tbuckley/cabot-search huggingface dataset:
miRNA and mammalian male germ cells
Authors: S.C. McIver, S.D. Roman, B. Nixon, E.A. McLaughlin
Journal: Human Reproduction Update (2011)

Achieving the correct spatial and temporal expression of germ-cell-specific genes is fundamental to the production of viable healthy spermatozoa. Notably, post-transcriptional gene regulation resulting in the repression of protein translation is central to many embryonic processes, and is particularly active during spermatogenesis. In this review, we discuss microRNA (miRNA) regulation of target gene expression in relation to mammalian spermatogenesis, the establishment of testicular germ cell tumours (TGCT) and the potential use of miRNA manipulation for cancer therapy and fertility regulation. Journal databases such as PubMed were searched using key words, including miRNA, testis, spermatogenesis, germ cell, testicular cancer and cancer. In the past decade, the deployment of small non-coding RNA molecules, including miRNA, by the cell, has been recognized as among the most important mechanisms of fine-tuning translational regulation in differentiating cell types. For key regulators of male gametogenesis, high levels of gene expression do not always correspond to elevated levels of protein expression. Cumulatively this indicates that enhancement and repression of post-transcriptional regulatory mechanisms are essential to the success of spermatogenesis. There is also growing evidence that this form of regulation contributes to the aetiology of both TGCT and spermatocytic tumours. miRNA plays an essential role in regulation of genes during the process of spermatogenesis. Disruption of this regulation has the ability to contribute to the neoplastic development of germ cell tumours. However, targeted knockdown of specific miRNA molecules has the potential to form both anti-oncogenic reagents and underpin the basis for novel contraceptive technologies.
COPD is associated with reduced pulmonary interstitial expression of pentraxin-3
Authors: G.R. Van Pottelberge, K.R. Bracke, N.S. Pauwels, F.E. Vermassen, G.F. Joos, G.G. Brusselle
Journal: European Respiratory Journal (2011)

Pentraxin (PTX)3 is involved in antimicrobial defence, apoptotic cell clearance and extracellular matrix stability. As these processes are altered in chronic obstructive pulmonary disease (COPD), we aimed to investigate PTX3 expression in patients with this disease. PTX3 expression was quantified by immunohistochemical staining of lung tissue from never-smokers, smokers without COPD, and in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I, II and III–IV. mRNA expression was examined in total lung tissue by quantitative RT-PCR. PTX3 concentration was measured in induced sputum and plasma by ELISA. PTX3 is mainly localised in the interstitium of the small airways and alveolar walls. There were no significant differences in pulmonary, sputum and plasma PTX3 expression between study groups. However, PTX3 expression in small airways correlated significantly with forced expiratory volume in 1 s (r=0.35, p=0.004). In the alveolar walls, PTX3 expression correlated significantly with carbon monoxide transfer coefficient (r=0.28, p=0.04). In sputum, PTX3 levels were highly correlated with the number of neutrophils. Finally, systemic levels of PTX3 tended to be lower in severe COPD compared with mild COPD. In COPD, airflow limitation and reduced transfer coefficient for carbon monoxide are associated with lower pulmonary interstitial expression of PTX3.
Characterizing the admixed African ancestry of African Americans
Authors: Fouad Zakharia, Analabha Basu, Devin Absher, Themistocles L Assimes, Alan S Go, Mark A Hlatky, Carlos Iribarren, Joshua W Knowles, Jun Li, Balasubramanian Narasimhan, Steven Sidney, Audrey Southwick, Richard M Myers, Thomas Quertermous, Neil Risch, Hua Tang
Journal: Genome biology (2009)

Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin. From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans. These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry.
Echocardiography of the intra-atrial baffle in dextro-transposition of the great vessels.
Authors: N D Nanda, S Stewart, R Gramiak, J A Manning
Journal: Circulation (1975)

Twelve patients with dextro-transposition of the great vessels (age eight months to four years) were studied by echocardiography following Mustard's procedure. Nine of them had also been studied preoperatively. Postoperatively all patients demonstrated structural echoes in the atrial cavity behind the pulmonary root. In ten, the motion pattern generally resembled that of a stenotic atrioventricular valve iwth a sharp anterior movement followed by flattening in diastole and rapid posterior excursion in systole. The maximum amplitude of motion ranged from 4 to 9 mm (average 6.6 mm). In the remaining two cases, the anterior diastolic movement was attenuated. Similar moving, linear echoes with larger amplitudes of motion (10-14 mm) were observed behind the tricuspid valve in four patients while poorly moving, multiple or thick conglomerate echoes (2-11 mm wide) were detected in seven cases. Echocardiographic contrast studies performed by injecting indocyanine green via catheters placed on either side of the intra-atrial baffle identified it as the source of these echoes. Following operation, coarse diastolic undulations of the mitral valve (ten cases) and the tricuspid valve (nine cases) were noted. Also, fine flutter of both atrioventricular valves, not present before, appeared after operation in three patients. These findings may be related to the altered pathway of blood flow and turbulence resulting from the insertion of the baffle in the atria. Echocardiography appears useful in delineating the character and movement pattern of the intra-atrial baffle and this may have potential in evaluating its long-term functional status.
The Structure of Dasatinib (BMS-354825) Bound to Activated ABL Kinase Domain Elucidates Its Inhibitory Activity against Imatinib-Resistant ABL Mutants
Authors: John S. Tokarski, John A. Newitt, Chieh Ying J. Chang, Janet D. Cheng, Michael Wittekind, Susan E. Kiefer, Kevin Kish, Francis Y.F. Lee, Robert Borzillerri, Louis J. Lombardo, Dianlin Xie, Yaqun Zhang, Herbert E. Klei
Journal: Cancer Research (2006)

Abstract Chronic myeloid leukemia (CML) is caused by the constitutively activated tyrosine kinase breakpoint cluster (BCR)-ABL. Current frontline therapy for CML is imatinib, an inhibitor of BCR-ABL. Although imatinib has a high rate of clinical success in early phase CML, treatment resistance is problematic, particularly in later stages of the disease, and is frequently mediated by mutations in BCR-ABL. Dasatinib (BMS-354825) is a multitargeted tyrosine kinase inhibitor that targets oncogenic pathways and is a more potent inhibitor than imatinib against wild-type BCR-ABL. It has also shown preclinical activity against all but one of the imatinib-resistant BCR-ABL mutants tested to date. Analysis of the crystal structure of dasatinib-bound ABL kinase suggests that the increased binding affinity of dasatinib over imatinib is at least partially due to its ability to recognize multiple states of BCR-ABL. The structure also provides an explanation for the activity of dasatinib against imatinib-resistant BCR-ABL mutants. (Cancer Res 2006; 66(11): 5790-7)
Emerging Risk Factors for Coronary Heart Disease: A Summary of Systematic Reviews Conducted for the U.S. Preventive Services Task Force
Authors: Mark Helfand, David I. Buckley, Michele Freeman, Rongwei Fu, Kevin Rogers, Craig Fleming, Linda L. Humphrey
Journal: Annals of Internal Medicine (2009)

Background: Traditional risk factors do not explain all of the risk for incident coronary heart disease (CHD) events. Various new or emerging risk factors have the potential to improve global risk assessment for CHD. Purpose: To summarize the results of 9 systematic reviews of novel risk factors to help the U.S. Preventive Services Task Force (USPSTF) evaluate the factors' clinical usefulness. Data Sources: Results from a MEDLINE search for English-language articles published from 1966 to September 2008, using the Medical Subject Heading terms cohort studies and cardiovascular diseases in combination with terms for each risk factor. Study Selection: Studies were included if the participants had no baseline cardiovascular disease and the investigators adjusted for at least 6 Framingham risk factors. Data Extraction: Study quality was evaluated by using USPSTF criteria and overall quality of evidence for each risk factor by using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation framework. Each factor's potential clinical value was evaluated by using a set of criteria that emphasized the importance of the effect of that factor on the reclassification of intermediate-risk persons. Data Synthesis: 9 systematic reviews were conducted. C-reactive protein (CRP) was the best candidate for use in screening and the most rigorously studied, but evidence that changes in CRP level lead to primary prevention of CHD events is inconclusive. The other evaluated risk factors were coronary artery calcium score as measured by electron-beam computed tomography, lipoprotein(a) level, homocysteine level, leukocyte count, fasting blood glucose, periodontal disease, ankle–brachial index, and carotid intima–media thickness. The availability and validity of the evidence varied considerably across the risk factors in terms of aggregate quality, consistency of findings, and applicability to intermediate-risk persons in the general population. For most risk factors, no studies assessed their usefulness for reclassifying intermediate-risk persons. Limitations: Because of lack of access to original data, no firm conclusions could be drawn about differences in risk prediction among racial and ethnic groups. The review did not emphasize within-cohort comparisons of multiple risk factors. Conclusion: The current evidence does not support the routine use of any of the 9 risk factors for further risk stratification of intermediate-risk persons.
Sinoatrial transmission and atrial invasion during normal rhythm in the rabbit heart.
Authors: M O Masuda, A Paes de Carvalho
Journal: Circulation Research (1975)

Intracellular microelectrodes and small unipolar leads applied to endocardial surface of the right atrium in vitro were used to study the complex extracellular wave patterns recorded from the neighborhood of the cardiac pacemaker during spontaneous activity. Sinus activity propagated slowly toward the site of atrial invasion on the venous border of the crista terminalis. Atrial activation was marked by a primary negative wave that appeared 20-40 msec after pacemaker firing. Two sources of complex multiphasic waves were found. First, potentials from transitional sinus tissue propagated toward the atrium and caused low-voltage waves that preceded and slurred the onset of the atrial initial negativity. Second, bundles and layers of the crista terminalis muscle were excited asynchronously around the invasion region, as if cross-connections were infrequent. Waves originating from this source occurred after the firing of the invasion site. No extracellular wave could be associated with the firing of the true pacemaker cells. The sinoatrial ring bundle (SARB) yielded a discrete biphasic deflection along most of its way toward the coronary sinus. This potential appeared most frequently after that of the adjoining cristal muscle, raising questions about the functional role of the SARB as an internodal preferential pathway.
Pathophysiological Mechanisms of Chronic Reversible Left Ventricular Dysfunction due to Coronary Artery Disease (Hibernating Myocardium)
Authors: Paolo G. Camici, William Wijns, Marcel Borgers, Ranil De Silva, Roberto Ferrari, Juhani Knuuti, Adriaan A. Lammertsma, A. James Liedtke, Giovanni Paternostro, Stephen F. Vatner
Journal: Circulation (1997)
Intrahepatic Cholangiocarcinoma: An International Multi-Institutional Analysis of Prognostic Factors and Lymph Node Assessment
Authors: Mechteld C. de Jong, Hari Nathan, Georgios C. Sotiropoulos, Andreas Paul, Sorin Alexandrescu, Hugo Marques, Carlo Pulitano, Eduardo Barroso, Bryan M. Clary, Luca Aldrighetti, Cristina R. Ferrone, Andrew X. Zhu, Todd W. Bauer, Dustin M. Walters, T. Clark Gamblin, Kevin T. Nguyen, Ryan Turley, Irinel Popescu, Catherine Hubert, Stephanie Meyer, Richard D. Schulick, Michael A. Choti, Jean-Francois Gigot, Gilles Mentha, Timothy M. Pawlik
Journal: Journal of Clinical Oncology (2011)

Purpose To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival. Patients and Methods From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. Results Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20; P &lt; .001), multiple lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P &lt; .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0; P &lt; .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34). Conclusion Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.
Coronary Vasomotor Function Is Abnormal in First-Degree Relatives of Patients With Type 2 Diabetes
Authors: Kumiko Hirata, Amudha Kadirvelu, Marco Di Tullio, Shunichi Homma, Anna Maria Choy, Chim C. Lang
Journal: Diabetes Care (2006)

Nondiabetic first-degree relatives of patients with type 2 diabetes are at increased risk of developing diabetes (1) and cardiovascular disease (CVD) (2). Endothelial dysfunction is regarded as an early step in the development of atherosclerosis (3). Abnormal peripheral endothelial dysfunction detected by flow-mediated, endothelium-dependent, forearm-mediated dilatation (FMD) has been reported in first-degree relatives (4,5). The abnormal FMD could not be explained by confounding variables including age, sex, ethnicity, obesity, lipids, blood pressure, glycemia, or insulin resistance (5). However, endothelial dysfunction detected in brachial arteries may not reflect the condition of the coronary vasculature, as brachial and coronary circulations differ in terms of the microvascular architecture, pattern of blood flow, their metabolic regulation, and the pathways that are activated to induce hyperemia (6). Coronary flow reserve measurement has been considered to be a useful physiologic index for coronary circulation (6). In this study, we report for the first time impaired coronary flow reserve in young nonobese normoglycemic first-degree relatives compared with healthy control subjects.

The study subjects were healthy volunteers recruited by advertisements for the University of Malaya. All gave written informed consent to participate in the study, which was approved by the local ethics committee. To be eligible as a first-degree relative, subjects had to have one or more parent with type 2 diabetes. To avoid any confounding influence on endothelial function, subjects were excluded if they had a history of smoking, manifest type 2 diabetes, hypertension, hypercholesterolemia (serum cholesterol ≥6.5 mmol/l), and concurrent CVD, including current or previous history of myocardial infarction and angina. None were on regular medication. At the screening visit, …
Effects of Methylphenidate on Functional Magnetic Resonance Relaxometry of the Cerebellar Vermis in Boys With ADHD
Authors: Carl M. Anderson, Ann Polcari, Steven B. Lowen, Perry F. Renshaw, Martin H. Teicher
Journal: American Journal of Psychiatry (2002)

The authors used functional magnetic resonance imaging (fMRI) to test the effects of methylphenidate on steady-state blood volume in the midline vermis of the cerebellum in boys with attention deficit hyperactivity disorder (ADHD). This region was selected as it has been observed to be significantly smaller in children with ADHD. Also, in preclinical studies, the vermis has been shown to modulate forebrain dopamine systems, to influence locomotor activity, and to contain a significant density of dopamine transporters.T(2) relaxometry was used to indirectly assess blood volume in the cerebellum (hemispheres and midline vermis) of 10 boys with ADHD who were administered placebo or one of three different doses of methylphenidate continuously for 1 week. T(2) relaxation time values are inversely proportional to local cerebral blood volume. After each week of treatment, and within 1-3 hours of the boys' afternoon dose, testing for drug efficacy was performed by using objective measures of activity.Moderate and high doses of methylphenidate increased T(2) relaxation time in a rate-dependent manner-increasing T(2) relaxation time in the most active children with ADHD and reducing T(2) relaxation time in subjects with ADHD who were not objectively hyperactive.This preliminary study supports a role for the vermis in ADHD and suggests that further research is needed to clarify the relationship between vermal size, vermal blood flow, stimulant response, and the developmental pathophysiology of ADHD.
Robotics for Surgery
Authors: Robert D. Howe, Yoky Matsuoka
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Robotic technology is enhancing surgery through improved precision, stability, and dexterity. In image-guided procedures, robots use magnetic resonance and computed tomography image data to guide instruments to the treatment site. This requires new algorithms and user interfaces for planning procedures; it also requires sensors for registering the patient’s anatomy with the preoperative image data. Minimally invasive procedures use remotely controlled robots that allow the surgeon to work inside the patient’s body without making large incisions. Specialized mechanical designs and sensing technologies are needed to maximize dexterity under these access constraints. Robots have applications in many surgical specialties. In neurosurgery, image-guided robots can biopsy brain lesions with minimal damage to adjacent tissue. In orthopedic surgery, robots are routinely used to shape the femur to precisely fit prosthetic hip joint replacements. Robotic systems are also under development for closed-chest heart bypass, for microsurgical procedures in ophthalmology, and for surgical training and simulation. Although results from initial clinical experience is positive, issues of clinician acceptance, high capital costs, performance validation, and safety remain to be addressed.
Critical role of cytosolic phospholipase A2 in bronchial mucus hypersecretion in CFTR-deficient mice
Authors: F. Dif, Y.-Z. Wu, P.-R. Burgel, M. Ollero, D. Leduc, J. Aarbiou, F. Borot, I. Garcia-Verdugo, C. Martin, M. Chignard, D. Israel-Biet, Y. Kita, B. J. Scholte, L. Touqui
Journal: European Respiratory Journal (2010)

Cystic fibrosis (CF) is due to mutations in the CF transmembrane conductance regulator gene <i>CFTR</i>. CF is characterised by mucus dehydration, chronic bacterial infection and inflammation, and increased levels of cytosolic phospholipase A2α (cPLA2α) products in airways. We aimed to examine the role of cPLA2α in the modulation of mucus production and inflammation in CFTR-deficient mice and epithelial cells. Mucus production was assessed using histological analyses, immuno-histochemistry and MUC5AC ELISA. cPLA2α activation was measured using an enzymatic assay and lung inflammation determined by histological analyses and polymorphonuclear neutrophil counts in bronchoalveolar lavages. In lungs from <i>Cftr<sup>-/-</sup></i> mice, lipopolysaccharide induced mucus overproduction and MUC5AC expression associated with an increased cPLA2α activity. Mucus overproduction was mimicked by instillation of the cPLA2α product arachidonic acid, and abolished by either a cPLA2α null mutation or pharmacological inhibition. An increased cPLA2α activity was observed in bronchial explants from CF patients. CFTR silencing induced cPLA2α activation and MUC5AC expression in bronchial human epithelial cells. This expression was enhanced by arachidonic acid and reduced by cPLA2α inhibition. However, inhibition of CFTR chloride transport function had no effect on MUC5AC expression. Reduction of CFTR expression increased cPLA2α activity. This led to an enhanced mucus production in airway epithelia independent of CFTR chloride transport function. cPLA2α represents a suitable new target for therapeutic intervention in CF.