tbuckley/cabot-search huggingface dataset:
A Comparison of the Molecular Structure of Integrated Hepatitis B Virus Genomes in Hepatocellular Carcinoma Cells and Hepatocytes Derived From the Same Patient
Authors: Norio Ogata, Takashi Tokino, Tomoteru Kamimura, Hitoshi Asakura
Journal: Hepatology (1990)

To elucidate critical genetic elements in the development of hepatocellular carcinoma associated with hepatitis B virus DNA integration, a single integrant in hepatocellular carcinoma cells and one species of multiple integrants in hepatocytes, both obtained from the same patient, were compared structurally using molecular cloning techniques. Both hepatitis B virus integrants showed similar inverted repeat sequences consisting of two defective virus genomes. The recombination of viral DNAs seemed to be mediated by short regions of base homology near the direct repeat 1 and at other regions of the virus genomes in both integrants. The virus component in the junction with host DNAs was the cohesive end region in each identical end of the viral integrant in hepatocellular carcinoma cells and in one end of the viral integrant in hepatocytes. The structure of the integrant in hepatocellular carcinoma cells was characterized by an inverted, duplicated conformation composed not only of integrated virus genomes but also of flanking cellular sequences. It was shown to be the so-called "alpha dimer" of satellite DNA. In contrast, the flanking, nonreiterated cellular DNA in the hepatocyte-derived clone did not show discernible rearrangement. These findings suggest that a common mechanism underlies the integration of hepatitis B virus DNA so that a similar organization of inverted repeat genomes is found in hepatocellular carcinoma cells and in hepatocytes. The unstable nature of cellular DNA where DNA integration occurs may be important in generating chromosome alterations found in hepatocellular carcinoma.
Large liver cell change in hepatitis B virus-related liver cirrhosis
Authors: Haeryoung Kim, Bong-Kyeong Oh, Massimo Roncalli, Chanil Park, So-Mi Yoon, Jeong Eun Yoo, Young Nyun Park
Journal: Hepatology (2009)

Abstract Large liver cell change (LLCC) refers to microscopic lesions often found in various chronic liver diseases; however, its nature is still controversial. Thirty-four formalin-fixed and 19 fresh frozen hepatitis B virus (HBV)-related cirrhosis samples were examined for the presence of LLCC, small liver cell change (SLCC), and hepatocellular carcinoma (HCC). The cell cycle checkpoint status (p21, p27, p16, Tp53), cell dynamics (proliferating cell nuclear antigen, Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, M30), DNA damage (γ-H2AX [H2A histone family, member X]), telomere lengths, chromosomal instability (micronuclei index), and senescence-associated β-galactosidase (SA-β-Gal) activity were evaluated using an in situ approach and compared to those in normal liver (n = 5) and liver with chronic cholestasis (34 cases of hepatolithiasis and three cases of primary biliary cirrhosis). In HBV-related cirrhosis, the p21, p27, and p16 cell cycle checkpoint markers were activated in normal-looking cirrhotic hepatocytes (NLCH), but diminished gradually from LLCC, SLCC, to HCC, with an increase in Tp53 expression. There was a general decrease in telomere length from NLCH, LLCC, SLCC, to HCC. Micronuclei, γ-H2AX foci, and net cellular gain were significantly increased from normal hepatocytes, NLCH, LLCC, SLCC, to HCC. The SA-β-Gal activity was weaker in LLCC compared to NLCH and absent in SLCC and HCC. In contrast, cholestatic LLCC showed retained expression of cell cycle checkpoint markers and decreased net cellular gain compared to adjacent normal-looking hepatocytes. HBV-related LLCC showed significantly higher Tp53 labeling index, γ-H2AX labeling index, and micronuclei index; shorter telomere length; decreased SA-β-Gal activity; and increased net cellular gain compared to cholestatic LLCC. Conclusion: The nature of LLCC is rather heterogeneous depending on the biological setting. The characteristics of HBV-related LLCC are more consistent with dysplastic rather than merely reactive hepatocytes, whereas cholestatic LLCC more likely represents reactive change with more stringent cell cycle checkpoint control. (Hepatology 2009.)
Renal microcirculation and tissue damage during acute ureteral obstruction in the rat: Effect of saline infusion, indomethacin and radiocontrast
Authors: Samuel N. Heyman, Shmuel Fuchs, Ronen Jaffe, Ahuva Shina, Lena Ellezian, Mayer Brezis, Seymour Rosen
Journal: Kidney International (1997)
Diabetes and Antiplatelet Therapy in Acute Coronary Syndrome
Authors: José Luis Ferreiro, Dominick J. Angiolillo
Journal: Circulation (2011)

C ardiovascular disease, particularly coronary artery dis- ease resulting from accelerated atherosclerosis, is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM). 1 Of note, DM patients without a history of coronary artery disease have overall the same cardiac risk as non-DM patients with a history of myocardial infarction (MI). 2 Furthermore, patients with DM also have a higher risk of cardiovascular complications and recurrent atherothrombotic events than non-DM patients. 3In fact, in the setting of acute coronary syndromes (ACS), the presence of DM is a strong independent predictor of short-term and long-term recurrent ischemic events, including mortality. 4,5he concomitant presence of cardiovascular risk factors and comorbidities that negatively affect the outcomes of ACS is higher in DM patients. 6The negative impact of DM on outcomes is maintained across the ACS spectrum, including unstable angina and non-ST-elevation MI (NSTEMI), 7 STelevation MI (STEMI) treated medically, 8 and ACS undergoing percutaneous coronary intervention (PCI). 9,102][13][14][15] This may play a role not only in the higher risk of developing ACS and the worse outcomes observed in DM, but also in the larger proportion of DM patients with inadequate response to antiplatelet agents compared with non-DM subjects, 13,16 -18 which may also contribute to the impaired outcomes observed in DM patients despite compliance with recommended antiplatelet treatment regimens.The aim of this article is to provide an overview of the current status of knowledge on platelet abnormalities that characterize DM patients, to analyze the benefits and limitations of currently available antiplatelet agents used in ACS, focusing on drawbacks of these therapies in DM patients, and to describe potential future directions to overcome these limitations, which include new agents and treatment strategies. Platelet Dysfunction in DM: The "Diabetic" PlateletPlatelets play a pivotal role in atherogenesis and its thrombotic complications such as those occurring in patients with ACS, 19 -22 which is a platelet-driven process.Platelets of DM patients have been proven to be hyperreactive with intensified adhesion, activation, and aggregation. 11-15Multiple mechanisms have been proposed to contribute to increased platelet reactivity.Although many of them are closely interrelated, these mechanisms are caused by metabolic and cellular abnormalities that occur in DM patients, which can be grouped together into the following categories: hyperglycemia, insulin resistance, associated metabolic conditions, and other cellular abnormalities (Figure 1).
Fibrous obliterative lesions of veins contribute to progressive fibrosis in chronic liver allograft rejection
Authors: Yuichi Nakazawa, Julie R. Jonsson, Neal I. Walker, Paul Kerlin, Charles Steadman, Stephen V. Lynch, Russell W. Strong, Andrew D. Clouston
Journal: Hepatology (2000)

Fibrosis in liver allografts undergoing chronic rejection (CR) is variable and poorly understood. The temporal and spatial relationships of venous, arterial, and biliary lesions were studied to clarify their potential contributions to graft fibrosis. The severity, prevalence, and morphology of intimal lesions of vessels were analyzed and compared with the fibrosis stage. Three groups were found; group 1 (n = 5) with no hepatic vein (HV) lesions, group 2 (n = 5) with HV lesions only, and group 3 with lesions of both HV and portal veins (PV). The earliest lesion to develop, in 71% of grafts, was concentric intimal thickening of small HV. This was significantly more severe and frequent in grafts from group 3. With increasing frequency and severity of small HV sclerosis, fibrosis developed in medium/large veins. The morphology of larger vessel lesions suggested organized thrombus. Centrilobular fibrosis was significantly more severe in group 3 and developed unpredictably and sometimes rapidly. Conversely, portal fibrosis scores were significantly higher in grafts with ductular proliferation and did not correlate with venous lesions. This suggests that in CR, veno-occlusive-like lesions develop commonly in terminal hepatic venules, probably caused by immune-mediated damage. In only a proportion, with increased frequency and severity of the lesions, stasis and thrombosis in portal and larger veins occur and could result in loss of hepatic and portal venous outflow, which leads to ischemia and fibrosis. The stage of fibrosis did not correlate with foam-cell arteriopathy. A second pathway of portal fibrosis occurs in patients with longstanding biliary proliferation.
Fenfluramine Therapy in Non-insulin-dependent Diabetic Patients: Effects on Body Weight, Glucose Homeostasis, Serum Lipoproteins, and Antipyrine Metabolism
Authors: P I Salmela, E A Sotaniemi, J Viikari, T Solakivi-Jaakkola, P Järvensivu
Journal: Diabetes Care (1981)

The usefulness of fenfluramine (F), in association with diet therapy, was investigated in 13 obese noninsulin- dependent diabetic patients with poor diabetes control on a previous sulfonylurea regimen (SU). A double-blind crossover comparison of F and placebo (P) consisted of two 7-wk treatment periods. F was administered in stepwise increased and subsequently reduced doses, while the doses of SU were kept unchanged. There was a significant weight loss in F-treated obese subjects as compared with treatment by P. The fasting levels, and particularly the postprandial blood glucose (BG) levels, were significantly lower during F than during P administration. Serum fasting insulin and blood lactate concentrations remained unchanged during the trial. Serum triglycerides and cholesterol decreased during F administration. HDL-cholesterol and apoprotein A-I increased slightly, while apoprotein B decreased during F, but not during P administration. The effect of fenfluramine on hepatic drug metabolism was assessed by using the antipyrine test. F did not cause significant changes in antipyrine metabolism. Fenfluramine therefore seems to be useful as an adjunct to diet and SU therapy in obese non-insulin-dependent diabetic patients.
Tea with Walter de la Mare
Authors: M. Eastwood
Journal: BMJ (2008)

When I was preparing for the membership examination I had a passing contact with Russell Brain’s textbook Diseases of the Nervous System . I was ignorant of the man’s intellect and his varied interests. Brain followed a variety of intellectual pursuits in addition to medicine in all of its facets, including reading and writing poetry. He was curious about the relation between mind and body. He wrote that the receptive function of the brain is to provide us with a symbolic representation of the world outside it. He read widely and came across Walter de la Mare’s book Pleasures and Speculations , which included …
THE REGISTRATION OF VITAL STATISTICS IN THE UNITED STATES.WHAT THE CENSUS BUREAU IS DOING TO IMPROVE IT.
Authors: CRESSY L. WILBUR
Journal: JAMA (1905)

The study of the development of registration methods in this country and of their relation to other branches of public health work will be an interesting part of the labors of the future historian of sanitary science. It is generally accepted as a fact that accurate vital statistics are absolutely indispensable to a satisfactory public health administration, and accordingly state and municipal boards of health are charged with the enforcement of registration laws. Nevertheless, while nearly every state in the Union is provided with a state board of health, less than a dozen states possess and enforce in a fairly effective way laws for the registration of deaths. States having approximately complete returns of deaths are designated "registration states" by the Census Bureau. The standard is not a high one, only about 90 per cent. of accuracy being required for admission to the class. Even thus, there were only nine
Acetylcysteine and fulminant hepatic failure
Authors: Patricia Sheiner, Wilfred de Majo, Gary A. Levy
Journal: Hepatology (1992)

Background. When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption. Methods. We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure and 8 patients with acute liver failure from other causes. The acetylcysteine was given in a dose of 150 mg per kilogram of body weight in 250 ml of 5 percent dextrose over a period of 15 minutes and then in a dose of 50 mg per kilogram in 500 ml of 5 percent dextrose over a period of 4 hours; measurements were made before treatment began and after 30 minutes of the regimen. Results. In the patients with acetaminophen-induced liver failure, the infusion of acetylcysteine resulted in an increase in mean oxygen delivery from 856 to 975 ml per minute per square meter of body-surface area (P = 0.0036), due to an increase in the cardiac index from 5.6 to 6.7 liters per minute per square meter (P = 0.0021). Mean arterial pressure rose from 88 to 95 mm Hg (P = 0.0054) despite a decrease in systemic vascular resistance from 1296 to 1113 dyn · sec · cm −6 per square meter (P = 0.027). There was an increase in oxygen consumption from 127 to 184 ml per minute per square meter (P = 0.0007) associated with an increase in the oxygen-extraction ratio from 16 to 21 percent (P = 0.022). The effects in the patients with acute liver failure from other causes were similar. Conclusions. The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen.
Health services outsourced to private sector increased from 6.9bn to 12.2bn in three years to 2013
Authors: G. Iacobucci
Journal: BMJ (2015)

The private sector increased its financial yield from medical services outsourced from the NHS by three quarters from 2010 to 2013, a major new audit has shown.

A report published by Oxford Economics for the Business Services Association (BSA)1 showed that the UK-wide market for “frontline health services” that are outsourced from the NHS is now worth £12.2bn (€16.4bn; …
Clinical and pathologic characteristics of dilated cardiomyopathy in hemodialysis patients
Authors: Jiro Aoki, Yuji Ikari, Hiroyoshi Nakajima, Masaya Mori, Tokuichiro Sugimoto, Mitsuharu Hatori, Shuzou Tanimoto, Eisuke Amiya, Kazuhiro Hara
Journal: Kidney International (2004)
Diagnosis of Esophagogastric Tumors
Authors: M. Moretó
Journal: Endoscopy (2005)

With regard to esophageal tumors, important reports on several topics have been published recently. 1) The place of endoscopic ultrasonography (EUS) as the best locoregional staging technique for cancer of the esophagus has been further consolidated. The addition of fine-needle aspiration makes EUS more sensitive than computed tomography (CT) and more accurate than CT or EUS alone for nodal staging. 2) High-resolution endoscopy with chromoendoscopy has been found to be very effective for mucosal lesions, but not for submucosal lesions. In combination with EUS, the sensitivity for submucosal tumors increases up to 60 %. 3) Autofluorescence-guided biopsy has been reported to be a good tool for detecting high-grade dysplasia. A narrow-band imaging system improved the overall accuracy for depth of invasion. 4) The incidence of hypopharyngeal cancer increases after resection for esophageal carcinoma. Patients with a scattered staining pattern after application of Lugol's solution are more prone to develop upper lesions. 5) Fluorescence imaging makes it possible to detect low-grade intraepithelial neoplasia in Barrett's mucosa, with fewer biopsies. 6) Patients with Barrett's esophagus with a length of over 3 cm had a significantly greater prevalence of dysplasia in comparison with those in the whom the Barrett's segment was shorter than 3 cm (23 % vs. 9 %, P = 0.0001).
DIVERTICULITIS (NOT MECKEL'S) CAUSING INTESTINAL OBSTRUCTION.MULTIPLE MESENTERIC (ACQUIRED) DIVERTICULA OF THE SMALL INTESTINE.
Authors: HERMON C. GORDINIER
Journal: JAMA (1906)

The so-called false or acquired diverticula of the small intestine have been of very little interest to clinicians because of their supposed rare occurrence and also because it was thought that they rarely or never give rise to any clinical symptoms. The following case with multiple mesenteric diverticula of the small intestine shows that, apparently, even in these heretofore considered benign diverticula inflammatory changes may occur which may give rise to clinical symptoms and even endanger the life of the individual. In this case, apparently, one of the diverticula became inflamed and a diverticulitis occurred, causing a partial obliteration of the diverticulum. As the diverticulum extended between the folds of the mesentery, the later became inflamed, thickened and puckered, thus causing an angular bending of the intestine and obstructing its lumen. The local peritonitis arising as the result of this gave rise to the formation of adhesions between the mesentery
EVALUATION OF RIGHT VENTRICULAR DYSFUNCTION IN PATIENTS WITH INTESTINAL CARCINOID DISEASE -ADDED VALUE BY MYOCARDIAL STRAIN ECHOCARDIOGRAPHY AND TRICUSPID ANNULAR PLANE SYSTOLIC EXCURSION
Authors: Kristina H. Haugaa, Laura G. Sahakyan, D.S. Bergestuen, Helge Skulstad, Espen Thiis-Evensen
Journal: Journal of the American College of Cardiology (2010)
Ulcerative Stomatitis Associated with Symptoms of Peptic Ulcer
Authors: T. H. Oliver
Journal: BMJ (1954)

DiscussionAlthough this series was kept small because of the pos- sible consequences of repeated arterial puncture, I feel that the results are significant.It seems that in intermittent c'audication the benefits do not warrant this treatment.In ischaemic necrosis it would appear to be a worth-while procedure, especially as it can be performed in an out- patient clinic.Moreover, it seems to be a good alternative to lumbar sympathectomy, and can, of course, be applied to patients unfit on general grounols for a major operation.
The Legitimacy of a Diverse Society
Authors: Kenneth J. Ryan
Journal: JAMA (1975)

IN THE aftermath of the abortion-manslaughter trial of Kenneth Edelin, MD, strident voices on both sides of the divisive moral issue of abortion seriously challenge the legitimacy of our diverse society. The Supreme Court decision in the now-famous cases of<i>Roe vs Wade</i>and<i>Doe vs Bolton</i>affirmed a constitutional right to differ in our personal morality, rather than what many believe was a judgment on the superiority of one moral view of abortion over another. Justice Blackmun, with six of the justices concurring, provides compelling reading in reaching the decision on state abortions statutes: The constitution is made for people of fundamentally differing views.... It should be sufficient to note briefly the wide divergence of thinking on this most sensitive and difficult question.... In a constitution for free people there can be no doubt that the meaning of liberty must be broad indeed.... It is the right of the
Nuclear Localization of Signal Transducer and Activator of Transcription 3 in Head and Neck Squamous Cell Carcinoma Is Associated with a Better Prognosis
Authors: Eirini Pectasides, Ann-Marie Egloff, Clarence Sasaki, Panteleimon Kountourakis, Barbara Burtness, George Fountzilas, Urania Dafni, Thomas Zaramboukas, Theodoros Rampias, David Rimm, Jennifer Grandis, Amanda Psyrri
Journal: Clinical Cancer Research (2010)

Abstract Purpose: A high frequency of head and neck squamous cell cancers (HNSCC) contain constitutively activated signal transducer and activator of transcription 3 (STAT3). To further elucidate the prognostic role of STAT3 in HNSCC, the expression pattern of STAT3 was correlated with outcome in two independent data sets. Experimental Design: STAT3 protein expression analysis was done on a test cohort of 102 patients with HNSCC recruited between 1992 and 2005. Automated quantitative analysis was used to assess STAT3 protein expression. We evaluated associations with clinicopathologic parameters and survival prognosis. Associations were validated in a second, independent cohort of 58 patients with confirmed HNSCC enrolled in the Early Detection Research Network–sponsored study who underwent surgical resection with curative intent at the University of Pittsburgh Medical Center between 2000 and 2004. Results: STAT3 displayed mixed nuclear and cytoplasmic staining. Survival analysis showed that high nuclear STAT3 expression (top tertile versus the rest) was associated with longer progression-free survival (n = 70, mean survival of 88.9 versus 46.7 months, P = 0.012 for the first cohort; n = 37, mean survival of 60.3 versus 33.0 months, P = 0.009 for the second cohort). After best model selection in the multivariable analysis context, only STAT3 was significant, revealing a lower risk of progression and death for patients with high nuclear STAT3-expressing tumors (hazard ratio, 0.28; 95% confidence interval, 0.10-0.82; P = 0.019; and hazard ratio, 0.23; 95% confidence interval, 0.07-0.76; P = 0.016, respectively). Conclusions: Our results indicate that high nuclear STAT3 expression levels by automated quantitative analysis are associated with favorable outcome in HNSCC. Clin Cancer Res; 16(8); 2427–34. ©2010 AACR.
Hepatitis B virus escape mutants: “pushing the envelope” of chronic hepatitis B virus infection
Authors: Larry Mimms
Journal: Hepatology (1995)

Hepatitis B virus (HBV) DNA was extracted from sera of six carriers with hepatitis B e antigen as well as antibody to hepatitis B surface antigen and sequenced within the pre-S regions and the S gene. HBV DNA clones from five of these carriers had point mutations in the S gene, resulting in conversion from IIe-126 or Thr-126 of the wild-type virus to Ser-126 or Asn-126 in three carriers and conversion from Gly-145 to Arg-145 in three of them; clones with Asn-126 or Arg-145 were found in one carrier. All 12 clones from the other carrier had an insertion of 24 bp encoding an additional eight amino acids between Thr-123 and Cys-124. In addition, all or at least some of the HBV DNA clones from these carriers had inphase deletions in the 5′ terminus of the pre-S2 region. These results indicate that HBV escape mutants with mutations in the S gene affecting the expression of group-specific determinants would survive in some carriers after they seroconvert to antibody against surface antigen. Carriers with HBV escape mutants may transmit HBV either by donation of blood units without detectable surface antigen or through community-acquired infection, which would hardly be prevented by current hepatitis B immunoglobulin or vaccines.