tbuckley/cabot-search huggingface dataset:
Recombinant thrombomodulin improves survival in acute exacerbation of idiopathic pulmonary fibrosis
Authors: Hiroyuki Taniguchi, Yasuhiro Kondoh, Tomoki Kimura, Kensuke Kataoka
Journal: European Respiratory Journal (2012)

Background:  Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are episodes of acute respiratory worsening caused by unknown etiology with high short-term mortality. The presence of disordered coagulation and endothelial damage in AE-IPF have been reported. Recombinant human soluble thrombomodulin (rhTM) binds to thrombin to inactivate coagulation, and the thrombin-rhTM complex activates protein C to produce activated protein C. The purpose of this study is to examine the efficacy of rhTM for treating patients with AE-IPF.  Methods:  Patients with AE-IPF in our hospital from 2006 to 2011 were enrolled. AE-IPF was defined using the revised Japanese criteria for AE-IPF (Eur Respir J. 2010;35:821-9.). All patients received corticosteroid pulse therapy and immunosuppressant (cyclosporine 3mg/kg/day, p.o). NPPV was the first line intervention. The initial 20 patients treated without rhTM (control group) and following 20 consecutive patients treated with rhTM (0.06 mg/kg/day) for six days (rhTM group) were compared. The predictors of 3-month survival (Cox proportional-hazards model) were evaluated.  Results:  Baseline characteristics show age(mean:72.2), PaO 2 /FiO 2 (220), APACHE II(9.9), C-reactive protein(CRP)(7.1) mg/dl, KL-6(1485) U/ml. In univaliate analysis, respiratory rate, CRP, rhTM therapy were significant predictors for 3M survival. In multivaliate analysis, CRP (p=0.008,HR=1.133), rhTM therapy(p=0.015,HR=0.172) were significant predictor for 3M survival.  Conclusion:  We found that rhTM therapy improves 3-month survival of AE-IPF in our case control study. The results observed here support further investigation of rhTM in randomized control trials.
Zag Expression during Aging Suppresses Proliferation after Kidney Injury
Authors: Roland Schmitt, Arnaud Marlier, Lloyd G. Cantley
Journal: Journal of the American Society of Nephrology (2008)

Recovery after acute kidney injury is impaired in the elderly, but mechanistic information regarding why this occurs is limited. In this study, aged mouse kidneys displayed a reduced epithelial proliferative reserve in vivo and in vitro. Microarray analysis identified increased expression of zinc-α (2)-glycoprotein (Zag) in aged proximal tubular cells. The addition of recombinant Zag to primary renal epithelial cell cultures decreased proliferation, whereas knockdown of Zag increased proliferation. In vivo, systemic small interference RNA suppressed expression of Zag in the mouse proximal tubule; this increased the rate of epithelial cell proliferation after renal ischemia/reperfusion in aged mice but also increased parenchymal fibrosis. These results demonstrate that increased Zag expression in the aged kidney acts to suppress the proliferative response to injury and introduce Zag as a modifier of the aging phenotype.
Antibody-defective, genetically susceptible CBA/N mice have an altered Salmonella typhimurium-specific B cell repertoire.
Authors: L W Duran, E S Metcalf
Journal: The Journal of Experimental Medicine (1987)

CBA/N mice, which express the X-linked immunodeficiency gene xid, are susceptible to Salmonella typhimurium. The basis for this susceptibility is currently unknown. However, previous studies (10) from this laboratory have provided evidence that susceptibility may be due to a defective anti-S. typhimurium antibody response. In that report we hypothesized that the defective antibody response may be a reflection of an altered S. typhimurium-specific B cell repertoire. In the studies described here, we have investigated this hypothesis using a modification of the in vitro splenic focus system. The frequency and characteristics of salmonella-specific B cells in normal, innately resistant, CBA/Ca mice have been compared with those of salmonella-susceptible, anti-S. typhimurium antibody-defective CBA/N mice. The results show that CBA/N mice express no primary or secondary S. typhimurium-specific B cell precursors after stimulation with an acetone-killed and dried (AKD) preparation of S. typhimurium strain TML. However, after three immunizations, the CBA/N tertiary frequency of 15.4 per 10(6) splenic B cells was similar to the primary precursor frequency in immunologically normal CBA/Ca mice, but 23-fold lower than the tertiary precursor frequency in CBA/Ca control mice. Moreover, CBA/N mice had an altered isotype distribution pattern after stimulation with AKD-TML. Greater than 70% of the tertiary CBA/N TML-specific B cells secreted IgG2, in contrast to either nonimmune or primed control mice. In addition, 80% of the CBA/N TML-specific B cells secreted only a single isotype, whereas the majority of B cells from primed normal mice secreted multiple isotypes. Fine specificity analysis of the TML-specific B cells indicated that the array of antigenic determinants to which CBA/N B cells could respond was restricted. Although the majority of primed CBA/Ca and primed CBA/N B cells were specific for LPS, the fine specificity pattern exhibited by CBA/N B cells was similar to that observed in unprimed normal mice, i.e., the vast majority were specific for the O antigen region of the LPS molecule. In contrast, a major portion of the LPS-specific B cells in primed CBA/Ca mice were directed against the KDO/lipid A region of the LPS molecule. Therefore, it appears that CBA/N mice lack or are unable to stimulate the B cell subset that predominates in primed, normal mice. Taken together, these studies indicate that the basis for susceptibility of CBA/N mice to S. typhimurium is multifactorial and suggests that the inability of some animals to respond to some infectious agents may be related to holes in their B cell repertoire.
Gastric intramucosal pH: an indicator of weaning outcome from mechanical ventilation in COPD patients
Authors: G Bouachour, MP Guiraud, JP Gouello, PM Roy, P Alquier
Journal: European Respiratory Journal (1996)

The aim of this study was to determine whether gastric intramucosal pH (pHim) and/or gastric intramucosal carbon dioxide tension (PCO2,im) measured by tonometry can be used to predict the success of weaning in chronic obstructive pulmonary disease (COPD) patients. Twenty six consecutive COPD patients, undergoing mechanical ventilation for acute respiratory failure and satisfying the criteria of weaning from mechanical ventilation with nasogastric tonometer in place, were studied. Arterial blood gas values and PCO2,im were measured 24 h before (H-24), just before (H0), and after 20 min of a weaning trial on T-piece (H20min). Weaning failure was defined as the development of respiratory distress and/or arterial blood gas impairments during the first 2 h of spontaneous breathing on T-piece, or reintubation within 24 h after extubation. Between the weaning failure (n = 6) and weaning success (n = 20) groups, there were no differences in blood gas analysis readings at H-24 and H0 before the weaning period, age, Simplified Acute Physiology Score (SAPS) on admission, SAPS on the day of weaning trial, and duration of ventilation. Clinical status, tonometric and arterial gasometric data were similar at H-24 and H0 in all patients. During mechanical ventilation, pHim was < or = 7.30 in patients who failed weaning and > 7.30 in patients who were successfully weaned (p < 0.001; 100% sensitivity and specificity). The threshold value for PCO2,im of 8.0 kPa (60 mmHg) represents a clear demarcation with respect to outcome before the weaning trial. PCO2,im values during mechanical ventilation are significantly different (p < 0.001) between patients who were successfully weaned and those who were not (6.9 +/- 0.9 vs 9.9 +/- 1.1 kPa (51.9 +/- 6.7 vs 74.3 +/- 8.0 mmHg, respectively)). At H20min, pHim and PCO2,im were still statistically different between the weaning failure and the weaning success group. We conclude that measurement of gastric intramucosal pH (or gastric intramucosal carbon dioxide tension) represents a simple and accurate index to predict weaning outcome in chronic obstructive pulmonary disease patients before attempting weaning.
Predictive Significance of the Alterations of p16INK4A, p14ARF, p53, and Proliferating Cell Nuclear Antigen Expression in the Progression of Cervical Cancer
Authors: Jian-Liu Wang, Bi-Ying Zheng, Xi-Dan Li, Tord Ångström, Mikael S. Lindström, Keng-Ling Wallin
Journal: Clinical Cancer Research (2004)

The purpose of this research was to evaluate the clinical significance of p16INK4A, p14ARF, p53, and proliferating cell nuclear antigen (PCNA) expression in tumor progression of cervical cancer.Seventeen patients (40 samples) with consecutive cervical lesions from normal squamous epithelium, inflammation of the cervix to cervical intraepithelial neoplasm (CIN) and invasive cervical squamous cell cancer (SCC), or from CIN to SCC were collected for this study. Expression of p16INK4A, p14ARF, p53, and PCNA were detected by immunohistochemistry on paraffin-embedded sections. Human papillomavirus DNA was detected simultaneously with PCR and typed according to its DNA sequence.p16INK4A overexpression was significantly higher in CIN (75%) and in SCC (75%) than in normal or inflammation of the cervix (12.5%; P < 0.01, P < 0.05, respectively). The positive rate of p14ARF expression was higher in SCC (83%) than in normal/inflammation of the cervix (25%; P < 0.05). PCNA expression was negative in normal or inflammation of the cervix, but an increased in expression was seen in 63.2% in CIN and 100% in SCC (P < 0.01, P < 0.05). When the time interval for disease progression from initial biopsy to CIN 3 or invasive cancer was compared with states of p16INK4A expression, cases stained positive for p16INK4A progressed within 64.2 months as compared with 122.3 months among those stained negatively (P < 0.01). Cases with increased p14ARF expression also had a short time interval for disease progression of 78.8 months as compared with 108.3 months in cases that were p14ARF negative. Cases with stable or decreased p53 expression had the shortest time interval for progression of 32.3 months in contrast to cases with no p53 expression (113.9 months). However, cases with increasing p53 expression progressed within 60.8 months.Our results suggested that altered states of p16INK4A, p14ARF, p53, and PCNA may be valuable markers to predict the progression of cervical neoplasia.
Comparison of cardiovascular risk between patients with type 2 diabetes and those who had had a myocardial infarction: cross sectional and cohort studies
Authors: J. M M Evans
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To compare risks of cardiovascular outcomes between patients with type 2 diabetes and patients with established coronary heart disease. <b>Design:</b> Cross sectional study and cohort study using routinely collected datasets. <b>Setting:</b> Tayside, Scotland (population 400 000) during 1988-95. <b>Subjects:</b> In the cross sectional study, among patients aged 45-64, 1155 with type 2 diabetes were compared with 1347 who had had a myocardial infarction in the preceding 8 years. In the cohort study 3477 patients of all ages with newly diagnosed type 2 diabetes were compared with 7414 patients who had just had a myocardial infarction. <b>Main outcome measures:</b> Risk ratios for death from all causes, cardiovascular death, and hospital admission for myocardial infarction were calculated by Cox proportional hazards analysis and adjusted for age and sex. <b>Results:</b> In the cross sectional study the adjusted risk ratio for death from all causes was 2.27 (95% confidence interval 1.82 to 2.83) for patients who had had myocardial infarction compared with those with diabetes, and the risk ratio for hospital admission for myocardial infarction was 1.33 (1.14 to 1.55). In the cohort study, patients who had just had a myocardial infarction had a higher risk of death from all causes (adjusted risk ratio 1.35 (1.25 to 1.44)), cardiovascular death (2.93 (2.54 to 3.41)), and hospital admission for myocardial infarction (3.10 (2.57 to 3.73)). <b>Conclusions:</b> Patients with type 2 diabetes were at lower risk of cardiovascular outcomes than patients with established coronary heart disease. <h3>What is already known on this topic</h3> A recent influential study suggested that patients with type 2 diabetes without established cardiovascular disease have as high a risk of cardiovascular events and death as non-diabetic patients who have had a myocardial infarction Some clinicians therefore advocate aggressive treatment of cardiovascular risk factors in the presence of diabetes <h3>What this study adds</h3> Patients with type 2 diabetes are at lower risk of death from all causes or cardiovascular causes and of hospital admission for myocardial infarction than patients with established coronary heart disease
Syndecan-4 Prevents Cardiac Rupture and Dysfunction After Myocardial Infarction
Authors: Yutaka Matsui, Masahiro Ikesue, Keiko Danzaki, Junko Morimoto, Mami Sato, Shinya Tanaka, Tetsuhito Kojima, Hiroyuki Tsutsui, Toshimitsu Uede
Journal: Circulation Research (2011)

Syndecan-4 (Syn4), a cell-surface heparan sulfate proteoglycan, has been detected in the infarct region after myocardial infarction (MI), but its functional significance has not been elucidated.We examined whether and how Syn4 regulates the cardiac healing process after MI.Although the heart in Syn4-deficient (Syn4(-/-)) mice was morphologically and functionally normal, Syn4(-/-) mice exhibited impaired heart function and increased mortality rate as a result of cardiac ruptures after MI. Cardiac ruptures in Syn4(-/-) mice were associated with reduced inflammatory reaction and impaired granulation tissue formation during the early phase of MI, as evidenced by reduced numbers of leukocytes, fibroblasts, myofibroblasts, macrophages, and capillary vessels, along with reduced extracellular matrix protein deposition in the infarct region after MI. Transforming growth factor-β1-dependent cell signaling was preserved, whereas cell migration, fibronectin-induced cell signaling, and differentiation into myofibroblasts were defective in Syn4(-/-) cardiac fibroblasts. We also found that Syn4 was involved in basic fibroblast growth factor-dependent endothelial cell signaling, cell proliferation, and tube formation. Finally, overexpression of the shed form of Syn4 before MI creation led to an increase in mortality due to cardiac rupture via its action as a dominant-negative inhibitor of endogenous Syn4 signaling, which suggested a protective role of Syn4 signaling in MI.These results suggest that Syn4 plays an important role in the inflammatory response and granulation tissue formation, thereby preventing cardiac rupture and dysfunction after MI.
Making the NHS more like Kaiser Permanente: Table 1
Authors: Donald Light, Michael Dixon
Journal: BMJ (2004)

The NHS needs to break down the barriers between primary, secondary, and tertiary care The US health maintenance organisation Kaiser Permanente has been highlighted as a successful model of integrated, cost effective care. A key policy of the NHS and other health systems is to learn from this model. However, the changes being made by the English government overlook the key features that have enabled Kaiser to develop and implement its clinical and operational programmes. We examine the importance of integrating clinical governance as well as collaborative contracting in achieving integrated, patient centred services. In a highly influential article, Feachem and colleagues compared the costs and performance of the NHS with those of Kaiser Permanente in California. They concluded that Kaiser provided much better value, largely by using only a third of the acute bed days used in the NHS.1 Several serious criticisms were levelled at the methods used, but even if they are taken into account, the Kaiser system has much lower hospital admissions and shorter lengths of stay, especially for serious illnesses. Ham and colleagues carried out a more methodologically sound and detailed study of the Kaiser system.2 The data show such a much higher rate of hospital admission in the NHS for bronchitis and asthma and for angina pectoris. However, the admission rates for acute myocardial infarction, heart failure, and urinary infection were so much higher in Kaiser than the NHS that specialists in the two systems could be practising different types of medicine. Nevertheless, the overall question is how do doctors in Kaiser Permanente achieve such low rates of hospital admission and lengths of stay? Ham and colleagues point to several factors in the Kaiser system:
Sustained repression and translocation of Ntcp and expression of Mrp4 for cholestasis after rat 90% partial hepatectomy
Authors: Takuya Miura, Norihisa Kimura, Toshiyuki Yamada, Takeshi Shimizu, Naoki Nanashima, Daisuke Yamana, Kenichi Hakamada, Shigeki Tsuchida
Journal: Journal of Hepatology (2010)
Dopamine is a novel, direct inducer of catagen in human scalp hair follicles<i>in vitro</i>
Authors: E.A. Langan, E. Lisztes, T. Bíró, W. Funk, J.E. Kloepper, C.E.M. Griffiths, R. Paus
Journal: British Journal of Dermatology (2012)

Although there are clinical reports of hair loss associated with levodopa and dopamine agonists, it is unclear whether dopamine exerts any direct effects on the human hair follicle (HF).Given the widespread use of dopamine agonists and antagonists in clinical medicine, we sought to determine whether dopamine exerts direct effects on human HF growth and/or pigmentation in vitro, and whether human HFs express dopamine receptors (DRs).Microdissected human scalp HFs from women were treated in serum-free organ culture for 7 days with dopamine (10-1000 nmol L ), and the effects on hair shaft production, HF cycling (i.e. anagen-catagen transition), hair matrix keratinocyte proliferation and apoptosis, and HF pigmentation were measured by quantitative (immuno-) histomorphometry.Dopamine had no consistent effect on hair shaft production, but did promote HF regression (catagen). It was also associated with significantly reduced proliferation of HF matrix keratinocytes (P < 0·01) and reduced intrafollicular melanin production. Dopamine receptor transcripts were identified in HFs and skin.These data provide evidence that dopamine is an inhibitor of human hair growth, via the promotion of catagen induction, at least in vitro. This may offer a rational explanation for the induction of telogen effluvium in some women treated with dopamine agonists such as bromocriptine. Moreover, dopaminergic agonists deserve further exploration as novel inhibitors of unwanted human hair growth (hirsutism, hypertrichosis).
Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis
Authors: Wendy De Roock, Bart Claes, David Bernasconi, Jef De Schutter, Bart Biesmans, George Fountzilas, Konstantine T Kalogeras, Vassiliki Kotoula, Demetris Papamichael, Pierre Laurent-Puig, Frédérique Penault-Llorca, Philippe Rougier, Bruno Vincenzi, Daniele Santini, Giuseppe Tonini, Federico Cappuzzo, Milo Frattini, Francesca Molinari, Piercarlo Saletti, Sara De Dosso, Miriam Martini, Alberto Bardelli, Salvatore Siena, Andrea Sartore-Bianchi, Josep Tabernero, Teresa Macarulla, Frédéric Di Fiore, Alice Oden Gangloff, Fortunato Ciardiello, Per Pfeiffer, Camilla Qvortrup, Tine Plato Hansen, Eric Van Cutsem, Hubert Piessevaux, Diether Lambrechts, Mauro Delorenzi, Sabine Tejpar
Journal: The Lancet Oncology (2010)
Infarct size limitation by gene transfer of baculoviral p35 into rat myocardium
Authors: Lorenz Bott-Fluegel, Karl-Ludwig Laugwitz, Melchlor Seyfarth, Christiane Faltermeier, Christine Baumgartner, Alessandra Moretti, Albert Schoemig
Journal: Journal of the American College of Cardiology (2002)
Response: Re: Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer
Authors: T. O. Nielsen, M. C. U. Cheang, S. K. Chia, D. Voduc, D. Gao, S. Leung, P. S. Bernard, C. M. Perou, M. J. Ellis
Journal: JNCI Journal of the National Cancer Institute (2009)
Steroids and bronchodilators for acute bronchiolitis in the first two years of life: systematic review and meta-analysis
Authors: L. Hartling, R. M. Fernandes, L. Bialy, A. Milne, D. Johnson, A. Plint, T. P. Klassen, B. Vandermeer
Journal: BMJ (2011)

<b>Objective</b> To evaluate and compare the efficacy and safety of bronchodilators and steroids, alone or combined, for the acute management of bronchiolitis in children aged less than 2 years. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Medline, Embase, Central, Scopus, PubMed, LILACS, IranMedEx, conference proceedings, and trial registers. <b>Inclusion criteria</b> Randomised controlled trials of children aged 24 months or less with a first episode of bronchiolitis with wheezing comparing any bronchodilator or steroid, alone or combined, with placebo or another intervention (other bronchodilator, other steroid, standard care). <b>Review methods</b> Two reviewers assessed studies for inclusion and risk of bias and extracted data. Primary outcomes were selected by clinicians a priori based on clinical relevance: rate of admission for outpatients (day 1 and up to day 7) and length of stay for inpatients. Direct meta-analyses were carried out using random effects models. A mixed treatment comparison using a Bayesian network model was used to compare all interventions simultaneously. <b>Results</b> 48 trials (4897 patients, 13 comparisons) were included. Risk of bias was low in 17% (n=8), unclear in 52% (n=25), and high in 31% (n=15). Only adrenaline (epinephrine) reduced admissions on day 1 (compared with placebo: pooled risk ratio 0.67, 95% confidence interval 0.50 to 0.89; number needed to treat 15, 95% confidence interval 10 to 45 for a baseline risk of 20%; 920 patients). Unadjusted results from a single large trial with low risk of bias showed that combined dexamethasone and adrenaline reduced admissions on day 7 (risk ratio 0.65, 0.44 to 0.95; number needed to treat 11, 7 to 76 for a baseline risk of 26%; 400 patients). A mixed treatment comparison supported adrenaline alone or combined with steroids as the preferred treatments for outpatients (probability of being the best treatment based on admissions at day 1 were 45% and 39%, respectively). The incidence of reported harms did not differ. None of the interventions examined showed clear efficacy for length of stay among inpatients. <b>Conclusions</b> Evidence shows the effectiveness and superiority of adrenaline for outcomes of most clinical relevance among outpatients with acute bronchiolitis, and evidence from a single precise trial for combined adrenaline and dexamethasone.