tbuckley/cabot-search huggingface dataset:
Silibinin Efficacy against Human Hepatocellular Carcinoma
Authors: Leyon Varghese, Chapla Agarwal, Alpana Tyagi, Rana P. Singh, Rajesh Agarwal
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Hepatocellular carcinoma (HCC) is one of the most common recurrent malignancies, for which, currently, there is no effective therapy. Considering the antihepatotoxic activity of silibinin, a widely used drug and supplement for various liver disorders, together with its strong preventive and anticancer efficacy against various epithelial cancers, we investigated the efficacy of silibin against human HCC cells. Experimental Design: Silibinin effects were examined on growth, cytotoxicity, apoptosis, and cell cycle progression in two different HCC cell lines, HepG2 (hepatitis B virus negative; p53 intact) and Hep3B (hepatitis B virus positive; p53 mutated). At molecular level, cell cycle effects of silibinin were assessed by immunoblotting and in-bead kinase assays. Results: Silibinin strongly inhibited growth of both HepG2 and Hep3B cells with a relatively stronger cytotoxicity in Hep3B cells, which was associated with apoptosis induction. Silibinin also caused G1 arrest in HepG2 and both G1 and G2-M arrests in Hep3B cells. Mechanistic studies revealed that silibinin induces Kip1/p27 but decreases cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)-2, and CDK4 levels in both cell lines. In Hep3B cells, silibinin also reduced the protein levels of G2-M regulators. Furthermore, silibinin strongly inhibited CDK2, CDK4, and CDC2 kinase activity in these HCC cells. Conclusion: Together, these results for the first time identify the biological efficacy of silibinin against HCC cells, suggesting the importance of conducting further investigations in preclinical HCC models, especially on in vivo efficacy, to support the clinical usefulness of silibinin against hepatocellular carcinoma in addition to its known clinical efficacy as an antihepatotoxic agent.
Y179C, F486L and N550H are BRCA1 variants that may be associated with breast cancer in a Sicilian family: results of a 5-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study
Authors: C. Augello, L. Bruno, V. Bazan, V. Calò, V. Agnese, S. Corsale, S. Cascio, G. Gargano, M. Terrasi, F. Barbera, S. Fricano, B. Adamo, M.R. Valerio, G. Colucci, E. Sumarcz, A. Russo
Journal: Annals of Oncology (2006)
Human renal carcinoma cells produce hypercalcemia in the nude mouse and a novel protein recognized by parathyroid hormone receptors.
Authors: G J Strewler, R D Williams, R A Nissenson
Journal: Journal of Clinical Investigation (1983)

When grown in nude mice, cultured renal carcinoma cells from a hypercalcemic patient produced marked hypercalcemia that was reversed by resection of tumor. Conditioned medium from this cell line contained a protein with activity in a renal adenylate cyclase bioassay for parathyroid hormone (PTH) which was blocked by the competitive PTH antagonist [8norleucyl, 18norleucyl, 34tyrosinyl]bPTH (3-34)amide. However, the biologically active protein was eluted from gel filtration columns as a larger molecular size component that PTH and was not recognized by any of four region-specific PTH antisera. The properties of this factor resemble those of the postulated PTH-like substance(s) in humoral hypercalcemia of malignancy.
Management of focal nodular hyperplasia and hepatocellular adenoma in young women: A series of 41 patients with clinical, radiological, and pathological correlations
Authors: Daniel Cherqui, Alain Rahmouni, Frédéric Charlotte, Hatem Boulahdour, Michel Meignan, Pierre-Louis Fagniez, Elie-Serge Zafrani, Didier Mathieu, Daniel Dhumeaux, Jean-Michel Métreau
Journal: Hepatology (1995)

Preoperative distinction between focal nodular hyperplasia (FNH) that should be managed conservatively and hepatocellular adenoma (HA) that should be resected remains difficult. The result is controversial management of these patients. The aims of this study were to report the value of modern imaging procedures for noninvasive diagnosis of these lesions, to assess the value of intraoperative frozen section studies, and to propose a management strategy in those patients. Forty-one consecutive women with FNH (35 cases) or HA (6 cases) treated at our institution between 1985 and 1992 were studied. New imaging techniques, including enhanced magnetic resonance imaging (MRI) and color Doppler ultrasonography (US), were prospectively appraised in addition to usual techniques. Histological examination of surgical specimens was obtained in all cases. A sixfold increase in the number of patients with FNH was observed during this study, whereas the number of patients with HA did not change. FNHs were incidental US findings in 74% of the cases. The best imaging procedure in the diagnosis of FNH was enhanced MRI with a sensitivity of 70% and a specificity of 98%. Color Doppler US was a useful adjunct. Intraoperative frozen section studies were performed in 16 patients with 19 tumors with a sensitivity of 89% and a specificity of 100%.(ABSTRACT TRUNCATED AT 250 WORDS)
Infection rate and spontaneous seroreversion of anti-hepatitis C virus during the natural course of hepatitis C virus infection in the general population
Authors: L A Kondili
Journal: Gut (2002)

Background: Hepatitis C virus (HCV) infection is common worldwide but there are different prevalence rates in different countries. Data on the incidence of HCV in the general population are scarce. Spontaneous viral clearance occurs in 10–25% of infected individuals after acute infection yet controversy exists regarding the frequency of spontaneous clearance during the natural course of HCV infection in the general population. Aims: Anti-HCV prevalence, HCV infection rate, and the kinetics of anti-HCV were studied in a cross section of the general population of central Italy. Study population and methods: Anti-HCV prevalence (EIA-3 Ortho, RIBA-3 Ortho Chiron) was estimated in 3884 randomly selected individuals. Infection rate and antibody kinetics were estimated in 2032 participants for whom a second blood sample was taken after a median follow up of seven years. HCV-RNA determination by polymerase chain reaction was performed on follow up sera. Results: The overall confirmed anti-HCV prevalence was 2.4%. Two participants seroconverted for anti-HCV, giving an overall infection rate of 1.4 cases per 10 000 person years (95% confidence interval 0.2–5.2 per 10 000 person years). Of the 36 individuals confirmed as anti-HCV positive at enrolment, seven (19.4%) showed complete seroreversion. Seven (87%) of the eight individuals with indeterminate results at enrolment were serologically non-reactive at the end of follow up. Of the 25 participants confirmed to be anti-HCV positive at both enrolment and follow up, 23 (92.0%) with stable serological profiles tested positive for HCV-RNA at the end of follow up. Conclusions: There is still a permanent risk, although low, of HCV spread in the general population in an area of low level endemicity. In this setting, a wide spectrum of modifications of viral and antibody patterns can be observed in HCV infected patients.
Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study
Authors: M. Spears, I. Donnelly, L. Jolly, M. Brannigan, K. Ito, C. McSharry, J. Lafferty, R. Chaudhuri, G. Braganza, I. M. Adcock, P. J. Barnes, S. Wood, N. C. Thomson
Journal: European Respiratory Journal (2009)

Smoking is common in asthma and is associated with worse asthma control and a reduced therapeutic response to corticosteroids. The present authors hypothesised that treating smokers with asthma with low-dose theophylline added to inhaled corticosteroids would enhance steroid sensitivity and thereby improve lung function and symptoms. In a double-blind, parallel group exploratory trial, 68 asthmatic smokers were randomised to one of three treatments for 4 weeks: inhaled beclometasone (200 μg·day −1 ), theophylline (400 mg·day −1 ) or both treatments combined. Outcome measures included change in lung function and Asthma Control Questionnaire (ACQ) scores. At 4 weeks, theophylline added to inhaled beclometasone produced an improvement in peak expiratory flow (39.9 L·min −1 , 95% confidence intervals (CI) 10.9–68.8) and ACQ score (-0.47, 95% CI -0.91– -0.04) and a borderline improvement in pre-bronchodilator forced expiratory volume in one second (mean difference 165 mL, 95% CI -13–342) relative to inhaled corticosteroid alone. Theophylline alone improved the ACQ score (-0.55, 95% CI -0.99– -0.11), but not lung function. In the present pilot study, the combination of low-dose theophylline and inhaled beclometasone produced improvements in both lung function and symptoms in a group of smokers with asthma. Larger trials are required to extend and confirm these findings.
BLOOD PLASMA PROTEIN REGENERATION CONTROLLED BY DIET
Authors: Russell L. Holman, Earle B. Mahoney, George H. Whipple
Journal: The Journal of Experimental Medicine (1934)

When blood plasma proteins are depleted by bleeding and return of the washed red cells (plasmapheresis) the regeneration of new plasma proteins can be controlled at will by diet. The amount and character of protein intake is all important. Liver protein and casein are efficient proteins to promote rapid regeneration of plasma proteins but some vegetable proteins are also efficient. The blood plasma proteins are reduced by plasmapheresis close to the edema level (3.5–4.0 per cent) and kept at this level by suitable exchanges almost daily. The amount of plasma protein removed is credited to the given diet period. A basal ration is used which is poor in vegetable protein (potato) and contains no animal protein. The dog on this ration can be kept in nitrogen balance but can produce only about 2 gm. plasma protein per kilo body weight per week. With liver or casein feeding this production can be increased three- or fourfold. A reserve of protein building material can be demonstrated in the normal dog when its plasma proteins are depleted. In the first 3 weeks of depletion this reserve in excess of the final basal output may amount to 3–20 gm. protein. This may be stored at least in part in the liver. As much as 50 per cent of this reserve may be albumin or albumin producing material. A reversal of the albumin-globulin ratio may be observed on the basal diet alone. The reversal will always follow plasmapheresis with the dog on the basal diet and the total plasma protein output will consist approximately of 2 parts globulin and 1 part albumin. Liver diet will raise the production and output of albumin and bring the ratio back toward normal. Albumin production may actually exceed the globulin output during liver diet periods. The change is less conspicuous with casein but in the same direction.
A new antiinflammatory compound, leumedin, inhibits modification of low density lipoprotein and the resulting monocyte transmigration into the subendothelial space of cocultures of human aortic wall cells.
Authors: M Navab, S Y Hama, B J Van Lenten, D C Drinkwater, H Laks, A M Fogelman
Journal: Journal of Clinical Investigation (1993)

Addition of leumedin, N-[9H-(2,7-dimethylfluorenyl-9-methoxy) carbon]-L-leucine at 30-60 microM together with LDL almost completely prevented the induction of monocyte chemotactic protein mRNA, reduced monocyte chemotactic protein 1 levels by 84%, and inhibited monocyte migration into the subendothelial space of cocultures of human aortic wall cells by < or = 98%. LDL incubated with leumedin formed a stable complex that remained intact even after refloating in an ultracentrifuge. Leumedin at 50 microM did not change conjugated diene formation during coculture modification of LDL or Cu++ catalyzed oxidation of LDL. Unlike LDL from control rabbits, LDL isolated from rabbits that were injected with 20 mg/kg leumedin was remarkably resistant to modification by the coculture and did not induce monocyte migration to a significant degree. Moreover, HDL isolated from rabbits injected with leumedin was far more effective in protecting against LDL modification by the artery wall cocultures than HDL from control rabbits. We conclude that leumedins can associate with lipoproteins in vivo, rendering LDL resistant to biological modification and markedly amplifying the protective capacity of HDL against in vitro LDL oxidation by artery wall cells.
The role of "fear of corticosteroids" in nonparticipation in early intervention with inhaled corticosteroids in asthma and COPD in general practice
Authors: PM van Grunsven, CP van Schayck, HJ van Kollenburg, K van Bosheide, HJ van den Hoogen, J Molema, C van Weel
Journal: European Respiratory Journal (1998)

Treatment of chronic airflow obstruction with inhaled corticosteroids at an early stage has been shown to preserve the lung function. We tested the hypothesis that "fear of corticosteroids" may be an important reason for nonparticipation in the Detection, early Intervention and Monitoring programme on Chronic obstruction pulmonary disease (COPD) and Asthma ("DIMCA") project. One thousand seven hundred and forty nine adult subjects from 10 general practices were invited to participate in the several parts of the "DIMCA" programme. Refusers were questioned about the reason(s) for nonparticipation. Together the screening, monitoring and three drug interventions of the study showed on average 25-35% refusers. The most frequent reasons for nonparticipation were absence of pulmonary symptoms and lack of time. For those invited to take part in one of the three drug interventions, "dislike of medication" was the most important reason for nonparticipation (33, 45 and 67% of the refusers). "Fear of corticosteroids" specifically was the reason for nonparticipation in 8% of the refusers on the basis of "dislike of medication". We concluded that a specific fear of corticosteroids was not a major obstacle for early intervention with inhaled corticosteroids.
Effect of Oral Appliance Therapy on Upper Airway Collapsibility in Obstructive Sleep Apnea
Authors: Andrew T Ng, Helen Gotsopoulos, Jin Qian, Peter A Cistulli
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Oral appliance therapy is emerging as an alternative to continuous positive airway pressure for the treatment of obstructive sleep apnea (OSA). However, its precise mechanisms of action are yet to be defined. We examined the effect of a mandibular advancement splint (MAS) on upper airway collapsibility during sleep in OSA. Ten patients with proven OSA had a custom-made MAS incrementally adjusted during an acclimatization period until the maximum comfortable limit of mandibular advancement was reached. Polysomnography with the splint was then performed. After a 1-week washout period, upper airway closing pressures during sleep (with and without MAS) were determined. Significant improvements with MAS therapy were seen in the apnea/hypopnea index (25.0 ± 3.1 vs. 13.2 ± 4.5/hour, p < 0.03) and upper airway closing pressure in Stage 2 sleep (–1.6 ± 0.4 vs. –3.9 ± 0.6 cm H2O, p < 0.01) and in slow wave sleep (–2.5 ± 0.7 vs. –4.7 ± 0.6 cm H2O, p < 0.02) compared with no therapy. These preliminary data indicate that MAS therapy is associated with improved upper airway collapsibility during sleep. The mediators of this effect remain to be determined.
Targeting siglec-E on murine dendritic cells inhibits antigen presentation and CD4 and CD8 t cell responses
Authors: M. Bax, W. Unger, S. Kaur Singh, E. J. McKenzie, M. Litjens, J. J. Garcia-Vallejo, E. Saeland, S. J. van Vliet, P. R. Crocker, Y. van Kooyk
Journal: Annals of the Rheumatic Diseases (2010)

Dendritic cells (DCs) are the most potent antigen presenting cells of the immune system. They are important regulators of immune responses by their capacity to induce tolerance or immunity, depending on the type of antigen they encounter with their cell surface receptors. An important group of cell surface receptors expressed by DCs are …
Genetic Architecture of Plasma Adiponectin Overlaps With the Genetics of Metabolic Syndrome–Related Traits
Authors: Peter Henneman, Yurii S. Aulchenko, Rune R. Frants, Irina V. Zorkoltseva, M. Carola Zillikens, Marijke Frolich, Ben A. Oostra, Ko Willems van Dijk, Cornelia M. van Duijn
Journal: Diabetes Care (2010)

OBJECTIVE Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome–related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs). RESEARCH DESIGN AND METHODS We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model. RESULTS Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin. CONCLUSIONS The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR.
Aetiology and trends in healthcare workers' occupational asthma
Authors: Gareth Walters, Paul Henneburger, Vicky Moore, Emmet McGrath, Sherwood Burge
Journal: European Respiratory Journal (2013)

There are a disproportionately high number of cases of work-related asthma (WRA) from healthcare occupations, due to agents such as gluteraldehyde, latex, and cleaning products. We reviewed data collected on occupational asthma (OA) notifications from the SHIELD database (West Midlands, UK), from 1991 to 2011, for a better understanding of the aetiology and time-trends of healthcare worker (HCW) related OA. There were 182 cases of HCW-associated OA (median annual incidence =7; IQR interquartile range=5-11), representing 5.1-18.9% of annual SHIELD notifications. Modal annual incidence was 20 in 1996; incidence has declined since then, in line with total SHIELD notifications. Nursing, operating theatre, endoscopy and radiology staff were implicated in the majority of cases (136; 75%). The most frequently encountered agents were gluteraldehyde (n=69), latex (n=47) and cleaning products (n=27), accounting for 79% of the 182 cases. The incidence of gluteraldehyde- and latex-related OA decreased after 1998 due to increased awareness and substitution within the UK National Health Service (NHS). Cleaning product-related OA is an emerging cause with 22 cases after 2001, and only 5 cases between 1991 and 2000. Control measures have seen a decline in HCW-associated OA, though it is still a problem amongst HCWs exposed to cleaning products, so effort is required to reduce such exposures to limit the number of cases in this industry.
Effect of a Pharmacist Intervention on Clinically Important Medication Errors After Hospital Discharge
Authors: Sunil Kripalani
Journal: Annals of Internal Medicine (2012)

Background: Clinically important medication errors are common after hospital discharge. They include preventable or ameliorable adverse drug events (ADEs), as well as medication discrepancies or nonadherence with high potential for future harm (potential ADEs). Objective: To determine the effect of a tailored intervention on the occurrence of clinically important medication errors after hospital discharge. Design: Randomized, controlled trial with concealed allocation and blinded outcome assessors. (ClinicalTrials.gov registration number: NCT00632021) Setting: Two tertiary care academic hospitals. Patients: Adults hospitalized with acute coronary syndromes or acute decompensated heart failure. Intervention: Pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and individualized telephone follow-up after discharge. Measurements: The primary outcome was the number of clinically important medication errors per patient during the first 30 days after hospital discharge. Secondary outcomes included preventable or ameliorable ADEs, as well as potential ADEs. Results: Among 851 participants, 432 (50.8%) had 1 or more clinically important medication errors; 22.9% of such errors were judged to be serious and 1.8% life-threatening. Adverse drug events occurred in 258 patients (30.3%) and potential ADEs in 253 patients (29.7%). The intervention did not significantly alter the per-patient number of clinically important medication errors (unadjusted incidence rate ratio, 0.92 [95% CI, 0.77 to 1.10]) or ADEs (unadjusted incidence rate ratio, 1.09 [CI, 0.86 to 1.39]). Patients in the intervention group tended to have fewer potential ADEs (unadjusted incidence rate ratio, 0.80 [CI, 0.61 to 1.04]). Limitation: The characteristics of the study hospitals and participants may limit generalizability. Conclusion: Clinically important medication errors were present among one half of patients after hospital discharge and were not significantly reduced by a health-literacy–sensitive, pharmacist-delivered intervention. Primary Funding Source: National Heart, Lung, and Blood Institute.