tbuckley/cabot-search huggingface dataset:
Corrigendum to “Restoration of HCV-specific T cell functions by PD-1/PD-L1 blockade in HCV infection: Effect of viremia levels and antiviral treatment” [J Hepatol 48 (2008) 548–558]
Authors: Simona Urbani, Barbara Amadei, Daniela Tola, Giuseppe Pedrazzi, Luca Sacchelli, Maria Cristina Cavallo, Alessandra Orlandini, Gabriele Missale, Carlo Ferrari
Journal: Journal of Hepatology (2008)
Time-dependent analysis of length of stay and mortality due to urinary tract infections in ten developing countries: INICC findings
Authors: Victor D. Rosenthal, Arpita Dwivedy, María Eugenia Rodríguez Calderón, Saban Esen, Héctor Torres Hernández, Rédouane Abouqal, Eduardo A. Medeiros, Teodora Atencio Espinoza, S.S. Kanj, Achilleas Gikas, Adrian G. Barnett, Nicholas Graves
Journal: Journal of Infection (2010)
Usefulness of the Serum Carcinoembryonic Antigen Kinetic for Chemotherapy Monitoring in Patients With Unresectable Metastasis of Colorectal Cancer
Authors: Isabelle Iwanicki-Caron, Frédéric Di Fiore, Isabelle Roque, Emilie Astruc, Monica Stetiu, Aude Duclos, David Tougeron, Sandrine Saillard, Sébastien Thureau, Jacques Benichou, Bernard Paillot, Jean Pierre Basuyau, Pierre Michel
Journal: Journal of Clinical Oncology (2008)

The aim of the study was to evaluate the relationship between serum carcinoembryonic antigen (CEA) kinetic and response to chemotherapy in patients with unresectable metastasis of colorectal cancer.The kinetic was calculated using the slope of an exponential-regressive curve connecting the semi-logarithmic values of CEA. Receiver operating characteristic (ROC) curves were drawn to select the CEA slope thresholds to define patients with progressive or responsive disease with the highest sensitivity, specificity, and diagnosis accuracy odds ratio (DOR). The correlation between the CEA slopes and progression-free survival (PFS) was evaluated by the Cox model and Kaplan-Meier methods.A total of 122 patients were included. Progression defined by CEA slope greater than +0.05 resulted in sensitivity of 85.7%, specificity of 85.1%, and DOR of 34. The area under the ROC (AUROC) curve was 0.885 (95% CI, 0.815 to 0.936; P = .0001). Response defined by CEA slope less than -0.2 resulted in sensitivity of 74.7%, specificity of 82.5%, and DOR of 16. The AUROC curve was 0.847 (95% CI, 0.770 to 0.906; P = .0001). The difference between AUROC curves calculated with six or four CEA values was not significant. PFS was correlated with CEA slopes (hazard ratio, 4.6; 95% CI, 2.48 to 8.57). The median PFS was 10 months for patients with CEA slope values less than -0.2 months versus 6 months for patients with CEA slope values greater than -0.2 (P < .0001).These results suggest that the CEA kinetic is an accurate, simple, and noninvasive method to identify the disease progression in patients with unresectable metastasis of colorectal cancer.
The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy
Authors: Junichi Sadoshima, Olivier Montagne, Qian Wang, Guiping Yang, Jill Warden, Jing Liu, Gen Takagi, Vijaya Karoor, Chull Hong, Gary L. Johnson, Dorothy E. Vatner, Stephen F. Vatner
Journal: Journal of Clinical Investigation (2002)

Mitogen-activated protein kinase kinase kinase (MEKK1) mediates activation of c-Jun NH(2)-terminal kinase (JNK). Although previous studies using cultured cardiac myocytes have suggested that the MEKK1-JNK pathway plays a key role in hypertrophy and apoptosis, its effects in cardiac hypertrophy and apoptosis are not fully understood in adult animals in vivo. We examined the role of the MEKK1-JNK pathway in pressure-overloaded hearts by using mice deficient in MEKK1. We found that transverse aortic banding significantly increased JNK activity in Mekk1(+/+) but not Mekk1(-/-) mice, indicating that MEKK1 mediates JNK activation by pressure overload. Nevertheless, pressure overload caused significant levels of cardiac hypertrophy and expression of atrial natriuretic factor in Mekk1(-/-) animals, which showed higher mortality and lung/body weight ratio than were seen in controls. Fourteen days after banding, Mekk1(-/-) hearts were dilated, and their left ventricular ejection fraction was low. Pressure overload caused elevated levels of apoptosis and inflammatory lesions in these mice and produced a smaller increase in TGF-beta and TNF-alpha expression than occurred in wild-type controls. Thus, MEKK1 appears to be required for pressure overload-induced JNK activation and cytokine upregulation but to be dispensable for pressure overload-induced cardiac hypertrophy. MEKK1 also prevents apoptosis and inflammation, thereby protecting against heart failure and sudden death following cardiac pressure overload.
Association of abnormal fibrin polymerisation with severe liver disease.
Authors: G Green, L Poller, J M Thomson, I W Dymock
Journal: Gut (1977)

The frequent occurrence of abnormal fibrin polymerisation in patients with liver disease has recently been reported. To investigate this further, fibrin polymerisation was studied in 68 patients with cirrhosis or chronic active liver disease. Thirty-three of these patients demonstrated impairment of this phase of blood coagulation. When other tests of liver function were compared in patients demonstrating this abnormality and those in whom fibrin polymerisation was normal, it was found that the former group demonstrated significantly reduced albumin concentrations (p less than 0.0002), raised bilirubin and aspartate aminotransferase levels (p less than 0.0006 and less than 0.003 respectively), and greater prolongation of the one-stage prothrombin time (p less than 0.001) with more marked reduction in factor VII levels (p less than 0.002) compared with the latter patients. It is concluded that defective fibrin polymerisation occurring in patients with liver disease indicates the presence of severely impaired hepatocellular function. This might account for the grave prognosis reported in cirrhotic patients with abnormal fibrin polymerisation who also suffer bleeding from gastro-oesophageal varices.
CD4+ murine T cell clones that express high levels of immunoglobulin binding belong to the interleukin 4-producing T helper cell type 2 subset.
Authors: M Sandor, T Gajewski, J Thorson, J D Kemp, F W Fitch, R G Lynch
Journal: The Journal of Experimental Medicine (1990)

A panel of 20 murine CD4+ clones was examined for the presence of surface membrane receptors for IgA, IgM, IgD, IgE, and IgG. High level expression of multiple Fc receptors (FcRs) was found on all Th2 clones. FcR expression was low or undetected on the Th1 clones. The preferential expression of FcR on activated Th2 cells suggests potential mechanisms for immunoregulatory interactions with B cells.
An Association between <scp>l</scp>-Arginine/Asymmetric Dimethyl Arginine Balance, Obesity, and the Age of Asthma Onset Phenotype
Authors: Fernando Holguin, Suzy A. A. Comhair, Stanley L. Hazen, Robert W. Powers, Sumita S. Khatri, Eugene R. Bleecker, William W. Busse, William J. Calhoun, Mario Castro, Anne M. Fitzpatrick, Benjamin Gaston, Elliot Israel, Nizar N. Jarjour, Wendy C. Moore, Stephen P. Peters, W. Gerald Teague, Kian Fan Chung, Serpil C. Erzurum, Sally E. Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Increasing body mass index (BMI) has been associated with less fractional exhaled nitric oxide (Fe(NO)). This may be explained by an increase in the concentration of asymmetric dimethyl arginine (ADMA) relative to L-arginine, which can lead to greater nitric oxide synthase uncoupling.To compare this mechanism across age of asthma onset groups and determine its association with asthma morbidity and lung function.Cross-sectional study of participants from the Severe Asthma Research Program, across early- (<12 yr) and late- (>12 yr) onset asthma phenotypes.Subjects with late-onset asthma had a higher median plasma ADMA level (0.48 μM, [interquartile range (IQR), 0.35-0.7] compared with early onset, 0.37 μM [IQR, 0.29-0.59], P = 0.01) and lower median plasma l-arginine (late onset, 52.3 [IQR, 43-61] compared with early onset, 51 μM [IQR 39-66]; P = 0.02). The log of plasma L-arginine/ADMA was inversely correlated with BMI in the late- (r = -0.4, P = 0.0006) in contrast to the early-onset phenotype (r = -0.2, P = 0.07). Although Fe(NO) was inversely associated with BMI in the late-onset phenotype (P = 0.02), the relationship was lost after adjusting for L-arginine/ADMA. Also in this phenotype, a reduced L-arginine/ADMA was associated with less IgE, increased respiratory symptoms, lower lung volumes, and worse asthma quality of life.In late-onset asthma phenotype, plasma ratios of L-arginine to ADMA may explain the inverse relationship of BMI to Fe(NO). In addition, these lower L-arginine/ADMA ratios are associated with reduced lung function and increased respiratory symptom frequency, suggesting a role in the pathobiology of the late-onset phenotype.
Multiple Genes of the Renin-Angiotensin System Are Novel Targets of Wnt/β-Catenin Signaling
Authors: Lili Zhou, Yingjian Li, Sha Hao, Dong Zhou, Roderick J. Tan, Jing Nie, Fan Fan Hou, Michael Kahn, Youhua Liu
Journal: Journal of the American Society of Nephrology (2014)

Activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of CKD and cardiovascular disease. However, current anti-RAS therapy only has limited efficacy, partly because of compensatory upregulation of renin expression. Therefore, a treatment strategy to simultaneously target multiple RAS genes is necessary to achieve greater efficacy. By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites, and β-catenin induced the binding of LEF-1 to these sites in kidney tubular cells. Overexpression of either β-catenin or different Wnt ligands induced the expression of all RAS genes. Conversely, a small-molecule β-catenin inhibitor ICG-001 abolished RAS induction. In a mouse model of nephropathy induced by adriamycin, either transient therapy or late administration of ICG-001 abolished established proteinuria and kidney lesions. ICG-001 inhibited renal expression of multiple RAS genes in vivo and abolished the expression of other Wnt/β-catenin target genes. Moreover, ICG-001 therapy restored expression of nephrin, podocin, and Wilms' tumor 1, attenuated interstitial myofibroblast activation, repressed matrix expression, and inhibited renal inflammation and fibrosis. Collectively, these studies identify all RAS genes as novel downstream targets of Wnt/β-catenin. Our results indicate that blockade of Wnt/β-catenin signaling can simultaneously repress multiple RAS genes, thereby leading to the reversal of established proteinuria and kidney injury.
Developmental and genetic disorders in spermatogenesis
Authors: T Diemer, C Desjardins
Journal: Human Reproduction Update (1999)

The most common cause of male infertility is idiopathic. Fresh insights based on genetic and molecular analysis of the human genome permit classification of formerly unexplained disorders in spermatogenesis. In this article, we review new procedures that expand diagnostic and therapeutic approaches to male infertility. Recombinant DNA technology makes it possible to detect specific chromosomal and/or genetic defects among infertile patients. The identification of genes linked to disorders in spermatogenesis and male sexual differentiation has increased exponentially in the past decade. Genetic defects leading to male factor infertility can now be explained at the molecular level, even though the germ cell profile of infertile patients is too variable to permit classification of the clinical phenotype. Increasing knowledge of genes that direct spermatogenesis provides important new information about the molecular and cellular events involved in human spermatogenesis. Molecular analysis of chromosomes and/or genes of infertile patients offers unique opportunities to uncover the aetiology of genetic disorders in spermatogenesis. Increasing numbers of cases, previously classified as idiopathic, can now be diagnosed to facilitate the treatment of infertile men. Advanced knowledge also poses ethical dilemmas, since children conceived with assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) are at risk for congenital abnormalities, unbalanced complements of chromosomes and male infertility. Keywords: chromosomal aberrations/infertility/male sexual differentiation/microdeletions/testis
Multiple pathogens in adult patients admitted with community-acquired pneumonia: a one year prospective study of 346 consecutive patients.
Authors: D. Lieberman, F. Schlaeffer, I. Boldur, D. Lieberman, S. Horowitz, M. G. Friedman, M. Leiononen, O. Horovitz, E. Manor, A. Porath
Journal: Thorax (1996)

The purpose of this study was to assess the causes of community-acquired pneumonia in adult patients admitted to hospital.A prospective study was performed on 346 consecutive adult patients (54% men) of mean (SD) 49.3 (19.5) years (range 17-94) admitted to a university affiliated regional hospital in southern Israel with community-acquired pneumonia over a period of one year. Convalescent serum samples were obtained from 308 patients (89%). The aetiological diagnosis for community-acquired pneumonia was based on positive blood cultures and/or significant changes in antibody titres to Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, respiratory viruses, Coxiella burnetii, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella sp.The aetiology of community-acquired pneumonia was identified in 279 patients (80.6%). The distribution of causal agents was as follows: S pneumoniae, 148 patients (42.8%); M pneumoniae, 101 (29.2%); C pneumoniae, 62 (17.9%); Legionella sp, 56 (16.2%); respiratory viruses, 35 (10.1%); C burnetii, 20 (5.8%); H influenzae 19 (5.5%); and other causes, 21 patients (6.0%). In patients above the age of 55 years C pneumoniae was the second most frequent aetiological agent (25.5%). In 133 patients (38.4%) more than one causal agent was found.The causal agents for community-acquired pneumonia in Israel are different from those described in other parts of the world. In many of the patients more than one causal agent was found. In all these patients treatment should include a macrolide antibiotic, at least in the first stage of their illness.
Effects of haem arginate on variegate porphyria
Authors: K. TIMONEN, P. MUSTAJOKI, R. TENHUNEN, J. LAUHARANTA
Journal: British Journal of Dermatology (1990)

Journal Article Effects of haem arginate on variegate porphyria Get access K. TIMONEN, K. TIMONEN Department of Dermatology, University of Helsinki, Helsinki, Finland Dr K.Timonen, Department of Dermatology, University Central Hospital, Snellmaninkatu 14, SF‐00170 Helsinki, Finland. Search for other works by this author on: Oxford Academic Google Scholar P. MUSTAJOKI, P. MUSTAJOKI Third Department of Medicine, University of Helsinki, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar R. TENHUNEN, R. TENHUNEN Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar J. LAUHARANTA J. LAUHARANTA Department of Dermatology, University of Helsinki, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 3, 1 September 1990, Pages 381–387, https://doi.org/10.1111/j.1365-2133.1990.tb06299.x Published: 01 September 1990
Hospitals' disregard of patient safety alerts is risking lives, claims charity
Authors: A. O'Dowd
Journal: BMJ (2010)

NHS trusts in England are failing to act on mandatory patient safety alerts issued by the National Patient Safety Agency and are leaving patients open to risk of harm, says a leading patient safety charity.

Action Against Medical Accidents (AvMA) said it had gathered evidence showing that 307 NHS trusts (around 75% of all trusts in England) had not complied with the required actions in at least one patient safety alert before the deadline specified by the alert.

The charity, which supports thousands of people who have been affected by medical accidents, has this week published a report on NHS bodies’ failure to implement patient safety recommendations issued by the …
Single-Agent Laromustine, A Novel Alkylating Agent, Has Significant Activity in Older Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia
Authors: Gary J. Schiller, Susan M. O'Brien, Arnaud Pigneux, Daniel J. DeAngelo, Norbert Vey, Jonathan Kell, Scott Solomon, Robert K. Stuart, Verena Karsten, Ann L. Cahill, Maher X. Albitar, Francis J. Giles
Journal: Journal of Clinical Oncology (2009)

PURPOSE An international phase II study of laromustine (VNP40101M), a sulfonylhydrazine alkylating agent, was conducted in patients age 60 years or older with previously untreated poor-risk acute myeloid leukemia (AML). PATIENTS AND METHODS Laromustine 600 mg/m(2) was administered as a single 60-minute intravenous infusion. Patients were age 70 years or older or 60 years or older with at least one additional risk factor-unfavorable AML karyotype, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2, and/or cardiac, pulmonary, or hepatic comorbidities. Results Eighty-five patients (median age, 72 years; range, 60 to 87 years) were treated. Poor-risk features included age 70 years or older, 78%; adverse karyotype, 47%; PS of 2, 41%; pulmonary disease, 77%; cardiac disease, 73%; and hepatic disease, 3%. Ninety-six percent of patients had at least two risk factors, and 39% had at least four risk factors. The overall response rate (ORR) was 32%, with 20 patients (23%) achieving complete response (CR) and seven (8%) achieving CR with incomplete platelet recovery (CRp). ORR was 20% in patients with adverse cytogenetics; 32% in those age 70 years or older; 32% in those with PS of 2; 32% in patients with baseline pulmonary dysfunction; 34% in patients with baseline cardiac dysfunction; and 27% in 33 patients with at least four risk factors. Twelve (14%) patients died within 30 days of receiving laromustine therapy. Median overall survival was 3.2 months, with a 1-year survival of 21%; the median duration of survival for those who achieved CR/CRp was 12.4 months, with a 1-year survival of 52%. CONCLUSION Laromustine has significant single-agent activity in elderly patients with poor-risk AML. Adverse events are predominantly myelosuppressive or respiratory. Response rates are consistent across a spectrum of poor-risk features.
Mechanisms of Sustained Ventricular Tachycardia in Myotonic Dystrophy
Authors: Jose L. Merino, Jose R. Carmona, Ignacio Fernández-Lozano, Rafael Peinado, Nuria Basterra, Jose A. Sobrino
Journal: Circulation (1998)

Ventricular arrhythmias have been documented and linked to the high incidence of sudden death seen in patients with myotonic dystrophy. However, their precise mechanism is unknown, and their definitive therapy remains to be established.We studied 6 consecutive patients with myotonic dystrophy and sustained ventricular tachycardia by means of cardiac electrophysiological testing. Particular attention was paid to establish whether bundle-branch reentry was the tachycardia mechanism, and when such was the case, radiofrequency catheter ablation of either the right or left bundle branch was performed. Clinical tachycardia was inducible in all patients and had a bundle-branch reentrant mechanism. In 1 patient, 2 other morphologies of sustained tachycardia were also inducible, neither of which had ever been clinically documented, and both had a bundle-branch reentrant mechanism. Ventricular tachycardia was no longer inducible after bundle-branch ablation, except for a nonclinically documented and nonsustained ventricular tachycardia in the only patient who had apparent structural heart disease.A high clinical suspicion of bundle-branch reentrant tachycardia is justified in patients with myotonic dystrophy who exhibit wide QRS complex tachycardia or tachycardia-related symptoms. Because catheter ablation will easily and effectively abolish bundle-branch reentrant tachycardia, myotonic dystrophy should always be considered in patients with sustained ventricular tachycardia. This is especially true if no apparent heart disease is found.
Strategies to increase limited donor resources
Authors: M. de Perrot, W. Weder, G.A. Patterson, S. Keshavjee
Journal: European Respiratory Journal (2004)

A number of strategies have been advocated to increase the number of lung donors including: 1) improvement in donor resuscitation; 2) better methods of lung preservation; 3) extension of the lung donor selection criteria; 4) development of a living-related lung donor programme; and 5) utilisation of nonheart beating donors. Other strategies such as the split-lung technique and techniques of lung reduction to accommodate large lungs into a small-size recipient have also been used successfully. In this article, each of these strategies have been reviewed and some recommendations are suggested based on the authors9 own experience and that of the literature.
T cell regulation of B cell activation. Lyt-1+,2-T cells modify the MHC-restricted function of heterogeneous and cloned T suppressor cells.
Authors: Y Asano, R J Hodes
Journal: The Journal of Experimental Medicine (1985)

Previous studies have shown the existence of both heterogeneous Lyt-1-,2+ suppressor (Ts) cells and cloned Lyt-1+,2- Ts cells which, despite the difference in their Lyt phenotypes, functioned in a similar antigen-specific and major histocompatibility complex (MHC)-restricted fashion to suppress the antibody responses generated by cloned helper T (Th) cells and hapten-primed B cells. Our studies were carried out to assess in further detail the genetically restricted cell interactions that mediate this immune response suppression. We show that the activation of both heterogeneous and cloned Ts cells is antigen-specific and MHC-restricted under our experimental conditions. After appropriate activation, the effector function of both cloned Lyt-1+,2-Ts cells and heterogeneous Lyt-1-,2+ Ts cells was also antigen-specific. In contrast, once activated, Ts cells suppressed the responses generated by cloned Th cells and hapten-primed B cells in an MHC-unrestricted fashion. We also showed, however, that a population of unprimed Lyt-1+,2-T cells was able to significantly alter the genetic restriction requirements for Ts cell function. The activity of this population was itself MHC-restricted, and was observed only when the unprimed Lyt-1+,2-T cells shared the MHC restriction specificity of the cloned Th cells functioning in a given response. When these requirements were satisfied, Lyt-1+,2- T cells significantly modified the suppression mediated by both heterogeneous and cloned Ts cells, resulting in suppression that was then MHC restricted in its effector function as well as in its activation requirements. Thus, our findings suggest that the observed MHC restriction in Ts function is the result of a complex interaction involving Ts cells, Th cells, and an additional population of MHC-restricted Lyt-1+,2- T cells. This newly characterized activity of Lyt-1+,2- T cells functionally resembles that of an MHC-restricted contrasuppressor population that selectively blocks a pathway of MHC-unrestricted Ts activity, while leaving intact susceptibility to MHC-restricted Ts effects.