tbuckley/cabot-search huggingface dataset:
Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia
Authors: J Herrmann
Journal: Cardiovascular Research (2001)

Objective: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. Methods: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. Results: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93±6%) and Group 2 (89±7%) but impaired in Group 3 (71±11%; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88±2.45 per-mm2) and Group 3 (4.50±1.37 per-mm2) compared to Group 1 (2.97±1.37 per-mm2; P<0.05 vs. Group 2 and 3). Conclusion: This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.
Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS
Authors: Daryl A Bosco, Gerardo Morfini, N Murat Karabacak, Yuyu Song, Francois Gros-Louis, Piera Pasinelli, Holly Goolsby, Benjamin A Fontaine, Nathan Lemay, Diane McKenna-Yasek, Matthew P Frosch, Jeffrey N Agar, Jean-Pierre Julien, Scott T Brady, Robert H Brown
Journal: Nature Neuroscience (2010)
Tivozanib Versus Sorafenib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma: Results From a Phase III Trial
Authors: Robert J. Motzer, Dmitry Nosov, Timothy Eisen, Igor Bondarenko, Vladimir Lesovoy, Oleg Lipatov, Piotr Tomczak, Oleksiy Lyulko, Anna Alyasova, Mihai Harza, Mikhail Kogan, Boris Y. Alekseev, Cora N. Sternberg, Cezary Szczylik, David Cella, Cristina Ivanescu, Andrew Krivoshik, Andrew Strahs, Brooke Esteves, Anna Berkenblit, Thomas E. Hutson
Journal: Journal of Clinical Oncology (2013)

Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), -2, and -3. This phase III trial compared tivozanib with sorafenib as initial targeted therapy in patients with metastatic renal cell carcinoma (RCC).Patients with metastatic RCC, with a clear cell component, prior nephrectomy, measurable disease, and 0 or 1 prior therapies for metastatic RCC were randomly assigned to tivozanib or sorafenib. Prior VEGF-targeted therapy and mammalian target of rapamycin inhibitor were not permitted. The primary end point was progression-free survival (PFS) by independent review.A total of 517 patients were randomly assigned to tivozanib (n = 260) or sorafenib (n = 257). PFS was longer with tivozanib than with sorafenib in the overall population (median, 11.9 v 9.1 months; hazard ratio [HR], 0.797; 95% CI, 0.639 to 0.993; P = .042). One hundred fifty-six patients (61%) who progressed on sorafenib crossed over to receive tivozanib. The final overall survival (OS) analysis showed a trend toward longer survival on the sorafenib arm than on the tivozanib arm (median, 29.3 v 28.8 months; HR, 1.245; 95% CI, 0.954 to 1.624; P = .105). Adverse events (AEs) more common with tivozanib than with sorafenib were hypertension (44% v 34%) and dysphonia (21% v 5%). AEs more common with sorafenib than with tivozanib were hand-foot skin reaction (54% v 14%) and diarrhea (33% v 23%).Tivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC.
The Molecular Evolution of Avian Ultraviolet- and Violet-Sensitive Visual Pigments
Authors: Livia S. Carvalho, Jill A. Cowing, Susan E. Wilkie, James K. Bowmaker, David M. Hunt
Journal: Molecular Biology and Evolution (2007)

The shortwave-sensitive SWS1 class of vertebrate visual pigments range in λmax from the violet (385–445 nm) to the ultraviolet (UV) (365–355 nm), with UV-sensitivity almost certainly ancestral. In birds, however, the UV-sensitive pigments present in a number of species have evolved secondarily from an avian violet-sensitive (VS) pigment. All avian VS pigments expressed in vitro to date encode Ser86 whereas Phe86 is present in all non-avian ultraviolet sensitive (UVS) pigments. In this paper, we show by site directed mutagenesis of avian VS pigments that Ser86 is required in an avian VS pigment to maintain violet-sensitivity and therefore underlies the evolution of avian VS pigments. The major mechanism for the evolution of avian UVS pigments from an ancestral avian VS pigment is undoubtedly a Ser90Cys substitution. However, Phe86, as found in the Blue-crowned trogon, will also short-wave shift the pigeon VS pigment into the UV whereas Ala86 and Cys86 which are also found in natural avian pigments do not generate short-wave shifts when substituted into the pigeon pigment. From available data on avian SWS1 pigments, it would appear that UVS pigments have evolved on at least 5 separate occasions and utilize 2 different mechanisms for the short-wave shift.
A search for messenger RNA molecules bearing immunoglobulin VH nucleotide sequences in T cells.
Authors: D J Kemp, J M Adams, P L Mottram, W R Thomas, I D Walker, J F Miller
Journal: The Journal of Experimental Medicine (1982)

Expression of VH-coded mRNA molecules in T cells, antigen-specific T cell lines, or T cell hybridomas was not detected using four different VH DNA probes under conditions that permitted cross-hybridization between distantly related VH genes. In contrast, VH gene expression was readily detected in two B cell lymphomas and in splenic B cells. Less than one molecule per cell of RNA, exactly complementary to the DNA probes used, would have been detected in these T cell populations. The results thus seriously question the proposition that T cells use the B cell VH repertoire to code for antigen receptors.
Prediction of oligodendroglial histology and LOH 1p/19q using dynamic [18F]FET-PET imaging in intracranial WHO grade II and III gliomas
Authors: N. L. Jansen, C. Schwartz, V. Graute, S. Eigenbrod, J. Lutz, R. Egensperger, G. Popperl, H. A. Kretzschmar, P. Cumming, P. Bartenstein, J.-C. Tonn, F.-W. Kreth, C. la Fougere, N. Thon
Journal: Neuro-Oncology (2012)

Oligodendroglial components (OC) and loss of heterozygosity on chromosomes 1p and 19q (LOH 1p/19q) are associated with better outcome in patients with glioma. We aimed to assess the fitness of [(18)F]fluoroethyltyrosine positron-emission-tomography (FET-PET) for noninvasively identifying these important prognostic/predictive factors. One hundred forty-four patients with MRI-suspected WHO grade II and III glioma underwent FET-PET scans prior to histological diagnosis. FET-PET analyses included maximal tumoral uptake (SUV(max)/BG), biological tumor volume (BTV), mean tumoral uptake (SUV(mean)/BG), total tumoral uptake (SUV(total)/BG), and kinetic analysis. Suspicion of OC was based on static and dynamic FET-uptake parameters. PET results were correlated with histology and 1p/19q status. OC tumors exhibited significantly higher uptake values, compared with astrocytomas (AC) (SUV(max)/BG 3.1 vs 2.3, BTV 15.5 mL vs 7.2 mL, SUV(total)/BG 38.5 vs 17.4, P < .01 each; SUV(mean)/BG 2.2 vs 2.1, P < .05). These differences were more pronounced in WHO grade II gliomas. Comparable results were found with respect to 1p/19q status. Kinetic analysis misclassified 18 of 34 low-grade OC tumors as high-grade glioma but misclassified only 5 of 45 of the low-grade ACs. FET-based suspicion of OC resulted in concordance rates of both 76% for the prediction of OC and LOH 1p/19q. FET-uptake was significantly higher in gliomas with OC, compared with AC, and likewise in 1p/19q codeleted, compared with noncodeleted tumors. However, FET-PET analysis did not reliably predict the presence of OC/LOH 1p/19q in the individual patient, mostly because of an overlap in PET characteristics of OC tumors and high-grade AC. Histological examination is still required for an accurate diagnosis.
Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe osteoporosis
Authors: C Roux, J Fechtenbaum, S Kolta, G Isaia, J B C. Andia, J-P Devogelaer
Journal: Annals of the Rheumatic Diseases (2008)

Early osteoporotic fractures have a great impact on disease progression, the first fracture being a major risk factor for further fractures. Strontium ranelate efficacy against vertebral fractures is presently assessed in a subset of women aged 50-65 years.
The PI3K/AKT/mTOR Pathway as a Therapeutic Target in Endometrial Cancer
Authors: Brian M. Slomovitz, Robert L. Coleman
Journal: Clinical Cancer Research (2012)

Endometrial cancer is the most common gynecologic malignancy in the United States. Overactivation of the PI3K/AKT/mTOR pathway, a signaling pathway that plays an important role in cellular growth and survival, has recently been implicated in endometrial cancer pathogenesis, and as such, inhibition of the PI3K/AKT/mTOR pathway is of therapeutic interest. Preclinical and clinical studies are proving useful in elucidating the antitumor effects of different PI3K/AKT/mTOR pathway inhibitors, and in defining which patient populations these inhibitors might be most effective in. For example, an increasing amount of preclinical data suggest that loss of PTEN or genetic alteration of PIK3CA may be indicators of sensitivity to PI3K/AKT/mTOR pathway inhibition, while activating KRAS mutations may predict resistance. In the latter case, combined inhibition of the RAS/RAF/MEK and PI3K/AKT/mTOR pathways has been suggested as a therapeutic strategy. In addition, the PI3K/AKT/mTOR pathway has been implicated in conferring resistance to conventional therapies, and so PI3K/AKT/mTOR pathway inhibitors in combination with hormonal and/or cytotoxic agents are being evaluated. In conclusion, preclinical models are providing insights into the antitumor activity of PI3K/AKT/mTOR pathway inhibition, and are helping define patient populations most likely to benefit from these therapies. Clinical validation of these findings is ongoing.
Development of the Action Potential of the Prenatal Rat Heart
Authors: JAMES R. COUCH, THEODORE C. WEST, HEBBEL E. HOFF
Journal: Circulation Research (1969)

Transmembrane action potentials were recorded from embryonic rat hearts at ages between 10½ days of gestation and birth (21 to 22 days). The resting potential averaged 30 to 40 mv at 10½ days and increased to around 80 mv by birth. Two periods of rapid increase in resting potential were noted: 1) from 10½ to 13½ days and 2) from 19½ days of gestation to birth. The maximal upstroke velocity of the action potential increased as the resting potential increased. The duration of the ventricular and atrial action potentials was inversely related to heart rate, and their rate sensitivity decreased with age. The atrial action potential lost its rate sensitivity by 13½ days of gestation and the ventricular action potential lost its by birth. At 10½ days diastolic depolarization was found in the area of the ventricle proximate to the A-V junction, the left and right atria, and the sinus venosus. The velocity of the diastolic depolarization was greatestin the sinus venosus and least in the ventricle. The diastolic depolarization decreased with growth and was lost by 13½ days of gestation.
Cross sectional study of effects of drinking green tea on cardiovascular and liver diseases
Authors: K Imai, K Nakachi
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To investigate the association between consumption of green tea and various serum markers in a Japanese population, with special reference to preventive effects of green tea against cardiovascular disease and disorders of the liver. <b>Design</b>: Cross sectional study. <b>Setting</b>: Yoshimi, Japan. <b>Subjects</b>: 1371 men aged over 40 years resident in Yoshimi and surveyed on their living habits including daily consumption of green tea. Their peripheral blood samples were subjected to several biochemical assays. <b>Results</b>: Increased consumption of green tea was associated with decreased serum concentrations of total cholesterol (P for trend &lt;0.001) and triglyceride (P for trend=0.02) and an increased proportion of high density lipoprotein cholesterol together with a decreased proportion oflow and very low lipoprotein cholesterols (P for trend=0.02), which resulted in a decreased atherogenic index (P for trend=0.02). Moreover, increased consumption of green tea, especially more than 10 cups a day, was related to decreased concentrations of hepatological markers in serum, aspartate aminotransferase (P for trend=0.06), alanine transferase (P for trend=0.07), and ferritin (P for trend=0.02). <b>Conclusion</b>: The inverse association between consumption of green tea and various serum markers shows that green tea may act protectively against cardiovascular disease and disorders of the liver. <h3>Key messages</h3> Key messages This cross sectional study in Japanese men shows that increased consumption of green tea is associated with decreased serum concentrations of total cholesterol, triglyceride, and atherogenic index High consumption of green tea may also protect against disorders of the liver in terms of serum markers
High prevalence of cutaneous warts in elementary school children and the ubiquitous presence of wart-associated human papillomavirus on clinically normal skin
Authors: M.N.C. de Koning, K.D. Quint, S.C. Bruggink, J. Gussekloo, J.N. Bouwes Bavinck, M.C.W. Feltkamp, W.G.V. Quint, J.A.H. Eekhof
Journal: British Journal of Dermatology (2014)

Background One-third of Dutch primary school children have cutaneous warts; each year around 20% of them seek medical treatment. However, little is known about the epidemiology of the types of human papillomavirus (HPV) causing these warts. Objectives To investigate the distribution of cutaneous wart-associated HPV types in three primary school classes by analysing skin swabs taken from warts, and the forehead, hand dorsum and sole of the foot of included children. Methods Using the hyperkeratotic skin lesion polymerase chain reaction/multiplex genotyping assay, each swab sample was used to genotype for 23 cutaneous wart-associated HPV types. Results Thirty-one (44%) of the 71 children had a total of 69 warts, with a maximum of six warts per child. In the wart swabs, HPV2, HPV27 and HPV57, members of Alphapapillomavirus species 4, were most frequently detected (27%, 32% and 14%, respectively), whereas HPV1 was only found in two plantar warts. The prevalence of HPV carriage, detected in swabs of clinically normal skin of the forehead, left hand and left sole was 80%, with the most prevalent types being HPV1 (59%), HPV2 (42%), HPV63 (25%) and HPV27 (21%). Conclusions Cutaneous wart-associated HPV types were highly prevalent in primary school children, but did not correlate with the HPV types in warts. In contrast to the existing literature, HPV1 was frequently detected on clinically normal skin but was much less frequent in warts.
A Brain-Based Endophenotype for Major Depressive Disorder
Authors: Bradley S. Peterson, Myrna M. Weissman
Journal: Annual Review of Medicine (2010)

We have identified a brain-based endophenotype for major depressive disorder (MDD) that includes thinning of the cortex of the lateral aspect of the right hemisphere and the medial aspect of the left, as well as bilateral hypoplasia of frontal and parietal white matter. The endophenotype status of these abnormalities is supported by their presence in a multigenerational cohort of persons who themselves do not have MDD but who are at increased familial risk for developing the illness. Those who have the endophenotype but who are not ill nevertheless still suffer from inattention and poor visual memory for social stimuli in direct proportion to the magnitude of cortical thinning and white matter hypoplasia within the endophenotype. Identification of this endophenotype and its cognitive correlates provides targets for devising new preventive and therapeutic interventions for MDD.
Regulating anxiety with extrasynaptic inhibition
Authors: Paolo Botta, Lynda Demmou, Yu Kasugai, Milica Markovic, Chun Xu, Jonathan P Fadok, Tingjia Lu, Michael M Poe, Li Xu, James M Cook, Uwe Rudolph, Pankaj Sah, Francesco Ferraguti, Andreas Lüthi
Journal: Nature Neuroscience (2015)
Mechanism of resistance to the phosphaturic effect of the parathyroid hormone in the hamster.
Authors: F G Knox, J Preiss, J K Kim, T P Dousa
Journal: Journal of Clinical Investigation (1977)

The effect of parathyroid hormone and calcitonin on the renal excretion of phosphate, calcium, and cyclic AMP was evaluated in the thyroparathyroidectomized hamster, a mammal apparently reisstant to the phosphaturic effect of parathyroid hormone. Parathyroid hormone did not increase phosphate excretion, although it decreased excretion of calcium and increased urinary excretion of cyclic AMP. This lack of a phosphaturic response to parathyroid hormone was not reversed by administration of 25-OH vitamin D or infusions of calcium or phosphate. Calcitonin, another potentially phosphaturic hormone, also vailed to increase phosphate excretion but markedly elevated urinary excretion of cyclic AMP. In hamsters pretreated with infusion of urinary ammonium chloride, which decreased plasma and urinary pH, both parathyroid hormone and calcitonin increased excretion of phosphate as well as that of cyclic AMP. Acetazolamide had no phosphaturic effect in ammonium chloride-loaded hamsters, and it decreased cyclic AMP and calcium excretion. Alkalinization of urine by acetazolamide did not prevent the phosphaturic effect of parathyroid hormone in ammonium chloride-loaded hamsters, but it blocked the increase in urinary cyclic AMP excretion. Parathyroid hormone and calcitonin both stimulated adenylate cyclase in a cell-free system (600-g pellet) from hamster renal cortex, elevated tissue cyclic AMP levels, and activated protein kinase in tissue slices from hamster renal cortex. In acid medium, the increase in cyclic AMP and activation of protein kinase in response to parathyroid hormone was diminished, but addition of acetazolamide restored responsiveness of both parameters to control values. Acetazolamide, on the other hand, did not influence adenylate cyclase or its response to parathyroid hormone or cyclic AMP phosphodiesterase activity. We conclude that the lack of a phosphaturic effect of parathyroid hormone and calcitonin in the hamster depends on steps in the cellular action of these hormones, steps that are sensitive to pH subsequent to cyclic AMP generation and protein kinase activation. In addition, acetazolamide may potentiate the phosphaturic effect of parathyroid hormone by promoting accumulation of cyclic AMP in tissue. Thus, the hamster is a particularly useful model for studies of syndromes in which there is renal resistance to phosphaturic hormones.
Targeted G-protein inhibition as a novel approach to decrease vagal atrial fibrillation by selective parasympathetic attenuation
Authors: Gary L. Aistrup, Roger Villuendas, Jason Ng, Annette Gilchrist, Thomas W. Lynch, David Gordon, Ivan Cokic, Steven Mottl, Rui Zhou, David A. Dean, J. Andrew Wasserstrom, Jeffrey J. Goldberger, Alan H. Kadish, Rishi Arora
Journal: Cardiovascular Research (2009)

The parasympathetic nervous system is thought to play a key role in atrial fibrillation (AF). Since parasympathetic signalling is primarily mediated by the heterotrimeric G-protein, Galpha(i)betagamma, we hypothesized that targeted inhibition of Galpha(i) interactions in the posterior left atrium (PLA) would modify the substrate for vagal AF.Cell-penetrating(cp)-Galpha(i)1/2 and cp-Galpha(i)3 C-terminal peptides were assessed for their ability to attenuate cholinergic-parasympathetic signalling in isolated feline atrial myocytes and in canine left atrium (LA). Confocal fluorescence microscopy indicated that cp-Galpha(i)1/2 and/or cp-Galpha(i)3 peptides moderated carbachol attenuation of cellular Ca(2+) transients in isolated atrial myocytes. High-density epicardial mapping of dog PLA, left atrial pulmonary veins (PVs), and left atrial appendage (LAA) indicated that the delivery of cp-Galpha(i)1/2 peptide or cp-Galpha(i)3 peptide into the PLA prolonged effective refractory periods at baseline and during vagal stimulation in the PLA and to varying extents also in the LAA and PV regions. After delivery of cp-Galpha(i) peptides into the PLA, AF inducibility during vagal stimulation was significantly diminished.These results demonstrate the feasibility of using specific G(i)-protein inhibition to achieve selective parasympathetic denervation in the PLA, with a resulting change in vagal responsiveness across the entire LA.
Pneumoproteinaemia: a new perspective in the assessment of lung disorders
Authors: C Hermans, A Bernard
Journal: European Respiratory Journal (1998)

Here we make the hypothesis that the determination of the concentration of lung specific secretory proteins in serum or pneumoproteinaemia could be used in the evaluation of lung disorders with a similar utility as proteinuria in kidney diseases involving the glomeruli. Human and experimental data indicate that comparable structural and functional features govern the passage of proteins across the lung epithelium/blood barrier and the glomerular filter. The concentrations in serum of some lung-specific secretory proteins, such as the bronchiolar Clara cell 16 kDa protein (CC16) and alveolar surfactant-associated proteins A and B (SP-A and SP-B, respectively), might be used to assess the integrity of the bronchoalveolar/blood barrier known to be disrupted in many lung disorders. In addition, if this barrier is intact or slightly compromised, these proteins might serve as peripheral markers to detect changes in secretory epithelial cells in the lung.