tbuckley/cabot-search huggingface dataset:
Cardiovascular neural regulation explored in the frequency domain.
Authors: A Malliani, M Pagani, F Lombardi, S Cerutti
Journal: Circulation (1991)

A consistent link appears to exist between predominance of vagal or sympathetic activity and predominance of HF or LF oscillations, respectively: RR variability contains both of these rhythms, and their relative powers appear to subserve a reciprocal relation like that commonly found in sympathovagal balance. In this respect, it is our opinion that rhythms and neural components always interact, just like flexor and extensor tones or excitatory and inhibitory cardiovascular reflexes, and that it is misleading to separately consider vagal and sympathetic modulations of heart rate. In humans and experimental animals, functional states likely to be accompanied by an increased sympathetic activity are characterized by a shift of the LF-HF balance in favor of the LF component; the opposite occurs during presumed increases in vagal activity. In addition, LF oscillation evaluated from SAP variability appears to be a convenient marker of the sympathetic modulation of vasomotor activity. Although based on indirect markers, the exploration in the frequency domain of cardiovascular neural regulation might disclose a unitary vision hard to reach through the assemblage of more specific but fragmented pieces of information.
mtDNA Data Indicate a Single Origin for Dogs South of Yangtze River, Less Than 16,300 Years Ago, from Numerous Wolves
Authors: J.-F. Pang, C. Kluetsch, X.-J. Zou, A.-b. Zhang, L.-Y. Luo, H. Angleby, A. Ardalan, C. Ekstrom, A. Skollermo, J. Lundeberg, S. Matsumura, T. Leitner, Y.-P. Zhang, P. Savolainen
Journal: Molecular Biology and Evolution (2009)

There is no generally accepted picture of where, when, and how the domestic dog originated. Previous studies of mitochondrial DNA (mtDNA) have failed to establish the time and precise place of origin because of lack of phylogenetic resolution in the so far studied control region (CR), and inadequate sampling. We therefore analyzed entire mitochondrial genomes for 169 dogs to obtain maximal phylogenetic resolution and the CR for 1,543 dogs across the Old World for a comprehensive picture of geographical diversity. Hereby, a detailed picture of the origins of the dog can for the first time be suggested. We obtained evidence that the dog has a single origin in time and space and an estimation of the time of origin, number of founders, and approximate region, which also gives potential clues about the human culture involved. The analyses showed that dogs universally share a common homogenous gene pool containing 10 major haplogroups. However, the full range of genetic diversity, all 10 haplogroups, was found only in southeastern Asia south of Yangtze River, and diversity decreased following a gradient across Eurasia, through seven haplogroups in Central China and five in North China and Southwest (SW)Asia, down to only four haplogroups in Europe. The mean sequence distance to ancestral haplotypes indicates an origin 5,400-16,300 years ago (ya) from at least 51 female wolf founders. These results indicate that the domestic dog originated in southern China less than 16,300 ya, from several hundred wolves. The place and time coincide approximately with the origin of rice agriculture, suggesting that the dogs may have originated among sedentary hunter-gatherers or early farmers, and the numerous founders indicate that wolf taming was an important culture trait.
Positive and negative factors in defensive medicine: a questionnaire study of general practitioners
Authors: N. Summerton
Journal: BMJ (1995)

(a) To investigate defensive medical practices among general practitioners; (b) to compare any such practices with general practitioners' understanding of certain aspects of the terms of service and medical negligence and practitioners' concerns about the risk of being sued or having a complaint lodged.Postal questionnaire survey. Each questionnaire was followed by a reminder.500 systematically selected general practitioners on the membership list of the Medical Defence Union.Answers to questions on defensive medical practices, understanding of certain aspects of the terms of service and medical negligence, and concerns about the risk of being sued or having a complaint lodged.300 general practitioners returned the questionnaire (response rate 60%). 294 (98%) claimed to have made some practice changes as a result of the possibility of a patient complaining. Of the defensive medical practices adopted, the most common (over half of doctors stating likely or very likely) seemed to be increased diagnostic testing, increased referrals, increased follow up, and more detailed patient explanations and note taking. Respondents practised defensive medicine as a possible consequence of concerns about the risks of being sued or having a complaint lodged. This association was particularly strong for negative defensive practices. Defensive medical practice did not correlate with any misunderstanding about the law of negligence or the general practitioners' terms of service.General practitioners are practising defensive medicine. Some defensive practices such as increased patient explanations or more detailed note taking are clearly beneficial. However, implementing the findings of the Wilson report may increase negative defensive medical practices.
Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element
Authors: Thierry Claudel, Ekkehard Sturm, Hélène Duez, Inés Pineda Torra, Audrey Sirvent, Vladimir Kosykh, Jean-Charles Fruchart, Jean Dallongeville, Dean W. Hum, Folkert Kuipers, Bart Staels
Journal: Journal of Clinical Investigation (2002)

Serum levels of HDL are inversely correlated with the risk of coronary heart disease. The anti-atherogenic effect of HDL is partially mediated by its major protein constituent apoA-I. In this study, we identify bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression. Intrahepatocellular accumulation of bile acids, as seen in patients with progressive familial intrahepatic cholestasis and biliary atresia, was associated with diminished apoA-I serum levels. In human apoA-I transgenic mice, treatment with the FXR agonist taurocholic acid strongly decreased serum concentrations and liver mRNA levels of human apoA-I, which was associated with reduced serum HDL levels. Incubation of human primary hepatocytes and hepatoblastoma HepG2 cells with bile acids resulted in a dose-dependent downregulation of apoA-I expression. Promoter mutation analysis and gel-shift experiments in HepG2 cells demonstrated that bile acid–activated FXR decreases human apoA-I promoter activity by a negative FXR response element mapped to the C site. FXR bound this site and repressed transcription in a manner independent of retinoid X receptor. The nonsteroidal synthetic FXR agonist GW4064 likewise decreased apoA-I mRNA levels and promoter activity in HepG2 cells.
Coronary Artery Pressure and Strength of Right Ventricular Contraction
Authors: PETER F. SALISBURY
Journal: Circulation Research (1955)

Experiments show that the right ventricle is weakened to the point of irreversible failure by decreased coronary artery pressure and also demonstrate that augmented coronary artery pressure can cause a remarkable increment of the right ventricular strength. Both ventricles, even when in otherwise irreversible decompensation, can be restored to full functional competence by various maneuvers which augment coronary blood flow. The studies reported appear to have important clinical applications in the treatment of circulatory disturbances of the right ventricle.
Myelin in multiple sclerosis is developmentally immature.
Authors: M A Moscarello, D D Wood, C Ackerley, C Boulias
Journal: Journal of Clinical Investigation (1994)

The etiology of multiple sclerosis (MS) is considered to involve genetic, environmental, infective, and immunological factors which affect the integrity of a normally assembled myelin sheath, either directly or indirectly resulting in demyelination. In a correlative study involving protein chemical, mass spectrometric, and electron microscopic techniques we have determined that myelin obtained from victims of MS is arrested at the level of the first growth spurt (within the first 6 yr of life) and is therefore developmentally immature. The data supporting this conclusion include (a) the pattern of microheterogeneity of myelin basic protein (MBP); (b) the NH2-terminal acylation of the least cationic component of MBP ("C-8"); (c) the phase transition temperature (Tc) of myelin isolated from victims of MS correlated with the increased proportion of the least cationic component of MBP; and (d) immunogold electron microscopy using an antibody specific for "C-8" showed that the distribution of gold particles in a 2-yr-old infant was similar to the distribution found in a victim of MS. We postulate that this developmentally immature myelin is more susceptible to degradation by one or a combination of factors mentioned above, providing the initial antigenic material to the immune system.
Genetic polymorphism of IGF-I predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy
Authors: K Shitara, S Ito, K Misawa, Y Ito, H Ito, S Hosono, M Watanabe, K Tajima, H Tanaka, K Muro, K Matsuo
Journal: Annals of Oncology (2011)
Isolated Atrioventricular Block in the Fetus
Authors: Håkan Eliasson, Sven-Erik Sonesson, Gurleen Sharland, Fredrik Granath, John M. Simpson, Julene S. Carvalho, Hana Jicinska, Viktor Tomek, Joanna Dangel, Paulo Zielinsky, Maria Respondek-Liberska, Matthias W. Freund, Mats Mellander, Joaquim Bartrons, Helena M. Gardiner
Journal: Circulation (2011)

Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome.We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000-2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1-21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age < 20 weeks, ventricular rate ≤ 50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥ 1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4 ± 2.9 versus 24.9 ± 4.9 weeks; P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy.Risk factors associated with a poor outcome were gestation < 20 weeks, ventricular rate ≤ 50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.
Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab
Authors: David F. McDermott, Charles G. Drake, Mario Sznol, Toni K. Choueiri, John D. Powderly, David C. Smith, Julie R. Brahmer, Richard D. Carvajal, Hans J. Hammers, Igor Puzanov, F. Stephen Hodi, Harriet M. Kluger, Suzanne L. Topalian, Drew M. Pardoll, Jon M. Wigginton, Georgia D. Kollia, Ashok Gupta, Dan McDonald, Vindira Sankar, Jeffrey A. Sosman, Michael B. Atkins
Journal: Journal of Clinical Oncology (2015)

Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts.A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation.Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible.Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.
Effect of n-3 fatty acids from fish oil on hemostasis, blood pressure, and lipid profile of dialysis patients.
Authors: S M Donnelly, M A Ali, D N Churchill
Journal: Journal of the American Society of Nephrology (1992)

Dialysis patients have an inordinate risk of cardiovascular events. Fish oils, rich in n-3 fatty acids, are believed to be beneficial in the prevention of atherosclerosis and thrombosis. Hence, the use of fish oils deserves consideration as a preventative or therapeutic intervention in dialysis patients. The suggestion has been made that n-3 fatty acids could increase the risk of bleeding, and thus, the safety of the use of these agents in dialysis patients must be established before long-term studies are undertaken. This study addresses the effect of n-3 fatty acids on the hemostatic profile of dialysis patients. Sixteen patients on chronic dialysis therapy were randomized to fish oil (MaxEPA) or placebo (olive oil) in a double-blind cross-over study. They received 3.6 g of n-3 fatty acids for 4 wk. Bleeding times were 4.8 +/- 0.4 min on MaxEPA and 4.5 +/- 0.3 min on placebo. Platelet aggregation to low-dose ADP or collagen also remained unchanged. There was a trend to lower serum triglyceride levels (2.7 +/- 0.5 versus 3.4 +/- 0.6 mmol/L, fish oil versus placebo) that did not reach statistical significance. Gastrointestinal side effects occurred in 10 of the 16 subjects and were severe in 5 patients. These side effects occurred in both the olive oil and the fish oil groups. The study had a 95% chance of detecting a clinically doubling significant increase in bleeding time, i.e., beta error less than 5%. In conclusion, n-3 fatty acids do not introduce a clinically important risk of bleeding for patients with end-stage renal disease.
A Paneth cell surrogate?
Authors: C A Rubio
Journal: Gut (2002)

We read with interest the article by Cunliffe et al ( Gut 2001; 48 :176–85) on defensin 5 stored in normal Paneth cells and in metaplastic Paneth cells in inflammatory bowel disease (IBD).

In recent years a great deal of interest has centred around Paneth cells as carriers of innate host defence, effective through their content of antimicrobial peptides and proteins.1 In humans, that mechanism seems to be conveyed by a complex system of proteins present in the granules of the Paneth cells: lysozyme, secretory phospholipase A, and probably α defensins (that is, cyptidins, so far recorded in mice).

The lysozyme rich granules in Paneth cells appears to be one of the main sources of antimicrobial peptide in the normal small bowel …
Abstract 99: Hypotonic Swelling Promotes Nitric Oxide Release in Cardiac Ventricular Myocytes
Authors: Luis Gonano, Malena Morell, Juan I Burgos, Martin Vila Petroff
Journal: Circulation Research (2014)

Cardiac myocyte swelling occurs in multiple pathological situations and in particular contributes to the deleterious effects of ischemia and reperfusion by promoting contractile dysfunction. We investigated whether hypotonic swelling promotes nitric oxide (NO) release in cardiac myocytes and if so, whether it impacts on swelling induced contractile dysfunction. Perfusing rat cardiac myocytes, loaded with the NO sensor DAF-FM, with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient amplitude and significantly increased DAF-FM fluorescence. When cells were exposed to the HS supplemented with 2.5 mM of the NO synthase inhibitor L-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the NOS1 inhibitor, Nitroguanidine. In addition, Colchicine (an inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either L-NAME, Nitroguandine or the guanylate cyclase inhibitor, ODQ, suggesting that NOS1-derived NO provides contractile support via a GMP-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and the HS-induced increment in ryanodine receptor (RyR2) phosphorylation at site Ser2808 suggesting that in the context of hypotonic swelling, cGMP may contribute to preserve contractile function by enhancing SR Ca2+ release. Our findings suggest a novel mechanism for NO release in cardiac myocytes with putative pathophysiological relevance in the context of ischemia and reperfusion, where it may be cardioprotective by reducing the extent of contractile dysfunction associated with hypotonic swelling.
Early Relapses, Onset of Progression, and Late Outcome in Multiple Sclerosis
Authors: Antonio Scalfari, Anneke Neuhaus, Martin Daumer, Gabriele C. DeLuca, Paolo A. Muraro, George C. Ebers
Journal: JAMA Neurology (2012)

To investigate the relationship among attacks in the first 2 years (early relapses), secondary progression (SP), and late disability in multiple sclerosis (MS).Cohort study with follow-up of 28 years.Referral MS center.Patients (N=730) with relapsing-remitting MS diagnosed according to Poser criteria, from the database of the London Multiple Sclerosis Clinic, London, Ontario, Canada.Long-term evolution of patients with high (≥ 3 attacks) and early (within the first 2 years of the disease) frequency of relapses. In the total SP population and in patients grouped by numbers of early relapses, we assessed the predictive effect of latency to progression (time to SP) on times to attain cane requirement (Disability Status Scale score of 6 [DSS 6]) and bedridden status (DSS 8).Among the group with frequent early relapses (n=158), outcomes were variable. Although 103 (65.2%) experienced rapid conversion to SP MS (median duration, 5 years) and rapidly attained DSS 6 and DSS 8 scores (7 and 17 years, respectively), the remainder (n=55) did not enter the SP phase, despite adverse early relapse features. Among the total SP population, longer latency to progression was associated with lower probability of attaining DSS 6 (odds ratio, 0.76 [95% CI, 0.69-0.84] and 0.44 [95% CI, 0.37-0.52] for 5- and 15-year latency, respectively) and longer times to severe disability. The same association between time to onset of SP and late outcomes was observed even in patients matched by number of early attacks. However, duration of the relapsing-remitting phase did not influence the times from SP onset to DSS levels.Our results indicate dissociation between early inflammatory attacks and onset of the SP phase and further question the validity of relapse frequency as a surrogate marker for late disability. Among the group with frequent early relapses, we observed a large variability of outcomes, ranging from one extreme to the opposite.
Allergen avoidance in a day‐care center
Authors: A. K. M. Munir, R. Einarsson, S. Dreborg
Journal: Allergy (1996)

The predominant sensitizing allergens in Swedish asthmatic children are furred pet animals. Poor ventilation and increased indoor humidity cause accumulation of pet allergens indoors. Indirect contacts with cats also increase pet allergen exposure. We investigated whether the concentration and the total amount of cat ( Fel d I) and dog ( Can f I) allergen in dust from various surfaces in a day‐care center were influenced by extensive renovation, installation of a new ventilation system, ventilation of floors, and avoidance by families and personnel of direct and indirect contacts with pets. The cleaning routine in the day‐care center was changed extensively after renovation. Old mattresses, pillowcases, curtains, sofas, and soft toys were removed, and new materials were purchased. Dust was collected from various surfaces before and after renovation from table and chair surfaces, floors, curtains, mattresses, pillows, cushion‐like toys, and sofas on five occasions during a 12‐month period. Fel d I and Can f I allergen levels were determined by sandwich ELISA. The reduction in the total amount of both Fel d I and Can f I/sampling area was more pronounced than the reduction in the concentration of allergen/g of dust. After renovation, the mean cat and dog allergen concentration was decreased by six and 10 times, respectively. After 1 year, the total amount of cat allergen was lower in all areas (from 24 ng to&lt;1 ng/sampling area, P&lt; 0.05). Already at the first sampling after renovation, the total amount of dog allergen had decreased more than 10 times. In a previous study, we found the median concentration of cat and dog allergen to be 10–30 times higher in ordinary day‐care centers. Our present study demonstrates that children changing from a normal center to the renovated center would be exposed to much lower levels of cat and dog allergen. Combined measures such as installation of mechanical ventilation, ventilated floors, regular extensive cleaning, and, probably most important, avoidance of direct and indirect contacts with pets, should decrease cat and dog allergen exposure in day‐care centers.
Immunosuppressive Protein Expression on Tumor and the Presence of Immune Cells Within Tumor Microenvironment in Curatively Resected Gastric Cancer
Authors: Kim Jin Won, Nam Kyung Han, Lee Hye Seung, Ahn Sang-Hoon, Park Do Joong, Kim Hyung-Ho, Kim Se-Hyun, Lee Jeong-Ok, Kim Yu Jung, Lee Keun-Wook, Kim Jee Hyun, Bang Soo-Mee, Lee Jong Seok
Journal: Annals of Oncology (2014)