tbuckley/cabot-search huggingface dataset:
Acellular human heart matrix: A critical step toward whole heart grafts
Authors: Pedro L Sánchez, M Eugenia Fernández-Santos, Salvatore Costanza, Andreu M Climent, Isabel Moscoso, M Angeles Gonzalez-Nicolas, Ricardo Sanz-Ruiz, Hugo Rodríguez, Stefan M Kren, Gregorio Garrido, Jose L Escalante, Javier Bermejo, Jaime Elizaga, Javier Menarguez, Raquel Yotti, Candelas Pérez del Villar, M Angeles Espinosa, María S Guillem, James T Willerson, Antonio Bernad, Rafael Matesanz, Doris A Taylor, Francisco Fernández-Avilés
Journal: Biomaterials (2015)
Polysomy 17 in HER-2/neu Status Elaboration in Breast Cancer: Effect on Daily Practice
Authors: Yan Ma, Laurence Lespagnard, Virginie Durbecq, Marianne Paesmans, Christine Desmedt, Maria Gomez-Galdon, Isabelle Veys, Fatima Cardoso, Christos Sotiriou, Angelo Di Leo, Martine J. Piccart, Denis Larsimont
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To assess the effect of chromosome 17 copy number on HER-2/neu status determination in breast cancers. Experimental Design: HER-2/neu gene copy and chromosome 17 centromere numbers were evaluated on 893 breast carcinomas using double color fluorescence in situ hybridization (FISH). The net and chromosome 17 corrected (ratio) HER-2/neu copy numbers were compared and related to immunohistochemistry done according to the Food and Drug Administration (FDA)–approved scoring system (0, 1+, 2+, and 3+) as a first screening step in 584 cases. Results: When a ratio ≥2 was considered as criterion for FISH positivity, 49.3% (440 of 893) of cases showed amplification versus 56.2% (502 of 893) by using a net HER-2/neu gene copy number &amp;gt;4 as a alternative criterion; 14.8% (67 of 453) of cases having a ratio &amp;lt;2 had a net HER-2/neu gene copy number &amp;gt;4 and 1.1% (5 of 440) with a ratio ≥2 had a net HER-2/neu gene copy number &amp;lt;4. Among discordant cases, 88.8% (64 of 72) were polysomic (&amp;gt;2.25 chromosomes 17/cell) and among polysomic cases, 12.8% (40 of 312) of the low polysomic (2.26-3.75 chromosomes 17/cell) and 36.9% (24 of 65) of the highly polysomic (&amp;gt;3.75 chromosomes 17/cell) cases showed discordance. In cases with a ratio &amp;lt;2, polysomy 17 incidences were 85.7% (6 of 7) in IHC 3+, 42.4% (79 of 186) in IHC 2+, 33.3% (15 of 45) in IHC 1+, and 29.1% (16 of 55) in IHC 0. Conclusion: A net increase in HER-2/neu gene copy number consecutive to polysomy 17 in the absence of specific gene amplification might lead to a strong protein overexpression in a small subset of breast carcinomas. HER-2/neu status determination by FISH is dependent on the criterion considered for positivity in clinical practice.
Pentosan Polysulfate Decreases Proliferation and Net Extracellular Matrix Production in Mouse Mesangial Cells
Authors: SHARON J. ELLIOT, LILIANE J. STRIKER, WILLIAM G. STETLER-STEVENSON, TERRY A. JACOT, GARY E. STRIKER
Journal: Journal of the American Society of Nephrology (1999)

In this review, the signal events regulated by angiotensin II (AngII) in vascular smooth muscle are analyzed based on activation of specific tyrosine kinases. AngII has been shown to play a critical role in the pathogenesis of hypertension, inflammation, atherosclerosis, and congestive heart failure. The expanding role of AngII indicates that multiple signal transduction pathways are likely to be activated in a tissue-specific manner. Although at least three AngII receptors have been characterized, it seems that the AngII type I receptor (AT1R) is physiologically most important since pharmacologic inhibitors of the AT1R block most AngII signal events and have beneficial effects on cardiovascular disease. The AT1R is a seven transmembrane-spanning G protein-coupled receptor that regulates intracellular signal events by activation of Gq and Gi. However, many recent data indicate that activation of tyrosine kinases by several different mechanisms contributes to AngII effects in target tissues. Tyrosine kinases activated by AngII include c-Src, focal adhesion kinase (FAK), Pyk2 (CADTK), Janus kinases (JAK2 and TYK2), and the receptor tyrosine kinases Ax1, epidermal growth factor, and platelet-derived growth factor. Finally, unknown tyrosine kinases may mediate tyrosine phosphorylation of paxillin, Shc, Raf, and phospholipase C-gamma after AngII stimulation. These AngII-regulated tyrosine kinases seem to be required for AngII effects such as vasoconstriction, proto-oncogene expression, and protein synthesis based on studies with tyrosine kinase inhibitors. Thus, understanding AngII-stimulated signaling events, especially those related to tyrosine kinase activity, may form the basis for the development of new therapies for cardiovascular diseases.
Immune networks. Frequencies of antibody- and idiotype-producing B cell clones in various steady states.
Authors: R R Bernabé, A Coutinho, C Martinez-A, P A Cazenave
Journal: The Journal of Experimental Medicine (1981)

In limiting dilution analysis, the absolute frequencies of lipopolysaccharide-reactive B cell precursors producing anti-trinitrophenyl antibodies or the MOPC460 idiotype were studied in BALB/c mice, either normal, or immunized with antigen (Ab1), the idiotype (Ab2), or a monoclonal anti-idiotype antibody (Ab3). Anti-idiotype immunity results in the suppression of the B cell precursors for the relevant idiotype, and anti-(anti-idiotype) immunity leads to a 10-fold increase in precursor B cell frequencies, with a comparatively lower increase in antibody-producing precursors. The findings can only be explained by variations in the composition of the B cell compartment in the various immune states.
Cluster of Legionnaires´ disease associated with a public whirlpool spa, France, April – May 2010
Authors: C Campese, D Roche, C Clément, F Fierobe, S Jarraud, P de Waelle, H Perrin, D Che
Journal: Eurosurveillance (2010)

In May 2010, a cluster of three cases of Legionnaires' disease was identified in France. The results of the epidemiological, environmental and microbiological investigations allowed the rapid identification of a public whirlpool spa as the most probable source of contamination and the implementation of appropriate control measures. This investigation has stressed the need for good cooperation between partners and the importance of the molecular analysis of Legionella strains.
A novel role of the aryl hydrocarbon receptor (AhR) in centrosome amplification - implications for chemoprevention
Authors: Nina Korzeniewski, Sarah Wheeler, Payel Chatterjee, Anette Duensing, Stefan Duensing
Journal: Molecular Cancer (2010)

Centrosome aberrations can cause genomic instability and correlate with malignant progression in common human malignancies such as breast and prostate cancer. Deregulation of cyclin/cyclin-dependent kinase 2 (CDK2) activity has previously been shown to be critically involved in centrosome overduplication. We therefore test here whether small molecule CDK inhibitors derived from the bis-indole indirubin can be used to suppress centrosome aberrations as a novel approach to chemoprevention of malignant progression.As expected, we found that the CDK inhibitor indirubin-3'-oxime (IO) suppresses centrosome amplification in breast cancer cells. However, we made the unexpected discovery that indirubin-derived compounds that have been chemically modified to be inactive as kinase inhibitors such as 1-methyl-indirubin-3'-oxime (MeIO) still significantly reduced centrosome amplification. All indirubins used in the present study are potent agonists of the aryl hydrocarbon receptor (AhR), which is known for its important role in the cellular metabolism of xenobiotics. To corroborate our results, we first show that the coincidence of nuclear AhR overexpression, reflecting a constitutive activation, and numerical centrosome aberrations correlates significantly with malignancy in mammary tissue specimens. Remarkably, a considerable proportion (72.7%) of benign mammary tissue samples scored also positive for nuclear AhR overexpression. We furthermore provide evidence that continued expression of endogenous AhR is critical to promote centriole overduplication induced by cyclin E and that AhR and cyclin E may function in the same pathway. Overexpression of the AhR in the absence of exogenous ligands was found to rapidly disrupt centriole duplication control. Nonetheless, the AhR agonists IO and MeIO were still found to significantly reduce centriole overduplication stimulated by ectopic AhR expression.Our results indicate that continued expression of endogenous AhR promotes centrosome amplification in breast cancer cells in a pathway that involves cyclin E. AhR agonists such as indirubins inhibit centrosome amplification even when stimulated by ectopic expression of the AhR suggesting that these compounds are potentially useful for the chemoprevention of centrosome-mediated cell division errors and malignant progression in neoplasms in which the AhR is overexpressed. Future studies are warranted to determine whether individuals in which nuclear AhR overexpression is detected in benign mammary tissue are at a higher risk for developing pre-cancerous or cancerous breast lesions.
Topical Capsaicin in Painful Diabetic Neuropathy: Controlled Study With Long-Term Follow-Up
Authors: Rup Tandan, Gloria A Lewis, Patricia B Krusinski, Gary B Badger, Timothy J Fries
Journal: Diabetes Care (1992)

Objective –We conducted an 8-wk controlled study with topical 0.075% capsaicin in subjects with chronic severe painful diabetic neuropathy who were unresponsive or intolerant to conventional therapy. Capsaicin is an alkaloid found in capsicum peppers and produces desensitization to noxious thermal, chemical, and mechanical stimuli when applied topically. Research Design and Methods In 22 randomly assigned subjects, either capsaicin or vehicle cream was applied to painful areas 4 times/day. Pain measurements were recorded at baseline and at 2-wk intervals for 8 wk. Results –Capsaicin treatment was more beneficial than vehicle treatment in the overall clinical improvement of pain status, as measured by physician's global evaluation (P = 0.038) and by a categorical pain severity scale (P = 0.057). Decrease in mean pain intensity by a visual analogue scale was 16% in capsaicin-treated and 4.1' in vehicle-treated subjects. Mean pain relief on visual analogue scale was 44.6 and 23.2', respectively. In a follow-up open-label study, – 50' of subjects reported improved pain control or were cured, and 25' each were unchanged or worse. A burning sensation at the application site was noted by some subjects but both its magnitude and duration decreased with time. Conclusions –Results from this preliminary study suggest that topical 0.075' capsaicin may be of value in subjects with diabetic neuropathy and intractable pain.
Downregulation of Notch Pathway by a γ-Secretase Inhibitor Attenuates AKT/Mammalian Target of Rapamycin Signaling and Glucose Uptake in an ERBB2 Transgenic Breast Cancer Model
Authors: Clay L. Efferson, Christopher T. Winkelmann, Christopher Ware, Timothy Sullivan, Saverio Giampaoli, Jennifer Tammam, Shailendra Patel, Giuseppe Mesiti, John F. Reilly, Raymond E. Gibson, Carolyn Buser, Timothy Yeatman, Domenico Coppola, Christopher Winter, Edwin A. Clark, Giulio F. Draetta, Peter R. Strack, Pradip K. Majumder
Journal: Cancer Research (2010)

ERBB2/neu and Notch signaling are known to be deregulated in many human cancers. However, pathway cross-talk and dependencies are not well understood. In this study, we use an ERBB2-transgenic mouse model of breast cancer (neuT) to show that Notch signaling plays a critical role in tumor maintenance. Inhibition of the Notch pathway with a gamma-secretase inhibitor (GSI) decreased both the Notch and the mammalian target of rapamycin/AKT pathways. Antitumor activity resulting from GSI treatment was associated with decreased cell proliferation as measured by Ki67 and decreased expression of glucose transporter Glut1. Positron emission tomography (PET) imaging showed that the functional consequences of decreased Glut1 translated to reduced glucose uptake and correlated with antitumor effects as measured by micro-computed tomography imaging. The decrease of Glut1 in neuT tumors was also observed in several human breast cancer cell lines following GSI treatment. We provide evidence that approximately 27% of ERBB2-positive human breast cancer specimens display high expression of HES1, phospho-S6RP, and GLUT1. Together, these results suggest that pathways downstream of Notch signaling are, at least in part, responsible for promoting tumor growth in neuT and also active in both neuT and a subset of human breast cancers. These findings suggest that GSI may provide therapeutic benefit to a subset of ERBB2-positive breast cancers and that [(18)F]FDG-PET imaging may be useful in monitoring clinical response.
Diffuse panbronchiolitis in rheumatoid arthritis
Authors: S Homma, M Kawabata, K Kishi, E Tsuboi, K Narui, T Nakatani, T Uekusa, S Saiki, K Nakata
Journal: European Respiratory Journal (1998)

The association of progressive obliterative bronchiolitis (OB) with rheumatoid arthritis (RA) is uncommon but has been reported previously. Diffuse panbronchiolitis (DPB) is a unique inflammation principally affecting the respiratory bronchioli and has been reported mainly in Japanese adults. Recently, DPB has also been noted in patients with RA in Japan. Therefore, there might be considerable overlap in clinical features between DPB and OB associated with RA in Japan. The aim of this study was to evaluate the clinicopathological characteristics of bronchiolitis in patients with RA. Three RA patients clinically diagnosed as having DPB were evaluated. All patients underwent chest radiographs, pulmonary function tests (PFT) and post mortem examination. Clinical features in all patients were a history of productive cough, exertional dyspnoea, wheezing and/or coarse crackles. Chest radiographs showed small nodular shadows up to 2 mm in diameter with bronchiolectasis throughout both lungs in all patients. The PFT revealed marked obstructive impairment in all patients. All patients died of progressive respiratory failure. Pathologically, two out of the three cases were confirmed as DPB, while the remaining one case was confirmed as OB, because the primary obstructive lesions were in the respiratory bronchioli in the former and in the membranous bronchioli and the proximal small bronchi in the latter. Thus, the clinical features of DPB and OB were strikingly similar, but the histopathological features revealed distinct differences. This study demonstrated that there was considerable overlap in clinical features between diffuse panbronchiolitis and obliterative bronchiolitis associated with rheumatoid arthritis, suggesting that diffuse panbronchiolitis might be a new manifestation of rheumatoid arthritis. The differentiation of these two disease entities is significant in making decisions on their therapeutic modality and is possible by analysing the precise histopathological findings of the lung.
ETIOLOGY AND PATHOGENESIS OF PARKINSON'S DISEASE
Authors: C. W. Olanow, W. G. Tatton
Journal: Annual Review of Neuroscience (1999)

▪ Abstract Parkinson's disease (PD) is an age-related neurodegenerative disorder that affects approximately 1 million persons in the United States. It is characterized by resting tremor, rigidity, bradykinesia or slowness, gait disturbance, and postural instability. Pathological features include degeneration of dopaminergic neurons in the substantia nigra pars compacta coupled with intracytoplasmic inclusions known as Lewy bodies. Neurodegeneration and Lewy bodies can also be found in the locus ceruleus, nucleus basalis, hypothalamus, cerebral cortex, cranial nerve motor nuclei, and central and peripheral components of the autonomic nervous system. Current treatment consists of a dopamine replacement strategy using primarily the dopamine precursor levodopa. While levodopa provides benefit to virtually all PD patients, after 5–10 years of treatment the majority of patients develop adverse events in the form of dyskinesia (involuntary movements) and fluctuations in motor response. Further, disease progression is associated with the development of dementia, autonomic dysfunction, and postural instability, which do not respond to levodopa therapy. Accordingly, research efforts have been directed toward understanding the etiology and pathogenesis of PD in the hope of developing a more effective therapy that will slow or halt the natural progression of PD. This paper reviews recent advances.
The Anti-CD25 Monoclonal Antibody 7G7/B6, Armed with the α-Emitter 211At, Provides Effective Radioimmunotherapy for a Murine Model of Leukemia
Authors: Meili Zhang, Zhengsheng Yao, Zhuo Zhang, Kayhan Garmestani, Vladimir S. Talanov, Paul S. Plascjak, Sarah Yu, Hyung-Sik Kim, Carolyn K. Goldman, Chang H. Paik, Martin W. Brechbiel, Jorge A. Carrasquillo, Thomas A. Waldmann
Journal: Cancer Research (2006)

Abstract Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. α-Particles are very attractive for cancer therapy, especially for isolated malignant cells, as is observed in leukemia, because of their high linear energy transfer and short effective path length. We evaluated an anti-CD25 [interleukin-2 receptor α (IL-2Rα)] monoclonal antibody, 7G7/B6, armed with 211At as a potential radioimmunotherapeutic agent for CD25-expressing leukemias and lymphomas. Therapeutic studies were done in severe combined immunodeficient/nonobese diabetic mice bearing the karpas299 leukemia and in nude mice bearing the SUDHL-1 lymphoma. The results from a pharmacokinetic study showed that the clearance of 211At-7G7/B6 from the circulation was virtually identical to 125I-7G7/B6. The biodistributions of 211At-7G7/B6 and 125I-7G7/B6 were also similar with the exception of a higher stomach uptake of radioactivity with 211At-7G7/B6. Therapy using 15 μCi of 211At-7G7/B6 prolonged survival of the karpas299 leukemia–bearing mice significantly when compared with untreated mice and mice treated with 211At-11F11, a radiolabeled nonspecific control antibody (P &amp;lt; 0.01). All of the mice in the control and 211At-11F11 groups died by day 46 whereas &amp;gt;70% of the mice in the 211At-7G7/B6 group still survived at that time. In summary, 211At-7G7/B6 could serve as an effective therapeutic agent for patients with CD25-expressing leukemias. (Cancer Res 2006; 66(16): 8227-32)
Is the construct for human affiliation too narrow?
Authors: Nancy Nyquist Potter
Journal: Behavioral and Brain Sciences (2005)

the construct for affiliation in depue &amp; morrone-strupinsky's (d&amp;m-s's) study is restricted to the interpersonal domain. this restriction is not found in other disciplines. it may be necessary in early stages of trait research. but the construct will need to be expanded to speak to the more complex, second-order affiliations of which humans are capable.
Cross-talk between cytokines and renin-angiotensin in hypothalamic paraventricular nucleus in heart failure: role of nuclear factor- B
Authors: Y.-M. Kang, Y. Ma, C. Elks, J.-P. Zheng, Z.-M. Yang, J. Francis
Journal: Cardiovascular Research (2008)

Nuclear factor-kappa B (NF-kappaB) is a potent inducer of pro-inflammatory cytokines (PIC) and oxidative stress in cardiovascular disease. In this study, we determined whether upregulation of NF-kappaB in the hypothalamic paraventricular nucleus (PVN) contributed to neurohumoral excitation either directly, or via interaction with the renin-angiotensin system (RAS), in heart failure (HF).Rats were implanted with intracerebroventricular (ICV) cannulae and subjected to coronary artery ligation, or sham surgery (SHAM). Subsequently, animals were ICV treated with the angiotensin type 1 receptor (AT1-R) antagonist losartan (LOS, 20 microg/h), or SN50 (2 microg/h), which inhibits nuclear translocation of NF-kappaB, or tempol (TEMP, 80 microg/h), a membrane-permeable superoxide scavenger, or vehicle for 4 weeks. HF induced a significant increase in the expression of AT1-R, PIC, and NAD(P)H oxidase genes and NF-kappaB p50 in the PVN and in plasma norepinephrine (NE) levels when compared with SHAM rats. In contrast, ICV LOS, SN50, or TEMP attenuated PIC, NF-kappaB p50, AT1-R and NAD(P)H oxidase genes in the PVN compared with vehicle-treated HF rats. Treatment with LOS, SN50, or TEMP also reduced plasma levels of NE, angiotensin II, and PIC, and decreased left ventricular end diastolic pressure.These findings indicate that NF-kappaB mediates the cross-talk between RAS and PIC in the PVN in HF, and that superoxide stimulates more NF-kappaB in the PVN and contributes to neurohumoral excitation.
Why Olanzapine Beats Risperidone, Risperidone Beats Quetiapine, and Quetiapine Beats Olanzapine: An Exploratory Analysis of Head-to-Head Comparison Studies of Second-Generation Antipsychotics
Authors: Stephan Heres, John Davis, Katja Maino, Elisabeth Jetzinger, Werner Kissling, Stefan Leucht
Journal: American Journal of Psychiatry (2006)

In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.
Functional Genomics of the Paraoxonase (PON1) Polymorphisms: Effects on Pesticide Sensitivity, Cardiovascular Disease, and Drug Metabolism
Authors: Lucio G. Costa, Toby B. Cole, Gail P. Jarvik, Clement E. Furlong
Journal: Annual Review of Medicine (2003)

This review focuses on the functional genomics of the human paraoxonase (PON1) polymorphisms. Levels and genetic variability of the PON1 position 192 isoforms (Gln/Arg) influence sensitivity to specific insecticides or nerve agents and risk for cardiovascular disease. A more recent area of investigation, the role of PON1 in drug metabolism, is also discussed. We emphasize the importance of considering both PON1 isoforms and PON1 levels in disease/sensitivity association studies.