEC 50, n = 65; FEC 100, n = 85) who were without disease and who gave their informed consent were enrolled for long-term cardiac assessment. The assessment included cardiac events occurring after the end of chemotherapy, vital signs, concomitant disease, ECG, isotopic left ventricular ejection fraction (LVEF), and echographic parameters. Abnormal files were blindly reviewed by cardiologists and oncologists. Results The median follow-up time was 102 months. After FEC 100, LVEF was less than 50% in five patients (radioisotopic method), and two patients experienced congestive heart failure (CHF) that was possibly related to treatment. Asymptomatic left ventricular dysfunction (LVD) was experienced in 18 patients after FEC 100 and in one patient after FEC 50. In these patients, treatment causality was probable in eight patients. Two additional years after this assessment, all 18 patients were still asymptomatic. CONCLUSION After more than 8 years of follow-up, the cardiac toxicity observed after adjuvant treatment with FEC 100 comprised two cases of well-controlled CHF and 18 cases of asymptomatic LVD. In the majority of women with primary breast cancer, the benefits of treatment with FEC 100 in terms of disease-free and overall survival outweigh the risks, and cardiac risk factors should be carefully evaluated in patient selection.
Oral cavity and oropharyngeal squamous cell carcinoma—an update
Authors: Angela C. Chi, Terry A. Day, Brad W. Neville
Journal: CA A Cancer Journal for Clinicians (2015)

Answer questions and earn CME/CNE Oral cavity squamous cell carcinoma (OC‐SCC) is the most common malignancy of the head and neck (excluding nonmelanoma skin cancer). Recent trends have shown a dramatic rise in the incidence of oropharyngeal squamous cell carcinoma (OP‐SCC), with a marked increase in lesions related to human papillomavirus infection. This update presents the latest evidence regarding OC‐SCC and OP‐SCC. In particular, the authors compare and contrast tumors at these two sites with respect to epidemiology, etiopathogenesis, clinicopathologic presentation, clinical assessment, imaging, management, and prognosis. It is important for clinicians to be aware of differences between OC‐SCC and OP‐SCC so that appropriate patient education and multidisciplinary care can be provided to optimize outcomes. CA Cancer J Clin 2015;65:401–421 . © 2015 American Cancer Society .
Respiratory health and indoor air pollutants based on quantitative exposure assessments
Authors: Marion Hulin, Marzia Simoni, Giovanni Viegi, Isabella Annesi-Maesano
Journal: European Respiratory Journal (2012)

We reviewed the main epidemiological studies that evaluate the respiratory effects of indoor air pollutants quantitatively in industrialised countries. Consistent results support short-term (aggravation) and, although more rarely, long-term (prevalence augmentation) effects on asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD) in indoor settings with poor air quality. Environmental tobacco smoke is one of the most important risks for respiratory symptoms and diseases worldwide. The evidence is also reliable for indoor nitrogen dioxide and particulate matter, which have been associated with asthma, bronchitis and COPD. Whereas formaldehyde and volatile organic compounds seem to be the main pollutants in indoor settings, relevant papers on their respiratory effects are still scarce, and limited to asthma and bronchitis. Moulds have been associated with an increased risk of asthma and COPD. Contradictory results have been found between endotoxins and asthma. The role of phthalates, persistent organic pollutants and flame retardants in respiratory diseases remains to be established. Results from rural areas of industrialised countries indicate that exposure to some indoor bio-contaminants might be protective in early life, while it is associated with adverse respiratory adverse effects in adulthood. Studies focusing on indoor air pollutants should be developed to better understand their involvement in the inception and aggravation of respiratory diseases.
Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180
Authors: Steven P. Treon, Leukothea Ioakimidis, Jacob D. Soumerai, Christopher J. Patterson, Patricia Sheehy, Marybeth Nelson, Michael Willen, Jeffrey Matous, John Mattern, Jakow G. Diener, George P. Keogh, Thomas J. Myers, Andy Boral, Ann Birner, Dixie L. Esseltine, Irene M. Ghobrial
Journal: Journal of Clinical Oncology (2009)

We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenström macroglobulinemia (WM).A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Twenty-three patients received a median of seven cycles of treatment.Median bone marrow disease involvement declined from 55% to 10% (P = .0004), serum immunoglobulin M levels declined from 4,830 to 1,115 mg/dL (P < .0001), and hematocrit increased from 29.8% to 38.2% (P = .0002) at best response. The overall response rates and major response rates were 96% and 83% with three complete responses, two near complete responses, three very good partial responses, 11 partial responses, and three minor responses. Responses occurred at a median of 1.4 months. With a median follow-up of 22.8 months, 18 of 23 patients remained free of disease progression. Peripheral neuropathy was the most common toxicity, and it resolved to grade < or = 1 in 13 of 16 patients at a median of 6.0 months. Four of the first seven treated patients developed herpes zoster, resulting in the institution of prophylactic antiviral therapy.The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued.
Liver “Tick Tock”
Authors: Nicholas A. Shackel, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2009)

In liver, most metabolic pathways are under circadian control, and hundreds of protein-encoding genes are thus transcribed in a cyclic fashion. Here we show that rhythmic transcription extends to the locus specifying miR-122, a highly abundant, hepatocyte-specific microRNA. Genetic loss-of-function and gain-of-function experiments have identified the orphan nuclear receptor REV-ERBalpha as the major circadian regulator of mir-122 transcription. Although due to its long half-life mature miR-122 accumulates at nearly constant rates throughout the day, this miRNA is tightly associated with control mechanisms governing circadian gene expression. Thus, the knockdown of miR-122 expression via an antisense oligonucleotide (ASO) strategy resulted in the up- and down-regulation of hundreds of mRNAs, of which a disproportionately high fraction accumulates in a circadian fashion. miR-122 has previously been linked to the regulation of cholesterol and lipid metabolism. The transcripts associated with these pathways indeed show the strongest time point-specific changes upon miR-122 depletion. The identification of PPARbeta/delta and the peroxisome proliferator-activated receptor alpha (PPARalpha) coactivator Smarcd1/Baf60a as novel miR-122 targets suggests an involvement of the circadian metabolic regulators of the PPAR family in miR-122-mediated metabolic control.
Glucomannan prevents postprandial hypoglycaemia in patients with previous gastric surgery.
Authors: W P Hopman, P G Houben, P A Speth, C B Lamers
Journal: Gut (1988)

Glucomannan (Propol), a potent gel forming dietary fibre, was added to a carbohydrate rich breakfast in eight patients with previous gastric surgery suffering from postprandial hypoglycaemia. Addition of only 2.6 g and 5.2 g glucomannan to the meal dose dependently improved reactive hypoglycaemia from 2.3 (0.2) mmol/l to 3.3 (0.2) mmol/l (p less than 0.0005) after 2.6 g and 4.1 (0.2) mmol/l (p = 0.0005) after 5.2 g, and decreased postprandial rise in plasma insulin (p less than 0.05). Expiratory breath hydrogen excretion tended to decrease reflecting improvement of carbohydrate metabolism. Addition of glucomannan to an intraduodenal sucrose solution significantly raised plasma glucose nadirs, indicating glucomannan to be effective during the intestinal phase. It is concluded that small amounts of glucomannan may be beneficial to patients with reactive postprandial hypoglycaemia, without the disadvantage of unpalatability and carbohydrate malabsorption.
Press: The milk of human kindness
Authors: G. Yamey
Journal: BMJ (2001)

How to make a simple morality tale out of a complex public health issue 

After years of being hated by advocates of breastfeeding, Nestle and the rest of the baby food industry must have wept with delight at articles in the Wall Street Journal last month.

Their early Christmas present came in the form of a front page, lead news story (5 December) and an accompanying editorial in the European edition (6 December), which painted the baby food manufacturers as heroes poised to save African children from certain death.

What was the nature of their heroism? “One major formula maker,” said the article, “Wyeth-Ayerst Laboratories Inc, says it stands ready to donate tons of free formula to HIV-infected women. No.1-ranked Nestle SA says it too would donate, if asked.” Such donations, argued the reporters, would stop the transmission of HIV from mothers to their children via infected breast milk, halting the spread of AIDS through sub-Saharan Africa.

All heroic tales need a villain, and this one was no exception. “Unicef,” said the paper, “refuses to greenlight the gifts, because it doesn't want to endorse an industry it has long accused of abusive practices in the Third World.”

If there was any doubt in readers' minds about the goodies and baddies in this epic struggle for infant health, the headline hit the message home: “African Babies Fall Ill as Unicef Fights Formula Makers.” The editorial went further still, blaming Unicef's “feud against the industry” for “killing millions of children.”

Formula fever soon spread west across the US, reaching the pages of the Houston Chronicle (December 10). Michelle Malkin, a nationally syndicated columnist, cited the Wall Street Journal report and accused Unicef's “breast feeding crusade” of “killing the children it's supposed to protect.” She also offered her advice to the agency: “There …
High Prevalence of Pancreatic Cysts Detected by Screening Magnetic Resonance Imaging Examinations
Authors: Koen de Jong, C. Yung Nio, John J. Hermans, Marcel G. Dijkgraaf, Dirk J. Gouma, Casper H.J. van Eijck, Eddy van Heel, Gunter Klass, Paul Fockens, Marco J. Bruno
Journal: Clinical Gastroenterology and Hepatology (2010)
Essential Role of Induced Nitric Oxide in the Initiation of the Inflammatory Response after Hemorrhagic Shock
Authors: Christian Hierholzer, Brian Harbrecht, John M. Menezes, John Kane, John MacMicking, Carl F. Nathan, Andrew B. Peitzman, Timothy R. Billiar, David J. Tweardy
Journal: The Journal of Experimental Medicine (1998)

Resuscitation from hemorrhagic shock induces profound changes in the physiologic processes of many tissues and activates inflammatory cascades that include the activation of stress transcriptional factors and upregulation of cytokine synthesis. This process is accompanied by acute organ damage (e.g., lungs and liver). We have previously demonstrated that the inducible nitric oxide synthase (iNOS) is expressed during hemorrhagic shock. We postulated that nitric oxide production from iNOS would participate in proinflammatory signaling. Using the iNOS inhibitor N6-(iminoethyl)-L-lysine or iNOS knockout mice we found that the activation of the transcriptional factors nuclear factor kappaB and signal transducer and activator of transcription 3 and increases in IL-6 and G-CSF messenger RNA levels in the lungs and livers measured 4 h after resuscitation from hemorrhagic shock were iNOS dependent. Furthermore, iNOS inhibition resulted in a marked reduction of lung and liver injury produced by hemorrhagic shock. Thus, induced nitric oxide is essential for the upregulation of the inflammatory response in resuscitated hemorrhagic shock and participates in end organ damage under these conditions.
Increased long-term mortality in heart failure due to sleep apnoea is not yet proven
Authors: T Roebuck, P Solin, D M Kaye, P Bergin, M Bailey, M T Naughton
Journal: European Respiratory Journal (2004)

Previous small-scale studies of the effect of sleep-disordered breathing (SDB) on prognosis in congestive heart failure (CHF) are either lacking or conflicting. The aim of this study was to assess the impact of the presence and type of SDB on mortality in a patient group with severe CHF referred to a specialised heart failure centre. Out of 78 patients ((mean±sd) 53±9 yrs, left ventricular ejection fraction 19.9±7.2% and pulmonary capillary wedge pressure 16.5±8.3 mmHg) followed-up over a median period of 52 months, 29% had no apnoea (CHF‐N), 28% had obstructive sleep apnoea (CHF‐OSA) and 42% had central sleep apnoea (CHF‐CSA). At 52 months, their overall mortality was 40%, and combined mortality and transplantation was 72%. Mortality rates were similar between the three apnoea groups. Survivors had a similar prevalence of SDB (71%) as the nonsurvivors (70%). Although a significant increase in mortality was evident at 500 days in those patients with either CHF‐SDB or CHF‐CSA as compared with CHF‐N, this was not significant at final follow-up (52 months) using Kaplan Meier analysis. Multivariate analysis identified transplantation but not SDB type or severity as a significant predictor of survival. In conclusion, sleep-disordered breathing impacts upon early (500 day), but not long-term (52 month), mortality in a specialised heart failure centre.
Influence of ?-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass
Authors: R Lango
Journal: Cardiovascular Research (2001)

Carnitine and its derivatives have recently been shown to protect cardiac metabolism and function in ischemic heart disease and other clinical conditions of myocardial ischemia. Potential mechanisms of this effect include an increase in glucose metabolism, a reduction of toxic effects of long-chain acyl-CoA and acyl-carnitine in myocytes, an increase in coronary blood flow and anti-arrhythmic effect. It has also been shown that propionyl-L-carnitine which penetrates faster than carnitine into myocytes is effective in inhibiting production of free radicals. Beneficial effects of carnitine supplementation have been demonstrated under a variety of clinical conditions such as acute cardiac ischemia, during extracorporeal circulation, in carnitine-dependent cardiomyopathy as well as in patients with chronic circulatory failure and in cardiogenic shock. However, further studies are required before carnitine administration could be recommended as a routine procedure in ischemic heart disease or before cardiopulmonary bypass.
A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia
Authors: S Piemontese, F Ciceri, M Labopin, A Bacigalupo, H Huang, S Santarone, N-C Gorin, Y Koc, D Wu, D Beelen, J Tischer, G Ehninger, W Arcese, A Nagler, M Mohty
Journal: Leukemia (2014)
A Preoperative Prognostic Model for Patients Treated with Nephrectomy for Renal Cell Carcinoma
Authors: Pierre I. Karakiewicz, Nazareno Suardi, Umberto Capitanio, Claudio Jeldres, Vincenzo Ficarra, Luca Cindolo, Alexandre de la Taille, Jacques Tostain, Peter F.A. Mulders, Karim Bensalah, Walter Artibani, Laurent Salomon, Richard Zigeuner, Antoine Valéri, Jean-Luc Descotes, Jean-Jacques Rambeaud, Arnaud Méjean, Francesco Montorsi, Roberto Bertini, Jean-Jacques Patard
Journal: European Urology (2008)
Extracellular ATP Determines 11β-Hydroxysteroid Dehydrogenase Type 2 Activity via Purinergic Receptors
Authors: Bert Kadereit, Pierre Fustier, Kushiar Shojaati, Brigitte M. Frey, Felix J. Frey, Markus G. Mohaupt
Journal: Journal of the American Society of Nephrology (2005)

Hypertension and sodium retention are features of a diminished 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). The activity of this enzyme is reduced in various disease states with abnormal renal sodium retention and hypertension, including preeclampsia. ATP release to the extracellular compartment is observed with shear stress, inflammation, and placental ischemia. It was hypothesized that ATP downregulates 11beta-HSD2 activity. For that purpose, cell lines from different tissues that previously were used to study the regulation of 11beta-HSD2 were investigated: JEG-3, a vascular trophoblastic; LLCPK1, a renal tubular; and SW620, a colonic epithelial cell line. The 11beta-HSD2 activity, assessed by the conversion of 3H-cortisol to cortisone, was reversibly reduced during incubation with ATP or its stable analogue ATPgammaS in intact JEG-3 and LLCPK1, but not in SW620 cells. In JEG-3 cells, the purinergic antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid but not suramin reversed the inhibition. Incubation with UTP and ADP and their degradation products including adenosine and alpha,beta-methylene-ATP did not inhibit 11beta-HSD2 activity. In contrast, 11beta-HSD2 activity increased almost 2.5-fold after incubation with 2'-methylthio-ATP. This indicates a bidirectional regulation by nucleotides via purinergic receptors. In JEG-3 cells, ATP/ATPgammaS did not alter 11beta-HSD2 promoter activity but reduced 11beta-HSD2 protein and mRNA concentration and half-life, suggesting a posttranscriptional regulation. In conclusion, ATP inhibits cell type specifically via purinergic receptors the expression and activity of the 11beta-HSD2 by a posttranscriptional mechanism.