tbuckley/cabot-search huggingface dataset:
Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis
Authors: Christopher Savard, Erica V. Tartaglione, Rahul Kuver, Geoffrey W. Haigh, Geoffrey C. Farrell, Savitha Subramanian, Alan Chait, Matthew M. Yeh, LeBris S. Quinn, George N. Ioannou
Journal: Hepatology (2012)

Abstract The majority of patients with nonalcoholic fatty liver disease (NAFLD) have “simple steatosis,” which is defined by hepatic steatosis in the absence of substantial inflammation or fibrosis and is considered to be benign. However, 10%-30% of patients with NAFLD progress to fibrosing nonalcoholic steatohepatitis (NASH), which is characterized by varying degrees of hepatic inflammation and fibrosis, in addition to hepatic steatosis, and can lead to cirrhosis. The cause(s) of progression to fibrosing steatohepatitis are unclear. We aimed to test the relative contributions of dietary fat and dietary cholesterol and their interaction on the development of NASH. We assigned C57BL/6J mice to four diets for 30 weeks: control (4% fat and 0% cholesterol); high cholesterol (HC; 4% fat and 1% cholesterol); high fat (HF; 15% fat and 0% cholesterol); and high fat, high cholesterol (HFHC; 15% fat and 1% cholesterol). The HF and HC diets led to increased hepatic fat deposition with little inflammation and no fibrosis (i.e., simple hepatic steatosis). However, the HFHC diet led to significantly more profound hepatic steatosis, substantial inflammation, and perisinusoidal fibrosis (i.e., steatohepatitis), associated with adipose tissue inflammation and a reduction in plasma adiponectin levels. In addition, the HFHC diet led to other features of human NASH, including hypercholesterolemia and obesity. Hepatic and metabolic effects induced by dietary fat and cholesterol together were more than twice as great as the sum of the separate effects of each dietary component alone, demonstrating significant positive interaction. Conclusion: Dietary fat and dietary cholesterol interact synergistically to induce the metabolic and hepatic features of NASH, whereas neither factor alone is sufficient to cause NASH in mice. (Hepatology 2013)
Three-dimensional culture model to distinguish normal from malignant human bronchial epithelial cells
Authors: Delphine Fessart, Hugues Begueret, Frederic Delom
Journal: European Respiratory Journal (2013)

In the present study, we have developed an in vitro three-dimensional model to differentiate normal lung cells from lung cancer cells in order to study the mechanisms resulting in lung cancer. Using a reconstituted laminin-rich basement membrane (Matrigel), we were able to culture normal human bronchial epithelial cells and a subset of malignant cells. The two cell types can be readily distinguished by the ability of normal cells to express a structurally and functionally differentiated phenotype within Matrigel. Human bronchial epithelial cells embedded in Matrigel as single cells were able to form multi-cellular spherical colonies with a final size close to that of true acini in situ . Sections of mature spheres revealed a central lumen surrounded by polarised epithelial cells. In contrast, none of malignant cells tested, cell lines and lung biopsies responded to basement membrane by lumen formation. These results demonstrated that this in vitro glandular tumour model can be useful for studies of bronchial oncogene. Indeed, these findings may provide the basis for a rapid assay to discriminate normal human bronchial epithelial cells from their malignant counterparts. In conclusion, the three-dimensional tumour bronchial epithelial acinar-like sphere represents a novel in vitro model to further investigate pathophysiological functions resulting in lung cancer.
Potent Tumor-Specific Immunity Induced by an <b> <i>In vivo</i> </b> Heat Shock Protein-Suicide Gene–Based Tumor Vaccine
Authors: Wenhong Ren, Randy Strube, Xiaoqing Zhang, Si-Yi Chen, Xue F. Huang
Journal: Cancer Research (2004)

Abstract Tumor cells harbor a repertoire of unique, mutated antigens and shared self-antigens but generally are incapable of provoking an effective immune response, likely because of inadequate antigen presentation by professional antigen-presenting cells. Heat shock proteins (HSPs) play important roles in eliciting innate and adaptive immunity by chaperoning peptides for antigen presentation and providing endogenous danger signaling. Although effective in inducing tumor-specific immunity in mice and in some clinical trials, tumor-derived HSPs have many limitations like vaccines, such as the technical difficulty of ex vivo preparation of adequate quantities of HSPs from the resected tumors of individual patients. Here we have developed an in vivo HSP-suicide gene tumor vaccine by generating a recombinant replication-defective adenovirus (Ad-HT) that coexpresses HSP70 and a herpes simplex virus thymidine kinase suicide gene. The combination of HSP70 overexpression in situ and tumor killing by thymidine kinase/ganciclovir treatment, but neither strategy alone, provoked potent systemic antitumor activities after intratumor injection of Ad-HT. Tumor-specific CD4+ and CD8+ T-cell responses were induced by Ad-HT intratumor injection. CD11c+ dendritic cells (DCs) isolated from mice treated with Ad-HT were able to prime tumor-specific CTLs. Collectively, these results indicate that the combination of tumor killing by activation of a suicide gene to release tumor antigens and in situ HSP70 overexpression to enhance DC antigen presentation overcomes host immune tolerance to tumor antigens, leading to the induction of potent antitumor immunity. Our findings may have broad relevance to the use of the in vivo HSP/suicide gene tumor vaccine in therapy for human solid tumors.
Manpower Issues for a Surgical Specialty: The Impact of Oversupply
Authors: Byron J. Bailey
Journal: JAMA (1985)

Physician manpower is an issue that deserves and is receiving considerable attention at present. The number of practicing physicians has increased by approximately one third during the past decade, and it is projected that it will increase in approximately the same amount during the next ten years. While most of us find drastic change upsetting and tend to resist change, the consequences of this dramatic event are fundamental to the manner in which all of us will conduct our professional activities for the remainder of our careers. Two facts seem clear: first, this is a complex area and does not lend itself to oversimplification or overgeneralization, and, second, there is likely to be considerable difference in the impact of this general manpower growth from one specialty to another. For the sake of further discussion, let us make the following two assumptions concerning the specialty of Otolaryngology— Head and Neck Surgery:
Subcapsular intrahepatic hematoma: an unusual complication of ERCP
Authors: C. Bhati, N. Inston, S. Wigmore
Journal: Endoscopy (2007)

Hemorrhagic complications following endoscopic retrograde cholangiopancreatography (ERCP) are generally manifest as gastrointestinal hemorrhage, and published studies report an incidence of 0.8 % to 4 % [1] [2].
Health-Care Communication and Selected Psychosocial Correlates of Adherence in Diabetes Management
Authors: Lynda A Anderson
Journal: Diabetes Care (1990)

Meeting the needs of older adults with diabetes mellitus requires understanding the multiple factors that interact to influence patient adherence to the prescribed regimen and adjustment to the disease. Herein, we propose a conceptual framework to explain patient adherence and to discuss practical strategies for enhancing adherence. The conceptual framework is based on the cycle of care and is expanded to incorporate major theories in health-behavior change. Based on this review, numerous factors were identified that can affect patient adherence. First, features of the regimen, such as complexity, duration, and extent of behavioral change, can negatively influence patient adherence. Second, psychosocial and environmental barriers to patient adherence are described. A major area of importance is patient-provider relationships. Specifically, patients' and professionals' attitudes, beliefs, communication processes, and subsequent reactions to the consultation can affect adherence. Suggestions are made regarding strategies to enhance adherence, including the need to assess and monitor the patient's beliefs and practices, enhance the communicative skills of health-care professionals and patients, and develop programs specifically targeted at promoting professional and patient problem-solving skills. The problem of generalizing from current research is that few empirical studies have focused on diabetes management among older adults.
Abacavir–Lamivudine versus Tenofovir–Emtricitabine for Initial HIV-1 Therapy
Authors: Paul E. Sax, Camlin Tierney, Ann C. Collier, Margaret A. Fischl, Katie Mollan, Lynne Peeples, Catherine Godfrey, Nasreen C. Jahed, Laurie Myers, David Katzenstein, Awny Farajallah, James F. Rooney, Belinda Ha, William C. Woodward, Susan L. Koletar, Victoria A. Johnson, P. Jan Geiseler, Eric S. Daar
Journal: New England Journal of Medicine (2009)

The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.In a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or > or = 200 copies per milliliter at or after 24 weeks).A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir-lamivudine group versus 26 (7%) in the tenofovir DF-emtricitabine group. The time to the first adverse event was also shorter in the abacavir-lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine. (ClinicalTrials.gov number, NCT00118898.)
Herbal tea induced hepatic veno-occlusive disease: quantification of toxic alkaloid exposure in adults.
Authors: C R Kumana, M Ng, H J Lin, W Ko, P C Wu, D Todd
Journal: Gut (1985)

Four young Chinese women took daily doses of an unidentified 9Indian9 herbal tea as treatment for psoriasis. Three (one of whom died), developed ascites, hepatomegaly and biochemical abnormalities within 19-45 days. The fourth patient discontinued herbal tea after 21 days when she developed a skin rash. Two patients had portal hypertension, while all had liver histology showing features of veno-occlusive disease. Pyrrolizidine alkaloids were identified spectrophotometrically in the brewed tea, and in the chopped leaves of the herbal mixture; the mean dose in the tea prepared for consumption being 12 mg/day of alkaloid base and 18 mg/day of N-oxide. The mean cumulative dose of alkaloids (base + N-oxide) before onset of symptoms (three patients), was estimated to be 18 mg/kg. In the asymptomatic patient with histological liver disease only, the corresponding dose was 15 mg/kg. These cases thus provide some measure of pyrrolizidine alkaloid toxicity in adults.
Use of the Polymerase Chain Reaction for Early Detection of the Proviral Sequences of Human Immunodeficiency Virus in Infants Born to Seropositive Mothers
Authors: Martha F. Rogers, Chin-Yih Ou, Mark Rayfield, Pauline A. Thomas, Ellie E. Schoenbaum, Elaine Abrams, Keith Krasinski, Peter A. Selwyn, Jennifer Moore, Aditya Kaul, Katherine T. Grimm, Mahrukh Bamji, Gerald Schochetman
Journal: New England Journal of Medicine (1989)

The early diagnosis of infection with human immunodeficiency virus (HIV) in infants born to infected mothers is essential for early treatment, but current tests cannot detect HIV infection in newborns because of the presence of maternal antibodies. We used the polymerase chain reaction, a new technique that amplifies proviral sequences of HIV within DNA, to detect HIV infection in peripheral-blood mononuclear cells obtained from infants of seropositive women during the neonatal (age less than 28 days) and postneonatal periods. In blood obtained during the neonatal period, the polymerase chain reaction was positive in five of seven infants in whom the acquired immunodeficiency syndrome (AIDS) later developed (a mean of 9.8 months after the test). The test was also positive in one of eight newborns who later had nonspecific signs and symptoms suggestive of HIV infection (mean follow-up, 12 months). No proviral sequences were detected in neonatal samples from nine infants who remained well (mean follow-up, 16 months). HIV proviral sequences were detected in samples obtained during the postneonatal period (median age, five months) in all of 6 infants tested who later had AIDS and in 4 of 14 infants with nonspecific findings suggestive of HIV infection. No proviral sequences were detected in 25 infants who remained well (mean follow-up, 17 months) after being born to HIV-seropositive mothers, or in 15 infants born to HIV-seronegative mothers. We conclude that the polymerase chain reaction will be a useful technique to diagnose HIV infection in newborns and to predict the subsequent development of AIDS. However, larger studies will be required to determine the sensitivity and specificity of the test.
Adverse Reactions to Antihypertensive Drugs
Authors: Kenneth M. Flegel
Journal: JAMA (1987)

<h3>To the Editor.—</h3> The report from the Hypertensive Detection and Follow-up Program (HDFP) found that adverse drug reactions (ADRs) to antihypertensive drugs were infrequent.<sup>1</sup>We recently completed a prospective study of ADRs in 1026 outpatients in a university teaching hospital. Using intensive surveillance for ADRs and a standardized method for assessing causality, we found that reactions to prescription drugs occurred in 3% to 5% of patients receiving new prescriptions. They were usually mild in their effects and nearly always reversible.<sup>2</sup>We examined in detail drugs used for lowering blood pressure and found that they were similarly well tolerated. <h3>Study.—</h3> Patients of six board-certified internists were enrolled for one calendar year. One third of the 1026 participants had hypertension. Surveillance for ADRs was carried out by frequent telephone calls at regular intervals. Any suspected ADRs were scored, according to a published algorithm,<sup>3</sup>to establish a likelihood score. Each
Disturbance of Serum Viscosity in Diabetes Mellitus
Authors: Donald E. McMillan
Journal: Journal of Clinical Investigation (1974)

The serum viscosity of diabetic patients has been found to be increased. The elevation averaged 8% above healthy subjects and 6% above nondiabetic patients. The serum viscosity elevation was greater when diabetic sequelae associated with microangiopathy were present. No relation of serum viscosity to age, sex, obesity, duration of disease, or type of treatment was demonstrated. Serum total protein and glucose levels were found to be correlated with serum viscosity, and increases in their serum concentrations were observed in diabetes. Analysis demonstrated that their elevation did not explain either the viscosity increase or the difference in viscosity between diabetics with and without sequelae.Intrinsic viscosity, abbreviated [eta], is a concentration-independent solute property related to molecular shape. [eta] was found to be 7% higher in diabetic than in normal serum. The [eta] difference accounted for at least half of the serum viscosity elevation. The rest of the increase was due to increased serum protein level and increased nonprotein solids, presumably glucose and lipid. Associated with increased [eta] was a decline in albumin: globulin ratio and elevation of the acute phase reactant proteins, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin. Studies comparing diabetic and normal serum fractionated by using 21.5% sodium sulfate showed that changes in [eta] were attributable to changes in serum protein composition rather than an inherent qualitative disturbance of protein present in one of the fractions. Since serum viscosity is elevated in early diabetes, it may be a part of the metabolic disturbance of diabetes and could play a role in the development of diabetic microangiopathy.
Abstract 16369: Characterization of Streptozotocin Induced Diabetes and Evaluation of Vascular Response to Current Drug-Eluting Stents in a Swine Model
Authors: Louis-Georges Guy, Steven Hsu, Alexander Sheehy, Donald Steinfeld, Amelie Bouchard, Julie Tai, Igor Polyakov, Guy Leclerc
Journal: Circulation (2010)

Introduction:  Characterization of long-term diabetes in large animal models is needed to advance the understanding of drug-eluting stent performance in diabetics. We hypothesized that streptozotocin (STZ) would induce physiologic changes characteristic of diabetes in a swine model with differential arterial responses to everolimus and paclitaxel-eluting stents.   Methods:  STZ was administered to 12 swine to induce hyperglycemia, with insulin therapy maintaining pre-prandial blood glucose level (∼20mM). After 2 months, physiologic diabetic changes were assessed by blood serum chemistry/ELISA, and each animal received one ML VISION ®  (ML), one XIENCE V ®  (XV), and one Taxus Liberte (TL) stent respectively in each coronary artery. After 3 months, angiography and histomorphometry were performed. Effects of everolimus and paclitaxel on insulin stimulated p-Akt and p-ERK levels were analyzed by Western blot/ELISA using carotid arteries from these animals cultivated  in vitro.    Results:  In comparison to baseline, STZ-injected swine displayed significant elevation of blood glucose (2.5 fold, p   Conclusions:  Our results indicate that STZ injection created a clinically relevant animal model that displayed several features of the diabetic pathophysiology. XV and ML significantly reduced neointimal area when compared to TL in this model. Molecular investigation of signaling pathways suggested that decreased Akt activation and increased p-ERK/p-Akt ratio may be linked with increases in restenosis.
Abstract 226: Aspirin alone or in combination with doxorubicin induced efficient apoptosis in human hepatocellular carcinoma cells
Authors: Mohammad Akbar Hossain, Min Young Kim, Dong Hwan Kim, Jin-Ah Kim, Yong Jung Kang, Jeon Ok Moon, Gi Young Kim, Yung Hyun Choi, Nam Deuk Kim
Journal: Cancer Research (2010)

Abstract Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is refractory to most anticancer drugs. Doxorubicin offers a survival benefit to patients with intermediate hepatocellular carcinoma. However, the favorable therapeutic response to doxorubicin is often associated with severe toxicity. The present research was aimed at developing a strategy of increasing doxorubicin sensitivity so that lower doses may be used without compromising efficacy. Recently, aspirin (ASA) and some other nonsteroidal anti-inflammatory drugs (NSAIDs) have drawn much attention for their protective effects against colon cancer and cardiovascular disease. Several studies also found that regular ASA use is significantly associated with reduced risk of lung cancer. We investigated the effects of ASA on HepG2 human hepatocellular carcinoma cell line. Growth inhibition effect of aspirin was measured by MTT assay. Flow cytometry analysis revealed that aspirin can induce G2/M phase arrest which we observed by the level of cell cycle regulatory proteins and DNA ladder formation indicates apoptosis dose dependently. We found that ASA treatment followed both extrinsic and intrinsic pathways for apoptosis induction. In addition to this, when administered in combination, doxorubicin (DOX) and ASA produced synergistic effect in growth inhibition in human hepatocellular carcinoma cells and induced apoptosis in caspase-dependent pathway. Therefore, clinically achievable concentrations of DOX and ASA used in combination may produce a strong anticancer synergy that warrants investigation as a therapeutic strategy to enhance the efficacy of doxorubicin for treating HCC. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2006-000-11117-0)]. 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 226.
Drinking and Flying — The Problem of Alcohol Use by Pilots
Authors: Jack G. Modell, James M. Mountz
Journal: New England Journal of Medicine (1990)

ALCOHOL is the most widely used and misused drug in the Western world. The cost to the United States in 1990 in terms of lost production, crime, accidents, and treatment related to alcohol misuse is expected to exceed $136 billion, and alcohol intoxication is a cause or contributing factor in approximately 40 percent of all fatal automobile accidents.1 Alcohol misuse is also a problem among the nearly 700,000 general-aviation pilots in this country. ( General aviation refers to all civil-aviation operations other than those conducted for remuneration or hire; therefore, it does not include the commercial airlines or military operations.) . . .
Localized Xanthomas in Lymphedema Praecox
Authors: Kenneth R. Woolling
Journal: JAMA (1970)

A girl, aged 14, had an extensive normolipemic xanthomatous eruption develop in one leg and foot, soon after the onset of lymphedema in the same limb. When the edema was reduced by treatment, the xanthomatous eruption greatly improved. It was speculated whether mechanical stretching of the skin might have been a factor contributing to the localized development of xanthomatosis in a xanthoma-prone individual.
Efficacy of rituximab in an aggressive form of multicentric Castleman disease associated with immune phenomena
Authors: Enrique M. Ocio, Fermin M. Sanchez‐Guijo, Maria Diez‐Campelo, Cristina Castilla, Oscar J. Blanco, Dolores Caballero, Jesus F. San Miguel
Journal: American Journal of Hematology (2005)

Abstract Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disorder for which the best therapeutic option is not yet well established. Immune‐related disorders are rare complications of MCD. We report on an MCD case in a 23‐year‐old patient with extensive abdominal involvement and associated immune hemolytic anemia and Raynaud phenomenon. He was negative for human immunodeficiency virus (HIV) and human herpesvirus‐8 (HHV‐8). After 8 courses of the anti‐CD20 monoclonal antibody (rituximab), the patient achieved complete remission. Interestingly, Raynaud phenomenon disappeared under treatment and no new hemolytic events occurred. Anti‐CD20 antibody treatment could be an attractive therapeutic approach for MCD, mainly when immune‐related disorders are associated. Am. J. Hematol. 78:302–305, 2005. © 2005 Wiley‐Liss, Inc.