tbuckley/cabot-search huggingface dataset:
Functional Organization of Neuronal and Humoral Signals Regulating Feeding Behavior
Authors: Gary J. Schwartz, Lori M. Zeltser
Journal: Annual Review of Nutrition (2013)

Energy homeostasis—ensuring that energy availability matches energy requirements—is essential for survival. One way that energy balance is achieved is through coordinated action of neural and neuroendocrine feeding circuits, which promote energy intake when energy supply is limited. Feeding behavior engages multiple somatic and visceral tissues distributed throughout the body—contraction of skeletal and smooth muscles in the head and along the upper digestive tract required to consume and digest food, as well as stimulation of endocrine and exocrine secretions from a wide range of organs. Accordingly, neurons that contribute to feeding behaviors are localized to central, peripheral, and enteric nervous systems. To promote energy balance, feeding circuits must be able to identify and respond to energy requirements, as well as the amount of energy available from internal and external sources, and then direct appropriate coordinated responses throughout the body.
Bin1 Ablation Increases Susceptibility to Cancer during Aging, Particularly Lung Cancer
Authors: Mee Young Chang, Janette Boulden, Jessica B. Katz, Liwei Wang, Thomas J. Meyer, Alejandro Peralta Soler, Alexander J. Muller, George C. Prendergast
Journal: Cancer Research (2007)

Abstract Age is the major risk factor for cancer, but few genetic pathways that modify cancer incidence during aging have been described. Bin1 is a prototypic member of the BAR adapter gene family that functions in vesicle dynamics and nuclear processes. Bin1 limits oncogenesis and is often attenuated in human cancers, but its role in cancer suppression has yet to be evaluated fully in vivo. In the mouse, homozygous deletion of Bin1 causes developmental lethality, so to assess this role, we examined cancer incidence in mosaic null mice generated by a modified Cre-lox technology. During study of these animals, one notable phenotype was an extended period of female fecundity during aging, with mosaic null animals retaining reproductive capability until the age of 17.3 ± 1.1 months. Through 1 year of age, cancer incidence was unaffected by Bin1 ablation; however, by 18 to 20 months of age, ∼50% of mosaic mice presented with lung adenocarcinoma and ∼10% with hepatocarcinoma. Aging mosaic mice also displayed a higher incidence of inflammation and/or premalignant lesions, especially in the heart and prostate. In mice where colon tumors were initiated by a ras-activating carcinogen, Bin1 ablation facilitated progression to more aggressive invasive status. In cases of human lung and colon cancers, immunohistochemical analyses evidenced frequent attenuation of Bin1 expression, paralleling observations in other solid tumors. Taken together, our findings highlight an important role for Bin1 as a negative modifier of inflammation and cancer susceptibility during aging. [Cancer Res 2007;67(16):7605–12]
HER2 staining intensity in HER2-positive disease: relationship with FISH amplification and clinical outcome in the HERA trial of adjuvant trastuzumab
Authors: L. Zabaglo, O. Stoss, J. Rüschoff, D. Zielinski, J. Salter, M. Arfi, I. Bradbury, U. Dafni, M. Piccart-Gebhart, M. Procter, M. Dowsett
Journal: Annals of Oncology (2013)
Hematopoietically expressed homeobox is a target gene of farnesoid X receptor in chenodeoxycholic acid-induced liver hypertrophy
Authors: Xiangbin Xing, Elke Burgermeister, Fabian Geisler, Henrik Einwächter, Lian Fan, Michaela Hiber, Sandra Rauser, Axel Walch, Christoph Röcken, Martin Ebeling, Matthew B. Wright, Roland M. Schmid, Matthias P.A. Ebert
Journal: Hepatology (2008)

Farnesoid X receptor (FXR/Fxr) is a bile acid–regulated nuclear receptor that promotes hepatic bile acid metabolism, detoxification, and liver regeneration. However, the adaptive pathways under conditions of bile acid stress are not fully elucidated. We found that wild-type but not Fxr knockout mice on diets enriched with chenodeoxycholic acid (CDCA) increase their liver/body weight ratios by 50% due to hepatocellular hypertrophy. Microarray analysis identified Hex (Hematopoietically expressed homeobox), a central transcription factor in vertebrate embryogenesis and liver development, as a novel CDCA- and Fxr-regulated gene. HEX/Hex was also regulated by FXR/Fxr and CDCA in primary mouse hepatocytes and human HepG2 cells. Comparative genomic analysis identified a conserved inverted repeat-1–like DNA sequence within a 300 base pair enhancer element of intron-1 in the human and mouse HEX/Hex gene. A combination of chromatin immunoprecipitation, electromobility shift assay, and transcriptional reporter assays demonstrated that FXR/Fxr binds to this element and mediates HEX/Hex transcriptional activation. Conclusion: HEX/Hex is a novel bile acid–induced FXR/Fxr target gene during adaptation of hepatocytes to chronic bile acid exposure. (HEPATOLOGY 2009.)
A rare variant in MYH6 is associated with high risk of sick sinus syndrome
Authors: Hilma Holm, Daniel F Gudbjartsson, Patrick Sulem, Gisli Masson, Hafdis Th Helgadottir, Carlo Zanon, Olafur Th Magnusson, Agnar Helgason, Jona Saemundsdottir, Arnaldur Gylfason, Hrafnhildur Stefansdottir, Solveig Gretarsdottir, Stefan E Matthiasson, Gu∂mundur Thorgeirsson, Aslaug Jonasdottir, Asgeir Sigurdsson, Hreinn Stefansson, Thomas Werge, Thorunn Rafnar, Lambertus A Kiemeney, Babar Parvez, Raafia Muhammad, Dan M Roden, Dawood Darbar, Gudmar Thorleifsson, G Bragi Walters, Augustine Kong, Unnur Thorsteinsdottir, David O Arnar, Kari Stefansson
Journal: Nature Genetics (2011)
Abstract 4055: The transcriptional regulator TBX3 promotes progression of cells representing early premalignant breast cancer
Authors: Connor D. MacMillan, Hon S. Leong, Allen G. Clifford, Milica Krstic, Siddika Pardhan, David W. Dales, Carl O. Postenka, Ann F. Chambers, Alan B. Tuck
Journal: Cancer Research (2014)

Abstract The transcriptional regulator TBX3 has been shown to be elevated in metastatic breast cancer and is thought to be involved in promoting malignancy of breast and other carcinomas. In a series of cell lines derived from the same patient with breast cancer, we previously showed that metastatic 21MT-1 cells express elevated levels of TBX3, while low levels are expressed by the ductal carcinoma in situ-like 21NT cells. Here we hypothesized that upregulation of TBX3 in 21NT cells would promote their progression to a more malignant phenotype. We found that 21NT cells engineered to overexpress either isoform of TBX3 (iso1, iso2) have an altered growth in 3D Matrigel, with increased colony-forming ability, higher number of cells per colony and less spherical, more irregular colonies, consistent with increased invasiveness. Transwell assays through Matrigel showed increased invasiveness of 21NT cells overexpressing either TBX3 isoform and in vivo assay in the chick embryo similarly showed increased propensity of TBX3 over-expressing 21NT cells for extravasation. These TBX3-induced changes were associated with increased vimentin expression, but minimal change in e-cadherin expression. Overall, these results indicate that TBX3 (iso1 or iso2) expression can promote progression in a model of early breast cancer, by altering cell properties involved in cell survival/colony formation and invasiveness. Citation Format: Connor D. MacMillan, Hon S. Leong, Allen G. Clifford, Milica Krstic, Siddika Pardhan, David W. Dales, Carl O. Postenka, Ann F. Chambers, Alan B. Tuck. The transcriptional regulator TBX3 promotes progression of cells representing early premalignant breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4055. doi:10.1158/1538-7445.AM2014-4055
Ciprofibrate Therapy Improves Endothelial Function and Reduces Postprandial Lipemia and Oxidative Stress in Type 2 Diabetes Mellitus
Authors: Marc Evans, Richard A. Anderson, John Graham, Gethin R. Ellis, Keith Morris, Stephen Davies, Simon K. Jackson, Malcolm J. Lewis, Michael P. Frenneaux, Alan Rees
Journal: Circulation (2000)

Background —Exaggerated postprandial lipemia (PPL) is a factor in atherogenesis, involving endothelial dysfunction and enhanced oxidative stress. We examined the effect of ciprofibrate therapy on these parameters in type 2 diabetes mellitus. Methods and Results —Twenty patients entered a 3-month, double-blind, placebo-controlled study. Each subject was studied fasting and after a fatty meal, at baseline, and after 3 months of treatment. Glucose and lipid profiles were measured over an 8-hour postprandial period. Endothelial function (flow-mediated endothelium-dependent vasodilatation [FMD]) and oxidative stress (electron paramagnetic resonance spectroscopy) were measured after fasting and 4 hours postprandially. At baseline, both groups exhibited similar PPL and deterioration in endothelial function. After ciprofibrate, fasting and postprandial FMD values were significantly higher (from 3.8±1.8% and 1.8±1.3% to 4.8±1.1% and 3.4±1.1%; P &lt;0.05). This was mirrored by a fall in fasting and postprandial triglycerides (3.1±2.1 and 6.6±4.1 mmol/L to 1.5±0.8 and 2.8±1.3 mmol/L, P &lt;0.05). Fasting and postprandial HDL cholesterol was also elevated (0.9±0.1 and 0.8±0.1 mmol/L and 1.2±0.2 and 1.2±0.1 mmol/L, P &lt;0.05). There were no changes in total or LDL cholesterol. Fasting and postprandial triglyceride enrichment of all lipoproteins was attenuated, with cholesterol depletion of VLDL and enrichment of HDL. There were similar postprandial increases in oxidative stress in both groups at baseline, which was significantly attenuated by ciprofibrate (0.3±0.6 versus 1.5±1.1 U, P &lt;0.05). Conclusions —This study demonstrates that fibrate therapy improves fasting and postprandial endothelial function in type 2 diabetes. Attenuation of PPL and the associated oxidative stress, with increased HDL cholesterol levels, may be important.
The Resurgence of Acute Rheumatic Fever in the United States
Authors: A L Bisno
Journal: Annual Review of Medicine (1990)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Formulation and evaluation of co-prodrug of flurbiprofen and methocarbamol
Authors: Neela Bhatia, Kiran Katkar, Snehal Ashtekar
Journal: Asian Journal of Pharmaceutical Sciences (2015)

The current work envisages synthesis of an ester prodrug of flurbiprofen whereby its carboxylic group was condensed with a skeletal muscle relaxant methocarbamol, with the aim of synergistic activity of two drugs, avoid flurbiprofen mediated gastro-intestinal damage and minimize the ulceration tendency of flurbiprofen. The synthesized prodrug was characterized and confirmed by physicochemical and spectroscopic studies. Solubility and partition coefficient studies indicated an increased lipophilicity and thus better suitability for oral administration than the parent drugs and the protein binding studies revealed a low protein binding capacity of the mutual prodrug. Subsequently, in-vitro hydrolysis was studied in different pH, simulated gastric fluid, simulated intestinal fluid and plasma and quantitative evaluation was performed by high performance liquid chromatography. It was found that the prodrug remained unhydrolyzed in the stomach after absorption however, underwent rapid cleavage by the esterases in blood to give the parent drug. Furthermore, the mutual ester prodrug was evaluated for its anti-inflammatory, analgesic, skeletal muscle relaxation, ulcerogenic and total acid content activity and was found to possess comparable activity with that of the parent drugs. Microscopic structures of the stomach tissues revealed significant reduction in gastric ulcer formation of mice gastric mucosa as compared to parent carboxylic acid drug.
Detection of precancerous gastric lesions and gastric cancer through exhaled breath
Authors: Haitham Amal, Marcis Leja, Konrads Funka, Roberts Skapars, Armands Sivins, Guntis Ancans, Inta Liepniece-Karele, Ilze Kikuste, Ieva Lasina, Hossam Haick
Journal: Gut (2015)

<h3>Objectives</h3> Timely detection of gastric cancer (GC) and the related precancerous lesions could provide a tool for decreasing both cancer mortality and incidence. <h3>Design</h3> 968 breath samples were collected from 484 patients (including 99 with GC) for two different analyses. The first sample was analysed by gas chromatography linked to mass spectrometry (GCMS) while applying t test with multiple corrections (p value&lt;0.017); the second by cross-reactive nanoarrays combined with pattern recognition. For the latter, 70% of the samples were randomly selected and used in the training set while the remaining 30% constituted the validation set. The operative link on gastric intestinal metaplasia (OLGIM) assessment staging system was used to stratify the presence/absence and risk level of precancerous lesions. Patients with OLGIM stages III–IV were considered to be at high risk. <h3>Results</h3> According to the GCMS results, patients with cancer as well as those at high risk had distinctive breath-print compositions. Eight significant volatile organic compounds (p value&lt;0.017) were detected in exhaled breath in the different comparisons. The nanoarray analysis made it possible to discriminate between the patients with GC and the control group (OLGIM 0–IV) with 73% sensitivity, 98% specificity and 92% accuracy. The classification sensitivity, specificity, and accuracy between the subgroups was as follows: GC versus OLGIM 0–II—97%, 84% and 87%; GC versus OLGIM III–IV—93%, 80% and 90%; but OLGIM I–II versus OLGIM III–IV and dysplasia combined—83%, 60% and 61%, respectively. <h3>Conclusions</h3> Nanoarray analysis could provide the missing non-invasive screening tool for GC and related precancerous lesions as well as for surveillance of the latter. <h3>Trial registration number</h3> Clinical Trials.gov number, NCT01420588 (3/11/2013).
Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome
Authors: Peter M Krawitz, Michal R Schweiger, Christian Rödelsperger, Carlo Marcelis, Uwe Kölsch, Christian Meisel, Friederike Stephani, Taroh Kinoshita, Yoshiko Murakami, Sebastian Bauer, Melanie Isau, Axel Fischer, Andreas Dahl, Martin Kerick, Jochen Hecht, Sebastian Köhler, Marten Jäger, Johannes Grünhagen, Birgit Jonske de Condor, Sandra Doelken, Han G Brunner, Peter Meinecke, Eberhard Passarge, Miles D Thompson, David E Cole, Denise Horn, Tony Roscioli, Stefan Mundlos, Peter N Robinson
Journal: Nature Genetics (2010)
Functional Neuroimaging of Anxiety: A Meta-Analysis of Emotional Processing in PTSD, Social Anxiety Disorder, and Specific Phobia
Authors: Amit Etkin, Tor D. Wager
Journal: American Journal of Psychiatry (2007)

Objective: The study of human anxiety disorders has benefited greatly from functional neuroimaging approaches. Individual studies, however, vary greatly in their findings. The authors searched for common and disorder-specific functional neurobiological deficits in several anxiety disorders. The authors also compared these deficits to the neural systems engaged during anticipatory anxiety in healthy subjects. Method: Functional magnetic resonance imaging and positron emission tomography studies of posttraumatic stress disorder (PTSD), social anxiety disorder, specific phobia, and fear conditioning in healthy individuals were compared by quantitative meta-analysis. Included studies compared negative emotional processing to baseline, neutral, or positive emotion conditions. Results: Patients with any of the three disorders consistently showed greater activity than matched comparison subjects in the amygdala and insula, structures linked to negative emotional responses. A similar pattern was observed during fear conditioning in healthy subjects. Hyperactivation in the amygdala and insula were, of interest, more frequently observed in social anxiety disorder and specific phobia than in PTSD. By contrast, only patients with PTSD showed hypoactivation in the dorsal and rostral anterior cingulate cortices and the ventromedial prefrontal cortex—structures linked to the experience and regulation of emotion. Conclusions: This meta-analysis allowed us to synthesize often disparate findings from individual studies and thereby provide neuroimaging evidence for common brain mechanisms in anxiety disorders and normal fear. Effects unique to PTSD furthermore suggested a mechanism for the emotional dysregulation symptoms in PTSD that extend beyond an exaggerated fear response. Therefore, these findings help refine our understanding of anxiety disorders and their interrelationships.
Shear Stress Regulates Endothelial Nitric Oxide Synthase Expression Through c-Src by Divergent Signaling Pathways
Authors: Michael E. Davis, Hua Cai, Grant R. Drummond, David G. Harrison
Journal: Circulation Research (2001)

In this study, we defined the signaling cascade responsible for increased eNOS mRNA expression in response to laminar shear stress. This pathway depends on the tyrosine kinase c-Src because shear induction of eNOS mRNA is blocked by the c-Src inhibitors PP1 and PP2, as well as an adenovirus encoding kinase inactive c-Src. After activation of c-Src, this pathway diverges. One arm is responsible for the short-term (6 hour) increase in eNOS mRNA. This involves a transient, 1-hour increase in eNOS transcription, as detected by nuclear run-on, that is dependent on activation of Ras and is blocked by adenoviral infection with dominant negative Ras. Downstream of Ras, MEK1/2 and ERK1/2 are important in this pathway, as 2 inhibitors of MEK1/2, PD98059 and UO126, completely prevented this early increase in eNOS mRNA. ERK1/2 was rapidly phosphorylated in response to shear, and this was prevented by c-Src and Ras inhibition. Further, Raf is phosphorylated in response to shear stress, and this is prevented by c-Src inhibition, suggesting that Raf may transduce the signal between Ras and ERK1/2. The second arm of the pathway linking activation of c-Src to eNOS expression involves stabilization of eNOS mRNA by shear stress. This response to shear is completely abrogated by the c-Src inhibitor PP1 but not altered by Ras or MEK1/2 inhibition. Thus, c-Src plays a central role in modulation of eNOS expression in response to shear stress via divergent pathways involving a short-term increase in eNOS transcription and a longer-term stabilization of eNOS mRNA.
Tick-borne virus diseases of human interest in Europe
Authors: R.N. Charrel, H. Attoui, A.M. Butenko, J.C. Clegg, V. Deubel, T.V. Frolova, E.A. Gould, T.S. Gritsun, F.X. Heinz, M. Labuda, V.A. Lashkevich, V. Loktev, A. Lundkvist, D.V. Lvov, C.W. Mandl, M. Niedrig, A. Papa, V.S. Petrov, A. Plyusnin, S. Randolph, J. Süss, V.I. Zlobin, X. de Lamballerie
Journal: Clinical Microbiology and Infection (2004)
TRMT12 overexpression in breast cancer cells and its effect on the wybutosine biosynthetic pathway
Authors: Virginia Rodriguez, Abdel Elkahloun, Jeffrey Green, Settara Chandrasekharappa
Journal: Cancer Research (2008)

2716  By combining the approaches of comparative genomic hybridization (CGH) using a high- resolution BAC array and a global expression analysis with a high density oligonucleotide array, we identified the overexpression of the TRMT12 (tRNA methyltransferase 12) gene in breast cancer cell lines. This gene is located on chromosome 8 in the 8q24 region, an area commonly amplified in many types of cancer. Seven out of eight breast cancer cell lines showed amplification at the genomic level in this region that extends from 125.5 Mb to 126.5 Mb. Within this region, the TRMT12 gene showed the highest expression across all the cell lines, and the correlation between the copy number and expression changes among the eight cell lines was significant. Validation by RT-qPCR using RNA from 30 breast tumors showed that the TRMT12 gene was overexpressed >2 fold in 87% (26/30) of the tumors. We have initiated studies to explore the consequence of overexpression of TRMT12 in cancer. The TRMT12 gene is homologous to the yeast TYW2, which is a tRNA methyltransferase that catalyzes the third step in the pathway that converts guanosine to a highly modified base, wybutosine (yW). This five-step pathway has been described for yW biosynthesis in yeast. Wybutosine is present only in phenylalanine tRNA (tRNA-Phe) at the 37th position, adjacent to the anticodon. This modification stabilizes the codon-anticodon interaction and functions to maintain the correct reading frame. It is likely that overexpression of the TRMT12 gene in cancer cells disrupts the yW biosynthetic pathway resulting in hypomodified tRNA-Phe. RT-qPCR using RNA from normal and mouse mammary tumor tissue showed that the TRMT12 gene was overexpressed (>20 fold) in the tumors. Preliminary results suggest that the major fraction of the tRNA-Phe from tumor lacks the fully modified yW base. Studies are underway to determine the exact modification status of the tRNA-Phe in mouse tumor samples. We also evaluated the expression of genes encoding enzymes catalyzing the remaining four steps of yW biosynthesis. The genes, TRM5, TYW1 and TYW2, encoding the enzymes for the first three steps are overexpressed in tumors, and those for the last two steps were unaltered. TRMT12 expression was brought down (77-95%) using three different siRNAs in a breast cancer cell line, SKBR3; global expression changes associated with this reduction in TRMT12 expression are being evaluated.
Combined hepatocellular carcinoma and cholangiocarcinoma: Clinical features and computed tomographic findings
Authors: Kazunori Aoki, Kenichi Takayasu, Toshinobu Kawano, Yukio Muramatsu, Noriyuki Moriyama, Fumihiko Wakao, Junji Yamamoto, Kazuaki Shimada, Tadatoshi Takayama, Tomoo Kosuge, Susumu Yamasaki, Michiie Sakamoto, Setsuo Hirohashi
Journal: Hepatology (1993)

Clinicoradiological features were studied in 20 patients with 22 mass lesions of combined hepatocellular carcinoma and cholangiocarcinomas and findings of computed tomography in 12 of these patients with 14 hepatocellular carcinoma-cholangiocarcinomas. Five of these patients also had single overt hepatocellular carcinomas. The incidence of hepatocellular carcinoma-cholangiocarcinoma was 3.3% among the patients with primary liver cancer treated in our hospital. HBsAg was present in 25%, and increased levels of serum alpha-fetoprotein (> 200 ng/ml) and carcinoembryonic antigen (> 5 ng/ml) were found in 25% and in 47%, respectively. Associated cirrhosis was present in 60%. Analysis of 14 hepatocellular carcinoma-cholangiocarcinomas in 12 patients in whom the enhancement pattern on dynamic computed tomography and pathological findings could be studied and compared suggested three tumor types. Nine lesions (type A) were demonstrated only as areas with high-density peripheries in the early phase of enhancement that evolved into a pattern of peripheral low density and central high density in the late phase. Four masses (type B) were shown as hyperdense tumors (early phase) that changed to low density in the late phase. One mass (type C) was seen as a low-density lesion that did not change. Histopathologically, type A comprised hepatocellular carcinoma-predominant components in the peripheral area, cholangiocarcinoma-predominant components with abundant fibrous stroma in the central area and a tissue transitional between the two in the midzone. By contrast, two of four type B masses comprised hepatocellular carcinoma with scattered cholangiocarcinoma components throughout the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)