tbuckley/cabot-search huggingface dataset:
Effect of Age and High Blood Pressure on Barorefiex Sensitivity in Man
Authors: Brian Gribbin, Thomas G. Pickering, Peter Sleight, Richard Peto
Journal: Circulation Research (1971)

The purpose of this study was to relate baroreflex sensitivity to age and arterial pressure in 61 male and 20 female untreated subjects, aged 19-66 years, whose mean arterial pressures ranged from 70 to 150 mm Hg. In this selected group of subjects there was no correlation between age and arterial pressure. The index of sensitivity used was the increase in pulse interval which occurs reflexly in response to a rise in systolic pressure induced by the intravenous injection of phenylephrine and is measured as the increase in pulse interval in milliseconds per mm Hg rise in systolic blood pressure. It ranged from 1.9 to 48.9 msec/mm Hg. Increasing age and arterial pressure act independently to reduce baroreflex sensitivity. Eight subjects who had normal blood pressure at the time of testing but whose pressure had been elevated in the past, had reflex sensitivities significantly less than expected in persons of the same age and mean arterial pressure. The heart rate in these subjects was not significantly different from that in the controls; the heart rate of the 12 hypertensive subjects aged under 40 years was significantly faster than that of age-matched normotensive subjects but not that of older hypertensive subjects.
Detection of herpesvirus-like DNA in the bronchoalveolar lavage fluid of patients with pulmonary Kaposi's sarcoma
Authors: G Cathomas, M Tamm, CE McGandy, AP Perruchoud, MJ Mihatsch, P Dalquen
Journal: European Respiratory Journal (1996)

Pulmonary involvement is a clinically important form of visceral Kaposi's sarcoma in immunocompromised patients. Recently, herpesvirus-like deoxyribonucleic acid (DNA) sequences, defining a new herpesvirus termed "human herpesvirus 8" (HHV8) or "Kaposi's sarcoma-associated herpesvirus" (KSHV), were detected in Kaposi's sarcoma of acquired immune deficiency syndrome (AIDS) and non-AIDS patients. We describe the successful detection of HHV8 DNA in the bronchoalveolar lavage (BAL) fluid of patients with pulmonary Kaposi's sarcoma. Three immunocompromised patients, two HIV seropositive and one after kidney transplantation, suffered from respiratory symptoms and showed pulmonary infiltrates on chest radiography after development of biopsy proven Kaposi's sarcoma of the skin. Bronchoscopy revealed the typical Kaposi like livid endobronchial lesions. BAL fluid was analysed for the presence of HHV8 DNA using a nested polymerase chain reaction (PCR) assay. HHV8 DNA was detected in the BAL fluid of all three patients. In addition, HHV8 DNA could be detected in the skin biopsy tissue, lymph node, and peripheral blood mononuclear cells of these patients. Our data show that human herpesvirus 8 deoxyribonucleic acid can be detected in the bronchoalveolar lavage fluid of patients with pulmonary Kaposi's sarcoma. If further studies reveal a high specificity for human herpesvirus 8 deoxyribonucleic acid detection, this test will improve the tools for the diagnosis of pulmonary Kaposi's sarcoma without further need of biopsies.
Percutaneous Left Ventricular Puncture with Catheterization of the Aorta
Authors: H. A. Fleming, E. W. Hancock, B. B. Milstein, D. N. Ross
Journal: Thorax (1958)

The technique of percutaneous puncture of the left ventricle for the assessment of patients with aortic stenosis was described by Brock, Milstein, and Ross (1956) and the results in the first 28 cases were analysed by Fleming and Gibson (1957). This procedure has now been carried out in 115 patients at these two hospitals and the technique has been extended to include catheterization of the aorta via the left ventricular needle. This paper describes our experience with catheterization of the aorta by this method in the first 36 attempts. It is desirable to catheterize the aorta for two reasons. First, pressure tracings recorded continuously during the withdrawal of the catheter tip from the aorta to the left ventricle may reveal subvalvar stenosis undietectable by any other method short of surgical exploration (Brock and Fleming, 1956). This is an important consideration in all patients with congenital aortic stenosis and in patients with severe left ventricular hypertrophy due to aortic valve stenosis or to hypertension (Brock, 1957b). Second, the systolic pressure gradient across the aortic valve is calculated more accurately from the aortic pressure pulse than from a peripheral arterial pulse. Although the difference between the central and peripheral pulse contours is usually small in aortic stenosis (Wright, Toscano-Barboza, and Brandenburg, 1956) the variability of this has not yet been fully explored.
Objective Measurement of the Dispersing Effect of Dextran 40 on Red Cells from Man, Dog, and Rabbit
Authors: J. Engeset, A. L. Stalker, N. A. Matheson
Journal: Cardiovascular Research (1967)

A brief outline is given of a method for the objective measurement of erythrocyte aggregation and dispersion. Using this method it is shown that dextran 40 (Rheomacrodex) has a specific dispersing effect on aggregated human and canine red cells. A species difference in the reaction of red blood cells to dextrans is confirmed in that dextran 40 has no dispersing effect on rabbit red cells.
Diabetic Neuropathic Foot Ulcers
Authors: David J. Margolis, Lynne Allen-Taylor, Ole Hoffstad, Jesse A. Berlin
Journal: Diabetes Care (2002)

OBJECTIVE—The goal of this study was to evaluate whether simple risk factors can be identified that successfully characterize who will heal and who will not heal among patients who have received standard therapy for diabetic neuropathic foot ulcers. RESEARCH DESIGN AND METHODS—For this cohort study, we evaluated &amp;gt;31,000 individuals with a diabetic neuropathic foot ulcer seen in the Curative Health Services System. Using multivariate logistic regression, we evaluated the association between wound size, wound duration, wound grade, and other variables and their effect on whether a patient would heal by the 20th week of care. RESULTS—We demonstrated that wound size, wound duration, and wound grade are all significantly associated with the likelihood of a wound healing by the 20th week of care. In addition, we noted that these associations were not significantly affected by the treating wound care center, whether the unit of analysis was one wound on a patient or all of their wounds, or current adjuvant therapies. CONCLUSIONS—We have shown that three easy-to-measure risk factors are associated with a wound healing. These results should help clinicians understand the likelihood that a wound will heal and help those conducting clinical investigations to design better trials.
New Strategies in Sarcoma: Linking Genomic and Immunotherapy Approaches to Molecular Subtype
Authors: Jamie Lim, Neal M. Poulin, Torsten O. Nielsen
Journal: Clinical Cancer Research (2015)

There are more than 100 sarcoma subtypes, each uncommon and diagnostically challenging. Conventional chemotherapy has little benefit for most soft-tissue sarcomas; new treatment strategies are needed. Multiple recent genomic studies have provided detailed insights into sarcoma biology, including more accurate classification by molecular subtype, identification of recurrent mutations in oncogenic pathways, and evidence of epigenetic dysregulation. Advances in immunotherapy (adoptive immune cell transfer, tumor vaccine strategies, and immune checkpoint inhibition) have also provided a better understanding of how immuno-oncology might best be applied to sarcoma treatment, including connections to oncogenic pathways that may support combination strategies with conventional and targeted therapies. In this article, we review the latest sarcoma genomic studies and immuno-oncology developments and discuss how the findings suggest potential strategies to improve diagnosis and treatment across multiple sarcoma subtypes.
Assessment of coronary flowreserve by coronary pressure measurement
Authors: Takashi Akasaka, Atsushi Yamamuro, Norio Kamiyama, Yuji Koyama, Maki Akiyama, Nozomi Watanabe, Yoji Neishi, Tsutomu Takagi, Evgeny Shalman, Chen Barak, Kiyoshi Yoshida
Journal: Journal of the American College of Cardiology (2003)
Hypervascular pancreatic mass
Authors: R. Spiller
Journal: Gut (2005)

Chemoprevention has been considered as a possible approach for cancer prevention.A significant effort has been made in the development of novel drugs for both cancer prevention and treatment over the past decade.Recent epidemiological studies and clinical trials indicate that long term use of aspirin and similar agents, also called non-steroidal anti-inflammatory drugs (NSAIDs), can decrease the incidence of certain malignancies, including colorectal, oesophageal, breast, lung, and bladder cancers.The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane.COX-2 derived prostaglandin E 2 (PGE 2 ) can promote tumour growth by binding its receptors and activating signalling pathways which control cell proliferation, migration, apoptosis, and/or angiogenesis.However, the prolonged use of high dosages of COX-2 selective inhibitors (COXIBs) is associated with unacceptable cardiovascular side effects.Thus it is crucial to develop more effective chemopreventive agents with minimal toxicity.Recent efforts to identify the molecular mechanisms by which PGE 2 promotes tumour growth and metastasis may provide opportunities for the development of safer strategies for cancer prevention and treatment.
Antidepressant Use in Pregnant and Postpartum Women
Authors: Kimberly A. Yonkers, Katherine A. Blackwell, Janis Glover, Ariadna Forray
Journal: Annual Review of Clinical Psychology (2013)

Women in their reproductive years are at risk of experiencing depressive and anxiety disorders. As such, it is likely that pregnant women will undergo treatment with antidepressants. We review the risk of adverse birth outcomes and neonatal complications subsequent to antidepressant use in pregnancy. An inconsistent literature shows that antidepressant exposure is associated with shortened gestations and diminished fetal growth; these effects are small. Transitory neonatal signs are seen in some neonates after exposure to antidepressants in utero. No specific pattern of malformations has been consistently associated with antidepressants, with the possible exception of paroxetine and cardiac malformations. There is inconclusive evidence of a link between antidepressants in late pregnancy and persistent pulmonary hypertension in the newborn. Extensive study finds that antidepressants cannot be considered major teratogens. It is likely that confounding factors contribute to a number of the adverse effects found to be associated with antidepressant use in pregnancy.
Peri-Conceptional A1C and Risk of Serious Adverse Pregnancy Outcome in 933 Women With Type 1 Diabetes
Authors: Dorte M. Jensen, Lars Korsholm, Per Ovesen, Henning Beck-Nielsen, Lars Moelsted-Pedersen, Jes G. Westergaard, Margrethe Moeller, Peter Damm
Journal: Diabetes Care (2009)

OBJECTIVE To study the association between peri-conceptional A1C and serious adverse pregnancy outcome (congenital malformations and perinatal mortality). RESEARCH DESIGN AND METHODS Prospective data were collected in 933 singleton pregnancies complicated by type 1 diabetes. RESULTS The risk of serious adverse outcome at different A1C levels was compared with the background population. The risk was significantly higher when peri-conceptional A1C exceeded 6.9%, and the risk tended to increase gradually with increasing A1C. Women with A1C exceeding 10.4% had a very high risk of 16%. Congenital malformation rate increased significantly at A1C above 10.4%, whereas perinatal mortality was increased even at A1C below 6.9%. CONCLUSIONS These results support recent guidelines of preconceptional A1C levels &amp;lt;7% in women with type 1 diabetes.
Pharmacological and rAAV Gene Therapy Rescue of Visual Functions in a Blind Mouse Model of Leber Congenital Amaurosis
Authors: Matthew L Batten, Yoshikazu Imanishi, Daniel C Tu, Thuy Doan, Li Zhu, Jijing Pang, Lyudmila Glushakova, Alexander R Moise, Wolfgang Baehr, Russell N. Van Gelder, William W Hauswirth, Fred Rieke, Krzysztof Palczewski
Journal: PLoS Medicine (2005)

Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for approximately 15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina.An animal model of LCA, the Lrat-/- mouse, recapitulates clinical features of the human disease. Here, we report that two interventions--intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds--each restore retinal function to Lrat-/- mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to approximately 50% of wild-type levels (p < 0.05 versus wild-type and knockout controls), and pupillary light responses (PLRs) of Lrat-/- mice increased approximately 2.5 log units (p < 0.05). Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration) also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from approximately 5% of wild-type levels in Lrat-/- mice to approximately 50% of wild-type levels in treated Lrat-/- mice (p < 0.05 versus wild-type and knockout controls). The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and approximately 1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined.Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness.
A restricted spectrum of NRAS mutations causes Noonan syndrome
Authors: Ion C Cirstea, Kerstin Kutsche, Radovan Dvorsky, Lothar Gremer, Claudio Carta, Denise Horn, Amy E Roberts, Francesca Lepri, Torsten Merbitz-Zahradnik, Rainer König, Christian P Kratz, Francesca Pantaleoni, Maria L Dentici, Victoria A Joshi, Raju S Kucherlapati, Laura Mazzanti, Stefan Mundlos, Michael A Patton, Margherita Cirillo Silengo, Cesare Rossi, Giuseppe Zampino, Cristina Digilio, Liborio Stuppia, Eva Seemanova, Len A Pennacchio, Bruce D Gelb, Bruno Dallapiccola, Alfred Wittinghofer, Mohammad R Ahmadian, Marco Tartaglia, Martin Zenker
Journal: Nature Genetics (2009)
Prognostic and Predictive Value of Tumor Vascular Endothelial Growth Factor Gene Amplification in Metastatic Breast Cancer Treated with Paclitaxel with and without Bevacizumab; Results from ECOG 2100 Trial
Authors: Bryan P. Schneider, Robert J. Gray, Milan Radovich, Fei Shen, Gail Vance, Lang Li, Guanglong Jiang, Kathy D. Miller, Julie R. Gralow, Maura N. Dickler, Melody A. Cobleigh, Edith A. Perez, Tamara N. Shenkier, Kirsten Vang Nielsen, Sven Müller, Ann Thor, George W. Sledge, Joseph A. Sparano, Nancy E. Davidson, Sunil S. Badve
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here. Experimental Design: E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification status for VEGFA was conducted on paraffin-embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was conducted. Results: Estrogen receptor (ER)+ or progesterone receptor (PR)+ tumors were less likely to have VEGFA amplification than ER/PR− tumors (P = 0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; P = 0.013) in univariate analysis with a trend for worse OS in multivariate analysis (P = 0.08). There was a significant interaction between VEGFA amplification, hormone receptor status, and study arm. Patients with VEGFA amplification and triple-negative breast cancers (TNBC) or HER2 amplification had inferior OS (P = 0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2−. Those who received bevacizumab with VEGFA amplification had inferior progression-free survival (PFS; P = 0.010) and OS (P = 0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant. Conclusion: VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab. Clin Cancer Res; 19(5); 1281–9. ©2012 AACR.
Clinical and molecular epidemiology of community-acquired, healthcare-associated and nosocomial methicillin-resistant Staphylococcus aureus in Spain
Authors: J. Rodríguez-Baño, M. Angeles Domínguez, A. Blas Millán, C. Borraz, M. Pau González, B. Almirante, E. Cercenado, B. Padilla, M. Pujol
Journal: Clinical Microbiology and Infection (2009)
Eosinophil Peroxidase Mediates Protein Nitration in Allergic Airway Inflammation in Mice
Authors: ALEXANDRE DUGUET, HIROAKI IIJIMA, SEOK-YONG EUM, QUTAYBA HAMID, DAVID H. EIDELMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The eosinophilic inflammatory response in asthma is associated with protein nitration, detected as immunostaining for 3-nitrotyrosine (3NT). As the presence of 3NT is strongly correlated with upregulation of the inducible form of nitric oxide synthase (NOS II), it has been hypothesized that 3NT formation results from the action of peroxynitrite (ONOO−), a highly reactive NO derivative produced from the reaction of molecular NO and O2 −. However, recent observations have suggested that the action of peroxidases, including eosinophil peroxidase (EPO), may be responsible for protein nitration. In this study, we used murine models of allergic asthma to address the relative contribution of EPO and NOS II to protein nitration. We studied EPO-deficient New Zealand White (NZW) mice, which were sensitized and challenged intranasally with ovalbumin (OVA). Despite comparable levels of eosinophilia, NO, and superoxide production, NZW mice exhibited markedly decreased 3NT staining around the airways after OVA challenge when compared with two other strains (A/J and C57BL/6J). Immunocytochemical analysis of bronchoalveolar lavage (BAL) cells and lung sections suggested that 3NT staining was largely confined to eosinophils. This was confirmed by Western Blot analysis of proteins from different subsets of BAL cells that demonstrated a marked decrease in 3NT formation in eosinophils from NZW mice. These results contrast with those obtained in OVA-sensitized and -challenged NOS II deficient mice, which despite decreased NO production, exhibited similar 3NT staining in the airways after OVA challenge as in wild-type control mice. In this model, protein nitration was thus not a function of NO production by NOS II. We conclude that in the mouse, 3NT formation after specific allergen challenge is dependent on EPO activity, particularly in eosinophils themselves. In contrast, 3NT formation is not driven by upregulation of NOS II expression in this model and does not appear to depend on increases in the level of NO production.
CD166/Activated leukocyte cell adhesion molecule is expressed on glioblastoma progenitor cells and involved in the regulation of tumor cell invasion
Authors: N. Kijima, N. Hosen, N. Kagawa, N. Hashimoto, A. Nakano, Y. Fujimoto, M. Kinoshita, H. Sugiyama, T. Yoshimine
Journal: Neuro-Oncology (2011)

For improvement of prognosis for glioblastoma patients, which remains poor, identification and targeting of glioblastoma progenitor cells are crucial. In this study, we found that the Cluster of Differentiation (CD)166/activated leukocyte cell adhesion molecule (ALCAM) was highly expressed on CD133+ glioblastoma progenitor cells. ALCAM+CD133+ cells were highly enriched with tumor sphere-initiating cells in vitro. Among gliomas with isocitrate dehydrogenase-1/R132H mutation, the frequencies of ALCAM+ cells were significantly higher for glioblastomas than for World Health Organization grade II or III gliomas. The function of ALCAM in glioblastoma was then investigated. An in vitro invasion assay showed that transfection of ALCAM small interfering RNA or small hairpin RNA into glioblastoma cells significantly increased cell invasion without affecting cell proliferation. A soluble isoform of ALCAM (sALCAM) was also expressed in all glioblastoma samples and at levels that correlated well with ALCAM expression levels. In vitro invasion of glioblastoma cells was significantly enhanced by administration of purified sALCAM. Furthermore, overexpression of sALCAM in U87MG glioblastoma cells promoted tumor progression in i.c. transplants into immune-deficient mice. In summary, we were able to show that ALCAM constitutes a novel glioblastoma progenitor cell marker. We could also demonstrate that ALCAM and its soluble isoform are involved in the regulation of glioblastoma invasion and progression.
Evolutionary conservation of sequence and secondary structures in CRISPR repeats
Authors: Victor Kunin, Rotem Sorek, Philip Hugenholtz
Journal: Genome biology (2007)

Abstract Background Clustered regularly interspaced short palindromic repeats (CRISPRs) are a novel class of direct repeats, separated by unique spacer sequences of similar length, that are present in approximately 40% of bacterial and most archaeal genomes analyzed to date. More than 40 gene families, called CRISPR-associated sequences (CASs), appear in conjunction with these repeats and are thought to be involved in the propagation and functioning of CRISPRs. It has been recently shown that CRISPR provides acquired resistance against viruses in prokaryotes. Results Here we analyze CRISPR repeats identified in 195 microbial genomes and show that they can be organized into multiple clusters based on sequence similarity. Some of the clusters present stable, highly conserved RNA secondary structures, while others lack detectable structures. Stable secondary structures exhibit multiple compensatory base changes in the stem region, indicating evolutionary and functional conservation. Conclusion We show that the repeat-based classification corresponds to, and expands upon, a previously reported CAS gene-based classification, including specific relationships between CRISPR and CAS subtypes.
The Hebbian paradigm reintegrated: Local reverberations as internal representations
Authors: Walter J. Freeman
Journal: Behavioral and Brain Sciences (1995)

Abstract Recurrent excitation is experimentally well documented in cortical populations. It provides for intracortical excitatory biases that linearize negative feedback interactions and induce macroscopic state transitions during perception. The concept of the local neighborhood should be expanded to spatial patterns as the basis for perception, in which large areas of cortex are bound into cooperative behavior with near-silent columns as important as active columns revealed by unit recording.