tbuckley/cabot-search huggingface dataset:
West Nile virus infection in Veneto region, Italy, 2008-2009
Authors: L Barzon, L Squarzon, M Cattai, E Franchin, S Pagni, R Cusinato, G Palù
Journal: Eurosurveillance (2009)

We report here an update on human cases of West Nile virus (WNV) infection in Veneto region, northeastern Italy. In addition to two cases of WNV neuroinvasive disease notified through a surveillance programme started in September 2008, further four cases were retrospectively identified (in May 2009) by investigating patients with aseptic meningoencephalitis of unknown aetiology occurring in Veneto region in June-September 2008. All six patients had symptom onset in August-September 2008 and were resident in a wetland area close to the Po river delta in Rovigo province. Further five cases of asymptomatic WNV infection, including four residents of the same area in Rovigo, were identified in a seroprevalence study in farm workers from Veneto region. To date, no human cases have been notified in 2009.
Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in glioblastoma
Authors: Ming Li, Akitake Mukasa, Maria del-Mar Inda, Jianhua Zhang, Lynda Chin, Webster Cavenee, Frank Furnari
Journal: The Journal of Experimental Medicine (2011)

Although GBP1 (guanylate binding protein 1) was among the first interferon-inducible proteins identified, its function is still largely unknown. Epidermal growth factor receptor (EGFR) activation by amplification or mutation is one of the most frequent genetic lesions in a variety of human tumors. These include glioblastoma multiforme (GBM), which is characterized by independent but interrelated features of extensive invasion into normal brain parenchyma, rapid growth, necrosis, and angiogenesis. In this study, we show that EGFR activation promoted GBP1 expression in GBM cell lines through a signaling pathway involving Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1 expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1) expression and glioma cell invasion in vitro. Although deregulation of GBP1 expression did not affect glioma cell proliferation, overexpression of GBP1 enhanced glioma cell invasion through MMP1 induction, which required its C-terminal helical domain and was independent of its GTPase activity. Reducing GBP1 levels by RNA interference in invasive GBM cells also markedly inhibited their ability to infiltrate the brain parenchyma of mice. GBP1 expression was high and positively correlated with EGFR expression in human GBM tumors and cell lines, particularly those of the neural subtype. Together, these findings establish GBP1 as a previously unknown link between EGFR activity and MMP1 expression and nominate it as a novel potential therapeutic target for inhibiting GBM invasion.
Aiming for the Outliers: Cancer Precision Medicine through Targeting Kinases with Extreme Expression
Authors: Srinivasan Yegnasubramanian, Anirban Maitra
Journal: Cancer Discovery (2013)

With the increasing availability of highly potent, pharmacologically active, and selective protein kinase inhibitors, identification of individuals who would benefit from targeted kinase inhibitors could facilitate application of precision medicine strategies for cancer therapy. A recent study by Kothari and colleagues reports preclinical studies that highlight the potential of targeting kinases with extreme expression for cancer precision medicine, warranting further clinical investigation of an individual-specific outlier kinase targeting approach.
Regulation of Phosphodiesterase 3 and Inducible cAMP Early Repressor in the Heart
Authors: Chen Yan, Clint L. Miller, Jun-ichi Abe
Journal: Circulation Research (2007)

Growing evidence suggests that multiple spatially, temporally, and functionally distinct pools of cyclic nucleotides exist and regulate cardiac performance, from acute myocardial contractility to chronic gene expression and cardiac structural remodeling. Cyclic nucleotide phosphodiesterases (PDEs), by hydrolyzing cAMP and cyclic GMP, regulate the amplitude, duration, and compartmentation of cyclic nucleotide-mediated signaling. In particular, PDE3 enzymes play a major role in regulating cAMP metabolism in the cardiovascular system. PDE3 inhibitors, by raising cAMP content, have acute inotropic and vasodilatory effects in treating congestive heart failure but have increased mortality in long-term therapy. PDE3A expression is downregulated in human and animal failing hearts. In vitro, inhibition of PDE3A function is associated with myocyte apoptosis through sustained induction of a transcriptional repressor ICER (inducible cAMP early repressor) and thereby inhibition of antiapoptotic molecule Bcl-2 expression. Sustained induction of ICER may also cause the change of other protein expression implicated in human and animal failing hearts. These data suggest that the downregulation of PDE3A observed in failing hearts may play a causative role in the progression of heart failure, in part, by inducing ICER and promoting cardiac myocyte dysfunction. Hence, strategies that maintain PDE3A function may represent an attractive approach to circumvent myocyte apoptosis and cardiac dysfunction.
Outbreak of diarrhoea due to Escherichia coli 0111:B4 in schoolchildren and adults: association of Vi antigen-like reactivity
Authors: M.K. Viljanen, T. Peltola, M. Kuistila, P. Huovinen, SYT Junnila, L. Olkkonen, H. Järvinen
Journal: The Lancet (1990)
HER-2 and topo-isomerase IIα as predictive markers in a population of node-positive breast cancer patients randomly treated with adjuvant CMF or epirubicin plus cyclophosphamide
Authors: A. Di Leo, D. Larsimont, D. Gancberg, T. Jarvinen, M. Beauduin, A. Vindevoghel, J. Michel, Ch. Focan, F. Ries, Ph. Gobert, M.-T. Closon-Dejardin, S. Dolci, G. Rouas, M. Paesmans, J.-P. Lobelle, J. Isola, M.J. Piccart
Journal: Annals of Oncology (2001)
HIV-1 Reservoirs in Breast Milk and Challenges to Elimination of Breast-Feeding Transmission of HIV-1
Authors: Philippe Van de Perre, Pierre-Alain Rubbo, Johannes Viljoen, Nicolas Nagot, Thorkild Tylleskär, Philippe Lepage, Jean-Pierre Vendrell, Edouard Tuaillon
Journal: Science Translational Medicine (2012)

The breast milk of HIV-infected mothers contains reservoirs of HIV, even when they are successfully treated with antiretroviral therapy; new approaches to prophylactic therapy are needed to prevent HIV transmission to their infants through breast-feeding.
Role of α-actin in muscle damage of injured athletes in comparison with traditional markers
Authors: Antonio Martínez Amat, Juan Antonio Marchal Corrales, Fernando Rodríguez Serrano, Houria Boulaiz, Jose Carlos Prados Salazar, Fidel Hita Contreras, Octavio Caba Perez, Esmeralda Carrillo Delgado, Ignacio Martín, Antonia Aranega Jimenez
Journal: British Journal of Sports Medicine (2007)

Objective: In order to identify a reliable marker for the early detection of muscle injuries in sports, α-actin protein and other markers of muscle damage were studied in sera of uninjured sportspeople and those with skeletal muscle injury. Methods: Blood samples were obtained from 20 sportspeople with skeletal muscle injury and 48 uninjured sportspeople. Immunoassays were performed to determine cardiac troponin I (TnI), troponin T, lactate dehydrogenase and myoglobin concentrations. Western blot and densitometry were used to measure α-actin concentrations. Skeletal muscle damage was diagnosed according to physical examination, MRI findings and the biochemical criterion of a creatine kinase value &gt;500 IU/l (Rosalki method, Beckman Instruments SL, Fullerton, California, USA). Results were also compared with previously obtained data on injured and uninjured non-sportspeople. Results: The mean serum concentration of α-actin was significantly higher in sportspeople with muscle damage (10.49 μg/ml) than in uninjured sportspeople (3.99 μg/ml). Sera from injured sportspeople showed higher levels of α-actin than of troponin or myoglobin. No significant difference in TnI levels was observed between the groups. Conclusions: According to these results, α-actin is a new and reliable marker of skeletal muscle damage in sportspeople which can be used for the detection of muscle injury. Possible cross interference between skeletal and cardiac muscle damage can be discriminated by the combined use of α-actin and TnI. These data suggest that early measurement of α-actin in sportspeople with suspected muscle damage will allow them to receive earlier and more effective treatment and to return sooner to the practice of their sport.
Inhibition of Tumor Cell Growth, Invasion, and Metastasis by EXEL-2880 (XL880, GSK1363089), a Novel Inhibitor of HGF and VEGF Receptor Tyrosine Kinases
Authors: Fawn Qian, Stefan Engst, Kyoko Yamaguchi, Peiwen Yu, Kwang-Ai Won, Lillian Mock, Tracy Lou, Jenny Tan, Connie Li, Danny Tam, Julie Lougheed, F. Michael Yakes, Frauke Bentzien, Wei Xu, Tal Zaks, Richard Wooster, Joel Greshock, Alison H. Joly
Journal: Cancer Research (2009)

The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a wide variety of human malignancies. Vascular endothelial growth factor (VEGF) receptors are expressed on the surface of vascular endothelial cells and cooperate with Met to induce tumor invasion and vascularization. EXEL-2880 (XL880, GSK1363089) is a small-molecule kinase inhibitor that targets members of the HGF and VEGF receptor tyrosine kinase families, with additional inhibitory activity toward KIT, Flt-3, platelet-derived growth factor receptor beta, and Tie-2. Binding of EXEL-2880 to Met and VEGF receptor 2 (KDR) is characterized by a very slow off-rate, consistent with X-ray crystallographic data showing that the inhibitor is deeply bound in the Met kinase active site cleft. EXEL-2880 inhibits cellular HGF-induced Met phosphorylation and VEGF-induced extracellular signal-regulated kinase phosphorylation and prevents both HGF-induced responses of tumor cells and HGF/VEGF-induced responses of endothelial cells. In addition, EXEL-2880 prevents anchorage-independent proliferation of tumor cells under both normoxic and hypoxic conditions. In vivo, these effects produce significant dose-dependent inhibition of tumor burden in an experimental model of lung metastasis. Collectively, these data indicate that EXEL-2880 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of invasion and angiogenesis mediated by HGF and VEGF receptors.
In the Spotlight: Tissue Engineering
Authors: Tejal A. Desai
Journal: IEEE Reviews in Biomedical Engineering (2010)

There are numerous studies that are being conducted in elucidating the biophysical effects of cells. The papers highlighted in this review present several different approaches to tease out the contribution of multiple factors in these highly complex systems. As the field moves forward, the ability to perturb the in vivo cellular microenvironment in order to promote tissue regeneration will directly benefit from our understanding of the physical (and chemical) factors that regulate cell behavior.
Microsatellite Instability and BRAF Mutation Testing in Colorectal Cancer Prognostication
Authors: Paul Lochhead, Aya Kuchiba, Yu Imamura, Xiaoyun Liao, Mai Yamauchi, Reiko Nishihara, Zhi Rong Qian, Teppei Morikawa, Jeanne Shen, Jeffrey A. Meyerhardt, Charles S. Fuchs, Shuji Ogino
Journal: JNCI Journal of the National Cancer Institute (2013)

BRAF mutation in colorectal cancer is associated with microsatellite instability (MSI) through its relationship with high-level CpG island methylator phenotype (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are routinely used for familial cancer risk assessment. To clarify clinical outcome associations of combined MSI/BRAF subgroups, we investigated survival in 1253 rectal and colon cancer patients within the Nurses' Health Study and Health Professionals Follow-up Study with available data on clinical and other molecular features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations. Compared with the majority subtype of microsatellite stable (MSS)/BRAF-wild-type, MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAF-wild-type subtypes showed multivariable colorectal cancer-specific mortality hazard ratios of 1.60 (95% confidence interval [CI] =1.12 to 2.28; P = .009), 0.48 (95% CI = 0.27 to 0.87; P = .02), and 0.25 (95% CI = 0.12 to 0.52; P < .001), respectively. No evidence existed for a differential prognostic role of BRAF mutation by MSI status (P(interaction) > .50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification.
Neuregulin Expression Modulates Clinical Response to Trastuzumab in Patients With Metastatic Breast Cancer
Authors: Enrique de Alava, Alberto Ocaña, Mar Abad, Juan Carlos Montero, Azucena Esparís-Ogando, César A. Rodríguez, Ana P. Otero, Teresa Hernández, Juan J. Cruz, Atanasio Pandiella
Journal: Journal of Clinical Oncology (2007)

Human epidermal growth factor receptor 2 (HER-2) overexpression has been associated with the genesis and progression of a subset of breast cancers. The function of HER-2 may be upregulated by overexpression or by the availability of neuregulins (NRGs), a group of transmembrane growth factors. Transmembrane NRGs strongly activated HER-2 and cell proliferation in breast cancer cells that did not overexpress HER-2, and treatment with trastuzumab prevented the proliferative action of transmembrane NRG. This raised the relevant clinical question of whether patients considered as HER-2 negative, but expressing transmembrane NRG, may benefit from treatment with trastuzumab.MCF7 cells expressing transmembrane NRG (MCF7-NRG2c) were injected into mice, and their sensitivity to trastuzumab was assessed. A retrospective study of 124 patients with early-stage or metastatic breast cancer was conducted. Expression of transmembrane NRG was evaluated by immunohistochemistry. In 11 patients, Western blot for NRGs was also carried out. Statistics were performed to analyze possible correlations between NRG expression and response to trastuzumab-based therapies, event-free survival, and overall survival (OS).Trastuzumab inhibited tumor growth in mice injected with MCF7-NRG2c cells. Transmembrane NRG was frequently expressed in breast cancer patients. Overexpression of transmembrane NRG significantly correlated with a longer event-free survival and OS in patients with low or normal HER-2 expression who were treated with trastuzumab-based therapies but not in patients with HER-2 overexpression.We suggest that the spectrum of patients who may benefit from trastuzumab-based therapies may be widened to include patients with metastatic breast cancer without HER-2 amplification but who express transmembrane NRGs.
Effects of exacerbations and seasonality on exhaled nitric oxide in COPD
Authors: A. Bhowmik
Journal: European Respiratory Journal (2005)

Exhaled nitric oxide (eNO) appears to be associated with airway inflammation seen in chronic obstructive pulmonary disease (COPD). The present authors studied the effects of exacerbation, season, temperature and pollution on eNO. eNO was measured seasonally and at exacerbations in 79 outpatients suffering from COPD (mean forced expiratory volume in one second = 42%). The effects of exacerbation symptoms, physiological and environmental parameters were analysed. Stable eNO levels were correlated positively with arterial oxygen tension. Median levels were found to be lower in smokers (5.3 ppb) than in ex- or nonsmokers (6.8 ppb). Levels were higher during October to December (6.9 ppb) than in April to June (4.6 ppb). Levels were also higher during 68 exacerbations in 38 patients (7.4 ppb) than in stable conditions (5.4 ppb), independent of the effects of smoking. The rise in eNO was greater in exacerbations that were associated with colds, a sore throat or dyspnoea combined with a cold. In conclusion, exhaled nitric oxide levels were higher in colder weather and in the autumn, perhaps related to the increased prevalence of viral infection at this time of year. The levels were lower in more severe chronic obstructive pulmonary disease. Exhaled nitric oxide levels were raised at the onset of exacerbation, particularly in the presence of a cold.
Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness
Authors: Luni Emdad, Aleksandar Janjic, Mohammad A. Alzubi, Bin Hu, Prasanna K. Santhekadur, Mitchell E. Menezes, Xue-Ning Shen, Swadesh K. Das, Devanand Sarkar, Paul B. Fisher
Journal: Neuro-Oncology (2014)

Malignant glioma is an aggressive cancer requiring new therapeutic targets. MicroRNAs (miRNAs) regulate gene expression post transcriptionally and are implicated in cancer development and progression. Deregulated expressions of several miRNAs, specifically hsa-miR-184, correlate with glioma development. Bioinformatic approaches were used to identify potential miR-184-regulated target genes involved in malignant glioma progression. This strategy identified a multifunctional nuclease, SND1, known to be overexpressed in multiple cancers, including breast, colon, and hepatocellular carcinoma, as a putative direct miR-184 target gene. SND1 levels were evaluated in patient tumor samples and human-derived cell lines. We analyzed invasion and signaling in vitro through SND1 gain-of-function and loss-of-function. An orthotopic xenograft model with primary glioma cells demonstrated a role of miR-184/SND1 in glioma pathogenesis in vivo. SND1 is highly expressed in human glioma tissue and inversely correlated with miR-184 expression. Transfection of glioma cells with a miR-184 mimic inhibited invasion, suppressed colony formation, and reduced anchorage-independent growth in soft agar. Similar phenotypes were evident when SND1 was knocked down with siRNA. Additionally, knockdown (KD) of SND1 induced senescence and improved the chemoresistant properties of malignant glioma cells. In an orthotopic xenograft model, KD of SND1 or transfection with a miR-184 mimic induced a less invasive tumor phenotype and significantly improved survival of tumor bearing mice. Our study is the first to show a novel regulatory role of SND1, a direct target of miR-184, in glioma progression, suggesting that the miR-184/SND1 axis may be a useful diagnostic and therapeutic tool for malignant glioma.
Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum–infected erythrocyte surface
Authors: Alexander G. Maier, Melanie Rug, Matthew T. O'Neill, James G. Beeson, Matthias Marti, John Reeder, Alan F. Cowman
Journal: Blood (2006)
Insulin resistance and steatosis in hepatitis C virus infection
Authors: A Zekry
Journal: Gut (2005)

Variability in detection of MAP by PCR (0-100% in Crohn's disease and ulcerative colitis tissues) 8 and serological testing 37 (6) No evidence of mycobacterial cell wall by histochemical staining (7) No worsening of Crohn's disease with immunosuppressive agents or HIV infection (8) No documented cell mediated immune responses to MAP in patients with Crohn's disease 20 (9) No therapeutic response to traditional antimycobacterial antibiotics 23 MAP, Mycobacterium avium subspecies paratuberculosis; PCR, polymerase chain reaction; FISH, fluorescent in situ hybridisation; HIV, human immunodeficiency virus.
Three-Year Outcomes of Maintenance Nortriptyline Treatment in Late-Life Depression: A Study of Two Fixed Plasma Levels
Authors: Charles F. Reynolds, James M. Perel, Ellen Frank, Cleon Cornes, Mark D. Miller, Patricia R. Houck, Sati Mazumdar, Jacqueline A. Stack, Bruce G. Pollock, Mary Amanda Dew, David J. Kupfer
Journal: American Journal of Psychiatry (1999)

This study compared the long-term efficacy of two fixed plasma levels of nortriptyline in preventing or delaying recurrence of major depression in elderly patients and in minimizing residual depressive symptoms and somatic complaints.The authors randomly assigned 41 elderly patients with histories of recurrent major depression to 3-year, double-blind maintenance pharmacotherapy using nortriptyline, with controlled plasma concentrations of 80-120 ng/ml versus 40-60 ng/ml. The authors compared times to, and rates of, recurrence of major depression. They also compared frequencies of side effects, noncompliance episodes, and subsyndromal symptomatic flare-ups.Major depressive episodes recurred for six (29%) of 21 subjects in the 80-120-ng/ml condition and eight (40%) of 20 subjects in the 40-60-ng/ml condition, a nonsignificant difference. Most recurrences took place in the first year of maintenance treatment. Hamilton depression scores in the subsyndromal range (higher than either 10 or 7) occurred significantly more often at 40-60 ng/ml, while constipation occurred significantly more often at 80-120 ng/ml. The proportions of patients reporting missed doses did not differ.Maintenance pharmacotherapy with nortriptyline at 80-120 ng/ml is associated with fewer residual depressive symptoms, that is, a less variable long-term response, than pharmacotherapy at 40-60 ng/ml, but constipation is more frequent and there is no difference in recurrence of syndromal major depressive episodes. Treatment at 80-120 ng/ml may be preferable, because of fewer residual symptoms and less variability of response, as long as side effect burden can be managed successfully.
Hand bone loss in early undifferentiated arthritis: evaluating bone mineral density loss before the development of rheumatoid arthritis
Authors: G Haugeberg
Journal: Annals of the Rheumatic Diseases (2005)

(1) To examine the change in regional bone mineral density (BMD), including the hands, and assess its role as a predictor of outcome in patients presenting with an early undifferentiated inflammatory arthritis; (2) to examine for associations with the changes in hand BMD.74 patients with undifferentiated hand arthritis of less than 12 months' duration were examined at baseline and then at three, six, and 12 months follow up, including BMD measurement of the femoral neck, spine (L2-4), and the whole hands using dual energy absorptiometry (DXA).During the study, 13 patients were diagnosed as having rheumatoid arthritis, 19 as having inflammatory non-rheumatoid joint disorders, and 42 as having non-inflammatory joint disorders. At the femoral neck and lumbar spine no significant bone loss was seen in any of the three subgroups. At the 12 months follow up the mean (95% confidence interval) hand BMD loss in the patients with rheumatoid arthritis was -4.27% (-1.41 to -7.13); in the inflammatory non-rheumatoid group, -0.49% (-1.33 to +0.35); and in the non-inflammatory joint disorder group, -0.87% (-1.51 to -0.23). In a multivariate linear regression model (including age, rheumatoid factor, mean C reactive protein, mean HAQ score, and cumulative glucocorticoid dose), only mean C reactive protein (p<0.001) and rheumatoid factor (p = 0.04) were independently associated with change in hand BMD during follow up.Hand DXA provides a very sensitive tool for measuring bone loss in early rheumatoid arthritis and may be useful in identifying patients at high risk of developing progressive disease. Further studies are needed to evaluate the role of hand bone loss as a prognostic factor and outcome measure in rheumatoid arthritis.