tbuckley/cabot-search huggingface dataset:
Low dose interferon alfa-2b for chronic hepatitis B in Asian countries.
Authors: E Mauracher
Journal: Gut (1993)

In a study of low dose interferon alfa-2b in 587 patients expected to show a good response to treatment, 76-87% patients in different countries had alanine amino-transferase activities returned to normal after four months9 treatment, 49-72% were negative for hepatitis B virus (HBV)-DNA, 51-66% were negative for hepatitis B e antigen (HBeAg), and 44-62% were anti-HBe positive. These effects were maintained after nine to 12 months9 follow up. Side effects were mild, but led to discontinuation of treatment in 12 patients.
Irinotecan in Combination With Fluorouracil in a 48-Hour Continuous Infusion As First-Line Chemotherapy for Elderly Patients With Metastatic Colorectal Cancer: A Spanish Cooperative Group for the Treatment of Digestive Tumors Study
Authors: Javier Sastre, Eugenio Marcuello, Bartomeu Masutti, Matilde Navarro, Silvia Gil, Antonio Antón, Albert Abad, Enrique Aranda, Joan Maurel, Manuel Valladares, Inmaculada Maestu, Alfredo Carrato, José María Vicent, Eduardo Díaz-Rubio
Journal: Journal of Clinical Oncology (2005)

Purpose Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. Patients and Methods Patients ≥ 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m 2 plus FU 3,000 mg/m 2 in a 48-hour continuous infusion. Results By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. Conclusion Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.
Role of the Reelin Signaling Pathway in Central Nervous System Development
Authors: Dennis S Rice, Tom Curran
Journal: Annual Review of Neuroscience (2001)

The neurological mutant mouse reeler has played a critical role in the evolution of our understanding of normal brain development. From the earliest neuroanatomic studies of reeler, it was anticipated that the characterization of the gene responsible would elucidate important molecular and cellular principles governing cell positioning and the formation of synaptic circuits in the developing brain. Indeed, the identification of reelin has challenged many of our previous notions and has led to a new vision of the events involved in the migration of neurons. Several neuronal populations throughout the brain secrete Reelin, which binds to transmembrane receptors located on adjacent cells triggering a tyrosine kinase cascade. This allows neurons to complete migration and adopt their ultimate positions in laminar structures in the central nervous system. Recent studies have also suggested a role for the Reelin pathway in axonal branching, synaptogenesis, and pathology underlying neurodegeneration.
Comparing the Number of R-Chop-Like Therapy Cycles (6 Vs. 8 Cycles) for Dlbcl Using Propensity Score-Modified Analysis
Authors: Hirotsugu Ariizumi, Bungo Saito, Yui Uto, Norimichi Hattori, Kouji Yanagisawa, Hidetoshi Nakashima, Hiroshi Harada, Hiraku Mori, Tsuyoshi Nakamaki
Journal: Annals of Oncology (2014)
SOME APPLICATIONS OF PHYSIOLOGY TO MEDICINE: IV.--HIGH BLOOD PRESSURE FROM THE PHYSIOLOGICAL ASPECT
Authors: J. A. MacWilliam
Journal: BMJ (1927)

From the Physiological Laboratory.) present writer22 on the remarkable rise of pressure that may be associated with disturbed sleep, exciting dreams of motor effort, nightmares, etc., afford ani explanation.In contrast with the definite low-ering of pressure attend- ing on sound sleep, the steep rise during disturbed sleep" may reach ani elevation attaiined in the same individual.in the wakinig state onily during vigorous or eveni violent muscular exertion-for example, systolic pressure rises to 182 and 200 mm.from normal levels of 125 to 130 mm.
Ryanodine wastes oxygen consumption for Ca2+ handling in the dog heart. A new pathological heart model.
Authors: T Takasago, Y Goto, O Kawaguchi, K Hata, A Saeki, T Nishioka, H Suga
Journal: Journal of Clinical Investigation (1993)

Ryanodine (RYA) at a low concentration (several tens of nM) is known to selectively bind to Ca2+ release channels in sarcoplasmic reticulum (SR) and to fix them open. The present study was designed to investigate the effects of the selective change in Ca2+ release channel activity on cardiac mechanoenergetics as a model of Ca(2+)-leaky SR observed in pathological hearts. We analyzed the negative inotropic effect of RYA at a low concentration (up to 30 +/- 13 nM) on left ventricular (LV) mechanoenergetics using frameworks of LV Emax (a contractility index) and the myocardial oxygen consumption (LV VO2)-systolic pressure-volume area (PVA) (a measure of total mechanical energy) relation in 11 isolated, blood-perfused dog hearts. RYA significantly decreased Emax by 42%, whereas PVA-independent VO2 remained disproportionately high (93% of control). This oxygen-wasting effect of RYA was quite different from ordinary inotropic drugs, which alter Emax and PVA-independent VO2 proportionally. The present result suggests that RYA suppresses force generation of cardiac muscle for a given amount of total sequestered Ca2+ by SR in a similar way to myocardial ischemia and stunning. We speculate about the underlying mechanism that RYA makes SR leaky for Ca2+ and thereby wastes energy for Ca2+ handling by SR.
Substrate Ambiguous Enzymes within the Escherichia coli Proteome Offer Different Evolutionary Solutions to the Same Problem
Authors: Sylvia Hsu-Chen Yip, Ichiro Matsumura
Journal: Molecular Biology and Evolution (2013)

Many enzymes exhibit some catalytic promiscuity or substrate ambiguity.These weak activities do not affect the fitness of the organism under ordinary circumstances, but can serve as potential evolutionary precursors of new catalytic functions.We wondered whether different proteins with the same substrate ambiguous activity evolve differently under identical selection conditions.
Serial Measurement of Cardiac Troponin T Using a Highly Sensitive Assay in Patients With Chronic Heart Failure
Authors: Serge Masson, Inder Anand, Chiara Favero, Simona Barlera, Tarcisio Vago, Federico Bertocchi, Aldo P. Maggioni, Luigi Tavazzi, Gianni Tognoni, Jay N. Cohn, Roberto Latini
Journal: Circulation (2011)

Cardiac troponins are emerging as important prognostic markers in chronic cardiovascular conditions like stable coronary artery disease or chronic heart failure (HF). Less is known about the relation between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and future events in HF. We determined the association between changes over time in hs-cTnT and outcome in patients with chronic HF.We analyzed 5284 patients with chronic HF from 2 independent randomized clinical trials, the Valsartan Heart Failure Trial (Val-HeFT) (n=4053) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial (n=1231). hs-cTnT was measured at randomization and after 3 months (GISSI-HF) or 4 months of follow-up (Val-HeFT). The association between changes over time of hs-cTnT and various outcomes was tested in multivariable models. In both studies, increases in hs-cTnT levels over time were associated with age, diabetes mellitus, worsening of renal function (reduction in estimated glomerular filtration rate), and baseline and increases in N-terminal pro-brain natriuretic peptide concentrations. Increases in hs-cTnT concentrations were associated with all-cause mortality (incidence rates, 8.19 [7.51-8.88] and 6.79 [5.98-7.61] per 100 person-years in Val-HeFT and GISSI-HF, respectively, with hazard ratios [95% confidence intervals] of 1.59 [1.39-1.82] and 1.88 [1.50-2.35]) after adjustment for conventional risk factors and baseline levels of hs-cTnT and N-terminal pro-brain natriuretic peptide. Changes in hs-cTnT concentration modestly improved prognostic discrimination beyond baseline values for fatal outcomes only.Despite very low circulating concentrations, changes in hs-cTnT concentrations over time are robust predictors of future cardiovascular events in patients with chronic HF but add limited prognostic discrimination.http://www.clinicaltrials.gov. Unique identifier: NCT00336336.
THE BUFFERING PROPERTIES OF KERATIN SCRAPINGS.
Authors: G. B. DOWLING, P. F. D. NAYLOR
Journal: British Journal of Dermatology (1960)

Journal Article THE BUFFERING PROPERTIES OF KERATIN SCRAPINGS. Get access G. B. DOWLING, G. B. DOWLING Department of Medicine, St. Thomas's Hospital Medical School, and Department of Dermatology, St. Thomas's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar P. F. D. NAYLOR P. F. D. NAYLOR Department of Medicine, St. Thomas's Hospital Medical School, and Department of Dermatology, St. Thomas's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 72, Issue 2, 1 February 1960, Pages 51–56, https://doi.org/10.1111/j.1365-2133.1960.tb13844.x Published: 01 February 1960
727 LONG-TERM EFFICACY AND IMPACT ON HEPATOCELLULAR CARCINOMA DEVELOPMENT OF NUCLEOSIDE ANALOGUE TREATMENT WITH LAMIVUDINE AND ENTECAVIR FOR CHRONIC HEPATITIS B AND CIRRHOSIS
Authors: H. Kobashi, Y. Miyake, F. Ikeda, T. Yasunaka, K. Nishino, A. Moriya, J.-I. Kubota, S. Nakamura, A. Takaki, K. Nouso, G. Yamada, K. Yamamoto
Journal: Journal of Hepatology (2011)
The role of negativity bias in political judgment: A cultural neuroscience perspective
Authors: Narun Pornpattananangkul, Bobby K. Cheon, Joan Y. Chiao
Journal: Behavioral and Brain Sciences (2014)

Abstract Hibbing et al. provide a comprehensive overview of how being susceptible to heightened sensitivity to threat may lead to conservative ideologies. Yet, an emerging literature in social and cultural neuroscience shows the importance of genetic and cultural factors on negativity biases. Promising avenues for future investigation may include examining the bidirectional relationship of conservatism across multiple levels of analysis.
The Clinical Significance of Asymmetric Dimethylarginine
Authors: Michiel P. C. Siroen, Tom Teerlink, Robert J. Nijveldt, Hubert A. Prins, Milan C. Richir, Paul A.M. van Leeuwen
Journal: Annual Review of Nutrition (2006)

▪ Abstract In 1992, asymmetrical dimethylarginine (ADMA) was first described as an endogenous inhibitor of the arginine-nitric oxide (NO) pathway. From then, its role in regulating NO production has attracted increasing attention. Nowadays, ADMA is regarded as a novel cardiovascular risk factor. The role of the kidney and the liver in the metabolism of ADMA has been extensively studied and both organs have proven to play a key role in the elimination of ADMA. Although the liver removes ADMA exclusively via degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), the kidney uses both metabolic degradation via DDAH and urinary excretion to eliminate ADMA. Modulating activity and/or expression of DDAH is still under research and may be a potential therapeutic approach to influence ADMA plasma levels. Interestingly, next to its association with cardiovascular disease, ADMA also seems to play a role in other clinical conditions, such as critical illness, hepatic failure, and preeclampsia. To elucidate the clinical significance of ADMA in these conditions, the field of research must be enlarged.
CITED4 Inhibits Hypoxia-Activated Transcription in Cancer Cells, and Its Cytoplasmic Location in Breast Cancer Is Associated with Elevated Expression of Tumor Cell Hypoxia-Inducible Factor 1α
Authors: Stephen B. Fox, José Bragança, Helen Turley, Leticia Campo, Cheng Han, Kevin C. Gatter, Shoumo Bhattacharya, Adrian L. Harris
Journal: Cancer Research (2004)

Abstract The interaction of hypoxia-inducible factor 1α and the CH1 domain of the transcriptional coactivator p300/CBP is necessary for the expression of hypoxia responsive genes and tumor angiogenesis. The transcription factor CITED2 binds p300/CBP at the CH1 domain and functions as a negative regulator of hypoxia signaling by competing with hypoxia-inducible factor 1α. CITED4, a recently identified member of the CITED family, binds p300/CBP via the CH1 domain and functions as a coactivator for transcription factor AP-2. Here, we show that CITED4 blocks the binding of hypoxia-inducible factor 1α to p300 in vitro and inhibits hypoxia-inducible factor-1α transactivation and hypoxia-mediated reporter gene activation. These studies suggest that CITED4 might function as an inhibitor of hypoxia-inducible factor 1α. To explore the function of CITED4 in breast cancer, we determined its expression in normal, in situ and invasive breast cancers. We also correlated its expression in 286 invasive breast tumors with clinicopathological, hypoxia markers and survival. In contrast to the nuclear localization of CITED4 in normal breast tissue, breast tumors were characterized by cytoplasmic and nuclear localization. Nuclear CITED4 expression was significantly inversely associated with tumor hypoxia-inducible factor 1α (P &amp;lt; 0.05), tumor size (P = 0.03), tumor grade (P = 0.0001), and Chalkley vessel count (P = 0.04). CITED4 showed no significant correlation with patient age (P = 0.45), estrogen receptor (P = 0.11), or epidermal growth factor receptor (P = 0.48). These results show that breast cancer development is characterized by either nuclear loss or cytoplasmic translocation of CITED4, with consequent loss of hypoxia-inducible factor-1α transcriptional antagonist activity. This may be an important mechanism by which tumors enhance hypoxia-inducible factor expression and result in an aggressive phenotype.
Functional p38 MAPK Identified by Biomarker Profiling of Pancreatic Cancer Restrains Growth through JNK Inhibition and Correlates with Improved Survival
Authors: Yi Zhong, Yoshiki Naito, Leslie Cope, Salvador Naranjo-Suarez, Tyler Saunders, Seung-Mo Hong, Michael G. Goggins, Joseph M. Herman, Christopher L. Wolfgang, Christine A. Iacobuzio-Donahue
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Numerous biomarkers for pancreatic cancer have been reported. We determined the extent to which such biomarkers are expressed throughout metastatic progression, including those that effectively predict biologic behavior. Experimental Design: Biomarker profiling was performed for 35 oncoproteins in matched primary and metastatic pancreatic cancer tissues from 36 rapid autopsy patients. Proteins of significance were validated by immunolabeling in an independent sample set, and functional studies were performed in vitro and in vivo. Results: Most biomarkers were similarly expressed or lost in expression in most samples analyzed, and the matched primary and metastases from a specific patient were most similar to each other than to other patients. However, a subset of proteins showed extensive interpatient heterogeneity, one of which was p38 MAPK. Strong positive pp38 MAPK immunolabeling was significantly correlated with improved postresection survival by multivariate analysis (median overall survival 27.9 months, P = 0.041). In pancreatic cancer cells, inhibition of functional p38 by SB202190 increased cell proliferation in vitro in both low-serum and low-oxygen conditions. High functional p38 activity in vitro corresponded to lower levels of pJNK protein expression, and p38 inhibition resulted in increased pJNK and pMKK7 by Western blot analysis. Moreover, JNK inhibition by SP600125 or MKK7 siRNA knockdown antagonized the effects of p38 inhibition by SB202190. In vivo, SP600125 significantly decreased growth rates of xenografts with high p38 activity compared with those without p38 expression. Conclusions: Functional p38 MAPK activity contributes to overall survival through JNK signaling, thus providing a rationale for JNK inhibition in pancreatic cancer management. Clin Cancer Res; 20(23); 6200–11. ©2014 AACR.
Case Number 27: Jaw claudication in Takayasu's disease
Authors: S E R Jeurissen, L Liauw, L N A Willems, T W J Huizinga
Journal: Annals of the Rheumatic Diseases (2003)

A 30 year old woman presented with a three week history of symmetrical jaw claudication and episodes of pain in the left arm with a blue discolouration and loss of strength. Two years previously she was given a tentative diagnosis of Takayasu’s disease after multiple large arterial vascular problems and …
EXPERIMENTALLY PRODUCED PSYCHOSES
Authors: PAUL H. HOCH
Journal: American Journal of Psychiatry (1951)

Intravenous injection of synthetic mescaline was used in a group of schizophrenic patients and on "normal" voluntary controls. The changes produced by mescaline in "normals" were described. In addition, the observations were made that mescaline is able to underscore in patients suffering from schizophrenia their schizophrenic symptoms or able to precipitate schizophrenic psychoses in persons suffering from latent schizophrenia. Different "therapeutic measures" were discussed as applied to the mescaline-produced abnormal mental states. Mescaline was also given to a number of patients before and after psychosurgery. It was found that with mescaline it was possible to reactivate the psychosis in patients who improved after psychosurgery but that their response to the drug was quantitatively less conspicuous than before.
Associations Between Kveim Test Results, Previous B.C.G. Vaccination, and Tuberculin Sensitivity in Healthy Young Adults
Authors: P. D. Hart, D. N. Mitchell, I. Sutherland
Journal: BMJ (1964)

A trial of tuberculosis vaccines in more than 54,000 adolescents, nearly all aged 14 to 5l years and attending school in urban or suburban areas, was started in England in 1950-2 (Medical Research Council, 1956, 1959, 1963).Those found to be tuberculin-negative on entry to the trial-that is, with no induration, or one of less than 5 mm., both to 3 and to 100 tuberculin units (T.U.) of Old Tuberculin-were vaccinated with B.C.G. or vole-bacillus vaccine or left unvaccinated, according to a method of random allocation.All the participants, including those who were tuberculin-positive to 3 or to 100 T.U.initially, were followed up intensively, with annual postal inquiries, home visits, radiographic examinations, and tuberculin tests, until September 1960 (which represented an average period of 8.8 years).Of the tuberculin-negative participants, 13,598 were allocated to the B.C.G.-vaccinated group.All had had a clear chest radiograph immediately before vaccination, and just over half, not selected in any special way, had further tuberculin tests within a year after vaccination (nearly all within six months) ; of these, 17 (0.23%) were still negative to 100 T.U. ; the remainder * From the Medical Research Council's Tuberculosis and Statistical Re- search Units, M.R.C. Laboratories, Hampstead, London.trial participants, not in the 52, whose first post-vaccination tuberculin test with 100 T.U.showed 5-9 mm.induration and who had never shown larger reactions subsequently.Thus, in all, 19 originally non-converted subjects were avail- able for the second B.C.G. vaccination and the subsequent No.
The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families
Authors: C. J. Grocock, V. Rebours, M. N. Delhaye, A. Andren-Sandberg, F. U. Weiss, R. Mountford, M. J. Harcus, E. Niemczyck, L. J. Vitone, S. Dodd, M. T. Jorgensen, R. W. Ammann, O. Schaffalitzky de Muckadell, J. V. Butler, P. Burgess, B. Kerr, R. Charnley, R. Sutton, M. G. Raraty, J. Deviere, D. C. Whitcomb, J. P. Neoptolemos, P. Levy, M. M. Lerch, W. Greenhalf
Journal: Gut (2009)

<h3>Objective</h3> To characterise the phenotypes associated with the p.A16V mutation of <i>PRSS1</i>. <h3>Design</h3> Clinical and epidemiological data were collected for any family in which a p.A16V mutation was identified, either referred directly to the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer or via a collaborator. DNA samples were tested for mutations in <i>PRSS1</i>, <i>SPINK1</i>, <i>CFTR</i> and <i>CTRC</i>. <h3>Patients</h3> Participants were recruited on the basis of either family history of pancreatitis (acute or chronic) or the results of genetic testing. Families were categorised as having hereditary pancreatitis (HP), idiopathic disease or pancreatitis in a single generation. HP was defined as ≥2 cases in ≥2 generations. <h3>Main outcome measures</h3> Onset of painful episodes of pancreatitis, death from pancreatic cancer, diagnosis of diabetes mellitus and exocrine pancreatic failure. <h3>Results</h3> Ten families with p.A16V mutations were identified (22 affected individuals): six HP families, three with idiopathic disease and one with only a single generation affected. The median age of onset, ignoring non-penetrants, was 10 years (95% CI 5 to 25). There were eight confirmed cases of exocrine failure, four of whom also had diabetes mellitus. There were three pancreatic cancer cases. Two of these were confirmed as p.A16V carriers, only one of whom was affected by pancreatitis. Those with p.A16V pancreatitis were compared to affected individuals with p.R122H, p.N29I and no <i>PRSS1</i> mutation. No significant differences were proven using logrank or Mann–Whitney U tests. <h3>Conclusions</h3> Penetrance of p.A16V is highly variable and family dependent, suggesting it contributes to multigenic inheritance of a predisposition to pancreatitis.