tbuckley/cabot-search huggingface dataset:
Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study.
Authors: M K Hellerstein, R A Neese, P Linfoot, M Christiansen, S Turner, A Letscher
Journal: Journal of Clinical Investigation (1997)

Fluxes through intrahepatic glucose-producing metabolic pathways were measured in normal humans during overnight or prolonged (60 h) fasting. The glucuronate probe was used to measure the turnover and sources of hepatic UDP-glucose; mass isotopomer distribution analysis from [2-13C1]glycerol for gluconeogenesis and UDP-gluconeogenesis; [U-13C6]glucose for glucose production (GP) and the direct UDP-glucose pathway; and [1-2H1]galactose for UDP-glucose flux and retention in hepatic glycogen. After overnight fasting, GP (fluxes in milligram per kilogram per minute) was 2.19+/-0.09, of which 0.79 (36%) was from gluconeogenesis, 1.40 was from glycogenolysis, 0.30 was retained in glycogen via UDP-gluconeogenesis, and 0.17 entered hepatic UDP-glucose by the direct pathway. Thus, total flux through the gluconeogenic pathway (1.09) represented 54% of extrahepatic glucose disposal (2.02) and the net hepatic glycogen depletion rate was 0.93 (46%). Prolonging [2-13C1]glycerol infusion slowly increased measured fractional gluconeogenesis. In response to prolonged fasting, GP was lower (1. 43+/-0.06) and fractional and absolute gluconeogenesis were higher (78+/-2% and 1.11+/-0.07, respectively). The small but nonzero glycogen input to plasma glucose (0.32+/-0.03) was completely balanced by retained UDP-gluconeogenesis (0.31+/-0.02). Total gluconeogenic pathway flux therefore accounted for 99+/-2% of GP, but with a glycogen cycle interposed. Prolonging isotope infusion to 10 h increased measured fractional gluconeogenesis and UDP-gluconeogenesis to 84-96%, implying replacement of glycogen by gluconeogenic-labeled glucose. Moreover, after glucagon administration, GP (1.65), recovery of [1-2H1]galactose label in plasma glucose (25%) and fractional gluconeogenesis (91%) increased, such that 78% (0.45/0.59) of glycogen released was labeled (i.e., of recent gluconeogenic origin). In conclusion, hepatic gluconeogenic flux into glycogen and glycogen turnover persist during fasting in humans, reconciling inconsistencies in the literature and interposing another locus of control in the normal pathway of GP.
Comparison of samples collected by sputum induction and bronchoscopy from asthmatic and healthy subjects.
Authors: J V Fahy, H Wong, J Liu, H A Boushey
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To compare markers of inflammation in secretions obtained by sputum induction (SI), bronchial wash (50 ml instillate [BW]), and bronchoalveolar lavage (4 x 60 ml instillates [BAL]), we analyzed markers of inflammation in samples obtained by these methods in 10 healthy and 10 asthmatic subjects. Of the asthmatic subjects 8 had mild disease (FEV1, % of predicted > 75%). Within subjects from both groups, we found that sputum, compared with either BW or BAL, had higher numbers of nonsquamous cells (p = 0.0001) and higher levels of eosinophil cationic protein (ECP) (p = 0.0001), albumin (p = 0.0001), and mucin-like glycoprotein (p = 0.0001). The eosinophil percentages and the ECP levels in sputum correlated more closely with those in BW (r = 0.67, p = 0.005; r = 0.69, p = 0.0008, respectively) than in BAL (r = 0.5, p = 0.03; r = 0.37, p = 0.11). Comparing the asthmatic and healthy subgroups, we found that eosinophil percentages were higher in sputum (p = 0.0003) and BW (p = 0.006) from asthmatic subjects and that ECP levels were higher in BW (p = 0.001) and BAL (p = 0.0005) from asthmatic subjects. We conclude that analysis of induced sputum reveals information qualitatively similar to that obtained by analysis of BW and BAL and that sputum induction is not only noninvasive and easily repeated but also yields samples more concentrated and richer in airway secretions than those obtained by bronchoscopy.
Premature adult lung study (PALS): Spirometry and lung clearance index are impaired in adult survivors of bronchopulmonary dysplasia
Authors: Steven Caskey, Aisling Gough, Stephen Rowan, Katherine O'Neill, Judy Bradley, Michael Tunney, Chris Patterson, Stuart Elborn, Mike Shields, Henry Halliday, Lorcan McGarvey
Journal: European Respiratory Journal (2012)

Introduction: We have previously reported increased respiratory symptoms in adult survivors of bronchopulmonary dysplasia (BPD) compared with very low birth weight (VLBW) (<1500g) and term controls. Here we report preliminary findings from spirometric and Lung Clearance Index (LCI) measurements.

Objective: To investigate whether adult survivors of BPD have greater impairment of lung function and LCI than age and gender matched VLBW and term controls.

Methods: Spirometry measurements (MicroLab ML3500 Mk8™) were obtained in 16 BPD [8male; mean (SD) age 24.9 (3.9) y] , 9 VLBW [Mean (SD) age 25.8 (3.73) y] and 55 term controls [30 male; mean (SD) age 26.0 (4.0) y]. LCI measurements (Innocor™ device) obtained in BPD and VLBW participants were compared to 17 healthy controls [6M, mean (SD) age 30.5 (7.5) y].

Results: For all spirometry end points (FEV1, FVC, FEV1/FVC and FEF25-75), BPD adults had significantly lower values than term controls (p  healthy control mean +2SD).

Conclusions: Our preliminary findings suggest persisting lung function impairment in adult survivors of BPD. LCI may be a useful tool in detecting early small airways disease in adult survivors of preterm birth.
Nonredundant Functions for Tumor Protein D52-Like Proteins Support Specific Targeting of TPD52
Authors: Mona Shehata, Ivan Bièche, Rose Boutros, Judith Weidenhofer, Susan Fanayan, Lisa Spalding, Nikolajs Zeps, Karen Byth, Robert K. Bright, Rosette Lidereau, Jennifer A. Byrne
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Tumor protein D52 (TPD52 or D52) is frequently overexpressed in breast and other cancers and present at increased gene copy number. It is, however, unclear whether D52 amplification and overexpression target specific functional properties of the encoded protein. Experimental Design: The expression of D52-like genes and MAL2 was compared in breast tissues using quantitative reverse transcription-PCR. The functions of human D52 and D53 genes were then compared by stable expression in BALB/c 3T3 fibroblasts and transient gene knockdown in breast carcinoma cell lines. In situ D52 and MAL2 protein expression was analyzed in breast tissue samples using tissue microarray sections. Results: The D52 (8q21.13), D54 (20q13.33), and MAL2 (8q24.12) genes were significantly overexpressed in breast cancer tissue (n = 95) relative to normal breast (n = 7; P ≤ 0.005) unlike the D53 gene (6q22.31; P = 0.884). Subsequently, D52-expressing but not D53-expressing 3T3 cell lines showed increased proliferation and anchorage-independent growth capacity, and reduced D52 but not D53 expression in SK-BR-3 cells significantly increased apoptosis. High D52 but not MAL2 expression was significantly associated with reduced overall survival in breast carcinoma patients (log-rank test, P &amp;lt; 0.001; n = 357) and was an independent predictor of survival (hazard ratio, 2.274; 95% confidence interval, 1.228-4.210; P = 0.009; n = 328). Conclusion: D52 overexpression in cancer reflects specific targeting and may contribute to a more proliferative, aggressive tumor phenotype in breast cancer.
Detection of Abnormal Glucose Tolerance in Africans Is Improved by Combining A1C With Fasting Glucose: The Africans in America Study
Authors: Anne E. Sumner, Caroline K. Thoreson, Michelle Y. O'Connor, Madia Ricks, Stephanie T. Chung, Marshall K. Tulloch-Reid, Jay N. Lozier, David B. Sacks
Journal: Diabetes Care (2014)

OBJECTIVE Abnormal glucose tolerance is rising in sub-Saharan Africa. Hemoglobin A1c by itself and in combination with fasting plasma glucose (FPG) is used to diagnose abnormal glucose tolerance. The diagnostic ability of A1C in Africans with heterozygous variant hemoglobin, such as sickle cell trait or hemoglobin C trait, has not been rigorously evaluated. In U.S.-based Africans, we determined by hemoglobin status the sensitivities of 1) FPG ≥5.6 mmol/L, 2) A1C ≥ 5.7% (39 mmol/mol), and 3) FPG combined with A1C (FPG ≥5.6 mmol/L and/or A1C ≥5.7% [39 mmol/mol]) for the detection of abnormal glucose tolerance. RESEARCH DESIGN AND METHODS An oral glucose tolerance test (OGTT) was performed in 216 African immigrants (68% male, age 37 ± 10 years [mean ± SD], range 20–64 years). Abnormal glucose tolerance was defined as 2-h glucose ≥7.8 mmol/L. RESULTS Variant hemoglobin was identified in 21% (46 of 216). Abnormal glucose tolerance occurred in 33% (72 of 216). When determining abnormal glucose tolerance from the OGTT (2-h glucose ≥7.8 mmol/L), sensitivities of FPG for the total, normal, and variant hemoglobin groups were 32%, 32%, and 33%, respectively. Sensitivities for A1C were 53%, 54%, and 47%. For FPG and A1C combined, sensitivities were 64%, 63%, and 67%. Sensitivities for FPG and A1C and the combination did not vary by hemoglobin status (all P &amp;gt; 0.6). For the entire cohort, sensitivity was higher for A1C than FPG and for both tests combined than for either test alone (all P values ≤ 0.01). CONCLUSIONS No significant difference in sensitivity of A1C by variant hemoglobin status was detected. For the diagnosis of abnormal glucose tolerance in Africans, the sensitivity of A1C combined with FPG is significantly superior to either test alone.
National Cancer Institute Prostate Cancer Genetics Workshop
Authors: William J. Catalona, Joan E. Bailey-Wilson, Nicola J. Camp, Stephen J. Chanock, Kathleen A. Cooney, Douglas F. Easton, Rosalind A. Eeles, Liesel M. FitzGerald, Matthew L. Freedman, Julius Gudmundsson, Rick A. Kittles, Elliott H. Margulies, Barry B. McGuire, Elaine A. Ostrander, Timothy R. Rebbeck, Janet L. Stanford, Stephen N. Thibodeau, John S. Witte, William B. Isaacs
Journal: Cancer Research (2011)

Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness--one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics.
Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest
Authors: Alfredo Falcone, Sergio Ricci, Isa Brunetti, Elisabetta Pfanner, Giacomo Allegrini, Cecilia Barbara, Lucio Crinò, Giovanni Benedetti, Walter Evangelista, Laura Fanchini, Enrico Cortesi, Vincenzo Picone, Stefano Vitello, Silvana Chiara, Cristina Granetto, Gianfranco Porcile, Luisa Fioretto, Cinzia Orlandini, Michele Andreuccetti, Gianluca Masi
Journal: Journal of Clinical Oncology (2007)

The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI).Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR).A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032).The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.
Development of an in vitro diesel exposure model for human bronchial epithelial cells
Authors: Maria C. Zarcone, Evert Duistermaat, Gimano D. Amatngalim, Pieter S. Hiemstra, Ingeborg Kooter
Journal: European Respiratory Journal (2013)

The adverse effects of diesel engine emissions on human health have been amply established. However, further investigations are needed to clarify the biological mechanisms underneath these effects. As most of the previous mechanistic studies were based on the use of aged diesel exhaust particles ( DEPs ) and cell lines, our aim was to develop a new model of  in vitro  exposure using well characterized whole diesel exhaust ( DE ) and completely differentiated primary bronchial epithelial cells ( PBECs ) cultured at the air-liquid interface ( ALI ). DE was produced on site by a diesel engine and directed onto the apical surface of ALI-PBEC using  VITROCELL©  exposure modules. Three serial DE-dilutions with humidified medical air were tested during 1h exposure using air-exposed cells as control. Already at 6h after the exposure, we observed a dose-dependent increase in hmox1 mRNA expression (with 4∼f.i. in the highest DE dose compared to controls) suggesting an oxidative stress response; inflammation and cytotoxicity effects occurred at the highest DE dose at 6h as shown by a decrease in resistance ( TEER ), and an increase in IL-8 release. At 24h, these effects persisted and LDH release was increased, whereas TEER values were restored. These results describe the feasibility of  in vitro  exposure of fully differentiated airway epithelial cells to whole DE, which better reflects real-life exposure than aged DEPs. Use of this model will allow comparisons of differential susceptibility of PBECs from different patient populations, as well as exploring the effect of exposure dose and exposure duration on the cellular response. This study was supported by the Netherlands Asthma Foundation (grant# 3.2.11.009).
Transforming growth factor beta1 and insulin-like growth factor 1 block collagen degradation induced by oncostatin M in combination with tumour necrosis factor alpha from bovine cartilage
Authors: W Hui
Journal: Annals of the Rheumatic Diseases (2003)

Oncostatin M (OSM) in combination with tumour necrosis factor α (TNFα) promotes marked collagen breakdown from bovine cartilage in explant culture. This release was dependent upon matrix metalloproteinases and could be prevented by transforming growth factor β1 (TGFβ1) or insulin-like growth factor 1. Both growth factors reduced the expression and secretion of collagenase enzymes, and TGFβ1 induced tissue inhibitor of metalloproteinase production. This study shows for the first time that these anabolic growth factors can protect cartilage against OSM+TNFα induced destruction.
GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice
Authors: Hyejung Won, Won Mah, Eunjin Kim, Jae-Won Kim, Eun-Kyoung Hahm, Myoung-Hwan Kim, Sukhee Cho, Jeongjin Kim, Hyeran Jang, Soo-Churl Cho, Boong-Nyun Kim, Min-Sup Shin, Jinsoo Seo, Jaeseung Jeong, Se-Young Choi, Daesoo Kim, Changwon Kang, Eunjoon Kim
Journal: Nature Medicine (2011)
Magnetic Resonance Angiography for the Evaluation of Lower Extremity Arterial Disease
Authors: Mark J. W. Koelemay, Jeroen G. Lijmer, Jaap Stoker, Dink A. Legemate, Patrick M. M. Bossuyt
Journal: JAMA (2001)

ContextMagnetic resonance angiography (MRA) is a rapidly evolving technique that has been reported to be accurate for assessment of lower extremity arterial disease.ObjectiveTo obtain the best available estimates of the diagnostic performance of MRA in patients with lower extremity arterial disease.Data SourcesStudies published from January 1985 through May 2000 in English, German, or French, identified from the MEDLINE, EMBASE, and Current Contents databases.Study SelectionStudies were included that allowed construction of 2 × 2 contingency tables for detection of stenosis greater than 50% or occlusion with MRA or arteriography in patients with claudication or critical ischemia.Data ExtractionTwo observers graded the following elements of study quality: consecutively enrolled patients, prospective study design, clear cut-off levels, blinded assessment, and clear description of MRA technique. Summary receiver operating characteristic analysis was performed to examine the influence of year of publication, all methodological criteria, arterial tract, number of subdivisions within arterial tracts, and MRA technique on diagnostic performance.Data SynthesisOf 3583 studies initially identified, 34 were included that evaluated MRA in 1090 patients (72% men; median age, 65 years). Magnetic resonance angiography was highly accurate for assessment of all lower extremity arteries. Three-dimensional gadolinium-enhanced (3-D Gd) MRA improved diagnostic performance compared with 2-D MRA (relative diagnostic odds ratio, 2.8 [95% confidence interval, 1.2-6.4]), adjusted for number of subdivisions within arterial tracts. The estimated points of equal sensitivity and specificity were 94% and 90% for 3-D Gd MRA and 2-D MRA, respectively.ConclusionsMagnetic resonance angiography is highly accurate for assessment of the entire lower extremity for arterial disease. Three-dimensional Gd-enhanced MRA improves diagnostic performance compared with 2-D MRA.
Prostaglandin E2 Inhibits Its Own Renal Transport by Downregulation of Organic Anion Transporters rOAT1 and rOAT3
Authors: Christoph Sauvant, Hildegard Holzinger, Michael Gekle
Journal: Journal of the American Society of Nephrology (2005)

Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) is the principal mediator of fever and inflammation. Recently, evidence emerged that during febrile response, PGE<sub>2</sub> that is generated in the periphery enters the hypothalamus and contributes to the maintenance of fever. In a rat model of fever generation, peripheral PGE<sub>2</sub> is increased, whereas clearance by metabolism of peripheral PGE<sub>2</sub> is downregulated. The major route of PGE<sub>2</sub> excretion is <i>via</i> the renal proximal tubular organic anion secretory system, where basolateral uptake that is mediated by renal organic anion transporter 1 (rOAT1) and rOAT3 is rate limiting. Therefore, it was hypothesized that PGE<sub>2</sub> itself will abolish its excretion by rOAT1 or rOAT3. Fluorescein was used as a prototypic organic anion, and NRK-52E cells from rat served as a proximal tubular model system. PGE<sub>2</sub> time-dependently downregulates basolateral organic anion uptake, without affecting cell volume or cell protein, recirculation of counter ions, or proximal tubular transport systems in general. In addition, PGE<sub>2</sub> diminishes expression of both rOAT1 and rOAT3. Both organic anion uptake and expression of rOAT1 and rOAT3 are dose-dependently downregulated by PGE<sub>2</sub>. These findings suggest that during fever or inflammation, renal secretory transport of PGE<sub>2</sub> is reduced, contributing to elevated PGE<sub>2</sub> levels in blood. These data fit into the hypothetical concept of peripheral PGE<sub>2</sub>'s playing a significant role in fever. The described regulatory mechanism may also be of relevance in chronic inflammatory events. Moreover, the data presented could explain why increased plasma urate levels occur in diseases that go along with increased levels of PGE<sub>2</sub>.
Fibroblasts are coupled to myocytes in heart muscle by nanotubes: a bigger and better syncytium?
Authors: Ian M.C. Dixon, Jared J.L. Davies
Journal: Cardiovascular Research (2011)

This editorial refers to ‘Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes’ by K. He et al. , pp. 39–47, this issue. 

In larger mammalian species including humans, cardiac fibroblasts represent the most numerous nonmyocytes in the myocardium. These cells function to synthesize and organize collagens, fibronectins, and other interstitial components and thus maintain the integrity of the cardiac extracellular matrix (matrix). The term ‘fibroblast’ itself designates a highly heterogenous group of cells that exhibit distinct differentiated phenotypes in different organs.1 In particular, the investigation of cardiac fibroblast and myofibroblast biology in specific organs is important but remains a largely understudied area. Their prevalence alone provides significant impetus for gaining a more complete understanding of their physiology. The common assumption that fibroblasts serve to support cardiomyocyte-mediated force transduction insofar as they synthesize and organize matrix proteins such as fibrillar collagens, elastin, and others to provide a complex interstitial weave and thus tether cardiomyocytes has been in place for many years. An extension of this traditional view is that the nature of the interstitial matrix may be to provide a hammock-like weave that, by its parallelogram structure, assists in protecting the muscle fibre from overstretching as well as contributes to active relengthening of the myocytes, and thus the matrix may lend a suction-pump function to the heart.2 Nonetheless, more recent advances in the field of intercellular communication, particularly in …
Human infection with avian influenza A H6N1 virus: an epidemiological analysis
Authors: Sung-Hsi Wei, Ji-Rong Yang, Ho-Sheng Wu, Ming-Chuan Chang, Jen-Shiou Lin, Chi-Yung Lin, Yu-Lun Liu, Yi-Chun Lo, Chin-Hui Yang, Jen-Hsiang Chuang, Min-Cheng Lin, Wen-Chen Chung, Chia-Hung Liao, Min-Shiuh Lee, Wan-Ting Huang, Pei-Jung Chen, Ming-Tsan Liu, Feng-Yee Chang
Journal: The Lancet Respiratory Medicine (2013)