tbuckley/cabot-search huggingface dataset:
Suberoylanilide Hydroxamic Acid Enhances Gap Junctional Intercellular Communication via Acetylation of Histone Containing <i>Connexin 43</i> Gene Locus
Authors: Takahiko Ogawa, Tomonori Hayashi, Masahide Tokunou, Kei Nakachi, James E. Trosko, Chia-Cheng Chang, Noriaki Yorioka
Journal: Cancer Research (2005)

A histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), induces apoptosis in neoplastic cells, but its effect on gap junctional intercellular communication in relation to apoptosis was unclear. Therefore, we carried out a comparative study of the effects of two HDAC inhibitors, SAHA and trichostatin-A, on gap junctional intercellular communication in nonmalignant human peritoneal mesothelial cells (HPMC) and tumorigenic ras oncogene-transformed rat liver epithelial cells (WB-ras) that showed a significantly lower level of gap junctional intercellular communication than did HPMC. Gap junctional intercellular communication was assessed by recovery rate of fluorescence recovery after photobleaching. Treatment of HPMC with SAHA at nanomolar concentrations caused a dose-dependent increase of recovery rate without inducing apoptosis. This effect was accompanied by enhanced connexin 43 (Cx43) mRNA and protein expression and increased presence of Cx43 protein on cell membrane. Trichostatin-A induced apoptosis in HPMC but was less potent than SAHA in enhancing the recovery rate. In contrast, treatment of WB-ras cells with SAHA or trichostatin-A induced apoptosis at low concentrations, in spite of smaller increases in recovery rate, Cx43 mRNA, and protein than in HPMC. Chromatin immunoprecipitation analysis revealed that SAHA enhanced acetylated histones H3 and H4 in the chromatin fragments associated with Cx43 gene in HPMC. These results indicate that SAHA at low concentrations selectively up-regulates Cx43 expression in normal human cells without induction of apoptosis, as a result of histone acetylation in selective chromatin fragments, in contrast to the apoptotic effect observed in tumorigenic WB-ras cells. These results support a cancer therapeutic and preventive role for specific HDAC inhibitors.
Left Septal Atrial Flutter
Authors: Nassir F. Marrouche, Andrea Natale, Oussama M. Wazni, Jie Cheng, Yanfei Yang, Harvey Pollack, Atul Verma, Phillip Ursell, Melvin M. Scheinman
Journal: Circulation (2004)

We describe the clinical and electrophysiological characteristics of a novel macroreentrant form of left atrial flutter circuit.A total of 11 patients were included in the study. The mean tachycardia cycle length was 278+/-41 ms. Nine of the 11 patients were treated with antiarrhythmic drugs at the time of the study for concomitant atrial fibrillation. With the use of entrainment pacing and either the CARTO Biosense mapping system (9 patients) or conventional mapping (2 patients), the flutter circuit was found to rotate around the left septum primum with a critical isthmus located between the pulmonary veins posteriorly and/or mitral annulus anteriorly and the septum primum. In 5 patients, radiofrequency ablation was performed from the septum primum to the right inferior pulmonary vein (group 1), and in 6 patients, a lesion was made from the septum primum to the mitral annulus (group 2). After a follow-up of 13+/-6 months, 2 patients in group 1 and all patients in group 2 remained in sinus rhythm without recurrence.Slowing of electric conduction in the left atrial septum due to antiarrhythmic drugs and/or atrial myopathy seems to promote left septal atrial flutter. Radiofrequency ablation of this arrhythmia is usually effective and safe. A line of block between the septum primum and the mitral annulus proved to be effective for cure of tachycardia.
1. Persistent Gene Expression in Mouse Nasal Epithelia Following Baculovirus GP64 Pseudotyped FIV-Based Gene Transfer
Authors: Patrick L. Sinn, Erin R. Burnight, Melissa A. Hickey, Gary W. Blissard, Paul B. McCray
Journal: Molecular Therapy (2005)

The use of gene transfer to treat or prevent cystic fibrosis lung disease has been limited in part by the inability of vectors to efficiently and persistently transduce airway epithelia. Influenza A is an enveloped virus with natural lung tropism; however, pseudotyping feline immunodeficiency virus (FIV)-based lentiviral vector with the HA and HEF envelope proteins proved unsuccessful. Conversely, influenza D has a single envelope protein (GP64) and pseudotyping FIV with influenza D GP64 (from Thogotovirus) resulted in titers of 10e6 TU/ml. Further, influenza D GP64 conferred FIV apical entry into well-differentiated human airway epithelial cells. Baculovirus GP64 envelope glycoproteins share sequence identity with influenza D envelope glycoproteins, the result of a postulated lateral transfer of genetic material during the evolution of the two viral families. Pseudotyping FIV with GP64 from 3 species of baculovirus resulted in titers ranging from 10e7|[ndash]|10e9 TU/ml. Of note, GP64 from Autographa californica multinuclear polyhedrosis virus resulted in high titer FIV preparations (upwards of 10e9 TU/ml) and also conferred apical entry into polarized primary cultures of human airway epithelia. These titers equal those obtained with VSV-G pseudotyping. Using a luciferase reporter gene and bioluminescent imaging, we observed persistent in vivo gene transfer in the mouse nose with A. californica GP64 pseudotyped FIV (AcGP64-FIV). Longitudinal bioluminescence analysis has documented the persistence of expression in the nasal epithelia for >7 months without significant decline. We used a nuclear targeted beta-galactosidase reporter and histologicial analysis to demonstrate that surface epithelial cells were transduced in the mouse sinuses. In addition, AcGP64-FIV transduced mouse nasal epithelia with much greater efficiency than VSV-G pseudotyped FIV, as determined by both bioluminescence and histological analysis. These data suggest that AcGP64-FIV efficiently and persistently transduces nasal epithelia in the absence of agents that disrupt the cellular tight junction integrity and have important implications for CF gene therapy.
59 NAFLD INDEX: A SIMPLE SCREENING TOOL REFLECTING NONALCOHOLIC FATTY LIVER DISEASE IN THE KOREAN POPULATION
Authors: J.-H. Lee, D. Kim, H.J. Kim, J.I. Yang, W. Kim, Y.J. Kim, J.-H. Yoon, S.-H. Cho, M.-W. Sung, H.-S. Lee
Journal: Journal of Hepatology (2009)
Patient privacy and secondary use of administrative databases
Authors: S. Kumar
Journal: JAMA (1996)

To the Editor.  —We commend Mr Gostin 1 for highlighting current issues and controversies regarding the acquisition, storage, and use of existing public health data. However, Gostin did not explicitly address how these state and federal statutes relate to the secondary use of administrative claims data such as Medicare data (Part A and B) and State Medicaid Management Information Systems databases, Veterans Affairs data, state repositories of data (Tumor Registry databases, Sudden Infant Death Syndrome database, and others), pharmaceutical databases, laboratory databases, and others. As of April 1996, a total of 38 states mandated the collection, analysis, and public dissemination of data from health care providers. 2 These data contain potentially vast amounts of useful information for public health purposes on populations considered to be vulnerable. For example, to examine health status of nursing home residents, cost issues, quality of care concerns (eg, pressure ulcers, methicillin-resistant Staphylococcus aureus , or nosocomial
Subclinical States of Glucose Intolerance and Risk of Death in the U.S.
Authors: Sharon H. Saydah, Catherine M. Loria, Mark S. Eberhardt, Frederick L. Brancati
Journal: Diabetes Care (2001)

OBJECTIVE—Although clinically evident type 2 diabetes is a well-established cause of mortality, less is known about subclinical states of glucose intolerance. RESEARCH DESIGN AND METHODS—Data from the Second National Health and Nutrition Examination Survey Mortality Study, a prospective study of adults, were analyzed. This analysis focused on a nationally representative sample of 3,174 adults aged 30–75 years who underwent an oral glucose tolerance test at baseline (1976–1980) and who were followed up for death through 1992. RESULTS—Using 1985 World Health Organization criteria, adults were classified as having previously diagnosed diabetes (n = 248), undiagnosed diabetes (n = 183), impaired glucose tolerance (IGT) (n = 480), or normal glucose tolerance (n = 2,263). For these groups, cumulative all-cause mortality through age 70 was 41, 34, 27, and 20%, respectively (P &amp;lt; 0.001). Compared with those with normal glucose tolerance, the multivariate adjusted RR of all-cause mortality was greatest for adults with diagnosed diabetes (RR 2.11, 95% CI 1.56–2.84), followed by those with undiagnosed diabetes (1.77, 1.13–2.75) and those with IGT (1.42, 1.08–1.87; P &amp;lt; 0.001). A similar pattern of risk was observed for cardiovascular disease mortality. CONCLUSIONS—In the U.S., there was a gradient of mortality associated with abnormal glucose tolerance ranging from a 40% greater risk in adults with IGT to a 110% greater risk in adults with clinically evident diabetes. These associations were independent of established cardiovascular disease risk factors.
Massive fatal pulmonary emboli with fibrinolytic therapy.
Authors: J C Goldsmith, P Lollar, J C Hoak
Journal: Circulation (1981)

A case is described in which massive fatal pulmonary emboli followed the initiation of thrombolytic therapy. Several important issues regarding anticoagulation and fibrinolytic therapy are addressed, including the possibility of anticoagulant failure and the risks of using fibrinolytic therapy in the setting of recent and remote thrombotic disease.
Severe case of pemphigoid gestationis with unusual target antigen
Authors: G. KIRTSCHIG, P.M. COLLIER, R.W. EMMERSON, F. WOJNAROWSKA
Journal: British Journal of Dermatology (1994)

Summary We report a severe case of pemphigoid gestationis (PG) with an unusual target antigen. The patient developed a severe itchy macular rash on the abdomen during her fifth pregnancy, at 38 weeks' gestation. The disease persisted for 8 months post-partum, and could only be controlled with high doses of systemic corticosteroids and dapsone. The diagnosis of PG was confirmed by direct and indirect immunofluorescence. A linear band of IgG and C3 was detected at the epidermal aspect of salt-split skin. Immunoblotting studies revealed circulating IgG antibodies binding to a single 200-kDa protein in epidermal extracts. Immunofluorescence studies using trypsinized human keratino- cytes demonstrated uniform staining around the cell peripheries, suggesting that the target antigen was not associated with hemidesmosomes. These findings differ from the usual immunological features seen in PG, and suggest further heterogeneity of the antigens involved in PG.
Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy
Authors: Guido Torzilli, Masami Minagawa, Tadatoshi Takayama, Kazuto Inoue, Ai-Min Hui, Keiichi Kubota, Kuni Ohtomo, Masatoshi Makuuchi
Journal: Hepatology (1999)

Fine-needle biopsy (FNB) is associated with problems, such as tumor seeding, which are probably underestimated. The aim of this study was to validate prospectively the accuracy of our diagnostic work-up without FNB, for defining indications for surgery in a cohort of patients with focal liver lesions (FLLs). Between January 1997 and December 1998, 160 consecutive patients carrying 225 FLLs admitted to our department were evaluated prospectively. Preoperative diagnoses were established by means of clinical histories, serum tumor marker levels, ultrasonography, and spiral computed tomography (CT). Angiography, magnetic resonance imaging (MRI), and Lipiodol-CT were performed when it was considered necessary to plan the surgical strategy. All the patients underwent surgery and results of pathological examinations were obtained for all of them. The preoperative diagnoses of 221 of the 225 lesions (98.2%) were confirmed, and the indications for liver resection in 156 of the 160 patients (97.5%) were correct. The respective accuracy, sensitivity, specificity, and positive and negative predictive values were 99.6%, 100%, 98.9%, 99.3%, and 100% for diagnosis of hepatocellular carcinoma (HCC); 99.1%, 100%, 98.8%, 96.9%, and 100% for metastases; 99.6%, 100%, 99.5%, 91%, and 100% for cholangiocellular carcinomas (CCCs); all 100% for mixed HCC-CCCs; and 98.7%, 57.1%, 100%, 100%, and 98.6% for benign tumors. In view of these results, the fact that the real risks of FNB have yet to be established and the possibility that tumor seeding has a major impact on patient prognosis, the use of FNB should be drastically limited.
Brief Intervention for Medical Inpatients with Unhealthy Alcohol Use
Authors: Richard Saitz, Tibor P. Palfai, Debbie M. Cheng, Nicholas J. Horton, Naomi Freedner, Kim Dukes, Kevin L. Kraemer, Mark S. Roberts, Rosanne T. Guerriero, Jeffrey H. Samet
Journal: Annals of Internal Medicine (2007)

Background: The efficacy of brief intervention in reducing alcohol consumption is well established for selected outpatients but not for medical inpatients. Objective: To determine whether brief intervention improves alcohol outcomes in medical inpatients who were identified by screening as having unhealthy alcohol use. Design: Randomized, controlled trial. Setting: Medical service of an urban hospital. Patients: 341 medical inpatients who were drinking risky amounts of alcohol (defined for eligibility as >14 drinks/wk or ≥5 drinks/occasion for men and >11 drinks/wk or ≥4 drinks/occasion for women and persons ≥66 y); 77% had alcohol dependence as determined by the Composite International Diagnostic Interview Alcohol Module. Intervention: A 30-minute session of motivational counseling given by trained counselors during a patient's hospitalization (n = 172) versus usual care (n = 169). Measurements: Self-reported primary outcomes were receipt of alcohol assistance (for example, alcohol disorders specialty treatment) by 3 months in dependent drinkers and change in the mean number of drinks per day from enrollment to 12 months in all patients. Results: The intervention was not significantly associated with receipt of alcohol assistance by 3 months among alcohol-dependent patients (adjusted proportions receiving assistance, 49% for the intervention group and 44% for the control group; intervention–control difference, 5% [95% CI, −8% to 19%]) or with drinks per day at 12 months among all patients (adjusted mean decreases, 1.5 for patients who received the intervention and 3.1 for patients who received usual care; adjusted mean group difference, −1.5 [CI, −3.7 to 0.6]). There was no significant interaction between the intervention and alcohol dependence in statistical models predicting drinks per day (P = 0.24). Limitations: Baseline imbalances existed between randomized groups. Patients who received usual care were assessed and advised that they could discuss their drinking with their physicians. Conclusions: Brief intervention is insufficient for linking medical inpatients with treatment for alcohol dependence and for changing alcohol consumption. Medical inpatients with unhealthy alcohol use require more extensive, tailored alcohol interventions.
P1-024: Relationship between tyrosine kinase domain gene mutations of epidermal growth factor receptor and respiratory function in non-small cell lung cancer
Authors: Kouki Ohtsuka, Hiroaki Ohnishi, Keiko Morita, Misaki Chiba, Wataru Ogura, Satsuki Matsushita, Tomonori Kishino, Tomoyuki Goya, Takashi Watanabe
Journal: Journal of Thoracic Oncology (2007)
Effects of nifedipine on diastolic function during brief periods of flow-limiting ischemia in the conscious dog.
Authors: R J Applegate, R A Walsh, R A O'Rourke
Journal: Circulation (1987)

To determine the contribution of transsarcolemmal calcium flux to abnormal diastolic function produced by brief periods of flow-limiting ischemia and reperfusion, we evaluated early and late diastolic function during transient coronary occlusion and reperfusion before and during administration of intravenous nifedipine (NIF) (10 +/- 1 microgram/kg/min) in nine preinstrumented conscious dogs. We also assessed the effects of nitroprusside (NTP) (2 +/- 0.2 micrograms/kg/min) during an identical period of ischemia and reperfusion to independently assess the consequences of altered loading alone on diastolic function. To minimize the effects of temporal dysynchrony and altered ventricular loading conditions on isovolumetric relaxation, we developed a conscious dog preparation of reversible transient (30 to 60 sec) bilateral coronary occlusion (BCO). BCO was characterized by significant systolic depression: maximum (+)dP/dt decreased (from 2617 +/- 600 to 1981 +/- 565 mm Hg/sec, p less than .05), left ventricular transverse dimension shortening diminished (from 20 +/- 5 to 9 +/- 5%, p less than .05), and the left ventricle dilated (42.4 +/- 6.4 to 43.8 +/- 6.3 mm, p less than .05). Concomitantly the time constants of isovolumetric relaxation prolonged (from 22 +/- 3 to 28 +/- 4 msec, p less than .05) and minimal diastolic left ventricular pressure increased (from -3 +/- 6 to 6 +/-6 mm Hg, p less than .05). The passive diastolic pressure-dimension relationship shifted upward and to the right and was associated with increased chamber stiffness (from 0.50 +/- 0.26 to 1.03 +/- 0.53 mm Hg/mm, p less than .05) and increased left ventricular end-diastolic pressure (from 7 +/- 7 to 19 +/- 7 mm Hg, p less than .05). Reperfusion immediately after BCO was characterized by prompt restoration of systolic contractile performance [maximum (+)dP/dt 3220 +/- 530 mm Hg/sec] but persistently abnormal early and late diastolic function (time constant of isovolumetric relaxation 30 +/- 6 msec, left ventricular end-diastolic pressure 20 +/- 7 mm Hg). The effects of drug administration on ventricular function during BCO were then evaluated under matched loading conditions. NTP improved time constant of isovolumetric relaxation (20 +/- 8 vs 28 +/- 4 msec, p less than .05) and minimal diastolic left ventricular pressure (2 +/- 5 vs 6 +/- mm Hg, p less than .05) during BCO, but NIF did not (time constant of isovolumetric relaxation 27 +/- 6 msec, minimal diastolic left ventricular pressure 7 +/- 5 mm Hg).(ABSTRACT TRUNCATED AT 400 WORDS)
Diffuse large B‐cell lymphoma in the young in Japan: A study by the Osaka Lymphoma Study Group
Authors: Amane Yamauchi, Shigeki Fujita, Junichiro Ikeda, Itsuko Nakamichi, Shiro Fukuhara, Masayuki Hino, Yuzuru Kanakura, Hiroyasu Ogawa, Haruo Sugiyama, Akihisa Kanamaru, Katsuyuki Aozasa
Journal: American Journal of Hematology (2007)

Abstract Clinicopathological and immunophenotypical characteristics in 24 patients with diffuse large B‐cell lymphoma (DLBCL) under 30 years of age in Osaka, Japan were examined, and the results compared to those of DLBCL patients aged over 40 years in Osaka and of young DLBCL patients in Western countries. The level of LDH and IPI score at initial diagnosis were significantly lower in young than older patients. The sex ratio (M:F) and age range (median) in the young and older groups were 1.18 and 11–30 (24.8) years and 1.59 and 42–87 (62.4) years, respectively. Extranodal presentation was higher in the young group (83.3% versus 60.0%, P &lt; 0.05). Based on immunophenotyping with anti‐CD10, bcl‐6, and MUM1 antibodies, the cases were categorized as germinal center B‐cell (GCB) (CD10+ or CD10–, bcl‐6+, MUM1+) or non‐GCB phenotype. The frequency of GCB type was significantly lower in the young group than older group (25% vs. 54%, P &lt; 0.05), and much lower than that reported for young patients in Western countries. In situ hybridization revealed one of the young patients to be positive for Epstein‐Barr virus (EBV). In the older group, none of 31 cases showed EBV positivity. Three year event‐free and overall survival rates of young patients were better than those of the older patients, although not significantly different. DLBCL in the young in Japan is characterized by a much lower frequency of the GCB phenotype compared to that in Western countries. Am. J. Hematol. 82:893–897, 2007. © 2007 Wiley‐Liss, Inc.
Mammon and Medicine: The Rewards of Clinical Trials
Authors: Marvin E. Jaffe
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Dr Lipper's and Dr Hammett's discussion<sup>1</sup>of the rewards of clinical trials seems to suggest that the interests of the physician and the interests of the patient are somehow dissociable. Since this is not the case in the day-to-day practice of medicine, how can they impute a less worthy motivation to the physician who partipates in clinical trials? I do not disagree with the commentary of Dr Spiro,<sup>2</sup>which states that patients should know if the physician is receiving a special bounty for enrolling them in clinical trials; however, such financial remuneration beyond the usual cost of care is not often offered. The patient should be informed if he will not be required to pay for clinic visits made while he is participating in the trial and if laboratory studies and medications will be free. Some physicians double bill a thirdparty payer in addition. Such
Safe drinking campaigns run by alcohol industry do not reduce consumption
Authors: I. Torjesen
Journal: BMJ (2011)

Efforts by the drinks industry to promote “responsible drinking” have little impact on reducing alcohol consumption and alcohol related harm, a report by Alcohol Concern says.

The report found that responsible drinking campaigns by the alcohol industry deliver ambiguous health messages and do not spell out what constitutes safe drinking behaviour.

These health messages appear in advertisements that promote drinking as a positive lifestyle choice and portray alcohol as something that causes problems only in the hands of irresponsible users.

The researchers from Glyndŵr and Bangor Universities in Wales looked at international evidence …
Renal Hemodynamics and Albumin Excretion Rate in Patients With Diabetes Secondary to Acquired Pancreatic Disease
Authors: Antonio Tiengo, Giustina Briani, Ennio Scaldaferri, Fausto Riva, Elisabetta Jori, Elena Sgnaolin, Rita Fenato, Michele D'Ambrosio, Paola Fioretto, Romano Nosadini, Gaetano Crepaldi, Roberto Trevisan
Journal: Diabetes Care (1992)

OBJECTIVE--To assess kidney function and AER in patients with PD. RESEARCH DESIGN AND METHODS--Thirty-three patients with PD (age 52 +/- 7 yr, duration of disease 11 +/- 6 yr, BMI 24 +/- 3 kg/m2) and 33 patients with IDDM were matched for sex, BMI, and duration of disease. GFR and RPF were determined by single injection of [51Cr]EDTA and [125I]hippurate. AER was measured by radioimmunoassay in a single timed overnight urine collection. RESULTS--GFR and RPF were, respectively, 113 +/- 35 and 441 +/- 145 ml.min-1.73 m2 in patients with PD and 123 +/- 30 and 549 +/- 94 (P < 0.001) in IDDM. FF was significantly higher in patients with PD (0.26 +/- 0.05 vs. 0.22 +/- 0.03; P < 0.001). Prevalence of hyperfiltration (GFR > 135 ml.min-1.1.73 m2) was similar in both groups (30% in patients with PD vs. 28% in those with IDDM). Geometric mean of urinary AER was 10.4 micrograms/min (range 1-186) in patients with PD and 11.2 (1-198) in IDDM patients. Some 30.3% of patients with PD and 18% of those with IDDM were microalbuminuric (AER > 20 micrograms/min). By multiple regression analysis, AER was significantly related to systolic (P < 0.04) and diastolic blood pressure (P < 0.01) and to BMI (P < 0.03) in patients with PD. Retinopathy was more frequent in microalbuminuric patients with PD than in those without elevated AER. CONCLUSIONS--We suggest that early renal abnormalities occur similarly in patients with PD and IDDM.