tbuckley/cabot-search huggingface dataset:
Evidence of Abnormal Epidermal Nerve Fiber Density in Fibromyalgia: Clinical and Immunologic Implications
Authors: Xavier J. Caro, Earl F. Winter
Journal: Arthritis & Rheumatology (2014)

Objective A subset of patients with fibromyalgia (FM) exhibit a large fiber demyelinating peripheral polyneuropathy akin to that seen in chronic inflammatory demyelinating polyneuropathy (CIDP). It has been suggested that this demyelinating process is likely to be immune mediated. Because it is known that similar large fiber neuropathic lesions may be associated with a cutaneous small fiber neuropathy, we sought to determine the prevalence of small fiber neuropathy, as measured by epidermal nerve fiber density (ENFD), in a series of patients with FM and clinically healthy control subjects. Methods Forty‐one consecutive patients with FM and 47 control subjects underwent a 3‐mm punch skin biopsy at the proximal thigh and distal leg near the ankle, for analysis of the ENFD. Patients with FM who had clinical evidence of a disorder known to be associated with small fiber neuropathy were excluded. The patients with FM also underwent pinwheel testing and vibratory testing for hypesthesia and serologic testing for a series of cytokine, circulating immune complex, and complement measurements. Results All patients with FM had evidence of stocking hypesthesia. The ENFD of patients with FM was lower than that of control subjects at both the calf (mean ± SD 5.8 ± 2.8 versus 7.4 ± 1.9; P = 0.0002) and thigh (9.3 ± 3.2 versus 11.3 ± 2.0; P = 0.0007). There was an inverse correlation between calf ENFD and age at the time of skin biopsy in patients with FM (r = −0.29, P = 0.03) but not in control subjects; however, analysis of covariance showed that this relationship could not be explained by aging alone. Serologic evaluation showed an inverse correlation between calf ENFD in patients with FM and the interleukin‐2 receptor (IL‐2R) level (r = −0.28, P = 0.04). However, an inverse correlation between thigh ENFD and serum IL‐2R levels did not reach significance ( P = 0.08). Analysis of thigh‐to‐calf ENFD ratios suggested that the ENFD decline in FM is affected by both a diffuse and a length‐dependent process. Conclusion The calf and thigh ENFD in patients with FM is significantly diminished compared with that in control subjects. Advancing age alone cannot explain this finding. Calf ENFD was inversely correlated, although weakly, with serum levels of IL‐2R. These findings suggest that small fiber neuropathy is likely to contribute to the pain symptoms of FM; that pain in this disorder arises, in part, from a peripheral immune‐mediated process; and that measurement of ENFD may be a useful clinical tool in FM.
Isocitrate dehydrogenase mutations in gliomas
Authors: Matthew S. Waitkus, Bill H. Diplas, Hai Yan
Journal: Neuro-Oncology (2015)

Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg132 of IDH1 and Arg172 of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy.
The Partner Gene of AML1 in t(16;21) Myeloid Malignancies Is a Novel Member of the MTG8(ETO) Family
Authors: Toshie Gamou, Eiko Kitamura, Fumie Hosoda, Kimiko Shimizu, Kenji Shinohara, Yasuhide Hayashi, Takahiro Nagase, Yasunobu Yokoyama, Misao Ohki
Journal: Blood (1998)
Association analysis of Β2-adrenergic receptor gene polymorphisms (Arg16Gly and Gln27Glu) with asthma in the Volga-Ural region of Russia
Authors: Yuliya Fedorova, Alexandra Karunas, Galiya Gimalova, Nailya Ramazanova, Regina Murzina, Lilya Muchtarova, Elena Galimova, Radik Gatiyatullin, Shamil Zagidullin, Esfir Etkina, Elza Khusnutdinova
Journal: European Respiratory Journal (2012)

The β2-adrenergic agonists are the most potent bronchodilators for the treatment of asthma. Genetic variation in the ADRB2 gene has been hypothesized to have a role in differential response to beta-agonist (BA) therapy in asthma. Two polymorphic variants rs1042713 (Gly16Arg) and rs1042714 (Gln27Glu) were genotyped in 618 patients with physician-diagnosed asthma, aged 2-60 years (192 Russians, 139 Tatars, 82 Bashkirs and 205 mixed origins), and 366 nonasthmatic individuals (123 Russians, 91 Tatars, 51 Bashkirs and 101 mixed origins) from the Volga-Ural region of Russia. Genotypes were determined by the PCR-RFLP method. Data were analyzed using the chi-square test with Haploview software. We found significant association of Gln27Glu polymorphism with mild decrease FEV1 (60-80% of the predicted value) in Russian patients. The frequencies of genotype ADRB2*27Gln/27Gln and allele ADRB2*27Gln were increased in asthmatics of this group compared to controls (p=0,03, OR=2,25 (95%CI 1,05-4,82) and p=0,02, OR=1,97 (95%CI 1,11-3,50), accordingly). The analysis of Arg16Gly polymorphism showed significant association with moderate asthma in Tatars. The higher frequency of the ADRB2*16Gly/16Arg heterozygotes was revealed in the patients compared with controls (p=0,02, OR=2,25 (95%CI 1,15-4,03)). In summary, these results suggest an important role for polymorphisms of gene ADRB2 in the development of asthma in the Volga-Ural region of Russia.
Case presentation: Should we always treat IgG4-related lung disease?
Authors: Erik Baltaxe, Tiberiu Shulimzon, Amir Onn, Michael J. Segel
Journal: European Respiratory Journal (2014)

Introduction: 

IgG4-related lung disease (IgG4-RLD) is part of a spectrum of inflammatory diseases that share similar pathological features and elevated serum IgG4. Recently chest involvement in IgG4-RLD has been characterized clinically and radiologically. Most reports advocate prompt immunosuppressive therapy and describe a fast and good response. We report 3 cases of untreated IgG4-RLD that on follow-up have been clinically asymptomatic and radiologically stable or improved.

Cases presentation: 

Case 1 : 44 yr old female with cough and shortness of breath. Chest CT showed mediastinal lymphadenopathy and bilateral alveolar and peribronchovascular infiltrates. Core needle biopsy showed a thickened lung interstitium, dense lymphoplasmocytic infiltrate, vasculitis and 30-40 IgG4+ cells/hpf. Serum IgG4: 573 mg/dl. On follow-up symptoms resolved spontaneously and radiological findings have partially regressed. Case 2 : 21 yr old male with productive cough and pleuritic chest pain. Chest CT showed a RUL solid mass with spiculated margins. Pathology from lobectomy showed lymphoplasmocytic infiltration without vasculitis. 20–25% IgG4+ cells. Serum IgG4: 416 mg/dl. Now asymptomatic. Case 3 : 58 yr old male presented with an incidental finding on chest CT of pleural thickening. PET-CT showed retroperitoneal fibrosis, mesenteric panniculitis and aortitis. Pathology from a thoracic core needle biopsy showed densely fibrotic paucicellular pleura, and dense lymphoplasmocytic infiltrates in the lung. No IgG4+ cells. No asbestos bodies or silica particles. Serum IgG4: 177 mg/dl. Asymptomatic on follow-up.

Conclusion: 

Immunosuppressive therapy may not be warranted in all cases of IgG4-RLD.
Circulating tumor cells in chronic obstructive pulmonary disease patients
Authors: Céline Sanfiorenzo, Karine Risso, Valérie Sellam, Véronique Hofman, Marius Ilie, Elodie Long, Eric Selva, Christelle Bonnetaud, Charles-Hugo Marquette, Paul Hofman
Journal: European Respiratory Journal (2011)

Introduction and hypothesis:  Migration of circulating tumor cells (CTC) in the blood stream is certainly an early event occurring during lung carcinogenesis. Chronic obstructive pulmonary disease (COPD), even in early stages, is associated with a higher incidence of lung cancer in smokers and ex-smokers. The purpose of this study was to look for the presence of CTC in a cohort of smokers having a COPD.   Methods:  The presence of CTC was searched in 50 COPD patients, using both the CellSearch (CS) and the isolation by size of epithelial tumor (ISET) cells methods. Results were compared to the detection of CTC in a group of 30 patients with stage IIIB or IV non-small cell lung cancer (NSCLC) and in a group of 30 healthy individuals.   Results:  4/50 (8%) COPD patients had CTC (mean=4; range, 2-8 CTC) detected by CS and/or ISET methods. 18/30 (60%) of advanced stages NSCLC patients showed CTC (mean=16; range, 2-86). No CTC were detected in healthy individuals.   Conclusion:  The detection of CTC using the CS and/or the ISET methods is a rare biological event in COPD smoker patients. In this regard, the potentiality of the CS and the ISET methods as tools for detecting early blood biomarkers of lung carcinogenesis is challenging.
Body Mass Index Is Prognostic in Metastatic Colorectal Cancer: Pooled Analysis of Patients From First-Line Clinical Trials in the ARCAD Database
Authors: Lindsay A. Renfro, Fotios Loupakis, Richard A. Adams, Matthew T. Seymour, Volker Heinemann, Hans-Joachim Schmoll, Jean-Yves Douillard, Herbert Hurwitz, Charles S. Fuchs, Eduardo Diaz-Rubio, Rainer Porschen, Christophe Tournigand, Benoist Chibaudel, Alfredo Falcone, Niall C. Tebbutt, Cornelis J.A. Punt, J. Randolph Hecht, Carsten Bokemeyer, Eric Van Cutsem, Richard M. Goldberg, Leonard B. Saltz, Aimery de Gramont, Daniel J. Sargent, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2015)

In recent retrospective analyses of early-stage colorectal cancer (CRC), low and high body mass index (BMI) scores were associated with worsened outcomes. Whether BMI is a prognostic or predictive factor in metastatic CRC (mCRC) is unclear.
Circulating tumor DNA as a cancer biomarker
Authors: F. Diehl, K. Schmidt, M. A. Choti, S. Goodman, K. Romans, K. Thornton, K. Kinzler, B. Vogelstein, L. A. Diaz
Journal: Journal of Clinical Oncology (2008)

4122 Background: Somatic mutations drive human tumorigenesis. Dying tumor cells release mutant gene fragments into the circulation, in principle providing exquisitely specific markers to detect the presence of neoplasia and to monitor therapeutic responses. However, the number of such mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with sufficient sensitivity for meaningful clinical use. Methods: We used an extraordinarily sensitive new approach termed BEAMing (Beads, Emulsions, Amplification, and Magnetics), to quantify the amount of circulating tumor DNA (ctDNA) in plasma. In a prospective study, we studied 162 samples collected longitudinally from 18 patients undergoing surgical therapy for primary or metastatic colorectal cancer. This cohort was used to assess whether detection of circulating tumor-derived DNA could be used to monitor the effects of therapy. Results: Circulating tumor DNA was present prior to therapy in 100% of patients. The level of ctDNA fell rapidly after surgical resection, but was still detectable in the immediate post-operative period in a subset of patients. This subset included all patients whose resections were incomplete. Patients who had complete resections but still had detectable ctDNA immediately after surgery generally relapsed within one year. In contrast, patients who had no detectable ctDNA did not relapse during the period of observation. In many cases, the presence of ctDNA preceded radiographic or biochemical evidence of recurrence. Conclusions: Quantification of ctDNA by BEAMing represents a personalized genetic strategy to monitor systemic tumor burdens in patients with advanced colorectal cancers. No significant financial relationships to disclose.
Abstract 9477: Gender Differences in Clinical Characteristics and Risk Factors of Patients with Vasospastic Angina -A Report from the Nationwide Multi-Center Registry by the Japanese Coronary Spasm Association
Authors: Akiko Kawana, Satoshi Yasuda, Yusuke Takagi, Ryusuke Tsunoda, Yasuhiro Ogata, Atsushi Seki, Tetsuya Sumiyoshi, Motoyuki Matsui, Toshikazu Goto, Yasuhiko Tanabe, Shozo Sueda, Toshiaki Sato, Satoshi Ogawa, Norifumi Kubo, Shin-ichi Momomura, Hisao Ogawa, Hiroaki Shimokawa
Journal: Circulation (2011)

Background: Recently, much attention has been paid to gender differences in cardiovascular medicine. Previous studies showed that vasospastic angina (VSA) is more common in male. However, the gender differences in clinical characteristics and outcomes of VSA patients remain to be fully elucidated. Thus, we addressed this important issue in the nationwide multi-center registry by the Japanese Coronary Spasm Association. Methods: We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median 66 years) from 47 institutes in Japan between September 2007 and December 2008 with a median follow-up period of 32 months. The primary endpoint was defined as major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction (MI), unstable angina and heart failure. Results: In comparison with the female patients, the male patients were characterized by younger age (median 66 vs. 69 years, P&lt;0.001), higher incidence of smoking (72 vs. 20%, P&lt;0.001), previous MI (7 vs. 3%, P=0.003), organic coronary stenosis &gt;50% (16 vs. 9%, P=0.001) and ST elevation during spontaneous angina attacks (21 vs. 11%, P&lt;0.001). For the treatment of VSA, Ca channel blocker was used in more than 90% of patients in both genders, whereas antiplatelet was more frequently used in male than in female (50 vs. 38%, P&lt;0.001). Although 5-year MACE-free survival rate was comparable (male 91 vs. female 94%), Cox proportional hazard model demonstrated that the risk factors of MACE were considerably different between genders; male patients were more associated with structural abnormality (e.g., organic stenosis, previous MI), whereas female patients with electrical abnormality (e.g., VT/VF during spontaneous attack) ( Table ). Conclusions: These results indicate that there are substantial gender differences in the clinical characteristics and the risk factors of MACE in VSA patients, suggesting the importance of gender-specific management of the disorder.
Processed meats are carcinogenic, says new review of evidence
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Processed meats such as sausages, bacon, ham, and corned beef have been classified as carcinogenic by the cancer arm of the World Health Organization. They now appear in the same risk group for cancer (group 1) as asbestos, cigarettes, and alcohol.

WHO’s International Agency for Research on Cancer issued the new ranking after reviewing the evidence and finding that eating processed meats causes colorectal cancer, publishing its findings in a monograph and a summary in Lancet Oncology .1 2 It also found that processed meats were associated with stomach cancer.

The 22 experts who considered the evidence on behalf of the agency concluded that each 50 g portion of processed meat eaten daily increased the risk of colorectal cancer by 18%.

Non-processed red meat was classified as probably carcinogenic (group 2A), with limited evidence linking its consumption with colorectal cancer and strong evidence that the breakdown of meat in …
Positron emission tomography of the cerebellum in autism
Authors: C. W. Chris Heh, R. Smith, J. Wu, E. Hazlett, A. Russell, R. Asarnow, P. Tanguay, M. S. Buchsbaum
Journal: American Journal of Psychiatry (1989)

On the basis of neurological evidence that autistic patients have fewer Purkinje and granule cells in the cerebellum as well as vermal cerebellar hypoplasia, the authors tested the hypothesis that autistic patients have cerebellar hypofunctioning. They used positron emission tomography of the cerebellum with 18F-labeled 2-deoxyglucose to study seven autistic patients and eight age-matched control subjects. The results showed no significant difference in mean cerebellar glucose metabolism between the two groups, but all mean glucose rates of the autistic patients were either equal to or greater than those of the control subjects. The implications of these findings are discussed.
On the effectiveness of steroids in acute lung injury: Experimental separation between inflammation and hypoxemia
Authors: Lucy Kathleen Reiss, Stefan Uhlig
Journal: European Respiratory Journal (2012)

Acute lung injury (ALI) is defined by hypoxemia in the presence of excessive inflammation. Despite of a multitude of clinical trials the role of glucocorticoids in the treatment of ALI is under constant debate. The present study was designed to investigate the effectiveness of dexamethasone in dependence on the type and severity of lung injury and the fraction of inspired oxygen (FiO 2 ).  C57BL/6 mice were instilled intratracheally with 50 μL HCl at pH 1.5 or 1.8 and were then ventilated with recruitment manoeuvres (RM) and FiO 2 =0.3 or 1.0. Another group was ventilated without acid instillation and without RM to induce atelectasis. Dexamethasone [1mg/kg] was injected intravenously at the beginning of ventilation. Lung mechanics were followed by the forced oscillation technique. Cardiovascular parameters, oxygen saturation and body temperature were monitored. Blood gases, cytokines, neutrophil recruitment, microvascular permeability and lung histology were examined.  Dexamethasone attenuated inflammation (neutrophil recruitment, edema formation, cytokine liberation) in all models. Hypoxemia and lung mechanics were improved in the groups instilled with acid pH 1.8 (moderate injury), but not in the groups instilled with acid pH 1.5 (severe injury) or in those with atelectasis. A high FiO 2 =1.0 augmented acid-induced lung injury, but did not affect the effectiveness of dexamethasone.  In the present study steroids were highly effective in preventing inflammation under all conditions, whereas they improved the clinical outcome in moderate, but not in severe lung injury or in cases of derecruitment, suggesting that steroids are effective only in a subclass of patients with ALI.
The impact of respiratory rehabilitation in COPD stage D patients
Authors: Catarina Lacerda, Paula Almeida, Rui Rolo, João Cunha
Journal: European Respiratory Journal (2014)

Introduction: According to the new classification, the benefit of respiratory rehabilitation programs (RRP) in patients with COPD stage D is not yet well documented. Objectives: To evaluate the impact of RRP on functional status and quality of life in patients COPD D. Methods: Retrospective analysis of COPD D patients who underwent to a RRP. Exercise capacity (6-min walk test-6MWT), symptoms/health status (mMRC; CAT), anxiety and depression (HADS), ability to perform activities of daily living (LCADL) and quality of life (SGRQ) were assessed before and after the RRP. Results: 21 patients were included: 85,7% males, mean age of 60.6 years and 85,7% had smoking history. FEV1 post-dilatation (mean) was 42.1±13.5 %; Distribution of patients by stages: 24% II, 57% III, 19% IV. Mean duration of the RRP was 12 weeks. Post-RRP reassessment at 8 month (mean). 6MWT was performed prior to RRP in 17 patients (81 %). The mean distance increased: 395m to 421m, verifying a minimal important difference (26 m) in 8 patients (47.1 %). An improved was found in the degree of dyspnea, health status, symptoms of depression and anxiety, activities of daily living and quality of life: mMRC (21 patients) with a mean improvement of 1 point in 47.6 % of patients (n = 10), CAT (12 patients) improved 8 points (mean) in 67 % (n = 8); LCADL (14 patients) improved 5 points (mean) in 79 % (n=11), HADS (15 patients) with improvement of 5 points on average in 47 % (n=7), SGRQ (16 patients) improved of 75 points (mean) in 14 % (n=14). 11 patients had a one year follow-up, which 2 made a “step-down to stage B. Conclusion: This study demonstrated the benefit of RRP in improving the functional capacity and quality of life of patients with COPD stage D.
The metabolic syndrome in patients with chronic obstructive pulmonary disease
Authors: Abdul-Ahad Daouud, Abdalla Khoury, Louai Shakerdi
Journal: European Respiratory Journal (2014)

Purpose :

This study was undertaken to evaluate the presence of the metabolic syndrome in COPD patients. The metabolic syndrome is characterized by the presence of abdominal obesity, atherogenic dyslipidemia, raised blood pressure, presence of insulin resistance, and prothrombotic and inflammatory states that predispose to cardiovascular diseases.

Method :

51 stable COPD patients (31 male, 20 female), and 51 control participants (31 male, 20 female) matched for age and gender are included in this study. The criteria for the identification of the metabolic syndrome include 3 or more of the following features:

1.Abdominal obesity (waist circumference: ≥ 102 cm in men, ≥ 88 cm in women). 2.Triglycerides (≥ 150 mg/dl).

3.HDL-Cholesterol (<40 mg/dl in men, <50 mg/dl in women).

4.Blood pressure (≥ 130/ ≥ 85 mm Hg).

5.Fasting plasma glucose (≥ 110 mg/dl ).

Result :

41.2% of COPD patients and 13.7% of control participants presented 3 or more determinants of the metabolic syndrome.

Conclusion :

The study showed that frequency of metabolic syndrome was higher in stable COPD patients than control subjects. Hence, this population should be considered for screening for the metabolic syndrome.
EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1
Authors: Yung-Sheng Chang, Wei-Yu Chen, Juan Juan Yin, Heather Sheppard-Tillman, Jiaoti Huang, Yen-Nien Liu
Journal: Cancer Research (2015)

Abstract Dysregulation of the EGFR signaling axis enhances bone metastases in many solid cancers. However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential. In this study, we demonstrated a role for EGFR translocation in regulating transcription of miR-1-1, which directly targets expression of TWIST1. Consistent with these findings, we observed decreased miR-1 levels that correlated with enhanced expression of activated EGFR and TWIST1 in a cohort of human prostate cancer specimens and additional datasets. Our findings support a model in which nuclear EGFR acts as a transcriptional repressor to constrain the tumor-suppressive role of miR-1 and sustain oncogenic activation of TWIST1, thereby leading to accelerated bone metastasis. Cancer Res; 75(15); 3077–86. ©2015 AACR.
Catheter-related bacteraemia and infective endocarditis caused by Kocuria species
Authors: C.C. Lai, J.Y. Wang, S.H. Lin, C.K. Tan, C.Y. Wang, C.H. Liao, C.H. Chou, Y.T. Huang, H.I. Lin, P.R. Hsueh
Journal: Clinical Microbiology and Infection (2010)
Studies on the Nature of Antihemophilic Factor (Factor VIII)
Authors: Bruce Bennett, Walter B. Forman, Oscar D. Ratnoff
Journal: Journal of Clinical Investigation (1973)

Normal human antihemophilic factor (AHF, factor VIII) and the protein antigenically related to it in hemophilic plasma both appeared in the void volume of columns of agarose (Sepharose 4B) during purification of these agents. On ultracentrifugation upon sucrose gradients, both agents had sedimentation characteristics similar to those of an S30 marker. After reduction, the polypeptide chains of purified normal AHF and of the nonfunctional agent from hemophilic patients had an apparent molecular weight of 200,000 as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. These observations suggest that AHF, purified as described, exists as a large molecule with subunits of molecular weight of approximately 200,000.