tbuckley/cabot-search huggingface dataset:
Five-Year Metabolic, Functional, and Safety Results of Patients With Type 1 Diabetes Transplanted With Allogenic Islets Within the Swiss-French GRAGIL Network
Authors: Sandrine Lablanche, Sophie Borot, Anne Wojtusciszyn, Francois Bayle, Rachel Tétaz, Lionel Badet, Charles Thivolet, Emmanuel Morelon, Luc Frimat, Alfred Penfornis, Laurence Kessler, Coralie Brault, Cyrille Colin, Igor Tauveron, Domenico Bosco, Thierry Berney, Pierre-Yves Benhamou
Journal: Diabetes Care (2015)

OBJECTIVE To describe the 5-year outcomes of islet transplantation within the Swiss-French GRAGIL Network. RESEARCH DESIGN AND METHODS Retrospective analysis of all subjects enrolled in the GRAGIL-1c and GRAGIL-2 islet transplantation trials. Parameters related to metabolic control, graft function, and safety outcomes were studied. RESULTS Forty-four patients received islet transplantation (islet transplantation alone [ITA] 24 patients [54.5%], islet after kidney [IAK] transplantation 20 patients [45.5%]) between September 2003 and April 2010. Recipients received a total islet mass of 9,715.75 ± 3,444.40 IEQ/kg. Thirty-four patients completed a 5-year follow-up, and 10 patients completed a 4-year follow-up. At 1, 4, and 5 years after islet transplantation, respectively, 83%, 67%, and 58% of the ITA recipients and 80%, 70%, and 60% of the IAK transplant recipients reached HbA1c under 7% (53 mmol/mol) and were free of severe hypoglycemia, while none of the ITA recipients and only 10% of the IAK transplant recipients met this composite criterion at the preinfusion stage. Thirty-three of 44 patients (75%) experienced insulin independence during the entire follow-up period, with a median duration of insulin independence of 19.25 months (interquartile range 2–58). Twenty-nine of 44 recipients (66%) exhibited at least one adverse event; 18 of 55 adverse events (33%) were possibly related to immunosuppression; and complications related to the islet infusion (n = 84) occurred in 10 recipients (11.9%). CONCLUSIONS In a large cohort with a 5-year follow-up and in a multicenter network setting, islet transplantation was safe and efficient in restoring good and lasting glycemic control and preventing severe hypoglycemia in patients with type 1 diabetes.
Evolutionary Dynamics and Preferential Expression of Homeologous 18S-5.8S-26S Nuclear Ribosomal Genes in Natural and Artificial Glycine Allopolyploids
Authors: S. Joly
Journal: Molecular Biology and Evolution (2004)

Polyploidy is an important evolutionary process in plants, but much remains to be learned about the evolution of gene expression in polyploids. Evolution and expression of the 18S-5.8S-26S ribosomal gene family was investigated at homeologous loci in the Glycine subgenus Glycine perennial soybean polyploid complex, which consists of several diploid genomes that have formed allopolyploids in various combinations, often recurrently. A semiquantitative PCR method targeting the internal transcribed spacer (ITS) of the 18S-5.8S-26S nuclear ribosomal DNA (nrDNA) was used to survey the ratio between homeologous repeats in polyploid genomes and to test for preferential expression of homeologous nrDNA loci. Most natural polyploids possess one predominant nrDNA homeolog in their genome. Analysis of F2 segregation in an artificial cross suggested that in some plants, most or all repeats at one homeologous locus have been lost, whereas in other plants two loci remain, but both have been homogenized by concerted evolution. In most natural allopolyploids harboring a relatively balanced ratio of homeologs, one homeolog was expressed preferentially, but in the majority of plants, low levels of transcription could be detected from the other homeolog. Individuals within some tetraploid taxa varied as to which homeolog was expressed preferentially. In some plants, the degree of preferential expression also varied among tissues. Preferential expression was absent in synthetic polyploids and in some artificial diploid hybrids, suggesting that nucleolar dominance is not necessarily a direct result of hybridization or polyploidization. The establishment of preferential expression in Glycine allopolyploids appears to be either stochastic within lineages or genotype specific.
Risk Model of Thoracic Aortic Surgery in 4707 Cases From a Nationwide Single-Race Population Through a Web-Based Data Entry System
Authors: Noboru Motomura, Hiroaki Miyata, Hiroyuki Tsukihara, Shinichi Takamoto
Journal: Circulation (2008)

Background— The objective of this study was to collect integrated data from nationwide hospitals using a web-based national database system to build up our own risk model for the outcome from thoracic aortic surgery. Methods and Results— The Japan Adult Cardiovascular Surgery Database was used; this involved approximately 180 hospitals throughout Japan through a web-based data entry system. Variables and definitions are almost identical to the STS National Database. After data cleanup, 4707 records were analyzed from 97 hospitals (between January 1, 2000, and December 31, 2005). Mean age was 66.5 years. Preoperatively, the incidence of chronic lung disease was 11%, renal failure was 9%, and rupture or malperfusion was 10%. The incidence of the location along the aorta requiring replacement surgery (including overlapping areas) was: aortic root, 10% ; ascending aorta, 47%; aortic arch, 44%; distal arch, 21%; descending aorta, 27%; and thoracoabdominal aorta, 8%. Raw 30-day and 30-day operative mortality rates were 6.7% and 8.6%, respectively. Postoperative incidence of permanent stroke was 6.1%, and renal failure requiring dialysis was 6.7%. OR for 30-day operative mortality was as follows: emergency or salvage, 3.7; creatinine &gt;3.0 mg/dL, 3.0; and unexpected coronary artery bypass graft, 2.6. As a performance metric of the risk model, C-index of 30-day and 30-day operative mortality was 0.79 and 0.78, respectively. Conclusion— This is the first report of risk stratification on thoracic aortic surgery using a nationwide surgical database. Although condition of these patients undergoing thoracic aortic surgery was much more serious than other procedures, the result of this series was excellent.
Mutation in hepatocyte nuclear factor–1β gene (TCF2) associated with MODY
Authors: Yukio Horikawa, Naoko Iwasaki, Manami Hara, Hiroto Furuta, Yoshinori Hinokio, Brian N. Cockburn, Tom Lindner, Kazuya Yamagata, Makiko Ogata, Osamu Tomonaga, Hiroyuki Kuroki, Tadasu Kasahara, Yasuhiko Iwamoto, Graeme I. Bell
Journal: Nature Genetics (1997)
Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males
Authors: José M. Di Diego, Jonathan M. Cordeiro, Robert J. Goodrow, Jeffrey M. Fish, Andrew C. Zygmunt, Guillermo J. Pérez, Fabiana S. Scornik, Charles Antzelevitch
Journal: Circulation (2002)

The Brugada syndrome displays an autosomal dominant mode of transmission with low penetrance. Despite equal genetic transmission of the disease, the clinical phenotype is 8 to 10 times more prevalent in males than in females. The basis for this intriguing sex-related distinction is unknown. The present study tests the hypothesis that the disparity in expression of the Brugada phenotype is a result of a more prominent I(to)-mediated action potential notch in the right ventricular (RV) epicardium of males versus females.We studied epicardial tissue slices, arterially perfused wedge preparations, and dissociated epicardial myocytes isolated from male and female canine hearts. RV epicardium action potential phase 1 amplitude was 64.8+/-2.0% of that of phase 2 in males compared with 73.8+/-4.4% in females (P<0.05) at a cycle length of 2000 ms. I(to) density was 26% smaller and time constant for inactivation 17% smaller at +40 mV in female versus male RV epicardial cells (P<0.05). The other functional characteristics of I(to), including the voltage dependence of inactivation and time course of reactivation, were no different between the sexes. Pinacidil caused loss of action potential dome in male, but not female, RV epicardial tissue slices. Terfenadine (5 micromol/L) induced phase 2 reentry in 6 of 7 male but only 2 of 7 female arterially perfused wedge preparations. Two of 6 male and 1 of 2 female preparations developed polymorphic ventricular tachycardia/ventricular fibrillation.Our results suggest that the predominance of the Brugada phenotype in males is a result of the presence of a more prominent I(to) in males versus females.
A METHOD OF STANDARDIZING BACTERIAL SUSPENSIONS
Authors: Frederick L. Gates
Journal: The Journal of Experimental Medicine (1920)

The opacity of a bacterial suspension is measured by the length of the column of the suspension required to cause the disappearance of a wire loop. By a simple formula the measured opacity is translated into terms of the concentration of bacteria per cc., and so made comparable with that of other suspensions of the same organism. An instrument for measuring the opacity of bacterial suspensions is described in detail.
ON THE PRACTICAL RESULTS OF QUARANTINE
Authors: T. S. Wells
Journal: BMJ (1854)

paper had been read, Dr. Milroy and Dr. Gavin (who had evidently studied it before it was read before the Society) replied at very considerable length; and several members, including myself, deeming the sub- ject too important to be dismissed without further dis- cussion, it was arranged that I should reintroduce it by means of a short paper, as the rules of the Society do not perit the adjournment of a debate.I trust, therefore, that these circumstances may be accepted as an excuse for the hasty and fagmentary manner in which this paper is 4lrawn up, my intention being simply to make such com- ments upon the papers and speeches of Sir Wim.Pym, Dr. two days, and a very large bubo in the let groin followed.He was conveyed to the pesthouse, and recovered.Two other emp o8e of the lazaret died on the 15th and 17th of July.Here, then, we have a city of 800,000 inhabitants, free from epide inuence; healy persons are placed in cott with plue patients, four tak the disease, and three die.
A Novel ALK Secondary Mutation and EGFR Signaling Cause Resistance to ALK Kinase Inhibitors
Authors: Takaaki Sasaki, Jussi Koivunen, Atsuko Ogino, Masahiko Yanagita, Sarah Nikiforow, Wei Zheng, Christopher Lathan, J. Paul Marcoux, Jinyan Du, Katsuhiro Okuda, Marzia Capelletti, Takeshi Shimamura, Dalia Ercan, Magda Stumpfova, Yun Xiao, Stanislawa Weremowicz, Mohit Butaney, Stephanie Heon, Keith Wilner, James G. Christensen, Michel J. Eck, Kwok-Kin Wong, Neal Lindeman, Nathanael S. Gray, Scott J. Rodig, Pasi A. Jänne
Journal: Cancer Research (2011)

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), including crizotinib, are effective treatments in preclinical models and in cancer patients with ALK-translocated cancers. However, their efficacy will ultimately be limited by the development of acquired drug resistance. Here we report two mechanisms of ALK TKI resistance identified from a crizotinib-treated non-small cell lung cancer (NSCLC) patient and in a cell line generated from the resistant tumor (DFCI076) as well as from studying a resistant version of the ALK TKI (TAE684)-sensitive H3122 cell line. The crizotinib-resistant DFCI076 cell line harbored a unique L1152R ALK secondary mutation and was also resistant to the structurally unrelated ALK TKI TAE684. Although the DFCI076 cell line was still partially dependent on ALK for survival, it also contained concurrent coactivation of epidermal growth factor receptor (EGFR) signaling. In contrast, the TAE684-resistant (TR3) H3122 cell line did not contain an ALK secondary mutation but instead harbored coactivation of EGFR signaling. Dual inhibition of both ALK and EGFR was the most effective therapeutic strategy for the DFCI076 and H3122 TR3 cell lines. We further identified a subset (3/50; 6%) of treatment naive NSCLC patients with ALK rearrangements that also had concurrent EGFR activating mutations. Our studies identify resistance mechanisms to ALK TKIs mediated by both ALK and by a bypass signaling pathway mediated by EGFR. These mechanisms can occur independently, or in the same cancer, suggesting that the combination of both ALK and EGFR inhibitors may represent an effective therapy for these subsets of NSCLC patients.
The Genetics of Anorexia Nervosa
Authors: Cynthia M. Bulik, Margarita C.T. Slof-Op't Landt, Eric F. van Furth, Patrick F. Sullivan
Journal: Annual Review of Nutrition (2007)

Anorexia nervosa is a perplexing illness marked by low body weight and persistent fear of weight gain. Anorexia nervosa has the highest mortality rate of any psychiatric disease. Historically, anorexia nervosa was viewed as a disorder primarily influenced by sociocultural factors; however, over the past decade, this perception has been challenged. Family studies have consistently demonstrated that anorexia nervosa runs in families. Twin studies have underscored the contribution of additive genetic factors to the observed familial aggregation. With these bodies of literature as a starting point, we evaluate critically the current state of research on molecular genetic studies of anorexia nervosa and provide guidance for future research.
Absence of MMP2 Expression Correlates with Poor Clinical Outcomes in Rectal Cancer, and Is Distinct from MMP1-Related Outcomes in Colon Cancer
Authors: John C.T. Wong, Simon K. Chan, David F. Schaeffer, Xavier Sagaert, Howard J. Lim, Hagen Kennecke, David A. Owen, Kwang W. Suh, Young-Bae Kim, Isabella T. Tai
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Treatments for colorectal cancer (CRC) are primarily disease stage based. However, heterogeneity in outcome within even a single stage highlights its limitations in predicting disease behavior. Recently, the role of gene expression as predictive and prognostic markers has been explored. Our objectives were to identify consistently differentially expressed genes through meta-analysis of high-throughput gene-expression studies, and evaluate their predictive and prognostic significance in colon (CC) and rectal (RC) cancers. Experimental Design: Publications applying high-throughput gene- expression technologies to specific CRC stages were identified. A vote counting strategy was used to identify the most significant differentially expressed genes. Their predictive and prognostic values were independently assessed in a tissue microarray of 191 cases of stage II-IV CC/RC from two tertiary care centers. Their biological effects were also examined in vitro. Results: MMP1 and MMP2 were identified as consistently underexpressed in liver metastasis compared with primary CRC. Shorter time to distant metastasis and overall survival occurred in stage III CC lacking MMP1 expression, and in stage III RC lacking MMP2. MMP1 levels in stage II and III CC were associated with increased likelihood of distant metastasis, whereas the risk of local recurrence in stage III RC could be stratified by MMP2. Promotion of cell invasion of CRC cell lines exposed to MMP1/2 inhibitors were confirmed in vitro. Conclusions: MMP1 and MMP2 may be useful biomarkers that can help stratify patients at higher risk of developing recurrence in colorectal cancer, and guide individualized treatment decisions to achieve better outcomes. Clin Cancer Res; 17(12); 4167–76. ©2011 AACR.
Physiology Is a Stronger Predictor of Survival than Pathology in Fibrotic Interstitial Pneumonia
Authors: Yangjin Jegal, Dong Soon Kim, Tae Sun Shim, Chae-Man Lim, Sang Do Lee, Younsuck Koh, Woo Sung Kim, Won Dong Kim, Jin Seong Lee, William D. Travis, Masanori Kitaichi, Thomas V. Colby
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The histopathologic pattern provides the most important prognostic marker for idiopathic interstitial pneumonia; however, studies have suggested that short-term changes in lung function may be more important. We investigated the prognostic factors for fibrotic interstitial pneumonia. The clinical features and follow-up course of 179 patients (131 with idiopathic pulmonary fibrosis and 48 with nonspecific interstitial pneumonia; 41 fibrotic types and 7 cellular) were analyzed retrospectively. The lung function indices improved or stabilized in most patients with fibrotic nonspecific interstitial pneumonia in contrast to the deterioration or stable condition of most patients with idiopathic pulmonary fibrosis. The 5-year survival of patients with fibrotic nonspecific interstitial pneumonia (76.2%) was better than for those with idiopathic pulmonary fibrosis (43.8%) (p = 0.007). Multivariate analysis at the time of presentation revealed that pathologic pattern, age, and diffusion capacity had important prognostic implications. However, after 6 months of follow-up, changes in FVC, initial diffusion capacity, and sex were the only independent prognostic factors, with no additional prognostic information conferred by the histologic diagnosis. Our data confirmed the importance of physiological parameters including short-term change in FVC. However, at the time of diagnosis, histopathology was important for the prediction of prognosis and future change in lung function.
Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer
Authors: Jeffrey A. Engelman, Pasi A. Jänne
Journal: Clinical Cancer Research (2008)

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib are effective therapies for non–small cell lung cancer patients whose tumors harbor somatic mutations in EGFR. All patients, however, ultimately develop resistance to these agents. Thus, there is a great need to understand how patients become resistant to develop effective therapies for these cancers. Studies over the last few years have identified two different EGFR tyrosine kinase inhibitor resistance mechanisms, a secondary mutation in EGFR, EGFR 790M, and amplification of the MET oncogene. These findings have led to clinical trials using newly designed targeted therapies that can overcome these resistance mechanisms and have shown promise in laboratory studies. Ongoing research efforts will likely continue to identify additional resistance mechanisms, and these findings will hopefully translate into effective therapies for non–small cell lung cancer patients.
Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthritis
Authors: Esperanza Naredo, Maria Antonietta D'Agostino, Richard J Wakefield, Ingrid Möller, Peter V Balint, Emilio Filippucci, Annamaria Iagnocco, Zunaid Karim, Lene Terslev, David A Bong, Jesús Garrido, David Martínez-Hernández, George A W Bruyn
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis (RA). <h3>Methods</h3> We undertook a Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16 countries. Then, we assessed the intraobserver and interobserver reliability of US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique. Ten patients with RA with symptoms in the hands or feet were recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed by Cohen9s κ. Interobserver reliability was assessed by Light9s κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. <h3>Results</h3> Four-grade semiquantitative scoring systems were agreed upon for scoring tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (κ value 0.72 for B-mode; κ value 0.78 for PD mode). Interobserver reliability assessment showed good κ values for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate κ values for B-mode tenosynovitis scoring (first round, 0.47; second round, 0.45). <h3>Conclusions</h3> US appears to be a reproducible tool for evaluating and monitoring tenosynovitis in RA.
Immunoglobulin Superfamily Receptor Translocation Associated 2 Protein on Lymphoma Cell Lines and Hairy Cell Leukemia Cells Detected by Novel Monoclonal Antibodies
Authors: Tomoko Ise, Hiroshi Maeda, Kenneth Santora, Laiman Xiang, Robert J. Kreitman, Ira Pastan, Satoshi Nagata
Journal: Clinical Cancer Research (2005)

The immunoglobulin superfamily receptor translocation associated 2 (IRTA2) gene encodes a cell surface receptor homologous to the family of Fc receptors. Because of the restricted expression of mRNA in B cell-lineage cells, IRTA2 is a new potential target for the immunotherapy of B cell malignancies. To study the expression of the IRTA2 gene product, we produced monoclonal antibodies (MAbs) specific to IRTA2.A mouse used for cell fusion was DNA-immunized with an expression plasmid encoding the IRTA2 cDNA. The reactivity of MAbs secreted from the hybridomas were characterized with recombinant proteins of IRTA family members in an enzyme immunoassay and a fluorescence-activated cell sorter (FACS). Nineteen human lymphoma cell lines and blood cells from five patients with hairy cell leukemia (HCL) were analyzed with IRTA2 expression using FACS.Three MAbs (F25, F56, and F119) were selected based on their specific reactivity with recombinant IRTA2 and lack of cross-reactivity with other IRTA family members. In a FACS analysis, MAbs F56 and F119 detected IRTA2 expression in six of seven B cell non-Hodgkin's lymphoma and one of six Burkitt's lymphoma cell lines. Reverse transcriptase-PCR experiments and Western blotting using MAb F25 confirmed the expression profile. We also found that HCL cells from five patients expressed IRTA2.Our results provide the first evidence that IRTA2 is expressed on the surface of human lymphoma cell lines and HCL cells. IRTA2 could be useful as a new target for immunotherapy.
Fcγ receptors enable anticancer action of proapoptotic and immune-modulatory antibodies
Authors: Jeong M. Kim, Avi Ashkenazi
Journal: The Journal of Experimental Medicine (2013)

Antibodies have important roles in controlling cellular immunity through interaction with activating or inhibitory Fcγ receptors (FcγRs). FcγR engagement can facilitate receptor cross-linking on target cells, or induce retrograde FcγR signals to stimulate or suppress antibody-dependent, cell-mediated depletion of antigen-bearing target cells. Recent studies uncover unexpectedly important roles for FcγRs in the anticancer action of antibodies designed to trigger tumor cell apoptosis or enhance antitumor immunity. Here, we outline a conceptual framework for understanding these findings and discuss their mechanistic and translational implications.
School-Based Health Clinics: Remaining Viable in a Changing Health Care Delivery System
Authors: Claire D. Brindis, Rupal V. Sanghvi
Journal: Annual Review of Public Health (1997)

▪ Abstract Adolescents are often vulnerable to particular health risks and face multiple barriers to accessing health care. School-based clinics and school-linked services represent an alternative model of care that has responded to the unique health issues of adolescents by offering preventive, comprehensive services, including mental health and other sensitive services. The current restructuring of the American health care delivery system presents a serious challenge to the continued existence of these services, which must link successfully with managed care organizations and adapt to significant changes in federal and state funding streams to remain viable. The continued success of school-based health services in improving adolescent health will largely depend on how well they can capitalize on their strategic position to reach adolescents, respond to their health needs, and reduce barriers to care, and how effectively they can integrate themselves into a rapidly evolving US health care delivery system.