tbuckley/cabot-search huggingface dataset:
Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease
Authors: Raphael B. Merriman, Linda D. Ferrell, Marco G. Patti, Shiobhan R. Weston, Mark S. Pabst, Bradley E. Aouizerat, Nathan M. Bass
Journal: Hepatology (2006)

In the absence of surrogate markers, the evaluation of suspected nonalcoholic fatty liver disease (NAFLD) is highly dependent on histological examination. The extent of sampling variability affecting the reliability of a single liver biopsy in patients with suspected NAFLD is poorly characterized. This prospective study aimed to correlate precise histological findings in paired biopsies—right and left lobe—in the diagnosis of NAFLD in morbidly obese subjects undergoing bariatric surgery employing both Brunt and Matteoni classifications and the NAFLD Activity Score (NAS). We also aimed to determine whether the composite histopathological findings of the two biopsies would improve diagnostic accuracy. Consecutive subjects had an intraoperative biopsy from both right and left lobes, evaluated and scored in a blinded manner. Intraobserver agreement was also assessed. Kappa coefficients of agreement were calculated. Forty-one subjects had acceptable biopsies. Agreement for steatosis was excellent and moderate for fibrosis. Concordance was only fair for most features of necroinflammation. Intraobserver agreement was only moderate for lobular inflammation. Excellent agreement was seen for the diagnosis of NASH using Brunt criteria and good agreement when using Matteoni and NAS scoring systems. Composite biopsy data particularly improved identification of hepatocyte ballooning. The diagnostic accuracy also improved substantially when composite features were compared with single-sided biopsy features, especially for the Matteoni and NAS scoring systems. In conclusion, significant sampling variability occurs in NAFLD, particularly for features of necroinflammation. This should be factored into the design of clinical trials and studies of the natural history of the disease. (HEPATOLOGY 2006;44:874–880.)
798 The immunoparalysis of acute liver failure (ALF) is reversed by orthotopic liver transplantation (OLT)
Authors: C ANTONIADES, E DAVIES, D VERGANI, J WENDON
Journal: Hepatology (2003)

Our purpose was to examine the impact of diabetes mellitus (DM) on vasoreactivity and endothelial function of radial artery (RA) grafts ex vivo.The arteriopathy associated with DM may influence the surgeon’s choice of conduits for revascularization. Arterial conduits and especially the RA are prone to vasospasm in the perioperative period.The study population consisted of 98 patients with coronary artery disease undergoing coronary artery bypass grafting by using RA grafts. The maximum contractions of RA segments induced by K+ (66 mmol/l) and clinically important vasoconstrictors such as adrenaline (5 × 10−5mol/l), angiotensin II (10−6mol/l), and prostaglandin F2α (PGF2α) (10−6mol/l) were recorded. Relaxation of RA rings to carbachol (10−4mol/l) was used as a measure of endothelial function. Multivariate analysis was then applied to determine the role of clinical characteristics on the vasomotor responses to these agents.Vessels from patients with DM had greater contractions in response to adrenaline (p < 0.05), angiotensin (p < 0.05), and PGF2α (p < 0.01) compared with non-DM vessels, despite the similar vasoconstrictions induced by high K+ (p = NS). Diabetes mellitus was also associated with smaller vasorelaxations in response to carbachol (p < 0.001). In multivariate analysis, DM was an independent predictor of RA contractions in response to adrenaline (β [SE] 3.085 [1.410], p = 0.031), angiotensin II (β [SE] 3.838 [1.552], p = 0.015), and PGF2α (β [SE] 4.609 [1.908], p = 0.018) but not K+ (p = NS). Diabetes mellitus was also independently associated with the vasorelaxations in response to carbachol (β [SE] −15.645 [2.622], p = 0.0001).Diabetes mellitus is associated with impaired endothelial function and greater contractions of RA grafts in response to all of the clinically relevant vasoconstrictors. These findings suggest that the RA of diabetic patients may be more prone to spasm in response to endogenous vasoconstrictors, an observation with important implications for surgeons’ choice of conduits in this cohort of patients.
Comparative Proteome Analysis of Breast Cancer and Adjacent Normal Breast Tissues in Human
Authors: Shi-Shan Deng, Tian-Yong Xing, Hong-Ying Zhou, Ruo-Hong Xiong, You-Guang Lu, Bin Wen, Shang-Qing Liu, Hui-Jun Yang
Journal: Genomics Proteomics & Bioinformatics (2006)

Abstract Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS), incorporated with online database searching, were performed to investigate differential proteins of breast cancer and adjacent normal breast tissues. Considering that serum albumin is abundantly presented in normal control samples, 15 differential spots detected in 11 out of 12 (91.7%) breast cancer samples were identified by online SIENA-2DPAGE database searching and MALDI-TOF/TOF-MS analysis. The results indicate that pathological changes of breast cancer are concerned with augmentation of substance metabolism, promotion of proteolytic activity, decline of activity of some inhibitors of enzymes, and so on. Some important proteins involved in the pathological process of breast cancer with changed expression may be useful biomarkers, such as alpha-1-antitrypsin, EF-1-beta, cathepsin D, TCTP, SMT3A, RPS12, and PSMA1, among which SMT3A, RPS12, and PSMA1 were first reported for breast cancer in this study.
Application of Mutated miR-206 Target Sites Enables Skeletal Muscle-specific Silencing of Transgene Expression of Cardiotropic AAV9 Vectors
Authors: Anja Geisler, Christian Schön, Tobias Größl, Sandra Pinkert, Elisabeth A Stein, Jens Kurreck, Roland Vetter, Henry Fechner
Journal: Molecular Therapy (2013)

Insertion of completely complementary microRNA (miR) target sites (miRTS) into a transgene has been shown to be a valuable approach to specifically repress transgene expression in non-targeted tissues. miR-122TS have been successfully used to silence transgene expression in the liver following systemic application of cardiotropic adeno-associated virus (AAV) 9 vectors. For miR-206-mediated skeletal muscle-specific silencing of miR-206TS-bearing AAV9 vectors, however, we found this approach failed due to the expression of another member (miR-1) of the same miR family in heart tissue, the intended target. We introduced single-nucleotide substitutions into the miR-206TS and searched for those which prevented miR-1-mediated cardiac repression. Several mutated miR-206TS (m206TS), in particular m206TS-3G, were resistant to miR-1, but remained fully sensitive to miR-206. All these variants had mismatches in the seed region of the miR/m206TS duplex in common. Furthermore, we found that some m206TS, containing mismatches within the seed region or within the 3' portion of the miR-206, even enhanced the miR-206- mediated transgene repression. In vivo expression of m206TS-3G- and miR-122TS-containing transgene of systemically applied AAV9 vectors was strongly repressed in both skeletal muscle and the liver but remained high in the heart. Thus, site-directed mutagenesis of miRTS provides a new strategy to differentiate transgene de-targeting of related miRs.
CELL REPLACEMENT IN THE HUMAN STRATUM CORNEUM IN OLD AGE
Authors: HARVEY BAKER, CICELY P. BLAIR
Journal: British Journal of Dermatology (1968)

SUMMARY. Staining of the human stratum corneum in vivo with fluorescent tetrachlorsalicylanilide has been used to measure the transit time of horny cells in the normal forearm skin of aged people. Stratum corneum thickness was estimated by counting the horny cell layers in biopsy specimens of epidermis, visualized by hydration in alkali. From the two parameters thus obtained, stratum corneum replacement rates were: calculated. In 6 aged men, transit times varied between 20 and 36 (mean 26) days, and replacement rates between 30 and 47 (mean 34) hr. per cell layer. These data suggest reduced epidermal mitotic activity compared with that of young men. In 5 aged women, transit times varied between 17 and 26 (mean 20) days and replacement rates between 16 and 31 (mean 24) hr. per cell layer. This faster replacement in old women compared with old men is not much slower than that observed in young adults.
Temporary left ventricular bypass: factors affecting patient survival.
Authors: W F Bernhard, R L Berger, J P Stetz, J G Carr, N A Colo, J R McCormick, M C Fishbein
Journal: Circulation (1979)

Circulatory support (range, 2 hours-8 days) was undertaken in eight cardiac surgical patients (with two survivors) exhibiting intractable cardiogenic shock. A paracorporeal, pneumatic, xenograft-valve pump was interposed between the left ventricular apex and ascending aorta. Pumping lowered left atrial and ventricular pressure while maintaining cardiac output (1.8--2.6 l/min/m2). Following implantation, plasma hemoglobin and erythrocyte mechanical fragility values were elevated but decreased to normal when renal function was not impaired. Mild thrombocytopenia was noted in three patients and was severe in five others with persistent hemorrhage. Anticoagulation agents were used during tapering of pump flow (three patients) after 100, 105 and 120 hours of bypass. Otherwise, for the major portion of the interval of mechanical circulatory support, anticoagulants were not administered. Despite this fact, no systemic embolization was detected in any of the patients. It appears that assist pump support can be life-saving in acute left ventricular failure in patients following cardiac surgery.
TREATMENT OF EDEMATOUS EXTREMITY WITH DIURETICS
Authors: Wallace C. Bedell
Journal: JAMA (1960)

This study concerned 56 patients with localized swelling in an upper or lower extremity occurring after thrombophlebitis, ulcer of the leg, radical mastectomy, trauma, or fracture. There was no reason for believing that cardiorenal disease or hypoproteinemia contributed to the edema in these cases. Appropriate local treatment was supplemented with diuretics, generally chlorothiazide, and restriction of oral salt intake. All patients showed measurable decrease in their edema, and the response was good or excellent in all but six. Particular advantage was found in the ambulatory management of ulcers of the leg. The improvement of these edematous extremities by systemic therapy points to the likelihood of significant systemic factors in the symptomatology of these cases.
Oestrogen only HRT increases risk of ovarian cancer
Authors: D. Josefson
Journal: BMJ (2002)

Women taking oestrogen only hormone replacement therapy (HRT) for 10 years or more face a 60% greater risk of developing ovarian cancer than if they had never taken it, a new study shows ( JAMA 2002;288:334-41)

The study follows recent research implicating HRT in small increased risks of cardiovascular disease, breast and uterine cancers, blood clots, and stroke. HRT is used by an estimated 13.5 million women in the United States—nearly eight million take oestrogen only pills and around six million take the combined oestrogen and progestogen form.

Dr James Lacey …
Enhanced leucocyte adhesion to interleukin-1 stimulated vascular smooth muscle cells is mainly through intercellular adhesion molecule-1
Authors: X. Wang, G. Z Feuerstein, R. K Clark, T.-L. Yue
Journal: Cardiovascular Research (1994)

The aim was to investigate whether interleukin-1 beta (IL-1 beta) plays a role in modulating the adhesion of monocytes and neutrophils to vascular smooth muscle cells, and to identify what molecules on these cells may be involved in the adhesion.Rat aortic smooth muscle cells were challenged with IL-1 beta and tested for adhesion of prelabelled monocytes and neutrophils. Northern analysis, reverse transcription/polymerase chain reaction (RT/PCR), and immunocytochemical staining were used to measure the changes of intercellular adhesion molecule-1 (ICAM-1) and other adhesion molecules in response to IL-1 beta stimulation. Neutralising antibody against ICAM-1 was used to demonstrate a role of ICAM-1 in this IL-1 beta induced adhesion.IL-1 beta induced the adhesion of monocytes and neutrophils to aortic smooth muscle cells in a concentration and time dependent manner. IL-1 beta-induced adhesion was inhibited by preincubation of the cells with an IL-1 receptor antagonist (IL-1ra). Northern analysis and RT/PCR showed that ICAM-1 mRNA represents a predominant adhesion molecule induced by IL-1 beta, and that the expression of ICAM-1 mRNA precedes and parallels the induced adhesion profiles of aortic smooth muscle cells for leucocytes. Immunocytochemical staining confirmed the IL-1 beta induced ICAM-1 expression on the smooth muscle cells. Moreover, a monoclonal anti-rat ICAM-1 antibody produced a concentration dependent inhibition of the IL-1 beta induced adhesion of monocytes and neutrophils to the smooth muscle cells.IL-1 beta actively regulates functional ICAM-1 expression in vascular smooth muscle cells. The IL-1 beta-induced expression of ICAM-1 on the smooth muscle cells may be an important contributor to the increased adhesion by monocytes and neutrophils to these cells and suggests that IL-1 beta might play a role in the proinflammatory and immune functions of the modified smooth muscle cells during atherosclerosis and restenosis.
Treatment of reflux strictures of the oesophagus by the Nissen-Rossetti operation
Authors: G. K. Harrison, B. M. Gompels
Journal: Thorax (1971)

Eight patients with bougie-resistant strictures of the oesophagus due to gastric reflux have been treated by the Nissen-Rossetti operation. Follow-up clinical and barium studies show the results to be encouraging. The principle involved is the prevention of reflux.
Wrong Medicine: Doctors, Patients, and Futile Treatment
Authors: C. Weijer
Journal: BMJ (1995)

Lawrence J Schneiderman, Nancy S Jecker Johns Hopkins University Press, pounds sterling21.50, pp 200 ISBN 0 8018 5036 3

Medical futility—the idea that doctors ought to refuse demands for treatment that is unlikely to work, or that merely prolongs states of permanent unconsciousness or dependence on intensive medical care—is an idee fixe for Lawrence Schneiderman and Nancy Jecker. The concept has been criticised for packaging an uncontroversial claim, “patients can't demand treatments that won't work,” with a controversial one, “unconscious life or life dependent on intensive care is not …
FUNCTION OF COMPONENTS OF COMPLEMENT IN IMMUNE HEMOLYSIS
Authors: L. Pillemer, S. Seifter, Fey Chu, E. E. Ecker
Journal: The Journal of Experimental Medicine (1942)

1. At a temperature of 1 degrees C., C'2, C'4, and C'1 combine with sensitized sheep erythrocytes, while C'3 does not combine. 2. C'1, although combining with sensitized cells in the absence of C'4, is hemolytically inert unless C'4 combines previous to, or simultaneously with it. 3. C'4 does not combine in the absence of C'1. 4. Although C'3 is not fixed by antibody-sheep cell aggregates, it is essential for hemolysis, operating on the sensitized red cell after the fixation of C'4, C'2, and C'1 and behaving as if it were a catalyst.
Role of protein kinase C as a cellular mediator of ischemic preconditioning: a critical review
Authors: B Simkhovich
Journal: Cardiovascular Research (1998)

Protein kinase C (PKC) has been proposed as a primary cellular mediator of ischemic preconditioning. However, the role of PKC in eliciting cardioprotection remains controversial. In this review, we summarize the evidence for and against the 'PKC hypothesis' of preconditioning, discuss the important technical limitations currently hampering PKC research, and suggest new approaches (i.e. PKC isoform-specific biochemical assays combined with immunoblotting techniques) that might aid in the definite resolution of this issue.
Flu hype and pharma failures: patients deserve better
Authors: E. Davies
Journal: BMJ (2013)

Epidemics, pandemics, new strains, and foreign scare stories are an annual event in the world of flu. It barely feels like winter until I’ve read an article about somebody thousands of miles away catching it from a farmyard animal.

We are bombarded with messages about flu whether we want them or not. And increasingly the noise is coming not from news outlets or drug manufacturers out to make a …
Allergic rhinitis in children
Authors: James G Barr, Hiba Al-Reefy, Adam T Fox, Claire Hopkins
Journal: BMJ (2014)

#### Summary points

Allergic rhinitis is a common paediatric condition. In a worldwide study of over one million adolescents aged 13 and 14 years the prevalence was 14.6%.1 Allergic rhinitis is characterised by rhinorrhoea, nasal obstruction, epiphora, and nasal itching. Many patients and parents think of seasonal, pollen induced “hay fever”; however, numerous aeroallergens may produce perennial symptoms, and these have an important impact on children’s quality of life.2 3 Evidence based guidelines, advances in drug treatments, and novel specific immunotherapy have all improved the management of allergic rhinitis. We review the current literature, with particular respect to the Allergic Rhinitis and its Impact on Asthma guidelines, produced by the World Health Organization.2

#### Sources and selection criteria

We searched Medline for randomised controlled trails, systematic reviews, and meta-analyses using the terms “allergic rhinitis” and “paediatrics”. We also reviewed the references used in the Allergic Rhinitis and its Impact on Asthma guidelines and consulted the Cochrane database of systematic reviews. Articles were included if all authors agreed on their relevance.

Allergic rhinitis is an IgE mediated disorder triggered by exposure of nasal mucosa to allergens. This results in rhinorrhoea, itching, and sneezing as …
HYPERACIDITY OF THE GASTRIC CONTENTS IN CHILDREN
Authors: CHARLES GILMORE KERLEY
Journal: JAMA (1922)

Exhaustive studies, voluminous literature and a great deal of discussion have centered around the condition known as hyperacidity of the stomach in the adult. That a similar condition may occur in the earlier years has evidently not been appreciated, if we are to judge by the attention paid to the disorder as we find it in children.  SYMPTOMATOLOGY  The symptoms, in their order of frequency, that bring the child to the pediatrician, are: abdominal pain that has not been relieved by previous treatment; nausea without vomiting; vomiting at irregular intervals, and loss of appetite.  The pain occurs most often before meals when the stomach is supposedly empty. In many, pain is complained of before the morning meal. In some, the child is awakened early because of the abdominal discomfort. When asked to locate the pain, the child usually places the hand over the abdomen above the umbilicus. In some, the
Abstract 905: Associations with breast cancer survival replicated for three SNPs: A report from the Shanghai Breast Cancer Survival Study and Shanghai Breast Cancer Study
Authors: Alicia C. Beeghly-Fadiel, Jirong Long, Yutang Gao, Ying Zheng, Qiuyin Cai, Kai Gu, Zhi Chen, Wei Lu, Wei Zheng, Xiao Ou Shu
Journal: Cancer Research (2010)

Abstract We have previously reported associations between nine single nucleotide polymorphisms (SNPs) and breast cancer outcomes from the Shanghai Breast Cancer Study (SBCS, Stage I). We evaluated these SNPs in association with overall survival (OS) and disease free-survival (DFS) among participants of the Shanghai Breast Cancer Survival Study (SBCSS) and participants of the second phase of SBCS (Stage 2). The mean follow-up time of the 1,115 Stage 1 participants was 6.5 years; the mean follow-up time of the 5,381 Stage 2 participants was 4.2 years. Models of effect and subgroup analyses were conducted based on published results from Stage 1. A missense SNP in exon 1 of TGFβ1 (rs1800470) was associated with improved overall survival in a recessive fashion (p-value = 0.028). Minor allele homozygotes (TT) fared slightly better than major allele carriers (CT and CC) (OS hazard ratio (HR): 0.8, 95% confidence interval (CI): 0.6-1.0); this effect was slightly attenuated after adjustment for known prognostic factors including age, disease stage, tumor estrogen and progesterone receptor status, and disease treatment (p-value = 0.052). A SNP downstream of the MMP7 gene (rs11225297), in high linkage disequilibrium with a nearby functional SNP, was associated with improved overall survival in an additive manner (p-value = 0.013). Compared to major allele homozygotes (AA), heterozygotes (AT) fared moderately better (OS HR: 0.8, 95% CI: 0.7-1.0), while homozygotes (TT) fared much better (OS HR: 0.5, 95% CI: 0.3-1.0); this affect was strengthened by adjusting for known covariates (p-value = 0.002). Finally, a functional promoter SNP in MMP8 (rs11225395) was found to be associated with better prognosis among early stage patients (TNM less than 3) in a dominant manner (p-value = 0.007). Early stage minor allele carriers (CT and TT) had better survival (DFS and OS HRs: 0.7, 95% CI: 0.5-0.9); these effects were unaltered by adjusting for covariates (p-values = 0.012). In summary, we were able to replicate associations with breast cancer survival for three of nine previously reported SNPs. These findings suggest that genetic polymorphism in genes governing the tumor microenvironment may play an important role in breast cancer prognosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 905.
Remodeling in Cells From Different Regions of the Reentrant Circuit During Ventricular Tachycardia
Authors: Shigeo Baba, Wen Dun, Candido Cabo, Penelope A. Boyden
Journal: Circulation (2005)

Background— Anisotropic reentrant excitation occurs in the remodeled substrate of the epicardial border zone (EBZ) of the 5-day infarcted canine heart. Reentry is stabilized because of the formation of functional lines of block. We hypothesized that regional differences of ionic currents in cells of the EBZ form these lines of block. Therefore, we first mapped reentrant circuits of sustained tachycardias, then dispersed cells (infarct zone cells, IZs) from the central common pathway of the circuit (IZc) as well as from the other side of the line of block (outer pathway, IZo) for study. Methods and Results— We mapped reentrant circuits in the EBZ of infarcted hearts during sustained ventricular tachycardias (&gt;30 seconds, n=17 episodes, cycle lengths=218±7.9 ms). I Na density was reduced in both IZc and IZo, and the kinetic properties of IZc I Na were markedly altered versus IZo. Structural remodeling of the sodium channel protein Na v 1.5 occurred in IZs, with cell surface localization differing from normal cells. Both IZc and IZo have similar but reduced I CaL , whereas IZc showed changes in Ca 2+ current kinetics with an acceleration of current decay. Computer simulations of the 2D EBZ showed that incorporating only differences between I Na in IZc and IZo prevented stability of the reentrant circuit. Incorporating only differences between I CaL in the IZc and IZo cells also prevented stability of the circuit. However, incorporating both I Na and I CaL current differences stabilized the simulated reentrant circuit, and lines of block formed between the 2 distinct regions. Conclusions— Despite differences in I Na and I CaL properties in cells of the center and outer pathways of a reentrant circuit, the resulting changes in effective refractory periods tend to stabilize reentry in this remodeled substrate.
Optimisation of breast cancer management in low-resource and middle-resource countries: executive summary of the Breast Health Global Initiative consensus, 2010
Authors: Benjamin O Anderson, Eduardo Cazap, Nagi S El Saghir, Cheng-Har Yip, Hussein M Khaled, Isabel V Otero, Clement A Adebamowo, Rajendra A Badwe, Joe B Harford
Journal: The Lancet Oncology (2011)