tbuckley/cabot-search huggingface dataset:
c-Met represents a potential therapeutic target for personalized treatment in hepatocellular carcinoma
Authors: Hanning You, Wei Ding, Hien Dang, Yixing Jiang, Bart C. Rountree
Journal: Hepatology (2011)

c-Met, a high-affinity receptor for hepatocyte growth factor (HGF), plays a critical role in cancer growth, invasion, and metastasis. Hepatocellular carcinoma (HCC) patients with an active HGF/c-Met signaling pathway have a significantly worse prognosis. Although targeting the HGF/c-Met pathway has been proposed for the treatment of multiple cancers, the effect of c-Met inhibition in HCC remains unclear. The human HCC cell lines Huh7, Hep3B, MHCC97-L, and MHCC97-H were used in this study to investigate the effect of c-Met inhibition using the small molecule selective c-Met tyrosine kinase inhibitor PHA665752. MHCC97-L and MHCC97-H cells demonstrate a mesenchymal phenotype with decreased expression of E-cadherin and increased expression of c-Met, fibronectin, and Zeb2 compared with Huh7 and Hep3B cells, which have an epithelial phenotype. PHA665752 treatment blocked phosphorylation of c-Met and downstream phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/Erk pathways, inhibited cell proliferation, and induced apoptosis in c-Met-positive MHCC97-L and MHCC97-H cells. In xenograft models, administration of PHA665752 significantly inhibited c-Met-positive MHCC97-L and MHCC97-H tumor growth, and PHA665752-treated tumors demonstrated marked reduction of both c-Met phosphorylation and cell proliferation. c-Met-negative Huh7 and Hep3B cells were not affected by c-Met inhibitor treatment in vitro or in vivo. In addition, c-Met-positive MHCC97-L and MHCC97-H cells demonstrated cancer stem cell-like characteristics, such as resistance to chemotherapy, tumor sphere formation, and increased expression of CD44 and ABCG2, and PHA665752 treatment suppressed tumor sphere formation and inhibited CD44 expression.c-Met represents a potential target of personalized treatment for HCC with an active HGF/c-Met pathway.
Exercise and Atherosclerosis
Authors: Norman M. Kaplan
Journal: Annals of Internal Medicine (2004)

Letters7 December 2004Exercise and AtherosclerosisNorman M. Kaplan, MDNorman M. Kaplan, MDFrom University of Texas Southwestern Medical Center, Dallas, TX 75390-8899.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-11-200412070-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The presentation of the study by Rauramaa and colleagues (1) was grossly misleading. The abstract stated that “aerobic physical exercise did not attenuate progression of atherosclerosis, except in a subgroup of men not taking statins,” a conclusion echoed by the Editors' Notes and the Summary for Patients (2). This appeared to be a truly negative study, one that could lead physicians and patients to take their statin and forget about exercise.Well, surprise: Only 15 of the 140 enrollees were taking statins, and among the 125 who weren't, progression of atherosclerosis was 40% less in the exercise ...References1. Rauramaa R, Halonen P, Väisänen SB, Lakka TA, Schmidt-Trucksäss A, Berg A, et al. Effects of aerobic physical exercise on inflammation and atherosclerosis in men: the DNASCO Study: a six-year randomized, controlled trial. Ann Intern Med. 2004;140:1007-14. [PMID: 15197018] LinkGoogle Scholar2. Summaries for patients. Does aerobic exercise slow progression of atherosclerosis? Ann Intern Med. 2004;140:I37. [PMID: 15197036] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Texas Southwestern Medical Center, Dallas, TX 75390-8899. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffects of Aerobic Physical Exercise on Inflammation and Atherosclerosis in Men: The DNASCO Study Rainer Rauramaa , Pirjo Halonen , Sari B. Väisänen , Timo A. Lakka , Arno Schmidt-Trucksäss , Aloys Berg , Ilkka M. Penttilä , Tuomo Rankinen , and Claude Bouchard Does Aerobic Exercise Slow Progression of Atherosclerosis?Exercise and Atherosclerosis Metrics 7 December 2004Volume 141, Issue 11Page: 890KeywordsAtherosclerosisExercisePreventive medicineStatins ePublished: 7 December 2004 Issue Published: 7 December 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Comparison of Laboratory Test Frequency and Test Results Between African-Americans and Caucasians With Diabetes: Opportunity for Improvement: Findings from a large urban health maintenance organization
Authors: Kimberlydawn Wisdom, Jon P Fryzek, Suzanne L Havstad, Robert M Anderson, Michael C Dreiling, Barbara C Tilley
Journal: Diabetes Care (1997)

To compare African-American and Caucasian patients with preexisting diabetes in a health maintenance organization (HMO) on: 1) frequency with which they received a subset of recommended laboratory tests according to the American Diabetes Association (ADA) consensus guidelines and 2) the results of laboratory test values (glycosylated hemoglobin, cholesterol, and creatinine).A cross-sectional study of 2,312 HMO members with diabetes continuously enrolled during 1991 was conducted using computerized medical record and billing data. Receipt of the ADA recommended tests for glycosylated hemoglobin, cholesterol, and creatinine was compared between African-Americans and Caucasians, stratified by insulin requirements. In addition, group comparisons were made based on the laboratory test results.Less than 20 percent of all subjects received the recommended number of ADA tests. This did not differ by race except for creatinine and cholesterol testing in insulin users only, where African-Americans had more tests. On average, after adjusting for covariates, African-Americans had significantly higher glycosylated hemoglobin and creatinine laboratory values. Both groups had elevated cholesterol values.The opportunity exists to improve the process of care for both African-Americans and Caucasians with diabetes in an HMO setting. The need to improve glycosylated hemoglobin results and subsequently limit complications is especially pressing among the African-American population.
The Hidradenitis Suppurativa Priority Setting Partnership
Authors: J.R. Ingram, R. Abbott, M. Ghazavi, A.B. Alexandroff, M. McPhee, T. Burton, T. Clarke
Journal: British Journal of Dermatology (2014)

Hidradenitis suppurativa (HS) has been neglected by medical researchers and society in general, despite being a relatively common, painful, chronic skin disease.To generate a top 10 list of HS research priorities, from the perspectives of patients with HS, carers and clinicians, to take to funding bodies.A priority setting partnership was established between patients with HS, carers and clinicians, following the James Lind Alliance process. Survey 1 requested submission of HS uncertainties, which were grouped into 'indicative uncertainties' for prioritization in survey 2. The 30 highest-ranked indicative uncertainties were reduced to a 'top 10' list using nominal group technique at a prioritization workshop attended by all relevant HS stakeholders.In total 1495 potential uncertainties were submitted in survey 1, including 57% from patients with HS and carers, and grouped into 55 indicative uncertainties. Ranking in survey 2 was completed by 371 participants, 50% of whom were patients and carers. The final workshop was attended by 22 HS stakeholders and four facilitators and produced a top 10 list, the three highest priorities in descending order being (i) What is the most effective and safe group of oral treatments in treating HS? (ii) What is the best management of an acute flare? (iii)What is the impact of HS and its treatment on people with HS?The top 10 HS research priorities have been directly disseminated to funders to raise awareness of HS. The next step is to generate research questions that will provide the evidence needed to improve care for patients with HS.
Serratia marcescens Septicemia with Osteomyelitis of the Cervical Spine: An Unusual Epidemic.
Authors: Russell A. Del Toro
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Serratia marcescens Septicemia with Osteomyelitis of the Cervical Spine: An Unusual Epidemic.Russell A. Del Toro, M.D., F.A.C.P., Jose A. Rullan, M.D., F.A.C.P., Mercedes Torregrosa, Ph.D., Anibal Lugo, M.D., Jose L. Freyre, M.D.Russell A. Del Toro, M.D., F.A.C.P.Search for more papers by this author, Jose A. Rullan, M.D., F.A.C.P.Search for more papers by this author, Mercedes Torregrosa, Ph.D.Search for more papers by this author, Anibal Lugo, M.D.Search for more papers by this author, Jose L. Freyre, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-796_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSerratia marcescens is being reported with increasing frequency as a cause of nosocomial infections. Previous reports show bacteremia to occur mainly in debilitated chronically ill individuals. Transmission has been through urinary and intravenous catheters and through contaminated positive pressure respirators. Mortality rate has been reported to be very high.Ninteen individuals in previous good health acquired the infection in the operating room through the intravenous injection of a contaminated solution of succinyl chloride. The clinical picture was characterized by sudden chills and fever 24 to 48 hr after surgery followed in a few days by nuchal pain. In six patients... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: San Juan, P.R. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 796-796KeywordsDeath ratesFeversIntravenous injectionsNosocomial infectionsOsteomyelitisRespiratorsSepsisSerratia marcescensSpineSurgery Issue Published: 1 May 1970 PDF downloadLoading ...
Clinical Efficacy of Orlistat Therapy in Overweight and Obese Patients With Insulin-Treated Type 2 Diabetes
Authors: David E. Kelley, George A. Bray, F. Xavier Pi-Sunyer, Samuel Klein, James Hill, John Miles, Priscilla Hollander
Journal: Diabetes Care (2002)

OBJECTIVE; Weight loss improves glycemic control, lipid profiles, and blood pressure in patients with type 2 diabetes. However, successful long-term weight loss is difficult for these patients, particularly those treated with insulin. The aim of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on weight loss, glycemic control, and cardiovascular risk factors in overweight or obese insulin-treated type 2 diabetic patients.This study was a 1-year multicenter, randomized, double-blind, placebo-controlled trial of orlistat (120 mg three times a day) or placebo combined with a reduced-calorie diet in overweight or obese adults (BMI 28-40 kg/m(2)) with type 2 diabetes treated with insulin alone or combined with oral agents, but with suboptimal metabolic control (HbA(1c) 7.5-12.0%). Outcome measurements included changes in body weight, glycemic control, blood pressure, and serum lipids. RESULTS; After 1 year, the orlistat group lost significantly more weight (-3.89 +/- 0.3% of baseline body weight, means +/- SE) than the placebo group (-1.27 +/- 0.3%, P < 0.001). Orlistat treatment, compared with placebo, produced greater decreases in HbA(1c) (-0.62 +/- 0.08 vs. -0.27 +/- 0.08%, P = 0.002), fasting serum glucose (-1.63 +/- 0.3 vs. -1.08 +/- 0.3 mmol/l, P = 0.02), and the required doses of insulin and other diabetic medications. Orlistat also produced greater improvements than placebo in serum total cholesterol (P = 0.0002) and LDL cholesterol concentrations (P = 0.001) and LDL/HDL ratio (P = 0.01). CONCLUSIONS; Orlistat therapy produces clinically significant weight loss, with improvements in glycemic control and cardiovascular disease risk factors, in overweight or obese patients with type 2 diabetes who have suboptimal metabolic control with insulin therapy.
Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles
Authors: Dongfei Liu, Luis M. Bimbo, Ermei Mäkilä, Francesca Villanova, Martti Kaasalainen, Barbara Herranz-Blanco, Carla M. Caramella, Vesa-Pekka Lehto, Jarno Salonen, Karl-Heinz Herzig, Jouni Hirvonen, Hélder A. Santos
Journal: Journal of Controlled Release (2013)
The localization of the bullous pemphigoid and cicatricial pemphigoid antigens: direct and indirect immunofluorescence of suction blisters
Authors: V.A. VENNING, J. ALLEN, P.R. MILLARD, F. WOJNAROWSKA
Journal: British Journal of Dermatology (1989)

The location of in vivo bound immunoreactants was studied in 37 patients with subepidermal blistering diseases by direct immunofluorescence (IMF) on suction blisters taken from uninvolved forearm skin. The patients studied included 18 with bullous pemphigoid (BP), nine with cicatricial pemphigoid (CP), three with acquired epidermolysis bullosa (EBA) and 7 hybrid cases. The patterns of IMF in the suction blisters were: BP, epidermal 1, dermal 1, combined 4, negative 12; CP, epidermal 1, dermal 2, negative 6; EBA, dermal 2, negative 1; and 'hybrid' patients, epidermal 3, negative 4. The different patterns of suction blister staining could not be correlated with the clinical features of the patients in respect of mucous membrane involvement, scars or milia or a history of skin fragility. Both BP and CP are probably heterogeneous in respect of their antigen specificity, and the two diseases cannot reliably be distinguished by the patterns of direct IMF on suction blisters. In addition, some individual patients with BP have more than one target antigen as indicated by a combined pattern of suction blister fluorescence. The lack of correlation between the pattern of suction blister fluorescence and the clinical features suggests that factors other than antigen specificity determine the clinical expression of subepidermal blistering diseases.
A Newly Created Splice Donor Site in Exon 25 of the MyBP-C Gene Is Responsible for Inherited Hypertrophic Cardiomyopathy With Incomplete Disease Penetrance
Authors: Johannes A. Moolman, Sebastian Reith, Kerstin Uhl, Sonja Bailey, Mathias Gautel, Brigitte Jeschke, Christine Fischer, Julia Ochs, William J. McKenna, Heinz Klues, Hans-Peter Vosberg
Journal: Circulation (2000)

Background —Hypertrophic cardiomyopathy is a myocardial disorder resulting from inherited sarcomeric dysfunction. We report a mutation in the myosin-binding protein-C (MyBP-C) gene, its clinical consequences in a large family, and myocardial tissue findings that may provide insight into the mechanism of disease. Methods and Results —History and clinical status (examination, ECG, and echocardiography) were assessed in 49 members of a multigeneration family. Linkage analysis implicated the MyBP-C gene on chromosome 11. Myocardial mRNA, genomic MyBP-C DNA, and the myocardial proteins of patients and healthy relatives were analyzed. A single guanine nucleotide insertion in exon 25 of the MyBP-C gene resulted in the loss of 40 bases in abnormally processed mRNA. A 30-kDa truncation at the C-terminus of the protein was predicted, but a polypeptide of the expected size (≈95 kDa) was not detected by immunoblot testing. The disease phenotype in this family was characterized in detail: only 10 of 27 gene carriers fulfilled diagnostic criteria. Five carriers showed borderline hypertrophic cardiomyopathy, and 12 carriers were asymptomatic, with normal ECG and echocardiograms. The age of onset in symptomatic patients was late (29 to 68 years). In 2 patients, outflow obstruction required surgery. Two family members experienced premature sudden cardiac death, but survival at 50 years was 95%. Conclusions —Penetrance of this mutation was incomplete and age-dependent. The large number of asymptomatic carriers and the good prognosis support the interpretation of benign disease.
Promoting Professionalism Through Self-Appraisal in This Critical Decade
Authors: George D. Lundberg
Journal: JAMA (1991)

The essence of professionalism is self-governance. Central to self-governance is self-criticism. 1 The public trusts medical professionals to be honest with themselves, with each other, and with them. Honesty is exemplified in quality assurance activities within organizations. These are based on the recognition of problem areas, identification of errors when they occur, and institution of corrective actions. The responsible action taken by the faculty and staff at the Beth Israel Hospital in Boston, Mass, and reported elsewhere in this issue in the article by Bedell and colleagues 2 should be lauded and considered a model for other institutions interested in ensuring quality.  The editors ofThe Journalhave chosen to publish a number of challenging articles of this nature. For example, the April 24, 1991, JAMA included two research papers on the frequency of substance abuse among resident physicians and medical students 3,4 and a remarkably candid Special Communication, Do
Strain-specific and common epitopes of gonococcal pili.
Authors: J B Rothbard, R Fernandez, G K Schoolnik
Journal: The Journal of Experimental Medicine (1984)

The antigenic structure of gonococcal pilin, strain MS11 (Tr), was investigated by assaying the binding of antisera engendered by intact pili from strains MS11 and R10 and their two major cyanogen bromide-generated fragments, CNBr-2 (residues 9-92) and CNBr-2 (residues 93-159), to synthetic peptides corresponding to the amino acid sequence of MS11 pilin. Four peptides were synthesized corresponding to regions of sequence variation between MS11 and R10 gonococcal pilin. Antisera against the homologous pilus filament and against its CNBr-3 fragment bind peptides equivalent to residues 121-134 and 135-151, which comprise the 30 amino acid disulfide loop near the carboxyl terminus of the protein. Heterologous pili antisera did not bind these peptides. Absorption studies proved that each peptide contained an independent, strain-specific epitope. Synthetic peptides corresponding to regions of identical sequence between MS11 and R10 pilin were used in similar binding experiments to localize a weakly immunogenic, common determinant between residues 48 and 60. less than 15% of the antibodies raised against intact pili were directed at this site. Antisera raised against MS11 or R10 CNBr-2 bind a separate peptide, residues 69-80. This region is immunogenic only as a fragment, not in the intact pilus filament.
Respiratory Control and Respiratory Sensation in a Patient with a Ganglioglioma within the Dorsocaudal Brain Stem
Authors: HAROLD L. MANNING, JAMES C. LEITER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We encountered a young woman with severe central sleep apnea caused by a medullary glioma located slightly dorsal to and to the right of the midline, a region not generally associated with CO2 chemosensitivity. The patient had normal spirometric readings, lung volumes, diffusing capacity, maximal inspiratory pressure, and alveolar–arterial oxygen difference. While awake, she displayed marked irregularity in her breathing pattern; her end-tidal CO2 (Fet CO2 ) ranged from 5.3 to 10.9%. During voluntary hyperpnea, she could quickly reduce her Fet CO2 to 4.2%, but her Pco 2 did not change after administration of acetazolamide or progesterone. Like patients with congenital central hypoventilation syndrome (CCHS), our patient had a relatively intact ventilatory response to exercise; her Pco 2 was high at the start of exercise and increased slightly thereafter. In contrast to CCHS patients, however, our patient had an intact hypoxic ventilatory response ( Δ Ve/ Δ SaO2 = − 0.37 L/min/SaO2 ). In further contrast to CCHS patients, our patient had a very short breathholding time and described a sensation of air hunger as the factor limiting her breathholding ability. Her heart rate and blood pressure responses to the Valsalva maneuver were normal.
Improvement in diastolic suction in patients with hypertrophic obstructive cardiomyopathy after septal ablation
Authors: Aleksandr Rovner, Marta Sitges, Rebecca Smith, Neil L. Greenberg, Irmien Vlassak, Takahiro Shiota, Murat E. Tuzcu, Nicholas Smedira, Harry M. Lever, James D. Thomas, Mario J. Garcia
Journal: Journal of the American College of Cardiology (2002)
Glucosephosphate-Isomerase (GPI) Deficiency: GPI Elyria
Authors: ERNEST BEUTLER
Journal: Annals of Internal Medicine (1974)

The erythrocytes of a 13-year-old girl with chronic nonspherocytic hemolytic anemia were found to be deficient in glucosephosphate isomerase (GPI). The ratio of erythrocyte glucose-6-phosphate to fructose-6-phosphate the equilibrium catalyzed by GPI was twice that of normal. Splenectomy produced clinical improvement and lengthening of the [51Cr]erythrocyte survival. Since her parents were related, the child was evidently homozygous for a mutant allele. The mutant enzyme, which is designated "Elyria," was found to be electrophoretically slow and thermolabile. An incidental finding was that the patient's mother also carried a gene that coded for an electrophoretically abnormal GPI with normal activity. This electrophoretic variant has been designated "GPI Ohio."
Plasmid Delivery in Vivo from Porous Tissue-Engineering Scaffolds: Transgene Expression and Cellular Transfection
Authors: Jae-Hyung Jang, Christopher B. Rives, Lonnie D. Shea
Journal: Molecular Therapy (2005)

Tissue engineering scaffolds capable of sustained plasmid release can promote gene transfer locally and stimulate new tissue formation. We have investigated the scaffold design parameters that influence the extent and duration of transgene expression and have characterized the distribution of transfected cells. Porous scaffolds with encapsulated plasmid were fabricated from poly(lactide-co-glycolide) with a gas foaming procedure, with wet granulation employed to mix the components homogeneously prior to foaming. Wet granulation enhanced plasmid incorporation relative to standard procedures and also enhanced in vivo transgene expression, possibly through the increased loading and maintenance of the scaffold pore structure. The plasmid loading regulated the quantity and duration of transgene expression, with expression for 105 days achieved at the highest dosage. Expression was localized to the implantation site, though the distribution of transfected cells varied with time. Transfected cells were initially observed at the scaffold periphery (day 3), then within the pores and adjacent to the polymer (day 17), and finally throughout the scaffold interior (day 126). Delivery of a plasmid encoding VEGF increased the blood vessel density relative to control. Correlating scaffold design with gene transfer efficiency and tissue formation will facilitate application of plasmid-releasing scaffolds to multiple tissues.
SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations
Authors: Hiroyuki Unoki, Atsushi Takahashi, Takahisa Kawaguchi, Kazuo Hara, Momoko Horikoshi, Gitte Andersen, Daniel P K Ng, Johan Holmkvist, Knut Borch-Johnsen, Torben Jørgensen, Annelli Sandbæk, Torsten Lauritzen, Torben Hansen, Siti Nurbaya, Tatsuhiko Tsunoda, Michiaki Kubo, Tetsuya Babazono, Hiroshi Hirose, Matsuhiko Hayashi, Yasuhiko Iwamoto, Atsunori Kashiwagi, Kohei Kaku, Ryuzo Kawamori, E Shyong Tai, Oluf Pedersen, Naoyuki Kamatani, Takashi Kadowaki, Ryuichi Kikkawa, Yusuke Nakamura, Shiro Maeda
Journal: Nature Genetics (2008)