tbuckley/cabot-search huggingface dataset:
Effect of taurohyodeoxycholic acid on biliary lipid secretion in humans
Authors: P Loria, M Bozzoli, M Concari, M E Guicciardi, F Carubbi, M Bertolotti, D Piani, A Nistri, M Angelico, M Romani, N Carulli
Journal: Hepatology (1997)

This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6α-hydroxylated bile acid with hydrophilic properties, on bile lipid secretion. Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours. In hourly bile samples collected for 8 hours after the beginning of the infusion, biliary bile acid composition (by high-performance liquid chromatography), biliary lipid concentrations (by standard methods), and distribution of biliary carriers (by gel chromatography) were evaluated. Blood liver function tests were performed before and after the infusions. Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary bile acids in all patients except for one infused with taurohyodeoxycholic acid. Taurohyodeoxycholic acid stimulated significantly greater ( P &lt; .05) cholesterol and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451 μmol/μmol, respectively) compared with tauroursodeoxycholic acid (0.061 μmol/μmol for cholesterol and 0.275 μmol/μmol for phospholipids). The secretory ratio between phospholipid and cholesterol was significantly higher after infusion of taurohyodeoxycholic acid (3.88 μmol/μmol) compared with taroursodeoxycholic acid (3.09 μmol/μmol) ( P &lt; .05). Biliary enrichment with taurohyodeoxycholic acid was positively related with percent concentration of phospholipids but not with that of cholesterol. The opposite trend was observed in tauroursodeoxycholic acid-enriched biles. In both taurohyodeoxycholic acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was carried in a gel-chromatographic fraction corresponding to an apparent molecular weight of 80 to 200 kd. No alteration in liver function test results was observed after taurohyodeoxycholic acid infusion. In conclusion, taurohyodeoxycholic acid stimulates greater cholesterol and phospholipid secretion than tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory ratio. In bile enriched with both bile acids, biliary cholesterol is transported in non-micellar aggregates. Finally, in the conditions of our study, taurohyodeoxycholic acid was not hepatotoxic.
Augmented expression of atrial natriuretic polypeptide gene in ventricles of spontaneously hypertensive rats (SHR) and SHR-stroke prone.
Authors: H Arai, K Nakao, Y Saito, N Morii, A Sugawara, T Yamada, H Itoh, S Shiono, M Mukoyama, H Ohkubo
Journal: Circulation Research (1988)

Tissue levels of atrial natriuretic polypeptide (ANP) and ANP messenger RNA (mRNA) in the atrium and ventricle were measured simultaneously in spontaneously hypertensive rats (SHR) and its substrain, SHR-stroke prone (SHRSP), and these levels were compared with those in control Wistar-Kyoto rats (WKY). At 27 weeks of age with established hypertension and ventricular hypertrophy, ANPmRNA levels in ventricles from SHR and SHRSP were markedly increased, and total contents of ventricular ANPmRNA in SHR and SHRSP were approximately 50% and 250%, respectively, of the corresponding atrial contents. However, levels and total contents of atrial ANPmRNA in SHR and SHRSP were similar to those of WKY, and the total content of ventricular ANPmRNA in WKY was only 6% of the content of atrial ANPmRNA. ANP concentrations in ventricles of SHR and SHRSP were increased in association with the augmentation of ANPmRNA levels. During the prehypertensive stage at 6 weeks of age, slight increases in levels and total contents of ANPmRNA and ANP in the ventricle were observed only in SHRSP. These results demonstrate that the expression of the ANP gene is markedly augmented in ventricles of SHR and SHRSP, especially of SHRSP, at the stage of established hypertension and ventricular hypertrophy, and they also suggest that these genetically hypertensive rats are one of the best animal models to investigate the biosynthesis, storage, and secretion of ventricular ANP.
Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy
Authors: Marc S. Penn, Abeel A. Mangi
Journal: Circulation Research (2008)

Cell-based therapies for the prevention and treatment of cardiac dysfunction offer the potential to significantly modulate cardiac function and improve outcomes in patients with cardiovascular disease. To date several clinical studies have suggested the potential efficacy of several different stem cell types; however, the benefits seen in clinical trials have been inconsistent and modest. In parallel, preclinical studies have identified key events in the process of cell-based myocardial repair, including stem cell homing, engraftment, survival, paracrine factor release, and differentiation that need to be optimized to maximize cardiac repair and function. The inconsistent and modest benefits seen in clinical trials combined with the preclinical identification of mediators responsible for key events in cell-based cardiac repair offers the potential for cell-based therapy to advance to cell-based gene therapy in an attempt to optimize these key events in the hope of maximizing clinical benefit. Below we discuss potential key events in cardiac repair and the mediators of these events that could be of potential interest for genetic enhancement of stem cell–based cardiac repair.
A Critical Role for the Inflammatory Response in a Mouse Model of Preneoplastic Progression
Authors: Kathryn L. Schwertfeger, Wa Xian, Alan M. Kaplan, Sandra H. Burnett, Donald A. Cohen, Jeffrey M. Rosen
Journal: Cancer Research (2006)

Abstract The tumor microenvironment, which includes inflammatory cells, vasculature, extracellular matrix, and fibroblasts, is a critical mediator of neoplastic progression and metastasis. Using an inducible transgenic mouse model of preneoplastic progression in the mammary gland, we discovered that activation of inducible fibroblast growth factor receptor-1 (iFGFR1) in the mammary epithelium rapidly increased the expression of several genes involved in the inflammatory response. Further analysis revealed that iFGFR1 activation induced recruitment of macrophages to the epithelium and continued association with the alveolar hyperplasias that developed following long-term activation. Studies using HC-11 mammary epithelial cells showed that iFGFR1-induced expression of the macrophage chemoattractant osteopontin was required for macrophage recruitment in vitro. Finally, conditional depletion of macrophages inhibited iFGFR1-mediated epithelial cell proliferation and lateral budding. These findings show that inflammatory cells, specifically macrophages, are critical for mediating early events in an inducible transgenic mouse model of preneoplastic progression. (Cancer Res 2006; 66(11): 5676-85)
When Will Adequate Pain Treatment Be the Norm?
Authors: C. Stratton Hill
Journal: JAMA (1995)

Inadequate treatment of pain continues to be a problem despite more knowledge about its causes and control and despite widespread efforts of governments and multiple medical and voluntary organizations to disseminate this knowledge, particularly at the postgraduate level. Of particular note are the recent publications of the Agency for Health Care Policy and Research of the US Public Health Service<sup>1,2</sup>and educational and dissemination efforts of the American Cancer Society, the American Pain Society,<sup>3</sup>and cancer pain initiatives in many states. The Cancer and Palliative Care Unit of the World Health Organization (WHO) has emphasized pain relief for cancer patients in developing countries because of limited cancer treatment facilities there. Most cancer in these countries is advanced, and treating its pain is the only practical approach available. To address this problem by educating health care professionals, the WHO<sup>4</sup>developed an "analgesic ladder" for pain treatment, which uses
Antiadhesive Effects of GRN163L—An Oligonucleotide N3′→P5′ <i>Thio</i>-Phosphoramidate Targeting Telomerase
Authors: Shalmica R. Jackson, Chun-Hong Zhu, Vera Paulson, Linda Watkins, Z. Gunnur Dikmen, Sergei M. Gryaznov, Woodring E. Wright, Jerry W. Shay
Journal: Cancer Research (2007)

Abstract We determined previously that a novel human telomerase RNA (hTR) antagonist, GRN163L, inhibited the tumorigenic potential of A549-luciferase (A549-luc) lung cancer cells in vitro and in vivo. Further studies revealed that A549-luc cells were also morphologically altered by GRN163L. A549-luc cells treated before cell attachment with a single dose of GRN163L only weakly attached to the substrate and remained rounded, whereas control mismatch-treated cells exhibited typical epitheloid appearance and adhesion properties. These morphologic changes were independent of hTR expression and telomerase inhibition and were unrelated to telomere length. This effect is dependent on the molecular properties of the lipid moiety, the phosphorothioate backbone, and the presence of triplet-G sequences within the GRN163L structure. Altered adhesion was manifested by a 50% reduction in rapid cellular attachment and a 3-fold decrease in total cell spreading surface area. Administration of a single dose of GRN163L (15 mg/kg) at the time of cell inoculation, using an in vivo model of lung cancer metastasis, resulted in significant reductions in tumor burden at days 13, 20, and 27 of tumor progression. Thus, the potent antimetastatic effects of GRN163L may be related, in part, to the antiadhesive effects of this novel cancer therapeutic conferred via specific structural determinants and that these effects are independent of telomerase inhibition or telomere shortening. [Cancer Res 2007;67(3):1121–9]
PKC Isozymes in Chronic Cardiac Disease: Possible Therapeutic Targets?
Authors: Eric Churchill, Grant Budas, Alice Vallentin, Tomoyoshi Koyanagi, Daria Mochly-Rosen
Journal: The Annual Review of Pharmacology and Toxicology (2007)

Cardiovascular disease is the leading cause of death in the United States. Therefore, identifying therapeutic targets is a major focus of current research. Protein kinase C (PKC), a family of serine/threonine kinases, has been identified as playing a role in many of the pathologies of heart disease. However, the lack of specific PKC regulators and the ubiquitous expression and normal physiological functions of the 11 PKC isozymes has made drug development a challenge. Here we discuss the validity of therapeutically targeting PKC, an intracellular signaling enzyme. We describe PKC structure, function, and distribution in the healthy and diseased heart, as well as the development of rationally designed isozyme-selective regulators of PKC functions. The review focuses on the roles of specific PKC isozymes in atherosclerosis, fibrosis, and cardiac hypertrophy, and examines principles of pharmacology as they pertain to regulators of signaling cascades associated with these diseases.
Responses to Liposomal Doxorubicin, Bevacizumab, and Temsirolimus in Metaplastic Carcinoma of the Breast: Biologic Rationale and Implications for Stem-Cell Research in Breast Cancer
Authors: Stacy Moulder, John Moroney, Thorunn Helgason, Jennifer Wheler, Daniel Booser, Constance Albarracin, Phuong K. Morrow, Kimberly Koenig, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2011)
Group therapy for adolescents with repeated self harm: randomised controlled trial with economic evaluation
Authors: J. M. Green, A. J. Wood, M. J. Kerfoot, G. Trainor, C. Roberts, J. Rothwell, A. Woodham, E. Ayodeji, B. Barrett, S. Byford, R. Harrington
Journal: BMJ (2011)

To examine the effectiveness and cost-effectiveness of group therapy for self harm in young people.Two arm, single (assessor) blinded parallel randomised allocation trial of a group therapy intervention in addition to routine care, compared with routine care alone. Randomisation was by minimisation controlling for baseline frequency of self harm, presence of conduct disorder, depressive disorder, and severity of psychosocial stress.Adolescents aged 12-17 years with at least two past episodes of self harm within the previous 12 months. Exclusion criteria were: not speaking English, low weight anorexia nervosa, acute psychosis, substantial learning difficulties (defined by need for specialist school), current containment in secure care. Setting Eight child and adolescent mental health services in the northwest UK.Manual based developmental group therapy programme specifically designed for adolescents who harm themselves, with an acute phase over six weekly sessions followed by a booster phase of weekly groups as long as needed. Details of routine care were gathered from participating centres.Primary outcome was frequency of subsequent repeated episodes of self harm. Secondary outcomes were severity of subsequent self harm, mood disorder, suicidal ideation, and global functioning. Total costs of health, social care, education, and criminal justice sector services, plus family related costs and productivity losses, were recorded.183 adolescents were allocated to each arm (total n = 366). Loss to follow-up was low (<4%). On all outcomes the trial cohort as a whole showed significant improvement from baseline to follow-up. On the primary outcome of frequency of self harm, proportional odds ratio of group therapy versus routine care adjusting for relevant baseline variables was 0.99 (95% confidence interval 0.68 to 1.44, P = 0.95) at 6 months and 0.88 (0.59 to 1.33, P = 0.52) at 1 year. For severity of subsequent self harm the equivalent odds ratios were 0.81 (0.54 to 1.20, P = 0.29) at 6 months and 0.94 (0.63 to 1.40, P = 0.75) at 1 year. Total 1 year costs were higher in the group therapy arm (£21,781) than for routine care (£15,372) but the difference was not significant (95% CI -1416 to 10782, P = 0.132).The addition of this targeted group therapy programme did not improve self harm outcomes for adolescents who repeatedly self harmed, nor was there evidence of cost effectiveness. The outcomes to end point for the cohort as a whole were better than current clinical expectations. Trial registration ISRCTN 20496110.
Low prevalence of hepatitis C virus infection in porphyria cutanea tarda in germany
Authors: Ulrich Stölzel, Erich Köstler, Christiane Koszka, Maricka Stöffler-Meilicke, Detlef Schuppan, Rajan Somasundaram, Manfred O. Doss, Karl O. Habermehl, Ernst O. Riecken
Journal: Hepatology (1995)

Previous studies from Spain, Italy, and France have demonstrated a high prevalence (71% to 91%) of antibodies against hepatitis C virus in patients with porphyria cutanea tarda (PCT). To determine the role of hepatitis C virus (HCV) in PCT in Germany, we have assessed the prevalence of antibodies against HCV and hepatitis B virus (HBV) in 106 patients (mean age, 60 ± 14 years) with the disease. Eight of 106 patients (8%) were positive for HCV antibodies and HCV RNA using second-generation enzyme-linked immunosorbent assay (ELISA), recombinant immunoblot assay, and polymerase chain reaction. Antibodies against HBV core antigen were found in 14 patients (13%). Of the patients with antibodies against HCV alanine transaminase (ALT) (aspartate transaminase [AST]) levels above normal occurred in 71% (86%). Because elevated ALT (AST) levels were also found in 51% (64%) of 88 patients without markers of HCV or HBV, we suggest that liver damage in PCT may exist in absence of these viruses. This is supported by the finding that in patients without HCV or HBV markers, higher serum ALT and AST activities were found in patients with overt disease or relapse (ALT, 59 ± 44 U/L; AST, 37 ± 21 U/L), whereas patients in remission displayed significantly lower serum enzyme activities (ALT, 16 ± 8 U/L; AST, 16 ± 7 U/L), ( P &lt; 0.001). These results indicate that HCV infection does not play a major role in the pathogenesis of PCT in Germany.
Molecular Analyses of MADS-Box Genes Trace Back to Gymnosperms the Invention of Fleshy Fruits
Authors: A. Lovisetto, F. Guzzo, A. Tadiello, K. Toffali, A. Favretto, G. Casadoro
Journal: Molecular Biology and Evolution (2011)

Botanical fruits derive from ovaries and their most important function is to favor seed dispersal. Fleshy fruits do so by attracting frugivorous animals that disperse seeds together with their own excrements (endozoochory). Gymnosperms make seeds but have no ovaries to be transformed into fruits. Many species surround their seeds with fleshy structures and use endozoochory to disperse them. Such structures are functionally fruits and can derive from different anatomical parts. Ginkgo biloba and Taxus baccata fruit-like structures differ in their anatomical origin since the outer seed integument becomes fleshy in Ginkgo, whereas in Taxus, the fleshy aril is formed de novo. The ripening characteristics are different, with Ginkgo more rudimentary and Taxus more similar to angiosperm fruits. MADS-box genes are known to be necessary for the formation of flowers and fruits in Angiosperms but also for making both male and female reproductive structures in Gymnosperms. Here, a series of different MADS-box genes have been shown for the first time to be involved also in the formation of gymnosperm fruit-like structures. Apparently, the same gene types have been recruited in phylogenetically distant species to make fleshy structures that also have different anatomical origins. This finding indicates that the main molecular networks operating in the development of fleshy fruits have independently appeared in distantly related Gymnosperm taxa. Hence, the appearance of the seed habit and the accompanying necessity of seed dispersal has led to the invention of the fruit habit that thus seems to have appeared independently of the presence of flowers.
An unusual example of exercise-induced asthma
Authors: G. K. Crompton
Journal: Thorax (1968)

OBJECTIVE: To study the characteristics of the Multidimensional Health Assessment Questionnaire (MDHAQ) in Finnish patients with rheumatoid arthritis. METHODS: The reliability of the questionnaire was tested by test-retest procedure. Construct validity was studied by factor analysis and convergent validity by calculating correlations between the Finnish MDHAQ (Finn-MDHAQ) scales and the Finnish Health Assessment Questionnaire (HAQ) and the Finnish Arthritis Impact Measurement Scales (Finn-AIMS2). Correlations between Finn-MDHAQ and measures of clinical characteristics, disease activity, and functional class were also measured. An item analysis was made of the Finn-MDHAQ scales Function (FN) and Psychological (PS). RESULTS: Internal consistency on the FN scale was 0.92 (95% lower limit 0.89) and 0.66 (0.56) on the PS scale. Reproducibility (95% CI) on FN was 0.93 (0.82 to 0.97) and on PS 0.84 (0.70 to 0.92). Factor analysis identified 2 factors, mobility of upper extremities and trunk, and mobility of lower extremities. Strong correlations were found between the FN scale and HAQ and physical subscales of Finn-AIMS2 and between PS and the psychological subscales of Finn-AIMS2. In item analysis corrected item correlation was high on the Finn-MDHAQ scales, except in one item on the PS scale. CONCLUSION: The Finn-MDHAQ is an applicable, reliable, and valid instrument for the part of the FN scale measuring functional ability in Finnish rheumatic patients. The incongruity in the PS scale structure that produced moderate internal consistency can be overcome with minor modifications.
Contributions of Basal and Postprandial Hyperglycemia Over a Wide Range of A1C Levels Before and After Treatment Intensification in Type 2 Diabetes
Authors: Matthew Riddle, Guillermo Umpierrez, Andres DiGenio, Rong Zhou, Julio Rosenstock
Journal: Diabetes Care (2011)

To determine the relative contributions of basal hyperglycemia (BHG) versus postprandial hyperglycemia (PPHG) before and after treatment intensification in patients with glycated hemoglobin A(1c) (A1C) >7.0% while on prior oral therapy.Self-measured, plasma-referenced glucose profiles and A1C values were evaluated from participants in six studies comparing systematically titrated insulin glargine with an alternative regimen (adding basal, premixed, or prandial insulin, or increasing oral agents). Hyperglycemic exposure (>100 mg/dL [5.6 mmol/L]) as a result of BHG versus PPHG was calculated.On prior oral therapy, 1,699 participants (mean age 59 years, diabetes duration 9 years) had mean fasting plasma glucose (FPG) of 194 mg/dL (10.8 mmol/L), and mean A1C was 8.7%. BHG contributed an average of 76-80% to hyperglycemia over the observed range of baseline A1C levels. Adding basal insulin for 24 or 28 weeks lowered mean FPG to 117 mg/dL (6.5 mmol/L), A1C to 7.0%, and BHG contribution to 32-41%. Alternative regimens reduced FPG to 146 mg/dL (8.1 mmol/L), A1C to 7.1%, and the contribution of BHG to 64-71%. BHG contributions for patients with A1C averaging 7.6-7.7% were 76% at baseline and 34 and 68% after adding basal insulin or other therapies, respectively.When A1C is >7.0% despite oral therapy, BHG routinely dominates exposure. Intensified therapy reduces A1C and changes this relationship, but BHG amenable to further intervention still accounts for one-third of total hyperglycemia after basal insulin treatment and two-thirds after alternative methods.
Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial
Authors: Camilla Zimmermann, Nadia Swami, Monika Krzyzanowska, Breffni Hannon, Natasha Leighl, Amit Oza, Malcolm Moore, Anne Rydall, Gary Rodin, Ian Tannock, Allan Donner, Christopher Lo
Journal: The Lancet (2014)
Severity scores and management of community acquired pneumonia
Authors: Jihen Ben Halima, Wided Ben Ahmed, Leila El Gharbi, Besma Dhari, Saloua Azzabi, Mohamed Ali Baccar, Hichem Aouina, Hend Bouacha
Journal: European Respiratory Journal (2013)

Background: International guidelines recommend a severity-based approach to management in community-acquired pneumonia(CAP). CURB65, CRB65 and the Pneumonia Severity Index (PSI) are the most widely recommended severity scores.

The aim of this study was to compare the performance characteristics of these scores for predicting mortality in CAP.

Methods: This retrospective study was carried on at Charles Nicolle hospital. 115 patients with an admission diagnosis of CAP were enrolled. Patients were stratified into 2 groups according to evolution: favorable (recovery after antibiotic therapy) or unfavorable (transfer to intensive care unit or deaths). Clinical and laboratory features at presentation were used to calculate severity scores using the PSI and BTS severity score (CRB65). We compared sensitivity, specificity, predictive values, likelihood ratios and the discriminatory power (area under the receiver operating characteristic curve) of these scores according to the evolution.

Results: The age of patients ranged from 17 to 87 years with an average of 60 years (72% male). Sixty patients (52 %) had more than 65 years. 11 patients (9.5%) died or required intensive care transfer. PSI and CRB65 were the only factors independently correlated to unfavorable evolution. PSI≥ IV and CRB65≥2 had a high sensitivity but lower specificity for predicting a bad evolution. CRB65 was more sensitive (90.9%) than the PSI (72.7%). The area under the receiver operating characteristic curve was 0.79 for both the PSI and the CRB65 (p=0.002, for each pairwise comparison).

Conclusions: Although, severity assessment tools are useful guides in the management of patients with CAP, clinical judgment must remain decisive.