tbuckley/cabot-search huggingface dataset:
Coronary Heart Disease Prediction From Lipoprotein Cholesterol Levels, Triglycerides, Lipoprotein(a), Apolipoproteins A-I and B, and HDL Density Subfractions
Authors: A.R. Sharrett, C.M. Ballantyne, S.A. Coady, G. Heiss, P.D. Sorlie, D. Catellier, W. Patsch
Journal: Circulation (2001)

Background — Despite consensus on the need for blood cholesterol reductions to prevent coronary heart disease (CHD), available evidence on optimal cholesterol levels or the added predictive value of additional lipids is sparse. Methods and Results — After 10 years follow-up of 12 339 middle-aged participants free of CHD in the Atherosclerosis Risk in Communities Study (ARIC), 725 CHD events occurred. The lowest incidence was observed in those at the lowest LDL cholesterol (LDL-C) quintile, with medians of 88 mg/dL in women and 95 mg/dL in men, and risk accelerated at higher levels, with relative risks (RRs) for the highest quintile of 2.7 in women and 2.5 in men. LDL-C, HDL-C, lipoprotein(a) [Lp(a)], and in women but not men, triglycerides (TG) were all independent CHD predictors, providing an RR, together with blood pressure, smoking, and diabetes, of 13.5 in women and 4.9 in men. Lp(a) was less significant in blacks than whites. Prediction was not enhanced by HDL-C density subfractions or apolipoproteins (apo) A-I or B. Despite strong univariate associations, apoB did not contribute to risk prediction in subgroups with elevated TG, with lower LDL-C, or with high apoB relative to LDL-C. Conclusions — Optimal LDL-C values are &lt;100 mg/dL in both women and men. LDL-C, HDL-C, TG, and Lp(a), without additional apolipoproteins or lipid subfractions, provide substantial CHD prediction, with much higher RR in women than men.
Inhibition of bovine factor viii‐induced guinea pig platelet aggregation by simple sugars and derivatives
Authors: Steven S. Kuwahara, Michael Malik
Journal: American Journal of Hematology (1977)

Abstract Working with the hypothesis that the binding of carbohydrate groups is important in the induction of platelet aggregation by bovine factor VIII, we studied 36 different sugars and sugar derivatives for their ability to inhibit the aggregation of guinea pig platelets. Concentrations that produced 50% inhibition of the aggregation response ranged from 232 mM (galactose) to 12 mM (glucosamine and galactosamine). Using these values, we found that several factors affected the ability of sugar structures to inhibit bovine factor VIII‐induced aggregation of guinea pig platelets. In general, galactose and its derivatives were not as effective as glucose and its derivatives. Sugars possessing α‐glycosidic linkages tended to be stronger inhibitors than those having β‐linkages. Polyols were better inhibitors than their corresponding aldoses. D‐fucose (129 mM) was a weaker inhibitor than L‐fucose (66 mM), but D‐and L‐arabinitol were not significantly different. N‐acetylation of glucosamine reduced its ability to inhibit aggregation. The number of free hydroxyl groups in a molecule did not appear to be a significant determinant of its ability to inhibit aggregation. The results support the hypothesis that a binding site for carbohydrate groups exists either on the platelet membrane or on the bovine factor VIII molecule. The binding of the carbohydrate to this site is an important step in the induction of aggregation, and this binding site is relatively specific for the carbohydrate structures that it will accept.
Down-regulation of Polo-like Kinase 1 Elevates Drug Sensitivity of Breast Cancer Cells<i>In vitro</i>and<i>In vivo</i>
Authors: Birgit Spänkuch, Sandra Heim, Elisabeth Kurunci-Csacsko, Christine Lindenau, Juping Yuan, Manfred Kaufmann, Klaus Strebhardt
Journal: Cancer Research (2006)

Abstract Human polo-like kinase 1 (Plk1) is a key player in different stages of mitosis and modulates the spindle checkpoint at the metaphase-anaphase transition. Overexpression of Plk1 is observed in various human tumors and it is a negative prognostic factor in patients suffering from diverse cancers. We used phosphorothioate antisense oligonucleotides (ASO) targeted against Plk1, together with paclitaxel, carboplatin, and Herceptin, for the treatment of breast cancer cells to identify conditions for enhanced drug sensitivity. After transfection of the breast cancer cell lines BT-474, MCF-7, and MDA-MB-435 with Plk1-specific ASOs, paclitaxel, carboplatin, or Herceptin was added and cell proliferation, cell cycle distribution, and apoptosis were measured. Whereas the dual treatment of breast cancer cells with Plk1-specific ASOs with carboplatin or Herceptin caused only a limited antiproliferative effect in breast cancer cells, we observed synergistic effects after combination of low doses of Plk1-specific ASOs with paclitaxel, which is used in a variety of clinical anticancer regimens. Plk1-specific ASOs also acted synergistically with paclitaxel in the arrest of the cell cycle at the G2-M phase and in the induction of apoptosis. Interestingly, in a human xenograft experiment using MDA-MB-435 cells, the combination of Plk1 ASOs with paclitaxel led to synergistic reduction of tumor growth after 3 weeks of treatment compared with either agent alone. This study suggests that antisense inhibitors against Plk1 at well-tolerated doses may be considered as highly efficient promoters for the antineoplastic potential of taxanes, such as paclitaxel, causing synergistic effects in breast cancer cells. (Cancer Res 2006; 66(11): 5836-46)
High-Altitude trekking in the Himalayas increases the activity of circulating endothelial cells
Authors: M.M. Ciulla, A. Giorgetti, L. Lazzari, M. Cortiana, I. Silvestris, G. Annoni, C. De Asmundis, A.V. Fiore, E. Montelatici, R. Paliotti, F. Magrini, P. Rebulla, A. Cortelezzi
Journal: American Journal of Hematology (2005)

Circulating endothelial progenitor cells (EPCs) are believed to contribute to vascular homeostasis; unfortunately, the response of EPCs in physiological conditions remains largely unknown. Herein we report our observations of a 44-year-old healthy subject after a trek in the Himalayas that support high-altitude hypoxia and exercise oxygen demands are strong stimuli for clonogenic endothelial cell activation and activity, as shown by the increase in the number of mature EPCs and in the endothelial colony-forming unit capacity. Both of these effects were completely reverted at sea level, 45 days after the subject's trek. Am. J. Hematol. 79:76–78, 2005. © 2005 Wiley-Liss, Inc.
Physiologic mechanisms governing hemodynamic responses to positive inotropic therapy in patients with dilated cardiomyopathy.
Authors: K M Borow, R M Lang, A Neumann, J D Carroll, S I Rajfer
Journal: Circulation (1988)

Clinical trials in patients with dilated cardiomyopathy (DCM) have shown a wide disparity in the hemodynamic responses to positive inotropic therapy. In addition, the response of the failing left ventricle to positive inotropic agents reflects the net interaction of multiple factors, including the magnitude of contractile abnormality and compensatory mechanisms. In the current study, left ventricular geometry, loading conditions, and contractile state were assessed in 13 patients with nonischemic DCM with the use of simultaneous high-fidelity pressure measurements and echocardiographic recordings. Comparisons were made with echocardiographic and calibrated carotid pulse data acquired in nine age-matched normal subjects. The patients with DCM were divided according to the left ventricular end-diastolic wall thickness-to-dimension ratio into groups with "appropriate" hypertrophy (i.e., less than or equal to 2 SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e., greater than 2 SDs from mean normal; n = 8; group 2). Age, New York Heart Association functional class, left ventricular wall mass index, and left ventricular end-diastolic pressure and dimension were similar for the DCM groups. Baseline left ventricular afterload (defined as circumferential end-systolic wall stress, sigma es) was 168% and 203% greater than normal in groups 1 and 2, respectively. The administration of the beta-adrenoceptor agonist dobutamine decreased left ventricular afterload by 12% in the normal subjects and by 10% in group 1 patients, while augmenting afterload by 5% in group 2 patients. The latter response occurred despite a 17% fall in systemic vascular resistance. Overall left ventricular performance, as assessed by the rate-corrected mean velocity of fiber shortening (Vcfc), was related to left ventricular afterload (i.e., sigma es). The resultant sigma es -Vcfc relationship, a sensitive measure of left ventricular contractility, was determined over a wide range of afterload conditions generated by methoxamine (normal subjects) or nitroprusside (DCM). Baseline left ventricular contractile state was 61% of normal for group 1 and 44% of normal for group 2. The contractile response to dobutamine infusion was 52% of normal for group 1 and only 22% of normal for group 2. Thus, positive inotropic therapy with dobutamine in patients with DCM is limited by (1) an attenuated contractile response and (2) elevated left ventricular afterload, which may be augmented further during its administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Screening remand prisoners for drug misuse would be improved by training doctors better
Authors: R. J Wool
Journal: BMJ (1997)

Editor—In their case study of substance misuse by remand prisoners Mason et al found that “present prison procedures fail to identify the extent to which substances are used and misused in people newly remanded to prison.”1 In a recent (unpublished) study of the health needs presented by prisoners remanded into La Moye prison, Jersey, I examined the …
Mycosis fungoides presenting as keratosis lichenoides chronica
Authors: None Bahadoran, None Wechsler, None Delfau-Larue, None Gabison, None Revuz, None Bagot
Journal: British Journal of Dermatology (1998)

We report a patient with a 17-year history of reticulated keratotic papules on the trunk and limbs, and telangiectatic eruption on the face, in whom the diagnosis of keratosis lichenoides chronica was first established. However, the biopsies showed an epidermotropic infiltrate of small irregular CD4 + lymphocytes, and detection of a T-cell clone in the lesions by polymerase chain reaction confirmed the diagnosis of mycosis fungoides. Thus, keratosis lichenoides chronica can be an unusual and potentially misleading presentation of mycosis fungoides.
A Microchannel Neuroprosthesis for Bladder Control After Spinal Cord Injury in Rat
Authors: Daniel J. Chew, Lan Zhu, Evangelos Delivopoulos, Ivan R. Minev, Katherine M. Musick, Charles A. Mosse, Michael Craggs, Nicholas Donaldson, Stéphanie P. Lacour, Stephen B. McMahon, James W. Fawcett
Journal: Science Translational Medicine (2013)

A severe complication of spinal cord injury is loss of bladder function (neurogenic bladder), which is characterized by loss of bladder sensation and voluntary control of micturition (urination), and spontaneous hyperreflexive voiding against a closed sphincter (detrusor-sphincter dyssynergia). A sacral anterior root stimulator at low frequency can drive volitional bladder voiding, but surgical rhizotomy of the lumbosacral dorsal roots is needed to prevent spontaneous voiding and dyssynergia. However, rhizotomy is irreversible and eliminates sexual function, and the stimulator gives no information on bladder fullness. We designed a closed-loop neuroprosthetic interface that measures bladder fullness and prevents spontaneous voiding episodes without the need for dorsal rhizotomy in a rat model. To obtain bladder sensory information, we implanted teased dorsal roots (rootlets) within the rat vertebral column into microchannel electrodes, which provided signal amplification and noise suppression. As long as they were attached to the spinal cord, these rootlets survived for up to 3 months and contained axons and blood vessels. Electrophysiological recordings showed that half of the rootlets propagated action potentials, with firing frequency correlated to bladder fullness. When the bladder became full enough to initiate spontaneous voiding, high-frequency/amplitude sensory activity was detected. Voiding was abolished using a high-frequency depolarizing block to the ventral roots. A ventral root stimulator initiated bladder emptying at low frequency and prevented unwanted contraction at high frequency. These data suggest that sensory information from the dorsal root together with a ventral root stimulator could form the basis for a closed-loop bladder neuroprosthetic.
Scientists Still Debate the Fate of Smallpox Virus
Authors: Rebecca Voelker
Journal: JAMA (1993)

ONE OF history's deadliest killers has been given a reprieve. The world's known remaining stocks of smallpox virus, set for destruction this New Year's Eve, apparently will live to see the new year. Their fate will be debated later next month when a World Health Organization (WHO) technical committee reviews data on the extent to which the smallpox virus genome has been sequenced. Based on those data, the World Health Assembly, composed of representatives from all the countries in the United Nations, will make a final decision. If the assembly decides that the sequencing is sufficient, destruction of the virus could take place in May. Whatever happens, the world's first planned extinction of a biological species has spawned an intricate debate. Those who favor the virus' demise say it is fruitless to maintain stocks that, if released accidentally or obtained by terrorist groups, could endanger countless lives. But supporters of
Prognostic Significance of Transforming Growth Factor β Receptor II in Estrogen Receptor-Negative Breast Cancer Patients
Authors: Miriam B. Buck, Peter Fritz, Juergen Dippon, Gerhard Zugmaier, Cornelius Knabbe
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The role of transforming growth factor β (TGF-β) in breast cancer is ambiguous; it can display both tumor suppressing and enhancing effects. Activation of the TGF-β signal transduction system is subject to hormonal regulation. This study was conducted to further analyze the role of TGF-β receptors in breast cancer and to evaluate their significance as prognostic markers. Experimental Design: Expression of TGF-β receptor I (TβRI) and TGFβ receptor II (TβRII) was retrospectively analyzed by immunohistochemistry in 246 breast cancer patients. Results: Expression of TβRI was strongly correlated with tumor size (P &amp;lt; 0.001) and nodal status (P = 0.012) but only weakly with overall survival (P = 0.056). In contrast, TβRII was prognostic for overall survival in univariate analysis (P = 0.0370). In estrogen receptor (ER) -negative patients TβRII expression was correlated with highly reduced overall survival (P = 0.0083). In multivariate analysis TβRII proved to be an independent and highly significant prognostic marker with a hazard ratio of 6.8. Simultaneous loss of both ER and TβRII was associated with longer overall survival times comparable with those of ER-positive patients. Conclusions: The results of this exploratory study show that TβRII is an independent, highly significant prognostic indicator for overall survival in ER-negative patients. In addition our results are supportive of a mechanism of breast cancer progression in which a selective loss of the tumor inhibitory action of TGFβ takes place, whereas tumor- promoting aspects remain intact.
Suppressed soluble Fms–like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease
Authors: Masaru Matsui, Yukiji Takeda, Shiro Uemura, Takaki Matsumoto, Ayako Seno, Kenji Onoue, Hideo Tsushima, Katsuhiko Morimoto, Tsunenari Soeda, Satoshi Okayama, Satoshi Somekawa, Ken-ichi Samejima, Hiroyuki Kawata, Rika Kawakami, Kimihiko Nakatani, Masayuki Iwano, Yoshihiko Saito
Journal: Kidney International (2013)
Effect of Tri-Iodothyronine on Rate of Alcohol Oxidation in Dogs
Authors: D. Edwards Smith, Norma E. Fallis, Léon Tétreault
Journal: New England Journal of Medicine (1963)

IT has been reported1 that tri-iodothyronine will accelerate the metabolism of ethyl alcohol. If this is true such an effect would have considerable implications for clinical practice as a relatively simple technic that could quickly restore a hostile or comatose inebriate to relative sobriety. It was therefore thought important to attempt to confirm these observations.Method and MaterialsFive mongrel dogs (4 male and 1 female) weighing from 20 to 25 kg. each were used in the experiment. After a sixteen-hour fast the animals were given 2 gm. of ethyl alcohol per kilogram of body weight as a 15 . . .
Cutaneous Epithelioid Sarcomalike (Pseudomyogenic) Hemangioendothelioma
Authors: Luis Requena, Carlos Santonja, Jose Luis Martinez-Amo, Carlos Saus, Heinz Kutzner
Journal: JAMA Dermatology (2013)

<h3>Importance</h3>Epithelioid sarcomalike (pseudomyogenic) hemangioendothelioma (ES-H) is a recently described and little-known vascular neoplasm that frequently presents with dermatologic lesions. Histopathologic characterization includes sheets or fascicles of plump, spindled and epithelioid, rhabdomyoblastlike neoplastic cells involving the dermis and often extending to subcutaneous tissue. Immunohistochemical analysis reveals neoplastic cells that show a constant immunophenotype characterized by immunoreactivity for cytokeratins and endothelial markers.<h3>Observations</h3>We described the clinical, histopathologic, and immunohistochemical features of 2 cases of cutaneous ES-H. Clinical examination revealed multifocal lesions that consisted of erythematous nodules on the leg and foot in case 1 and small perioral papules in case 2. Neoplastic cells had a rhabdomyoblastic appearance, with large nuclei and ample eosinophilic cytoplasm. Immunohistochemical analysis revealed expression of cytokeratin AE1/AE3, CD31, ERG, and FLI-1, with focal and weak positivity for CAM 5.2 and smooth muscle actin. The nuclei of neoplastic cells showed intact expression of INI-1. This immunoprofile, especially the ERG positivity, demonstrated the endothelial nature of proliferating cells.<h3>Conclusions</h3>We recommend adding the low-grade neoplasm ES-H to the large list of cutaneous vascular proliferations. Dermatologists should be aware of this low-grade cutaneous vascular tumor.
Abstract 4304: PPP1R1B-STARD3 fusion gene promotes gastric tumorigenesis through activation of PI3K/Akt signaling.
Authors: Sun Mi Yun
Journal: Cancer Research (2013)

Abstract Fusion genes result from genomic aberrations such as translocation, amplification and rearrangement. They have the potential to be new targets for the diagnosis and therapeutics in several different types of cancers. To identify fusion genes in gastric cancer, we conducted RNA sequencing with 18 gastric cancer cell lines and 11 pairs of primary human gastric cancer tissues and their adjacent normal tissues. We identified PPP1R1B-STARD3 fusion gene and validated the expression of this fusion gene by Real-Time PCR in the expanded panel of the human gastric tissue samples. Interestingly, PPP1R1B-STRAD3 fusion gene was detected in approximately 30% of primary human gastric cancers, but not in adjacent matched normal gastric tissues. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of PI3K/Akt signaling. To confirm if the expression of PPP1R1B-STARD3 fusion gene affects the tumorigenic capacity of gastric cancer cells in vivo, we performed the xenograft assay with MKN-28 cells that stably express PPP1R1B-STARD3 fusion gene. Overexpression of the fusion gene enhanced the MKN-28 tumor growth in nude mice. Hence, PPP1R1B-STARD3 fusion gene overexpression gives growth advantage in vitro and in vivo. Taken together, these findings indicate that PPP1R1B-STRAD3 fusion gene increased cell proliferation through the activation of PI3K/Akt signaling in gastric cancer cells. Citation Format: Sun Mi Yun. PPP1R1B-STARD3 fusion gene promotes gastric tumorigenesis through activation of PI3K/Akt signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4304. doi:10.1158/1538-7445.AM2013-4304
The Slow Inward Current and Cardiac Arrhythmias
Authors: Jay W. Mason
Journal: JAMA (1982)

This is a timely and unique publication. Despite its 1980 copyright and the two years that have passed since its preparation, the book retains its accuracy and immediacy. It represents a new compilation of information regarding the kinetically slow inward current. Coverage of the subject is remarkably complete. This text will be required reading as an important and singular reference source for any basic or clinical scientist who intends to study the cardiac calcium channel. Since Reuter and other investigators convincingly demonstrated 15 years ago the existence of a small, prolonged inward current occurring during the plateau of the cardiac action potential, activated at low transmembrane potentials and dependent on calcium rather than sodium ion, a huge quantity of research data characterizing this current has been amassed. These data are summarized and interpreted succinctly in this book by 37 respected investigators who are, in fact, largely responsible for the existence
On Turning in Labours Rendered Difficult by Distortion of the Pelvis
Authors: T. Radford
Journal: BMJ (1847)

Abstract  Amphibians are undergoing global-scale declines due to the increased incidence of anthropogenic stressors. The loss of species with unique evolutionary histories and functional traits poses a serious risk to the maintenance of ecosystem functions in aquatic environments, already directly affected by several anthropogenic land-use changes. Here, we investigated the influence of anthropogenic stressors (roads and Pinus monocultures) on functional, phylogenetic and taxonomic composition and functional dispersion of an anuran metacommunity of 33 ponds in southern Brazil. We expected for the relative influence of anthropogenic stressors to vary according to the compositional facet, with a greater influence of these stressors on the functional and phylogenetic than on the taxonomic facet. We also expected traits related to habitat exploration (head shape and eye size and position) to be more influenced by Pinus monocultures, while the traits related to the dispersion and the physiological control of individuals (limb length and body mass) to be similarly influenced by roads and Pinus. To evaluate this, we used PERMANOVA analyses for each of the compositional facets and anthropogenic stressor, and path models to verify all possible relationships between patterns of functional dispersion and anthropogenic stressors. We found that, while the distance from ponds to Pinus monocultures influences the phylogenetic composition, distance to roads influences the functional composition; distance to roads affects mostly the functional dispersion of the communities. These anthropogenic stressors affect the structure of anuran communities, even those formed by generalist species in terms of habitat use. There is a decline in diversity in communities located close to Pinus and roads, leading to losses in the evolutionary history accumulated in these communities. The control of vehicle traffic during reproduction periods and the maintenance of areas with natural vegetation, particularly around ponds, may help mitigate the negative effects of anthropogenic stressors on anuran communities.