tbuckley/cabot-search huggingface dataset:
Clinical Significance of Epidermal Growth Factor Receptor Protein Overexpression and Gene Copy Number Gains in Prostate Cancer
Authors: Thorsten Schlomm, Patrick Kirstein, Liv Iwers, Birte Daniel, Thomas Steuber, Jochen Walz, Felix H.K. Chun, Alexander Haese, Jens Kollermann, Markus Graefen, Hartwig Huland, Guido Sauter, Ronald Simon, Andreas Erbersdobler
Journal: Clinical Cancer Research (2007)

The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level.Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations.Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P < 0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P < 0.0001), high grade (P < 0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (>20 EGFR gene copies per cell). This amplification was heterogeneous, involving only approximately 30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed.Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.
Prediction of Prostate Cancer for Patients Receiving Finasteride: Results From the Prostate Cancer Prevention Trial
Authors: Ian M. Thompson, Donna Pauler Ankerst, Chen Chi, Phyllis J. Goodman, Catherine M. Tangen, Scott M. Lippman, M. Scott Lucia, Howard L. Parnes, Charles A. Coltman
Journal: Journal of Clinical Oncology (2007)

Using data from men in the finasteride group of the Prostate Cancer Prevention Trial (PCPT), we evaluated the impact of prostate-specific antigen (PSA) and other risk factors on the risk of prostate cancer.Four thousand four hundred forty men in the finasteride group of the PCPT underwent prostate biopsy, had at least one PSA and a digital rectal exam (DRE) during the year before biopsy, had at least two PSA values from the 3 years before biopsy, and were on finasteride at the time of PSA evaluation. Logistic regression was conducted using the variables age, race, family history of prostate cancer, PSA, PSA velocity, and DRE adjusting for history of prior prostate biopsy.Six hundred forty-nine (14.6%) of 4,440 men were diagnosed with prostate cancer; 250 had Gleason 7 or higher cancer. Factors associated with an increased risk of prostate cancer included high PSA value and a rising PSA (24.9% risk for PSA value of 1.0 ng/mL and 24.8% risk for a rising PSA), family history of prostate cancer, abnormal DRE result, African American race, and older age. Factors associated with an increased risk of Gleason 7 or higher grade prostate cancer included PSA, abnormal DRE, and older age. A prior negative biopsy was associated with decreased risk of prostate cancer and high-grade prostate cancer.Risk factors for prostate cancer on biopsy for men receiving finasteride include PSA, DRE, age, race, family history, and history of a prior negative biopsy. With the exception of the approximate reduction of PSA by half with finasteride, the impact of these risk factors is similar to men who do not receive finasteride.
Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor: A Report From the Swedish-Norwegian Testicular Cancer Group
Authors: Sven-Erik Olofsson, Torgrim Tandstad, Mats Jerkeman, Olav Dahl, Olof Ståhl, Olbjørn Klepp, Roy M. Bremnes, Gabriella Cohn-Cedermark, Carl W. Langberg, Anna Laurell, Arne Solberg, Ulrika Stierner, Rolf Wahlqvist, Hans Wijkström, Harald Anderson, Eva Cavallin-Ståhl
Journal: Journal of Clinical Oncology (2011)

From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response.Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for β-human chorionic gonadotropin (β-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2.Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients.With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.
Badminton injuries--a prospective epidemiological and socioeconomic study.
Authors: K Høy, B E Lindblad, C J Terkelsen, H E Helleland, C J Terkelsen
Journal: British Journal of Sports Medicine (1994)

During a 1-year period 100 badminton players were registered and treated in the casualty ward of Randers City Hospital, Denmark. The injuries to the badminton players constituted 5% of all sports injuries registered during the same period in the casualty ward. At follow-up questionnaires were sent to all participants. Replies were received from 89 patients. Over the same period all sports participants in the hospital catchment area (30,254) were registered according to their sport affiliation (2620 badminton players-1650 men and 970 women). Of those injured 58% were men (mean age 31 years) and 42% were women (mean age 25 years). Of the injuries 55% occurred in club players, the remainder occurring during company and school sports activities. The active players were classified into three groups according to age: Group 1 under 18 years (31%); Group 2 18-25 years (16%); Group 3 more than 25 years (53%). According to the Abbreviated Injury Scale (AIS) 17% of the injuries were classified as minor, 56% as moderate, and 27% as severe, respectively. Of the severe injuries (AIS = 3) 56% were found in the oldest age group. AIS correlated with time absent from sport (P &lt; 0.001). Nine players (9%) reported that earlier injuries had influenced the actual accident. Most players (96%) trained one to three times a week. Sprains were the injury most commonly diagnosed (56%), fractures accounted for 5%, torn ankle ligaments were found in 10%, and 13% had ruptures to the Achilles tendon. Overall, 21% were admitted to hospital. None of the patients treated as inpatients was kept in hospital for more than 7 days. The injury caused 56% of players to be absent from work of whom 23% were absent for more than 3 weeks. After the injury 12% of the players gave up their sport, and only 4% restarted their training/sport within 1 week. As many as 28% had to avoid training and playing in matches for 8 weeks or more.
Decreased pressor reactivity to angiotensin II in cirrhotic rats. Evidence for a post-receptor defect in angiotensin action.
Authors: B M Murray, M S Paller
Journal: Circulation Research (1985)

We used a model of cirrhosis in the rat, produced by inhalation of carbon tetrachloride for 6 weeks, to investigate the mechanism of resistance to the pressor effects of angiotensin II. The pressor response to angiotensin II was significantly lower in conscious cirrhotic animals than in controls. On the other hand, cirrhotic animals had normal pressor responses to norepinephrine, indicating that a generalized defect in vascular reactivity does not cause the decreased pressor response to angiotensin II. Enhanced baroreceptor activity was not the cause of the decreased pressor response to angiotensin II, since baroreflex control of heart rate after angiotensin II was similar in cirrhotics and controls. Pretreatment with either the converting enzyme inhibitor captopril to reduce circulating angiotensin II or the prostaglandin synthesis inhibitor meclofenamate failed to normalize the response to angiotensin II. Thus, neither prior occupancy of receptors with endogenous angiotensin II nor the production of vasodilatory prostaglandins was responsible for the decreased angiotensin II response. Studies of angiotensin II binding by mesenteric artery smooth muscle particles showed that, in cirrhotic animals, receptor affinity for angiotensin II, was significantly lower than in controls (kd: cirrhosis 1.11 +/- 0.09 nM, control 0.94 +/- 0.13 nM; P less than 0.02), whereas receptor number was significantly increased (cirrhosis 315 +/- 42 fmol/mg protein, control 277 +/- 43 fmol/mg protein, P less than 0.01). However, total binding of AII by vascular receptors from cirrhotics was no different than in controls, since the decrease in affinity negated the increase in receptor number.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagnostic value of a synthetic peptide derived from Echinococcus granulosus recombinant protein.
Authors: M Chamekh, H Gras-Masse, M Bossus, B Facon, C Dissous, A Tartar, A Capron
Journal: Journal of Clinical Investigation (1992)

A specific monoclonal antibody (MAb; EG 02 154/12) directed against a protein epitope of Echinococcus granulosus antigen 5 was used to screen a cDNA library constructed from E. granulosus protoscoleces RNA. One clone designated Eg14 was selected and shown to code for an amino acid sequence partially homologous to that of the clone Eg6 previously identified with the same MAb. Hydrophobic cluster analysis showed that both recombinant antigens may adopt a similar alpha-helical organization and share a common conformational epitope. A synthetic peptide (89-122) mimicking the conformational site of Eg6 and Eg14 was constructed and demonstrated to be able to inhibit binding of the MAb and human hydatid sera to the Eg6 fusion protein (FP6) or to native hydatid antigens. To assess the diagnostic value of the peptide 89-122, we tested sera from patients infected with different parasites for their antibody reactivity with this peptide in ELISA. A high binding sensitivity and specificity of IgG-A-M antibodies were obtained with E. granulosus-infected patient sera. Moreover, the peptide 89-122 was found to be specifically recognized by IgE antibodies from patients with hydatid disease. These results indicate the particular interest of this synthetic peptide as a standardized antigen in diagnosis and treatment surveillance of hydatidosis.
Gene Therapy to Inhibit the Calcium Channel β Subunit
Authors: Eugenio Cingolani, Genaro A. Ramirez Correa, Eddy Kizana, Mitsushige Murata, Hee Cheol Cho, Eduardo Marbán
Journal: Circulation Research (2007)

Calcium cycling figures prominently in excitation-contraction coupling and in various signaling cascades involved in the development of left ventricular hypertrophy. We hypothesized that genetic suppression of the L-type calcium channel accessory beta-subunit would modulate calcium current and suppress cardiac hypertrophy. A short hairpin RNA template sequence capable of mediating the knockdown of the L-type calcium channel accessory beta-subunit gene was incorporated into a lentiviral vector (PPT.CG.H1.beta(2)). Transduction of ventricular myocytes in vivo with the active short hairpin RNA partially inhibited the L-type calcium current. In neonatal rat cardiomyocytes, L-type calcium channel accessory beta-subunit gene knockdown reduced calcium transient amplitude. Similarly, [(3)H]leucine incorporation was attenuated in PPT.CG.H1.beta(2)-transduced neonatal rat cardiomyocytes compared with nonsilencing controls in a phenylephrine-induced hypertrophy model. In vivo gene transfer attenuated the hypertrophic response in an aortic-banded rat model of left ventricular hypertrophy, with reduced left ventricular wall thickness and heart weight/body weight ratios in PPT.CG.H1.beta(2)-injected rats at four weeks post transduction. Fractional shortening was preserved in rats treated with PPT.CG.H1.beta(2). These findings indicate that knockdown of L-type calcium channel accessory beta-subunit is capable of attenuating the hypertrophic response both in vitro and in vivo without compromising systolic performance. Suppression of the calcium channel beta subunit may represent a novel and useful therapeutic strategy for left ventricular hypertrophy.
Splanchnic Regulation of Glucose Production
Authors: John Wahren, Karin Ekberg
Journal: Annual Review of Nutrition (2007)

The liver plays a key role for the maintenance of blood glucose homeostasis under widely changing physiological conditions. In the overnight fasted state, breakdown of hepatic glycogen and synthesis of glucose from lactate, amino acids, glycerol, and pyruvate contribute about equally to hepatic glucose production. Postprandial glucose uptake by the liver is determined by the size of the glucose load reaching the liver, the rise in insulin concentration, and the route of glucose delivery. Hepatic glycogen stores are depleted within 36 to 48 hours of fasting, but gluconeogenesis continues to provide glucose for tissues with an obligatory glucose requirement. Glucose output from the liver increases during exercise; during short-term intensive exertion, hepatic glycogenolysis is the primary source of extra glucose for skeletal muscle, and during prolonged exercise, hepatic gluconeogenesis becomes gradually more important in keeping with falling insulin and rising glucagon levels. Type 1 diabetes is accompanied by diminished hepatic glycogen stores, augmented gluconeogenesis, and increased basal hepatic glucose production in proportion to the severity of the diabetic state. The hyperglycemia of type 2 diabetes is in part caused by an overproduction of glucose from the liver that is secondary to accelerated gluconeogenesis.
Calprotectin - A marker of mortality in COPD? Results from a prospective cohort study
Authors: Dennis Back Holmgaard, Lone Hagens Mygind, Ingrid Louise Titlestad, Hanne Madsen, Svend Stenvang Pedersen, Ole Hartvig Mortensen, Court Pedersen
Journal: European Respiratory Journal (2012)

Background – Neutrophil involvement in chronic obstructive pulmonary disease (COPD) is well established. Calprotectin comprises more than 45 % of the cytosolic content of neutrophils, and has been shown to be useful as a marker of inflammatory activity in inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Since disease activity in COPD seems dependent, in part, by neutrophil driven inflammation we decided to investigate whether plasma level of calprotectin (p-calprotectin) was associated with mortality in COPD.

Methods - We measured p-calprotectin in blood samples from 458 patients suffering from moderate to very severe COPD in stable phase. Patients were stratified into three groups according to p-calprotectin. Outcome measure was mortality in a 3 year follow-up period. Analyses were adjusted for factors known to influence mortality using multivariate cox proportional hazard regression analysis (Cox PH).

Results - Absolute mortality increased from 16.2 % (p-calprotectin  200 ng/ml). In Cox PH p-calprotectin level > 200 ng/ml [HR 2.16 (CI 95%: 1.19-3.91)] when adjusting for factors known to influence mortality.

![Figure][1] 



Conclusions - p-calprotectin levels > 200 ng/ml are associated with increased mortality in patients with moderate to very severe COPD in stable phase. P-calprotectin is a potential marker of airway inflammatory activity.

 [1]: pending:yes
Paracrine interactions of basic fibroblast growth factor and interleukin-6 in multiple myeloma
Authors: Guido Bisping, Regine Leo, Doris Wenning, Berno Dankbar, Teresa Padró, Martin Kropff, Christian Scheffold, Matthias Kröger, Rolf M. Mesters, Wolfgang E. Berdel, Joachim Kienast
Journal: Blood (2003)
Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon: A multicenter sequential trial
Authors: Jean-Claude Trinchet, Beverley Balkau, Renée E. Poupon, François Heintzmann, Patrice Callard, Cécile Gotheil, Jean-Didier Grange, Denis Vetter, Arnaud Pauwels, Hélène Labadie, Olivier Chazouilleres, Philippe Mavier, Hervé Desmorat, Jean-Pierre Zarski, Jean-Claude Barbare, Jean-françois Chambre, Alexandre E. Pariente, Dominique Roulot, Michel Beaugrand
Journal: Hepatology (1992)

Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with α = 0.05, β = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity ≤ 50%, bilirubinemia ≥ 100 μmol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk. The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events. Only one minor case of hypoglycemia was observed. Treatment by the infusion of an association of insulin and glucagon is not beneficial in patients with severe biopsy-proven alcoholic hepatitis. (Hepatology 1992;15:76-81).
Mite allergens. Collection, determination, expression of results, and risk levels for sensitization and symptom induction
Authors: S. Dreborg
Journal: Allergy (1998)

The presence of mite allergens in dust can be determined by counting mites at different stages of development in dust and by determination of the major allergen content (Der p 1) in dust and air, which is crucially important to allergic patients. For comparison of results, similar methods for collection of dust and air must be used. Due to their size, mite bodies and fecal particles are airborne only directly after disturbance. Special filters should be used for dust collection, and upholstered surfaces should be vacuumed for 2 min/m 2 (minimum 4 m 2 ) and hard surfaces for 1 min/m 2 (minimum 8 m 2 ). Heavy contaminations should be removed. Preferably, the method given in the ISAAC study should be followed. Samples should be deep‐frozen for at least some days to kill the mites. ELISA techniques, preferably using polyclonal antibodies and antigen with all isoforms present, should be used for determination of allergens. The allergen load has been given in ng/g of dust, but allergen/m 2 or per sample area should be preferred. Allergen in the air should be given in pg/m 3 . A tentative limit of 2000 ng/g was proposed for sensitization and asthma. This limit is still valid on a population basis, but recent data indicate that highly susceptible young children become sensitized at concentrations 10–100 times lower and that ng levels of cat allergen/m 3 , as found in schools, induce chronic asthma.
Risk of herpes zoster infection in patients with pemphigus on mycophenolate mofetil
Authors: M. Saha, M.M. Black, R.W. Groves
Journal: British Journal of Dermatology (2008)

Journal Article Risk of herpes zoster infection in patients with pemphigus on mycophenolate mofetil Get access M. Saha, M. Saha Department of Immunodermatology, St John’s Institute of Dermatology, St Thomas’ Hospital, London, U.K. E‐mail: monikasaha@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar M.M. Black, M.M. Black Department of Immunodermatology, St John’s Institute of Dermatology, St Thomas’ Hospital, London, U.K. E‐mail: monikasaha@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar R.W. Groves R.W. Groves Department of Immunodermatology, St John’s Institute of Dermatology, St Thomas’ Hospital, London, U.K. E‐mail: monikasaha@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 5, 1 November 2008, Pages 1212–1213, https://doi.org/10.1111/j.1365-2133.2008.08854.x Published: 01 November 2008
The ratio of high molecular weight (HMW) to total adiponectin correlates with insulin resistance in fatty liver disease
Authors: Thien Nguyen, Therese L. Murphy, Geraldine Lipka, Linda M. Fletcher, Graeme A. Macdonald
Journal: Hepatology (2008)

Background and AimAdiponectin, an insulin-sensitizing adipokine, is present in serum as multimers of varying size. High molecular weight (HWM) multimers appear to play a major role in hepatic insulin sensitivity, which in turn has beenimplicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Therefore, our aim was to study the relationship between adiponectin multimers and NAFLD. MethodsThe study population consisted of 32 patients with NAFLD(19 male), 21 with chronic HBV (10 male) and 28 healthy volunteers (15 male). The ratio of HMW: Total adiponectin (know as Sa) was determined by velocity sedimentation, followed by SDS-PAGE and Western blotting. Sa was correlated with BMI, age, ALT, AST, lipids, insulin resistance (as determined by the HOMA score). ResultsSerum triglycerides were higher and HDL cholesterol lower in NAFLD patients compared with controls (p < 0.0001). The Sa in NAFLD (0.35 ± 0.15) was significantly lower than in patients with HBV (0.52 ± 0.13, p<0.0001) or healthy volunteers (0.54 ± 0.16, p< 0.0001). As expected, the Sa was significantly higher in females than males (p = 0.0002) in the control group, however this was not seen in either liver disease groups. There was a negative correlationbetween the Sa and HOMA in the NAFLD group (p=0.006).ConclusionsThe ratio of HMW to total adiponectin correlateswith the presence of NAFLD. This suggests adiponectin multimers may be involved in the pathogenesis of NAFLD