tbuckley/cabot-search huggingface dataset:
Peripheral Blood Leukocyte Telomere Length and Mortality Among 64 637 Individuals From the General Population
Authors: Line Rode, Børge G. Nordestgaard, Stig E. Bojesen
Journal: JNCI Journal of the National Cancer Institute (2015)

Short telomeres in peripheral blood leukocytes are associated with older age and age-related diseases. We tested the hypotheses that short telomeres are associated with both increased cancer mortality and all-cause mortality.Individuals (n = 64637) were recruited from 1991 onwards from two Danish prospective cohort studies: the Copenhagen City Heart Study and the Copenhagen General Population Study. All had telomere length measured by quantitative polymerase chain reaction and the genotypes rs1317082 (TERC), rs7726159 (TERT), and rs2487999 (OBFC1) determined. The sum of telomere-shortening alleles from these three genotypes was calculated. We conducted Cox regression analyses and instrumental variable analyses using the allele sum as an instrument. All statistical tests were two-sided.Among 7607 individuals who died during follow-up (0-22 years, median = 7 years), 2420 had cancer and 2633 had cardiovascular disease as causes of death. Decreasing telomere length deciles were associated with increasing all-cause mortality (P(trend) = 2*10(-15)). The multivariable-adjusted hazard ratio of all-cause mortality was 1.40 (95% confidence interval [CI] = 1.25 to 1.57) for individuals in the shortest vs the longest decile. Results were similar for cancer mortality and cardiovascular mortality. Telomere length decreased 69 base pairs (95% CI = 61 to 76) per allele for the allele sum, and the per-allele hazard ratio for cancer mortality was 0.95 (95% CI = 0.91 to 0.99). Allele sum was not associated with cardiovascular, other, or all-cause mortality.Short telomeres in peripheral blood leukocytes were associated with high mortality in association analyses. In contrast, genetically determined short telomeres were associated with low cancer mortality but not with all-cause mortality.
Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma
Authors: Jaw-Ching Wu, Yi-Hsiang Huang, Gar-Yang Chau, Chien-Wei Su, Chung-Ru Lai, Pui-Ching Lee, Teh-Ia Huo, I-Jane Sheen, Shou-Dong Lee, Wing-Yiu Lui
Journal: Journal of Hepatology (2009)
Influence of Health Care Providers on the Development of Diabetes Complications
Authors: Janice C. Zgibor, Thomas J. Songer, Sheryl F. Kelsey, Allan L. Drash, Trevor J. Orchard
Journal: Diabetes Care (2002)

OBJECTIVE—To quantify total diabetes care received (generalist or specialist) from diagnosis onward and its association with the incidence of diabetes complications in a representative cohort of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 429 subjects from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective follow-up study of childhood-onset type 1 diabetic subjects first seen between 1986 and 1988 (mean age 28 years, mean duration 19 years), followed biennially for up to 10 years were studied. Specialist care was defined as care received from a board-certified endocrinologist, diabetologist, or diabetes clinic and quantified as the percent of diabetes duration spent in specialist care. RESULTS—There was a significant trend for a higher incidence of neuropathy, overt nephropathy, and coronary artery disease with lower use of specialist care. Multivariate analyses controlling for diabetes duration, demographic characteristics, health care practices, and physiological risk factors demonstrated that higher past use of specialist care was found to be significantly protective against the development of overt nephropathy (risk ratio 0.43, 95% CI 0.21–0.88) and neuropathy (0.54, 0.35–0.83) and weakly protective against coronary artery disease (0.65, 0.37–1.1). CONCLUSIONS—A higher proportion of diabetes duration spent in specialist care may result in delayed development of certain diabetes complications independent of other risk factors. This study thus supports the concept that the benefits of specialist care should be available to all patients with type 1 diabetes.
CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1–2 study
Authors: Takashi Seto, Katsuyuki Kiura, Makoto Nishio, Kazuhiko Nakagawa, Makoto Maemondo, Akira Inoue, Toyoaki Hida, Nobuyuki Yamamoto, Hiroshige Yoshioka, Masao Harada, Yuichiro Ohe, Naoyuki Nogami, Kengo Takeuchi, Tadashi Shimada, Tomohiro Tanaka, Tomohide Tamura
Journal: The Lancet Oncology (2013)
Simultaneous dorsal dislocation of both interphalangeal joints in a finger.
Authors: B. Krebs, L. K. Gron
Journal: British Journal of Sports Medicine (1984)

Following simultaneous dorsal dislocation of both interphalangeal joints of a finger, attention must be paid to the risk of a long period of recovery because of the severity of the lesion. Approximately one year after such an accident to a footballer arthrodesis was performed on the proximal interphalangeal joint, as the patient was still suffering from constant pain in the finger.
MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity
Authors: N. M. Teplyuk, B. Mollenhauer, G. Gabriely, A. Giese, E. Kim, M. Smolsky, R. Y. Kim, M. G. Saria, S. Pastorino, S. Kesari, A. M. Krichevsky
Journal: Neuro-Oncology (2012)

An accurate, nonsurgical diagnostic test for brain tumors is currently unavailable, and the methods of monitoring disease progression are not fully reliable. MicroRNA profiling of biological fluids has recently emerged as a diagnostic tool for several pathologic conditions. Here we tested whether microRNA profiling of cerebrospinal fluid (CSF) enables detection of glioblastoma, discrimination between glioblastoma and metastatic brain tumors, and reflects disease activity. We determined CSF levels of several cancer-associated microRNAs for 118 patients diagnosed with different types of brain cancers and nonneoplastic neuropathologies by quantitative reverse transcription PCR analysis. The levels of miR-10b and miR-21 are found significantly increased in the CSF of patients with glioblastoma and brain metastasis of breast and lung cancer, compared with tumors in remission and a variety of nonneoplastic conditions. Members of the miR-200 family are highly elevated in the CSF of patients with brain metastases but not with any other pathologic conditions, allowing discrimination between glioblastoma and metastatic brain tumors. Quantification of as few as 7 microRNAs in CSF enables differential recognition of glioblastoma and metastatic brain cancer using computational machine learning tools (Support Vector Machine) with high accuracy (91%–99%) on a test set of samples. Furthermore, we show that disease activity and treatment response can be monitored by longitudinal microRNA profiles in the CSF of glioblastoma and non–small cell lung carcinoma patients. This study demonstrates that microRNA-based detection of brain malignancies can be reliably performed and that microRNAs in CSF can serve as biomarkers of treatment response in brain cancers.
Induction Chemoradiation and Surgical Resection for Superior Sulcus Non–Small-Cell Lung Carcinomas: Long-Term Results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160)
Authors: Valerie W. Rusch, Dorothy J. Giroux, Michael J. Kraut, John Crowley, Mark Hazuka, Timothy Winton, David H. Johnson, Lawrence Shulman, Frances Shepherd, Claude Deschamps, Robert B. Livingston, David Gandara
Journal: Journal of Clinical Oncology (2007)

Traditional treatment for superior sulcus non-small-cell lung cancers (SS NSCLC), radiation plus surgery, yields a 50% rate of complete resection and a 30% 5-year survival. On the basis of improved outcomes in other subsets of stage III NSCLC, this trial tested the feasibility of induction chemoradiotherapy for SS NSCLC.Patients with T3-4, N0-1 SS NSCLC received two cycles of cisplatin and etoposide concurrently with radiation (45 Gy). Patients with stable or responding disease underwent thoracotomy. All patients received two more cycles of chemotherapy. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed by Cox regression analysis.From April 1995 to November 1999, 110 eligible patients (76 men, 34 women) were entered onto the study (78 T3, 32 T4 tumors). Induction therapy was completed by 104 (95%) patients. Of 95 patients eligible for surgery, 88 (80%) underwent thoracotomy, two (1.8%) died postoperatively, and 83 (76%) had complete resection. Pathologic complete response (CR) or minimal microscopic disease was seen in 61 (56%) resection specimens. Five-year survival was 44% for all patients and 54% after complete resection, with no difference between T3 and T4 tumors. Pathologic CR led to better survival than when any residual disease was present (P = .02). Disease progression occurred mainly in distant sites.This combined-modality approach is feasible and is associated with high rates of complete resection and pathologic CR in both T3 and T4 tumors. Local control and overall survival seem markedly improved relative to previous studies of radiation plus resection.
A Plasmablast Biomarker for Nonresponse to Antibody Therapy to CD20 in Rheumatoid Arthritis
Authors: Kasia Owczarczyk, Preeti Lal, Alexander R. Abbas, Kristen Wolslegel, Cecile T. J. Holweg, Wolfgang Dummer, Ariella Kelman, Paul Brunetta, Nicholas Lewin-Koh, Marco Sorani, Diane Leong, Paul Fielder, David Yocum, Carole Ho, Ward Ortmann, Michael J. Townsend, Timothy W. Behrens
Journal: Science Translational Medicine (2011)

Plasmablast biomarkers predict whether rheumatoid arthritis patients will respond to therapeutic antibodies to CD20.
Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial
Authors: L. Mauriac, A. Keshaviah, M. Debled, H. Mouridsen, J.F. Forbes, B. Thürlimann, R. Paridaens, A. Monnier, I. Láng, A. Wardley, J.-M. Nogaret, R.D. Gelber, M. Castiglione-Gertsch, K.N. Price, A.S. Coates, I. Smith, G. Viale, M. Rabaglio, N. Zabaznyi, A. Goldhirsch
Journal: Annals of Oncology (2007)
Collagenous colitis: an unrecognised entity.
Authors: W V Bogomoletz, J J Adnet, P Birembaut, P Feydy, P Dupont
Journal: Gut (1980)

A patient is reported with chronic abdominal pain, diarrhoea, and associated radiological and endoscopic abnormalities of the sigmoid colon. Light and electron microscopic study of colorectal mucosa showed abnormal collagenous thickening of the subepithelial basement membrane. The authors felt that the clinical and morphological features justified a diagnosis of collagenous colitis. Review of the literature suggested that collagenous colitis was still an unrecognised entity.
Regulation of adrenergic nerve-mediated contraction of canine pulmonary artery by K+ channels
Authors: E Tagaya, J Tamaoki, H Takemura, A Nagai
Journal: European Respiratory Journal (1998)

The aim of the present study was to investigate the role of certain subtypes of K+ channels in nerve-evoked contractions of pulmonary artery in vitro. The lobar or segmental pulmonary arteries were dissected from dogs, cut into ring segments, and the contractile responses to electrical field stimulation (EFS) and noradrenaline were measured under isometric conditions. Addition of iberiotoxin, a big conductance Ca2+-activated K+ channel blocker, and apamin, a small conductance Ca2+-activated K+ channel blocker, did not change the resting tension but augmented the contractile responses to EFS, so that the electric stimulus frequency required to produce a half-maximal contraction (ES50) was decreased from 18.2+/-3.5 to 7.4+/-2.3 Hz (p<0.01) and from 16.8+/-2.2 to 11.4+/-2.0 Hz (p<0.05), respectively, whereas glibenclamide, an adenosine triphosphate (ATP)-sensitive K+ channel blocker, had no effect. In contrast, none of the K+ channel blockers altered the contractile response to noradrenaline. Incubation of tissues with iberiotoxin and apamin increased the release of 3H-noradrenaline evoked by EFS. We conclude that big conductance Ca2+-activated K+ channels and small conductance Ca2+-activated K+ channels may play a role in the regulation of adrenergic neurotransmission in the pulmonary artery, probably by inhibiting the exocytotic release of noradrenaline from the adrenergic nerve terminals.
β-Adrenergic Stimulation Synchronizes Intracellular Ca <sup>2+</sup> Release During Excitation-Contraction Coupling in Cardiac Myocytes
Authors: Long-Sheng Song, Shi-Qiang Wang, Rui-Ping Xiao, Harold Spurgeon, Edward G. Lakatta, Heping Cheng
Journal: Circulation Research (2001)

Abstract —To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by β-adrenergic receptor (β-AR) stimulation, we examined local Ca 2+ release function, ie, Ca 2+ spikes at individual transverse tubule–sarcoplasmic reticulum (T-SR) junctions, using confocal microscopy and our recently developed technique for release flux measurement. β-AR stimulation by norepinephrine plus an α 1 -adrenergic blocker, prazosin, increased the amplitude of SR Ca 2+ release flux (J SR ), its running integral (∫J SR ), and L-type Ca 2+ channel current ( I Ca ), and it shifted their bell-shaped voltage dependence leftward by ≈10 mV, with the relative effects ranking I Ca &gt; J SR &gt;∫J SR . Confocal imaging revealed that the bell-shaped voltage dependence of SR Ca 2+ release is attributable to a graded recruitment of T-SR junctions as well as to changes in Ca 2+ spike amplitudes. β-AR stimulation increased the fractional T-SR junctions that fired Ca 2+ spikes and augmented Ca 2+ spike amplitudes, without altering the SR Ca 2+ load, suggesting that more release units were activated synchronously among and within T-SR junctions. Moreover, β-AR stimulation decreased the latency and temporal dispersion of Ca 2+ spike occurrence at a given voltage, delivering most of the Ca 2+ at the onset of depolarization rather than spreading it out throughout depolarization. Because the synchrony of Ca 2+ spikes affects Ca 2+ delivery per unit of time to contractile myofilaments, and because the myofilaments display a steep Ca 2+ dependence, our data suggest that synchronization of SR Ca 2+ release represents a heretofore unappreciated mechanism of β-AR modulation of cardiac inotropy.
THE FUNCTION OF THE KIDNEY WHEN DEPRIVED OF ITS NERVES
Authors: William C. Quinby
Journal: The Journal of Experimental Medicine (1916)

1. By means of vascular suture it is possible to remove the dog's kidney from the body and later to restore it to its former position. 2. Such a kidney is removed from the control of the nervous system, at least for a time. 3. Examination of the function of a kidney so treated shows an initial period of overaction, as compared with that of the normal kidney. 4. This is followed by balanced action. 5. The more recent tests of renal function show that a single, reimplanted kidney is able to maintain normal life indefinitely. 6. The results of these experiments, together with the evidence already at hand, suggest strongly that secretory nerves to the kidney do not exist.
Hypoxia-Inducible Protein 2 (<i>HIG2</i>), a Novel Diagnostic Marker for Renal Cell Carcinoma and Potential Target for Molecular Therapy
Authors: Akira Togashi, Toyomasa Katagiri, Shingo Ashida, Tomoaki Fujioka, Osamu Maruyama, Yoshiaki Wakumoto, Yoshiro Sakamoto, Makoto Fujime, Yoshio Kawachi, Taro Shuin, Yusuke Nakamura
Journal: Cancer Research (2005)

Abstract To identify molecules to serve as diagnostic markers for renal cell carcinoma (RCC) and as targets for novel therapeutic drugs, we investigated genome-wide expression profiles of RCCs using a cDNA microarray. We subsequently confirmed that hypoxia-inducible protein-2 (HIG2) was expressed exclusively in RCCs and fetal kidney. Induction of HIG2 cDNA into COS7 cells led to secretion of the gene product into culture medium and resulted in enhancement of cell growth. Small interfering RNA effectively inhibited expression of HIG2 in human RCC cells that endogenously expressed high levels of the protein and significantly suppressed cell growth. Moreover, addition of polyclonal anti-HIG2 antibody into culture medium induced apoptosis in RCC-derived cell lines. By binding to an extracellular domain of frizzled homologue 10 (FZD10), HIG2 protein enhanced oncogenic Wnt signaling and its own transcription, suggesting that this product is likely to function as an autocrine growth factor. ELISA analysis of clinical samples identified secretion of HIG2 protein into the plasma of RCC patients even at an early stage of tumor development, whereas it was detected at significantly lower levels in healthy volunteers or patients with chronic glomerulonephritis. The combined evidence suggests that this molecule represents a promising candidate for development of molecular-targeting therapy and could serve as a prominent diagnostic tumor marker for patients with renal carcinomas.
Enhancement of Human Lymphocyte Transformation by Aggregated Human Gamma Globulin
Authors: T. Douglas Kinsella
Journal: Journal of Clinical Investigation (1974)

The effect of heat-aggregated human gamma globulin (aggFII) on the induction of in vitro lymphocyte transformation, measured by the uptake of tritiated thymidine into newly synthesized DNA, was studied with peripheral blood lymphocytes derived from 12 patients with rheumatoid arthritis (RA), six with ankylosing spondylitis (AS), two with systemic lupus erythematosus (SLE), and seven normal subjects. It was found that 200 μg aggFII induced significant transformation of the lymphocytes of eight patients with RA, five with AS, one with SLE, and one normal subject. Neither deaggregated FII nor heat-aggregated human serum albumin induced significant transformation of the lymphocytes of any subject tested. A source of complement appeared necessary to support aggFII-induced blastogenesis, since enhanced transformation occurred only in the presence of fresh plasma. Heat-inactivated plasma and fetal calf serum (FCS), and FCS devoid of hemolytic complement, failed to support enhanced blastogenesis in the presence of aggFII. Since substrates similar to those employed in these studies are present in vivo in the rheumatoid joint, it is suggested that aggFII may enhance intra-articular lymphocyte transformation in subjects with RA.
Estimation of hepatitis C virus infections resulting from vertical transmission in Egypt
Authors: Lenka Benova, Susanne F. Awad, F. DeWolfe Miller, Laith J. Abu‐Raddad
Journal: Hepatology (2014)

Despite having the highest hepatitis C virus (HCV) prevalence in the world, the ongoing level of HCV incidence in Egypt and its drivers are poorly understood. Whereas HCV mother‐to‐child infection is a well‐established transmission route, there are no estimates of HCV infections resulting from vertical transmission for any country, including Egypt. The aim of this study was to estimate the absolute number of new HCV infections resulting from vertical transmission in Egypt. We developed a conceptual framework of HCV vertical transmission, expressed in terms of a mathematical model and based on maternal HCV antibody and viremia. The mathematical model estimated the number of HCV vertical infections nationally and for six subnational areas. Applying two vertical transmission risk estimates to the 2008 Egyptian birth cohort, we estimated that between 3,080 and 5,167 HCV infections resulted from vertical transmission among children born in 2008. HCV vertical transmission may account for half of incident cases in the &lt;5‐year age group. Disproportionately higher proportions of vertical infections were estimated in Lower Rural and Upper Rural subnational areas. This geographical clustering was a result of higher‐area‐level HCV prevalence among women and higher fertility rates. Conclusion : Vertical transmission is one of the primary HCV infection routes among children &lt;5 years in Egypt. The absolute number of vertical transmissions and the young age at infection highlight a public health concern. These findings also emphasize the need to quantify the relative contributions of other transmission routes to HCV incidence in Egypt. (H epatology 2015;61:834–842)
β2 Microglobulin Knockout Mice Are Resistant to Lethal Intraabdominal Sepsis
Authors: Edward R. Sherwood, Cheng Y. Lin, Weike Tao, Christopher A. Hartmann, Jay E. Dujon, Andrew J. French, Tushar K. Varma
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

beta 2 microglobulin knockout (beta2M-/-) mice lack CD8+ T and natural killer T cells. We hypothesized that beta 2M-/- mice are resistant to lethal intraabdominal sepsis. To test this hypothesis, mortality, cytokine production, and physiologic function were assessed in beta 2M-/- mice during sepsis caused by cecal ligation and puncture (CLP). beta 2M-/- mice survived significantly longer than wild-type mice after CLP but ultimately exhibited 100% mortality. Treatment of beta 2M-/- mice with anti-asialoGM1 to deplete natural killer cells conferred greater than 70% long-term survival. Compared with wild-type mice, beta 2M-/- mice treated with anti-asialoGM1 produced decreased amounts of proinflammatory cytokines and did not exhibit hypothermia or metabolic acidosis after CLP. Adoptive transfer of CD8+ T and natural killer cells into beta 2M-/- mice treated with anti-asialoGM1 re-established CLP-induced mortality. CD8 knockout mice treated with anti-asialoGM1, which are specifically deficient in CD8+ T and natural killer cells, exhibited 40% long-term survival after CLP. Furthermore, treatment of wild-type mice with antibodies to CD8 and asialoGM1 conferred a significant survival benefit compared with wild-type mice treated with nonspecific IgG. These findings demonstrate that beta 2M-/- mice treated with anti-asialoGM1 are resistant to CLP-induced mortality and that depletion of CD8+ T and natural killer cells largely accounts for the survival benefit observed in these mice.
SUPPRESSOR CELL FUNCTION IN CHRONIC LIVER DISEASE
Authors: G Robaeys, J De Groote, M Vandeputte, V Barnaba, M Levrero, A Musca, F Balsano, Fabrizio Spinozzi, Ivano Gernini, Roberto Gerli, Antonio Frascarelli, Francesco Rossetti, Francesco Rondoni
Journal: The Lancet (1983)
Extreme blood pressure fluctuations in a patient with intact autonomic reflexes and intact sodium conservation.
Authors: Y M Barri, M C Limacher, C S Wilcox
Journal: Journal of the American Society of Nephrology (1995)

A patient who had episodes of profound hypotension alternating with severe hypertension without an obvious precipitating cause is reported. The hypotensive episodes were accompanied by tiredness, syncope, bradycardia, and a low norepinephrine concentration while supine or standing. In contrast, the hypertensive episodes were associated with marked tachycardia, sweating, anxiety, abdominal pain, and very high levels of plasma norepinephrine concentration. Extensive investigations failed to support a diagnosis of pheochromocytoma. The testing of baroreceptor function and autonomic reflexes was normal. Blood pressure was not salt sensitive. It was concluded that this patient has a unique clinical syndrome of extreme fluctuation of blood pressure and sympathetic nervous activity yet intact cardiovascular reflexes and normal sodium conservation. The abnormal blood pressure regulation most likely has a central origin.