tbuckley/cabot-search huggingface dataset:
Subcutaneous vitamin E ameliorates liver injury in anin vivo model of steatocholestasis
Authors: Jason S. Soden, Michael W. Devereaux, Joel E. Haas, Eric Gumpricht, Rolf Dahl, Jane Gralla, Maret G. Traber, Ronald J. Sokol
Journal: Hepatology (2007)

Several genetic metabolic liver diseases share the pathological features of combined steatosis and cholestasis, or steatocholestasis. The aims of this study were to develop and characterize an in vivo model for steatocholestasis and to evaluate the effects of an antioxidant treatment on liver injury, oxidative stress, and mitochondrial perturbations in this model. Obese and lean Zucker rats received intravenous (IV) injections of glycochenodeoxycholic acid (GCDC) and were killed 4 hours later. Liver enzymes were measured; the liver histology was assessed, and hepatic mitochondria were analyzed for mitochondrial lipid peroxidation. In separate experiments, rats received daily injections of subcutaneous (SQ) vitamin E before GCDC infusion. Bile acid-induced injury (serum AST and ALT and liver histology) was more severe in the obese rats than in the lean rats, characterized predominantly by extensive cell necrosis with minimal evidence of apoptosis. SQ vitamin E provided significant protection against IV GCDC-induced hepatic injury, in vitro GCDC-induced permeability transition, and cytochrome C and apoptosis-inducing factor release from isolated mitochondria.Steatosis sensitizes the liver to bile acid-induced necrotic hepatocyte injury, which is responsive to vitamin E therapy.
Analyzing and minimizing PCR amplification bias in Illumina sequencing libraries
Authors: Daniel Aird, Michael G Ross, Wei-Sheng Chen, Maxwell Danielsson, Timothy Fennell, Carsten Russ, David B Jaffe, Chad Nusbaum, Andreas Gnirke
Journal: Genome biology (2011)

Abstract Despite the ever-increasing output of Illumina sequencing data, loci with extreme base compositions are often under-represented or absent. To evaluate sources of base-composition bias, we traced genomic sequences ranging from 6% to 90% GC through the process by quantitative PCR. We identified PCR during library preparation as a principal source of bias and optimized the conditions. Our improved protocol significantly reduces amplification bias and minimizes the previously severe effects of PCR instrument and temperature ramp rate.
Modulation of Peroxidation in Murine Melanoma by Dietary Tyrosine-Phenylalanine Restriction, Levodopa Methylester Chemotherapy, and Sodium Ascorbate Supplementation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H F Pierson, G G Meadows
Journal: JNCI Journal of the National Cancer Institute (1985)

Treatment with the drug combination of levodopa methylester and benserazide, supplemental ascorbate, and dietary deficiencies of tyrosine and phenylalanine more than doubled the median survival time of female (C57BL/6 X DBA/2)F1 mice bearing B16 melanoma tumors. The mechanism for this antitumor effect was not well defined. This study was designed to test the hypothesis that the antitumor activity of levodopa methylester and ascorbate against B16 melanoma is related to the generation of free radicals of oxygen, which peroxidize lipid constituents of cell membranes leading to cell death. As an indication of lipid peroxidation, the individual and combined effects of drug treatment and ascorbate supplementation on host and tumor malondialdehyde levels were examined in mice fed one of three test diets (commercial, purified, or deficient) containing decreasing amounts of tyrosine and phenylalanine. Malondialdehyde levels were increased in the livers of all untreated tumor-bearing mice, which suggests that the tumor alters host antioxidant defenses. Drug treatment and ascorbate supplementation alone and in combination increased hepatic malondialdehyde levels inversely to the amounts of tyrosine and phenylalanine in the diet, and the effects of drug and ascorbate on malondialdehyde levels were additive. Plasma levels remained unchanged by drug treatment, ascorbate supplementation, or tumors in mice fed the commercial or purified diets. Higher levels were observed only in tumor-bearing mice fed the deficient diet and given both drug treatment and ascorbate supplementation. Changes in tumor malondialdehyde levels generally correlated with the effects of the drug and ascorbate on survival time of mice bearing B16 melanoma. Tumors from mice fed the commercial diet accumulated little malondialdehyde, and therapy was relatively ineffective in this dietary group. In mice fed purified or deficient diets, drug treatment and ascorbate supplementation alone increased survival and tumor malondialdehyde levels, but the level of peroxidation in mice receiving the ascorbate supplementation was low compared to its greater antitumor effect on B16 melanoma. Although ascorbate enhanced the peroxidative activity of the drug on B16 melanoma tumors, the effects of the drug and ascorbate on malondialdehyde levels were not additive. Ascorbate enhanced survival of tumor-bearing mice that were fed the deficient diet and that were treated with drug, which indicated that ascorbate supplementation acted via other mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
Is chondroitin sulfate plus glucosamine superior to placebo in the treatment of knee osteoarthritis?
Authors: Chao Zeng, Jie Wei, Guang-hua Lei
Journal: Annals of the Rheumatic Diseases (2015)

We read with interest the article by Hochberg et al 1 related to the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain. The study suggested that CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months with a good safety profile. These results were ‘promising’. We really appreciate the work that was done by the authors. However, there are worthwhile issues that need to be explored.

The study was designed as a non-inferiority trial without placebo arm. The authors explained that, ‘The use of a placebo group was not considered …
Endobronchial ultrasound for the diagnosis of pheripheral pulmonary lesions. A controlled study With fluoroscopy
Authors: Albert Sánchez-Font, Iván Vollmer, Lara Pijuan, Laia Giralt, Víctor Curull
Journal: European Respiratory Journal (2013)

Introduction:  Fluoroscopy-guided bronchoscopy is usually performed for the diagnosis of peripheral pulmonary lesions (PPLs), but the diagnostic yield varies widely among studies. Endobronchial ultrasound (EBUS) can increase the diagnostic yield of bronchoscopic diagnosis of PPLs.  Objective:  A prospective randomized controlled trial involving two diagnostic arms: fluoroscopy-guided bronchoscopy and EBUS plus fluoroscopy guidance.  Methods:  All patients who underwent bronchoscopy to study PPLs from January 2009 to December 2012 were prospectively included. One hundred and forty-five consecutive patients were randomly distributed in two groups: EBUS plus fluoroscopy (50 patients, 71.3 ± 8.2 years) or fluoroscopy alone (95 patients, 68 ± 10.5 years). The mean diameter of the lesion was 41.9 ± 19.2 mm. Bronchial washing, cytological brushing and transbronchial biopsies were obtained. EBUS was performed using a 20-MHz radial miniprobe into a guide-seath. Bronchoscopist, cytologist, study protocol, techniques and tools were the same ones in two arms.  Results:  One hundred and twenty-nine (89%) patients had malignant disease. A diagnosis with bronchoscopy was established in 104 (71.7%) patients. EBUS plus fluoroscopy obtained a diagnostic yield in 78% of patients and fluoroscopy alone in 69.5% (ns). In contrast, for lesions smaller than 30 mm, EBUS plus fluoroscopy guidance provided significantly greater diagnostic performance than fluoroscopy alone (90 vs. 52%;  p =0.05). There were no significant complications related with procedures.  Conclusions:  Bronchoscopy under EBUS plus fluoroscopy guidance improved the diagnostic yield of PPLs in lesions smaller than 30 mm in diameter.
Finite entecavir therapy is a feasible alternative to indefinite therapy
Authors: Wen-Juei Jeng
Journal: Hepatology (2014)

We highly appreciate the editorial comments of Dr. Reijnders and Janssen1 on our study concerning off-therapy durability of response to entecavir therapy published in the December issue of Hepatology.2 They raised several points requiring clarification or further discussion. First, 193 patients were excluded because their off-therapy duration was <48 weeks, although they had not encountered clinical relapse. With this, the relapse rate may be overestimated, at least not underestimated. Second, our current estimates show that the cumulative incidence of relapse rate does increase slightly from 45% at 1 year to 54% at 2 year, minimally to 57% at 3 years, and no more up to now. Third, using baseline hepatitis B virus (HBV) DNA >2 × 105 IU/mL as the predictor of the off-therapy relapse, the sensitivity was 79% and the specificity was 42.3%. Although the rates are not high enough, it was the only factor for clinical relapse in logistic analysis (P = 0.012), and was able to carefully discriminate the cumulative incidence of clinical relapse (53 versus 29%, P = 0.036), as shown in fig. 2 of the article.2 Fourth, they seem to suggest that clinical relapse occurred in approximately one-third of the patients, while longer consolidation duration is still too high. However, two-thirds of the patients had sustained remission and free of medication is in fact a very promising finding to practicing physicians. The finding also indicates that the glass is not half empty! Fifth, indeed the spontaneous remission rate (21%) and hepatitis B virus surface antigen (HBsAg) clearance rate (4.2%) of our patients with clinical relapse was lower than 55% and 39%, respectively, in the patients of Hadziyannis et al.3 Besides much longer maintained remission in that study, different genotype and duration of HBV infection (perinatal versus horizontal) may also play some role in these differences. However, it remains to be studied using head-to-head comparisons. We have to emphasize that cirrhosis patients did not have a higher relapse rate and only one who failed to follow the monitoring schedule developed decompensation. This speaks against the notion that all cirrhosis patients require indefinite therapy if proper monitoring is provided. In conclusion, discontinuing entecavir therapy in HBeAg-negative patients by the stopping rule of Asian-Pacific guidelines4 is a feasible alternative to indefinite therapy, even in cirrhosis patients if proper off-therapy monitoring is provided. Wen-Juei Jeng, M.D.1-3 1Liver Research Unit, Chang Gung Memorial HospitalTaipei, Taiwan 2Division of Hepatology, Department of Hepatology and Gastroenterology, Linkou Medical CenterChang Gung Memorial Hospital, Taipei, Taiwan 3College of Medicine, Chang Gung UniversityTaipei, Taiwan
Hiatus hernia and coronary disease
Authors: D. E. Bedford
Journal: BMJ (1967)

SIR,-Your leading article "Postoperative Gas Gangrene " (14 October, p. 68) is a timely reminder of the unexpected and, fortunately, unusual risk run by the patient after surgery.This risk exists despite exhaustive efforts to control the environmental and personal sources of Clostridium welchii.I believe clostridial cellulitis and myositis occur more commonly than is realized.Since the opening of a small hyperbaric oxygen unit three years ago 16 cases of postoperative and post-traumatic gas gangrene have been admitted from a relatively small population.Answers from a group of ortho- paedic surgeons indicated that more than 50 cases had occurred in a population of three million in five years.You state that gas gangrene is a rare and terrifying disease, as indeed many diseases have been prior to methods of control.Gas gangrene, however, has yielded over the last 10 years to a most effective form of treatment, hyperbaric oxygen, first reported by Boerema.' Van Zyl,' reporting on 200
Expression of the Na-K-2Cl cotransporter by macula densa and thick ascending limb cells of rat and rabbit nephron.
Authors: N Obermüller, S Kunchaparty, D H Ellison, S Bachmann
Journal: Journal of Clinical Investigation (1996)

Sodium and chloride transport by the macula densa and thick ascending limb of Henle's loop participates importantly in extracellular fluid volume homeostasis, urinary concentration and dilution, control of glomerular filtration, and control of renal hemodynamics. Transepithelial Na and Cl transport across the apical membrane of thick ascending limb (TALH) cells is mediated predominantly by a loop diuretic sensitive Na-K-2Cl cotransport pathway. The corresponding transport protein has recently been cloned. Functional studies suggest that the cotransporter is expressed by macula densa cells as well as by TALH cells. The current studies were designed to identify sites of Na-K-2Cl cotransporter expression along distal nephron in rabbit and rat. Non-isotopic high-resolution in situ hybridization, using an antisense probe for the apical form of the Na-K-2Cl cotransporter identified expression throughout the TALH, from the junction between inner and outer medulla to the transition to distal convoluted tubule. Expression by macula densa cells was confirmed by colocalization using markers specific for macula densa cells. First, Na-K-2Cl cotransporter mRNA was detected in macula densa cells that did not stain with anti-Tamm-Horsfall protein antibodies. Second, Na-K-2Cl cotransporter mRNA was detected in macula densa cells that show positive NADPH-diaphorase reaction, indicating high levels of constitutive nitric oxide synthase activity. In rat, levels of Na-K-2Cl cotransporter mRNA expression were similar in TALH and macula densa cells. In rabbit, expression levels were higher in macula densa cells than in surrounding TALH cells. The present data provide morphological support for a previously established functional concept that Na-K-2Cl cotransport at the TALH is accomplished by the expression of a well-defined cotransporter. At the macula densa, this transporter may establish a crucial link between tubular salt load and glomerular vascular regulation.
Outbreak of &lt;EMPH TYPE="ITAL"&gt;Pseudomonas aeruginosa&lt;/EMPH&gt; Infections Caused by Commercial Piercing of Upper Ear Cartilage
Authors: William E Keene, Amy C Markum, Mansour Samadpour
Journal: JAMA (2004)

Sporadic infections following ear piercing are well documented, but common-source outbreaks are rarely recognized.To investigate reports of auricular chondritis subsequent to commercial ear piercing.Outbreak investigation by Oregon public health agencies, including cohort study of persons pierced at a jewelry kiosk in August-September 2000, environmental sampling, and molecular subtyping of isolates. Confirmed cases had Pseudomonas aeruginosa cultured from ear wounds. Suspected cases had signs and symptoms of external ear infection, including drainage of pus or blood for at least 14 days.Risk factors for infection and comparison of bacterial isolates by molecular subtyping.From 186 piercings in 118 individuals, we identified 7 confirmed P aeruginosa infections and 18 suspected infections. Confirmed cases were 10 to 19 years old. Most were initially treated with antibiotics ineffective against Pseudomonas. Four were hospitalized, 4 underwent incision and drainage surgeries (1 as an outpatient), and several were cosmetically deformed. Upper ear cartilage piercing was more likely to result in either confirmed or suspected infection than was lobe piercing (confirmed: RR undefined, P<.001; suspected: RR, 3.6; 95% confidence interval, 1.5-8.5). All persons with confirmed infections had their ear cartilage pierced with an open, spring-loaded piercing gun. Patient isolates were indistinguishable by molecular subtyping, and matching isolates were recovered from a disinfectant bottle and nearby sink. At least 1 worker admitted sometimes spraying the disinfectant on the ear studs before piercing.Ear cartilage piercing is inherently more risky than lobe piercing. Clinicians should respond aggressively to potential auricular chondritis and consider Pseudomonas a possible cause pending culture results.
Phasic secretion of newly synthesized atrial natriuretic factor from unstimulated atrial myocytes in culture.
Authors: H Iida, Y Shibata
Journal: Circulation Research (1994)

We have examined kinetics and composition of newly synthesized proteins secreted from cultured atrial myocytes from adult rats. Under unstimulated conditions, noncontracting cultured atrial myocytes, which were pulse-labeled for 10 minutes with [35S]methionine, rapidly released a considerable portion of newly synthesized atrial natriuretic factor (ANF) in a phasic secretion with a peak at 40 to 80 minutes of chase time. The phasic secretion almost ceased after 80 minutes of chase, after which relatively slow release of the hormone was observed. The ability to stimulate the phasic secretion with secretagogues and a marked resemblance of the radiochemical composition of released proteins in the unstimulated phasic secretion to that in stimulated secretion suggest that the proteins discharged from the cells during the phasic secretion might be derived from secretory granules. Examination of the quantitative change of intracellular ANF showed that approximately 60% of newly synthesized labeled ANF was still retained in the cells after the termination of the phasic secretion, indicating that the termination of the phasic secretion was not due to depletion of the labeled protein in the cells. These results suggest that a proportion of newly synthesized ANF was rapidly released from the unstimulated atrial myocytes via a secretory route that shares certain features with both the regulated and the constitutive secretory pathway and that a part of newly synthesized ANF is processed for rapid release while the remainder is destined for slow release or storage within the cells.
5′RNA-Seq identifies Fhl1 as a genetic modifier in cardiomyopathy
Authors: Danos C. Christodoulou, Hiroko Wakimoto, Kenji Onoue, Seda Eminaga, Joshua M. Gorham, Steve R. DePalma, Daniel S. Herman, Polakit Teekakirikul, David A. Conner, David M. McKean, Andrea A. Domenighetti, Anton Aboukhalil, Stephen Chang, Gyan Srivastava, Barbara McDonough, Philip L. De Jager, Ju Chen, Martha L. Bulyk, Jochen D. Muehlschlegel, Christine E. Seidman, J.G. Seidman
Journal: Journal of Clinical Investigation (2014)

The transcriptome is subject to multiple changes during pathogenesis, including the use of alternate 5′ start-sites that can affect transcription levels and output. Current RNA sequencing techniques can assess mRNA levels, but do not robustly detect changes in 5′ start-site use. Here, we developed a transcriptome sequencing strategy that detects genome-wide changes in start-site usage (5′RNA-Seq) and applied this methodology to identify regulatory events that occur in hypertrophic cardiomyopathy (HCM). Compared with transcripts from WT mice, 92 genes had altered start-site usage in a mouse model of HCM, including four-and-a-half LIM domains protein 1 (Fhl1). HCM-induced altered transcriptional regulation of Fhl1 resulted in robust myocyte expression of a distinct protein isoform, a response that was conserved in humans with genetic or acquired cardiomyopathies. Genetic ablation of Fhl1 in HCM mice was deleterious, which suggests that Fhl1 transcriptional changes provide salutary effects on stressed myocytes in this disease. Because Fhl1 is a chromosome X–encoded gene, stress-induced changes in its transcription may contribute to gender differences in the clinical severity of HCM. Our findings indicate that 5′RNA-Seq has the potential to identify genome-wide changes in 5′ start-site usage that are associated with pathogenic phenotypes.
Effect of Dopamine and Calcium on Lipolysis and Myocardial Ischemic Injury following Acute Coronary Occlusion in the Dog
Authors: JON LEKVEN, GUDMUND SEMB
Journal: Circulation Research (1974)

Ischemic myocardial injury was quantified as the sum of S-T segment elevations in epicardial electrocardiogram recordings (ΣS-T) following acute coronary artery occlusions in 17 dogs. ΣS-T rose from 3 ± 1 mv to 26 ± 4 mv ( P &lt; 0.001) following occlusion. Myocardial contractility was similarly stimulated by intravenous infusions of dopamine or calcium. At reocclusions of the coronary artery, ΣS-T increased to 73 ± 12 mv ( P &lt; 0.001) with dopamine and to 41 ± 7 mv ( P &lt; 0.001) with calcium; the difference was statistically significant ( P &lt; 0.005). Arterial concentrations of free fattv acids (FFA a ) were raised from 248 ± 33 µEq/liter to 888 ± 161 µEq/liter ( P &lt; 0.005) with dopamine, but administration of calcium did not influence FFA a . After inhibition of lipolysis with β-pyridyl carbinol, no difference in ΣS-T or FFA a was observed; the mean values were 31 ± 4 mv for ΣS-T and 144 ± 13 µEq/liter for FFA a . Myocardial lipolysis was suggested in three experiments in which β-pyridyl carbinol reduced ΣS-T with dopamine, although FFA a remained unchanged. These measurements suggest that dopamine-induced lipolysis contributes significantly to the enlargement of ischemic injury in the myocardium following acute coronary artery occlusion, probably due to the metabolic stimulation of myocardial oxygen requirements. Test doses of dopamine given to seven patients raised FFA a by 225 ± 87 µEq/liter ( P &lt; 0.03).
Signalling mechanisms of mammalian oocyte activation
Authors: C. J. Williams
Journal: Human Reproduction Update (2002)

Intensive study over the past 10 years has resulted in major advances in our understanding of the signalling mechanisms required for the transformation of the oocyte into an embryo capable of developing into a new individual. This review focuses on the signal transduction events that occur subsequent to the initial sperm–oocyte plasma membrane interaction, with particular emphasis on the mechanism(s) by which sperm initiate these signalling pathways. Downstream signalling/effector molecules that respond to sperm-induced calcium oscillations and appear to have important roles in oocyte activation are then discussed. Finally, the mechanisms of physiological oocyte activation are compared with events of oocyte activation that occur after ICSI.
Measurement of spinal mobility.
Authors: F D Hart, D Strickland, P Cliffe
Journal: Annals of the Rheumatic Diseases (1974)

In the assessment of deterioration or improvement in spinal stiffness it is important to have a measure of spinal range of movement which is reproducible, little subject to observer error, and takes only a short time to perform.In a study ofpatients with ankylosing spondylitis by one of us (FDH), which has continued since 1946, measurements by existing techniques were at first unsatisfactory and unreliable.After 3 years, however, Dunham (1949) reported the use of his spondylometer and since 1950 this has been in con- stant use in our clinic.We have now records of spondylometry using this instrument over a period of 23 years and have found it reliable, quick, and
Regulation of<i>CYP3A</i>Gene Transcription by the Pregnane X Receptor
Authors: Bryan Goodwin, Matthew R. Redinbo, Steven A. Kliewer
Journal: The Annual Review of Pharmacology and Toxicology (2002)

The pregnane X receptor (PXR) is a promiscuous nuclear receptor that has evolved to protect the body from toxic chemicals. PXR is activated by a structurally diverse collection of xenobiotics, including several widely used prescription drugs. Various lipophilic compounds produced by the body, such as bile acids and steroids, also activate PXR. PXR stimulates the transcription of cytochrome P450 3A monooxygenases and other genes involved in the detoxification and elimination of these potentially harmful chemicals. Assays that detect PXR activation have important implications for the design of future drugs in two respects. On the one hand, PXR activation assays can be used to determine whether candidate drugs are likely to induce CYP3A gene expression and interact with other medicines. On the other hand, PXR agonists may prove useful in the treatment of diseases in which toxic metabolites accumulate, such as cholestatic liver disease.