tbuckley/cabot-search huggingface dataset:
Abstract 381: Prolonged Renal Failure Leads to Reduced Number of Active Cardiac Mitochondria in a Rat Model for Long Term Chronic Kidney Disease
Authors: Einat A Hertzberg-Bigelman, Michal Entin-Meer, Genya Aharon-Hananel, Ann Saada, Ran Levy, Lena Cohen, Zach Rozenbaum, Gad Keren
Journal: Circulation Research (2015)

Objectives - Cardiorenal syndrome type 4 is characterized by primary chronic kidney disease (CKD) leading to an impairment of cardiac function. We recently showed a reduced expression of several cardiac mitochondrial genes in short-term CKD rat model. We aimed to evaluate whether cardiac mitochondrial structure and function is modified in long-term CKD and if so, to characterize the potential associated mechanisms. Methods - Lewis rats underwent 5/6 nephrectomy for induction of CKD. Upon necroscopy, eight months later, cardiac sections were analyzed by histology and electron microscopy (EM). Mitochondrial DNA content was determined by the mitochondrial gene, cytochrome B. Mitochondrial content was assessed by citrate synthase (CS) activity in tissue homogenate and respiratory chain function was determined by the activity of complexes I-IV in isolated mitochondria. The levels of PGC1a, a transcription factor for mitochondrial biogenesis, Angiotensin II type 1 receptor and cytosolic cytochrome C were assayed by western blot. Cytokine serum profile was determined by microarray. Results - Long-term CKD leads to cardiac hypertrophy and increased interstitial fibrosis. EM analysis revealed a massive spatial disarrangement accompanied by a considerably increased volume of swollen-damaged mitochondria in CKD hearts (32±3%, n=5, 48±6%, n=4; respectively; p&lt;0.05). Total mitochondrial DNA content was decreased in cardiac tissue of CKD rats. Concomitantly, active mitochondrial content was significantly reduced. Conversely, no differences were observed in respiratory chain enzymes’ functions (complexes I-IV) in isolated active mitochondria. Moreover, inflammatory response and activation of Renin-Angiotensin-Aldosterone-System (RAAS) were detected in the CKD setting. Conclusion - CKD results in a marked reduction of active mitochondria in the heart. Inflammatory cytokines and RAAS, may set a deleterious environment to cardiac mitochondria, as suggested in non-CKD models. The data may represent a significant milestone in the personalized medicine strategy for treating CKD patients who present with normal cardiac function accompanied by positive biomarkers for cardiac mitochondria damage.
Trials and Tribulations
Authors: Jeffrey L. Brown
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THU0417 Peripheral neuropathy in patients with gout. alterations beyond local damage
Authors: CO Lopez Lopez, E Corzo Dominguez, MDLL Montes-Castillo, H Llinas, E Alvarez Hernandez, I Peláez Ballestas, R Burgos Vargas, J Vazquez-Mellado
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Peripheral neuropathies (PN), are peripheral nervous system disorders associated to several causes. According to distribution are classified as: Local (mononeuropathy [MNP]) or Systemic (Multiple mononeuropathy [MNPM] and polyneuropathy [PNP]). PN in gout has been scarcely described. Previous reports only consider MNP of median nerve at the wrist and MNP of the ulnar nerve at the elbow, due to tophus compression. <h3>Objectives</h3> To describe the frequency and characteristics of PN in patients with gout and its association to gout related variables, co-morbidity and treatment. <h3>Methods</h3> Consecutive patients from GRESGO, a cohort of 450 gout (ARA/CGD/ACR-EULAR) patients seen for the first time at Rheumatology department and treated according to published guidelines for gout. Variables included: demographic, clinical, biochemical data, HAQ and 3 questionnaires for PN (DN4, LANSS and MNSI) previously translated and validated in our country. We performed Nerve Conduction Studies (NCS) following AAME guidelines (Include:Sensory action potential [sural, ulnar and median nerves], Compound muscle action potential [peroneal, tibial, median and ulnar nerves] and late F-wave [tibial and ulnar nerves]). This protocol was approved by the local IRB and the patients signed an informed consent. <i>Statistical analysis:</i> Student9s t test, Mann–Whitney U test and X2. <h3>Results</h3> We included 162 gout patients, 98% males, 72% tophaceous gout, 48% severe tophaceous gout (STG), mean age 49.4±12 years, 14±10 years of disease duration, educational level 8±4 years, BMI 27.9±4.6kg/m<sup>2</sup>. According to questionnaires: 56% DN4, 45% MNSI and 36% LANSS could be classified as PN. Sixty five percent had abnormal NCS: MNP: 52%, most of them (58%) neuropraxia. PNP 35% and 13% MNPM in them, axonal damage was reported in 88%. MNP localization: Median nerve/carpal tunnel (89%); peroneal nerve/fibula head (7.4%); ulnar nerve/elbow (1.8%) and tibial nerve/ankle (1.8%). For associated factors, Gout+Local PN (L-PN) patients were compared with Gout without PN as well as Gout+Systemic PN (S-PN) (see table). Hypertriglyceridemia and dyslipidemia were significantly more frequent among L-PN patients; in other hand, frequency of tophi, STG and mean HAQ values were significantly more frequent in S-PN patients, there were no significant differences among other clinical data associated with gout itself. <h3>Conclusions</h3> PN is common among gout patients, PN could be diagnosed by questionnaires (particularly DN4) and NCS in 65%. L-PN (median nerve most of them) explain 52% of the cases, in 48% S-PN was found, in these group PNP is more frequent. Hypertriglyceridemia is associated with L-PN and STG to S-PN. The role of uric acid and/or crystals needs to be evaluated. <h3>Disclosure of Interest</h3> None declared
What Do Implanted Cardiac Monitors Reveal About Atrial Fibrillation?
Authors: Jeff S. Healey
Journal: JAMA Cardiology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Validation of the biopsy tissue microarray technique using Ki-67 expression in untreated localized prostate cancer managed by active surveillance.
Authors: Sameer Jhavar, Jaclyn Bartlett, Gyula Kovacs, Daniel Brewer, Cyril Fisher, Cathy Corbishley, David Dearnaley, Andy Norman, Rosalind Eeles, Colin Cooper, Chris Parker
Journal: Cancer Research (2008)

5134   Background: Active surveillance provides a unique opportunity to study the natural history of untreated early prostate cancer, but only needle biopsy specimens, often containing small amounts of cancer tissue are available from these patients making them unsuitable for construction of conventional tissue microarrays (TMAs). We have previously described a “checkerboard” method to construct TMAs from needle biopsy specimens to analyze multiple markers (Jhavar S  et al , 2005).  Purpose: We aimed to demonstrate the feasibility of the biopsy tissue microarray (TMA) approach to evaluate a candidate biomarker, Ki-67, in the active surveillance setting.  Methods: Biopsy TMAs were constructed using diagnostic needle biopsies from 59 patients with favorable risk disease (Gleason score
固形腫瘍癌の治療を進めるための埋込と制御された薬物放出絹フィブロインナノ繊維状マトリックス【Powered by NICT】
Authors: Xie Maobin, Fan Dejun, Chen Yufeng, Zhao Zheng, He Xiaowen, Li Gang, Chen Aizheng, Wu Xiaojian, Li Jiashen, Li Zhi, A Hunt John, Li Yi, Lan Ping
Journal: Biomaterials (2016)
Quantitative Microbial Risk Assessment for Spray Irrigation of Dairy Manure Based on an Empirical Fate and Transport Model
Authors: Tucker R. Burch, Susan K. Spencer, Joel P. Stokdyk, Burney A. Kieke, Rebecca A. Larson, Aaron D. Firnstahl, Ana M. Rule, Mark A. Borchardt
Journal: Environmental Health Perspectives (2017)

Background: Spray irrigation for land-applying livestock manure is increasing in the United States as farms become larger and economies of scale make manure irrigation affordable. Human health risks from exposure to zoonotic pathogens aerosolized during manure irrigation are not well understood. Objectives: We aimed to a) estimate human health risks due to aerosolized zoonotic pathogens downwind of spray-irrigated dairy manure; and b) determine which factors (e.g., distance, weather conditions) have the greatest influence on risk estimates. Methods: We sampled downwind air concentrations of manure-borne fecal indicators and zoonotic pathogens during 21 full-scale dairy manure irrigation events at three farms. We fit these data to hierarchical empirical models and used model outputs in a quantitative microbial risk assessment (QMRA) to estimate risk [probability of acute gastrointestinal illness (AGI)] for individuals exposed to spray-irrigated dairy manure containing Campylobacter jejuni, enterohemorrhagic Escherichia coli (EHEC), or Salmonella spp. Results: Median risk estimates from Monte Carlo simulations ranged from 10−5 to 10−2 and decreased with distance from the source. Risk estimates for Salmonella or EHEC-related AGI were most sensitive to the assumed level of pathogen prevalence in dairy manure, while risk estimates for C. jejuni were not sensitive to any single variable. Airborne microbe concentrations were negatively associated with distance and positively associated with wind speed, both of which were retained in models as a significant predictor more often than relative humidity, solar irradiation, or temperature. Conclusions: Our model-based estimates suggest that reducing pathogen prevalence and concentration in source manure would reduce the risk of AGI from exposure to manure irrigation, and that increasing the distance from irrigated manure (i.e., setbacks) and limiting irrigation to times of low wind speed may also reduce risk. https://doi.org/10.1289/EHP283
Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner
Authors: P Peña-Martínez, M Eriksson, R Ramakrishnan, M Chapellier, C Högberg, C Orsmark-Pietras, J Richter, A Andersson, T Fioretos, M Järås
Journal: Leukemia (2017)

Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apoptosis-related gene expression signatures. Consistent with these findings, we found that IL4 stimulation of AML cells induced Stat6 phosphorylation and that disruption of Stat6 using CRISPR/Cas9-genetic engineering rendered cells partially resistant to IL4-induced apoptosis. To evaluate whether IL4 inhibits AML cells in vivo, we expressed IL4 ectopically in AML cells transplanted into mice and also injected IL4 into leukemic mice; both strategies resulted in the suppression of the leukemia cell burden and increased survival. Notably, IL4 exposure caused reduced growth and survival of primary AML CD34+CD38− patient cells from several genetic subtypes of AML, whereas normal stem and progenitor cells were less affected. The IL4-induced apoptosis of AML cells was linked to Caspase-3 activation. Our results demonstrate that IL4 selectively induces apoptosis of AML cells in a Stat6-dependent manner—findings that may translate into new therapeutic opportunities in AML.
Mixed-histology small cell lung cancer: The University of Missouri, Columbia, experience.
Authors: Audrey S Wallace, Donald C. Doll
Journal: Journal of Clinical Oncology (2012)

e17525 Background: In 1999, we reported demographics, staging, and treatment outcomes of patients with mixed histology small cell lung cancer (MHSCLC). The purpose of this abstract is to report pattern of presentation and survival in patients during 2000-2009. Methods: Records from 24 patients diagnosed with MHSCLC were reviewed under an institutional review board outcomes study. One patient was excluded as records were missing. Patient and disease characteristics, treatment, and outcomes were analyzed. Results: Twenty-three patients were analyzed, with median age at diagnosis of 63 (range 50 to 84). Twenty (86%) patients were Caucasian. Fourteen (61%) patients were female, 9 (39%) were male. Twenty-one (91%) patients were current or former smokers. Staging was as follows: 1-2: 3, 3: 6, 4: 11, extensive-stage: 1, limited-stage: 2. Sites of diagnosis were lung in 18 (78%), and metastatic sites in 5 (22%). Presenting symptoms were cough or shortness of breath in 12 (52%), CNS in 4 (17%), chest pain in 2 (9%), various others in 5 patients. Paraneoplastic syndrome was seen in 2 patients, and 6 patients reported weight loss of 10-15 lbs within 3-6 months of diagnosis. Metastatic presentation was as follows: 4 brain, 1 bone, and 1 soft tissue. Histology included 15 large cell, 6 adenocarcinoma, and 1 squamous cell. Seventeen patients were treated as follows: chemotherapy (14), 5 thoracic radiotherapy (RT), 3 cranial RT, with treatment status unknown in 1 patient with 3 year survival. Twenty-one (91%) patients had expired, with median survival of 4.6 months (range &lt;1 month-53 months). Two patients were alive at 24.1 and 38.5 months. Conclusions: This review revealed female predominance, which is in line with the increasing number of women diagnosed with small cell lung cancer (SCLC), but could be due to exclusion of veteran administration patients. Best survival was seen in one patient with squamous cell carcinoma, followed by patients with adenocarcinoma, opening a possible role for targeted biologics in this subset of MHSCLC. In memory of Michael Perry, MD, 1945-2011, dedicated physician, researcher, and teacher who started as primary mentor on this project before his passing.
Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle.
Authors: J Hansen, G D Thomas, S A Harris, W J Parsons, R G Victor
Journal: Journal of Clinical Investigation (1996)

Metabolic products of skeletal muscle contraction activate metaboreceptor muscle afferents that reflexively increase sympathetic nerve activity (SNA) targeted to both resting and exercising skeletal muscle. To determine effects of the increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured changes in tissue oxygen stores and mitochondrial cytochrome a,a3 redox state in rhythmically contracting human forearm muscles with near infrared spectroscopy while simultaneously measuring muscle SNA with microelectrodes. The major new finding is that the ability of reflex-sympathetic activation to decrease muscle oxygenation is abolished when the muscle is exercised at an intensity > 10% of maximal voluntary contraction (MVC). During high intensity handgrip, (45% MVC), contraction-induced decreases in muscle oxygenation remained stable despite progressive metaboreceptor-mediated reflex increases in SNA. During mild to moderate handgrips (20-33% MVC) that do not evoke reflex-sympathetic activation, experimentally induced increases in muscle SNA had no effect on oxygenation in exercising muscles but produced robust decreases in oxygenation in resting muscles. The latter decreases were evident even during maximal metabolic vasodilation accompanying reactive hyperemia. We conclude that in humans sympathetic neural control of skeletal muscle oxygenation is sensitive to modulation by metabolic events in the contracting muscles. These events are different from those involved in either metaboreceptor muscle afferent activation or reactive hyperemia.
Effects of sleep changes on pain-related health outcomes in the general population: A systematic review of longitudinal studies with exploratory meta-analysis
Authors: Esther F. Afolalu, Fatanah Ramlee, Nicole K.Y. Tang
Journal: Sleep Medicine Reviews (2017)

Emerging longitudinal research has highlighted poor sleep as a risk factor of a range of adverse health outcomes, including disabling pain conditions. In establishing the causal role of sleep in pain, it remains to be clarified whether sleep deterioration over time is a driver of pain and whether sleep improvement can mitigate pain-related outcomes. A systematic literature search was performed using PubMed MEDLINE, Ovid EMBASE, and Proquest PsycINFO, to identify 16 longitudinal studies involving 61,000 participants. The studies evaluated the effect of sleep changes (simulating sleep deterioration, sleep stability, and sleep improvement) on subsequent pain-related outcomes in the general population. A decline in sleep quality and sleep quantity was associated with a two- to three-fold increase in risk of developing a pain condition, small elevations in levels of inflammatory markers, and a decline in self-reported physical health status. An exploratory meta-analysis further revealed that deterioration in sleep was associated with worse self-reported physical functioning (medium effect size), whilst improvement in sleep was associated with better physical functioning (small effect size). The review consolidates evidence that changes in sleep are prospectively associated with pain-related outcomes and highlights the need for further longitudinal investigations on the long-term impact of sleep improvements.
Multi‐slice,spiral CTによって診断しえた右冠動脈soft plaqueの1症例 血管内超音波との対比
Authors: 隈部威道, 斎藤文雄, 斎藤美穂, 久代登志男, 古屋真吾, 渡辺和宏, 菊池学, 長尾建, 上松瀬勝男
Journal: Circulation (2002)
Ectopy from Interatrial Septum as a Trigger for Atrial Fibrillation and Its Structural Characteristics
Authors: Yamashita Soichiro, Okajima Katsunori, Shimane Akira, Yokoi Kiminobu, Aoki Kosuke, Matsuo Koki, Fujimoto Wataru, Maeda Daichi, Takahashi Yu, Kono Shingo, Matsuyama Sonoko, Miyata Taishi, Ohishi Shogo, Ohsue Tsuyoshi, Sawada Takahiro, Tsukishiro Yasue, Ohnishi Tetsuari, Kobayashi Seiichi, Taniguchi Yasuyo, Yasaka Yoshinori, Kawai Hiroya
Journal: Circulation (2016)
Chromatin-Associated Protein SIN3B Prevents Prostate Cancer Progression by Inducing Senescence
Authors: Anthony J. Bainor, Fang-Ming Deng, Yu Wang, Peng Lee, David J. Cantor, Susan K. Logan, Gregory David
Journal: Cancer Research (2017)

Distinguishing between indolent and aggressive prostate adenocarcinoma remains a priority to accurately identify patients who need therapeutic intervention. SIN3B has been implicated in the initiation of senescence in vitro Here we show that in a mouse model of prostate cancer, SIN3B provides a barrier to malignant progression. SIN3B was required for PTEN-induced cellular senescence and prevented progression to invasive prostate adenocarcinoma. Furthermore, SIN3B was downregulated in human prostate adenocarcinoma correlating with upregulation of its target genes. Our results suggest a tumor suppressor function for SIN3B that limits prostate adenocarcinoma progression, with potential implications for the use of SIN3B and its target genes as candidate diagnostic markers to distinguish indolent from aggressive disease. Cancer Res; 77(19); 5339-48. ©2017 AACR.
Active Surveillance Versus Watchful Waiting for Localized Prostate Cancer: A Model to Inform Decisions
Authors: Stacy Loeb, Qinlian Zhou, Uwe Siebert, Ursula Rochau, Beate Jahn, Nikolai Mühlberger, H. Ballentine Carter, Herbert Lepor, R. Scott Braithwaite
Journal: European Urology (2017)
Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma
Authors: Matthew L. Hedberg, Gerald Goh, Simion I. Chiosea, Julie E. Bauman, Maria L. Freilino, Yan Zeng, Lin Wang, Brenda B. Diergaarde, William E. Gooding, Vivian W.Y. Lui, Roy S. Herbst, Richard P. Lifton, Jennifer R. Grandis
Journal: Journal of Clinical Investigation (2016)

In the process of transferring the miR-182-flox and LSL-miR-182 mice to the Jackson Laboratory, the authors realized that the description of how the LSL-miR-182 mice were generated in the manuscript contained an error.Although the miR-182-flox mice were generated by crossing the mice to a flpO deleter strain to delete the Neo cassette, as was stated in the Methods section, the R26-LSL-miR-182 mice were not crossed to a deleter strain.Instead, the R26-LSL-miR-182 mice that were utilized in this work retained the Neo cassette.Two corrected sentences for the Methods section are below.Chimeric males were mated to WT C57BL/6 females to generate heterozygotes.These mice were subsequently crossed to a flpO deleter strain to excise the frt-Neo-frt cassette to generate miR-182-flox mice.