tbuckley/cabot-search huggingface dataset:
TCT-558 Adjunctive Rotational Atherectomy Before Drug-Eluting Stent Deployment is not an Essential Strategy for Severely Calcified Stenosis Identified by Pre-procedural Intravascular Ultrasound: Mid-term Angiographic and Clinical Outcomes.
Authors: Satoko Tahara, Yusuke Fujino, Hiroto Yabushita, Kensuke Takagi, Michihiko Sato, Satoru Mitomo, Hiroyoshi Kawamoto, Takahiro Matsumoto, Takayuki Warisawa, Yusuke Watanabe, Hisaaki Ishiguro, Keiko Fukino, Naoyuki Kurita, Koji Hozawa, Shotaro Nakamura, Sunao Nakamura
Journal: Journal of the American College of Cardiology (2013)
THE INFLUENCE OF HIGH ALTITUDE ON ALBUMINURIA.
Authors: EDWARD C. HILL
Journal: JAMA (1900)

I have devised and am now using, in the treatment of cases by means of concentrated light, a reflector which is so constructed that the direct rays of the sun falling on it are focussed at a distance of eight feet, on an area six inches in diameter, the reflector being thirty inches in diameter.Thus a light is produced equal in inten- sity to twenty times that of direct sunlight, and covering an area of twenty-eight square inches.As the actinic rays of the sun are desired rather than the heat rays, blue glass is placed in front of the reflector, which per- mits of the passage of the light in nearly its full strength, but excludes a large percentage of the heat rays.The reflector is mounted on a metal stand which permits of motion in all directions.The light from THE KIME PHOTOTHERAPY BEFLECTOB.this reflector is as powerful as it is possible to make use of on account of the accompanying heat.The method of using the instrument is as follows: The part on which the intense light is to be used is made bare and the patient is placed in front of the re- flector, and at a distance of eight feet from it; the rays of the sun fall directly on it, it being so placed that the reflected rays will be focussed on the part to be treated.If the heat be too great at the focal point, the patient may be seated either within or beyond the focal point of
CD4+ T cells from elite controllers resist HIV-1 infection by selective upregulation of p21
Authors: Huabiao Chen, Chun Li, Jinghe Huang, Thai Cung, Katherine Seiss, Jill Beamon, Mary F. Carrington, Lindsay C. Porter, Patrick S. Burke, Yue Yang, Bethany J. Ryan, Ruiwu Liu, Robert H. Weiss, Florencia Pereyra, William D. Cress, Abraham L. Brass, Eric S. Rosenberg, Bruce D. Walker, Xu G. Yu, Mathias Lichterfeld
Journal: Journal of Clinical Investigation (2011)

Elite controllers represent a unique group of HIV-1–infected persons with undetectable HIV-1 replication in the absence of antiretroviral therapy. However, the mechanisms contributing to effective viral immune defense in these patients remain unclear. Here, we show that compared with HIV-1 progressors and HIV-1–negative persons, CD4+ T cells from elite controllers are less susceptible to HIV-1 infection. This partial resistance to HIV-1 infection involved less effective reverse transcription and mRNA transcription from proviral DNA and was associated with strong and selective upregulation of the cyclin-dependent kinase inhibitor p21 (also known as cip-1 and waf-1). Experimental blockade of p21 in CD4+ T cells from elite controllers resulted in a marked increase of viral reverse transcripts and mRNA production and led to higher enzymatic activities of cyclin-dependent kinase 9 (CDK9), which serves as a transcriptional coactivator of HIV-1 gene expression. This suggests that p21 acts as a barrier against HIV-1 infection in CD4+ T cells from elite controllers by inhibiting a cyclin-dependent kinase required for effective HIV-1 replication. These data demonstrate a mechanism of host resistance to HIV-1 in elite controllers and may open novel perspectives for clinical strategies to prevent or treat HIV-1 infection.
Histiocytosis X With Pericardial Effusion: Diagnosis Questioned
Authors: David L. Pittman
Journal: JAMA (1982)

<h3>To the Editor.—</h3> I read the article by Peter V. Pickens, MD, and Marc Rosenshein, MD (1981;246:1810). I question their interpretation that the process involving the pericardial space represents infiltration by histiocytosis X cells. Do they have ultrastructural confirmation (which was deleted) that these histiocytic cells contained Langerhans' granules? Langerhans' granules are cytoplasmic organelles observed ultrastructurally, which are present in the neoplastic cells (Langerhans' cells) in histiocytosis X.<sup>1</sup>They are rarely encountered in other diseases. From the published photograph (Fig 2), the cells are entirely consistent with mesothelial cells that are present in pericardial fluid. Mesothelial cells can mimic Langerhans' cells (vesicular nucleus with grooves and abundant acidophilic cytoplasm).<sup>2</sup>The article that they referenced as two cases with pleural involvement is likewise not well documented.<sup>3</sup> I appreciate the clinical possibility that the patient might have pericardial involvement; however, to emphasize I quote from a current surgical pathology
Safety of complementary medicines should be monitored
Authors: H. M. Saw
Journal: BMJ (1996)

The safety profile and observed high acceptability of products containing desogestrel or gestodene allow their continued use, subject to thorough, unbiased counselling in the context of all the recent studies and the letter from the Committee on Safety of Medicines.10The faculty is committed to developing evidence based guidelines, and until further data are available it endorses the guidelines given in the box.
A Simple Way to Record Heart Sounds
Authors: William Dock
Journal: JAMA (1963)

ALTHOUGH LEWIS, in 1909, observed that ligating the coronary arteries produced specific changes in the dog's electrocardiogram and Herrick, in 1918, confirmed this phenomenon in man, over a decade passed before practitioners and even consultants in internal medicine adopted the practice of taking electrocardiograms in cases of suspected coronary obstructive disease. The delay was due largely to the bulky instruments available for recording the cardiac action currents and ended within 5 yr of the introduction of electronic amplifiers and portable machines with small electrodes.  The recording of heart sounds and murmurs was of little value prior to the acceptance of surgery for congenital and then for acquired heart disease. Extensive work in this field, by Einthoven and by Lewis, had been reported by 1914, but even today many thousands of patients have had cardiac catheterization and cardiac surgery without any records of their heart sounds. While auscultation led to
Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice
Authors: Sarah M. King, Rachel A. McNamee, Aiilyan K. Houng, Rakesh Patel, Michael Brands, Guy L. Reed
Journal: Circulation (2009)

Platelet aggregation plays a critical role in myocardial infarction and stroke; however, the role of platelet secretion in atherosclerotic vascular disease is poorly understood. Therefore, we examined the hypothesis that platelet dense-granule secretion modulates thrombosis, inflammation, and atherosclerotic vascular remodeling after injury.Functional deletion of the Hermansky-Pudlak syndrome 3 gene (HPS3(-/-)) markedly reduces platelet dense-granule secretion. HPS3(-/-) mice have normal platelet counts, platelet morphology, and alpha-granule number, as well as maximal secretion of the alpha-granule marker P-selectin; however, their capacity to form platelet-leukocyte aggregates is significantly reduced (P<0.05). To examine the role of platelet dense-granule secretion in these processes, atherosclerosis-prone mice with combined genetic deficiency of apolipoprotein E and HPS3 (ApoE(-/-), HPS3(-/-)) were compared with congenic, atherosclerosis-prone mice with normal platelet secretion (ApoE(-/-), HPS3(+/+)). After 16 to 18 weeks on a high-fat diet, both groups of mice had similar fasting cholesterol levels and body weight. Carotid arteries of ApoE(-/-), HPS3(+/+) mice thrombosed rapidly after FeCl(3) injury, but ApoE(-/-), HPS3(-/-) mice were completely resistant to thrombotic arterial occlusion (P<0.01). Three weeks after injury, neointimal hyperplasia (from alpha-smooth muscle actin-positive cells) was significantly less (P<0.001) in arteries from ApoE(-/-), HPS3(-/-) mice. In ApoE(-/-), HPS3(-/-) mice, there were also pronounced reductions in arterial inflammation, as indicated by a 74% decrease in CD45-positive leukocytes (P<0.01) and a 73% decrease in Mac-3-positive macrophages (P<0.05).In atherosclerotic mice, reduced platelet dense-granule secretion is associated with marked protection against the development of arterial thrombosis, inflammation, and neointimal hyperplasia after vascular injury.
Blood pressure response and renin release following 4 days of treatment with dihydralazine and urapidil in conscious dogs
Authors: S BACHER, O KRAUPP, A BECK, R SEITELBERGER, G RABERGER
Journal: Cardiovascular Research (1984)

The magnitude and the persistence of blood pressure reduction by dihydralazine and urapidil were investigated following treatment over a period of 4 days. The experiments were performed on six normotensive dogs, trained to submit to puncture of the femoral artery and to stand quietly in a special frame. The first-dose effects of orally administered dihydralazine (1.42, 7.1 mg·kg−1) and urapidil (2.0, 10.0 mg·kg−1) on heart rate, arterial blood pressure and plasma renin activity (PRA) were compared with the effects of the substances after 4 days of treatment. Both compounds caused a dose-dependent decrease in blood pressure but in contrast to urapidil the effect of dihydralazine was accompanied by large increases in heart rate and PRA. Dose-dependent tolerance to dihydralazine but not to urapidil was observed after treatment over only 4 days. However, basal blood pressure was significantly lowered after 4 days of treatment with urapidil at the high dosage and no further reduction was achieved on the fifth day. The importance of persistent counterregulation in the development of tolerance to the antihypertensive effect of dihydralazine is discussed.
Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis progression: Proof of concept and first application in a large population
Authors: Thierry Poynard, Mona Munteanu, Olivier Deckmyn, Yen Ngo, Fabienne Drane, Jean Marie Castille, Chantal Housset, Vlad Ratziu, Françoise Imbert-Bismut
Journal: Journal of Hepatology (2012)
Abstract 2518: TAK-733 is a Potent and Selective Inhibitor of Mammalian MEK Kinases Capable of Inducing Apoptosis in BRAF Driven Cells Both <i>in vitro</i> and <i>in vivo</i>
Authors: Robyn Fabrey, O'Connell Shawn, Shuntarou Tsuchiya, Akira Hori, Patrick Vincent
Journal: Cancer Research (2010)

Abstract Mutations in BRAF a serine/threonine protein kinase are frequently observed in human cancers. A valine to glutamic acid mutation at amino acid position 600 accounts for nearly 80% of all the activating mutations found for this kinase. This mutation (V600E) forces BRAF to become constitutively active and phosphorylate its substrates regardless of upstream signaling. Numerous cancers in tissues such as skin, colon, thyroid, and ovary have been attributed to uncontrolled proliferation driven by this mutation. TAK-733 represents a novel and distinct chemotype which is capable of allosteric inhibition of the BRAF substrates MEK-1 and MEK-2 at low nanomolar concentrations. Viability assays in established human cancer cell lines which bear the BRAF V600E mutation demonstrate this compound was also capable of lowering NADH levels with single digit nanomolar EC50s. Loss of NADH production can be attributed to the induction of programmed cell death pathways involving Caspases 3 and 7. Induction of these apoptosis markers was confirmed in vitro by a Caspase-GLO assay. TAK-733 induces apoptosis more potently in COLO 205 (BRAF V600E) human colo-rectal carcinoma cells when compared to other MEK inhibitors. Pharmacodynamic analysis of COLO 205 tumor bearing mice confirmed TAK-733, unlike other MEK inhibitors tested, is capable of inducing apoptosis 36 hours after a single oral administration. To determine whether the anti-tumor effect of TAK-733 is associated with apoptosis, A375 (BRAF V600E) human melanoma tumors were harvested at sacrifice and protein extracted to determine cleavage products of PARP. A single oral treatment with 1, 10, and 30 mg/kg TAK-733 increased protein expression of cleaved PARP in a dose and time dependent manner. Elevated cleaved PARP protein expression was detected as early as 0.5-hours in tumors following 30 mg/kg dose and detectable at all groups by 4-hours. The increase cleaved PARP protein levels persisted for at least 24-hours and returned to control expression levels by 48-hours. Daily oral administration of 1, 10, and 30 mg/kg/day TAK-733 for 14 days potently inhibited tumor growth resulting in tumor growth delay of 3.4, 10.8, and 26.6 days in A375 cell implanted mice. A 60% partial regression response rate (tumor volume reduced by more than 50% of initial volume) was observed in mice that received 30 mg/kg/day TAK-733. These data suggest a possible explanation as to why TAK-733 is capable of inducing regressions in COLO 205 and A375 tumor growth inhibition studies, and may represent a differentiation point from other MEK inhibitors currently in clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2518.
In vivo efficacy of anti-MPL agonist antibody in promoting primary human hematopoietic cells
Authors: Masayuki Kai, Tetsuya Hagiwara, Chie Emuta, Yukiko Chisaka, Kumi Tsuruhata, Chisato Endo, Yoshimasa Inagaki, Hiroshi Miyazaki, Shiro Kataoka
Journal: Blood (2008)
High Risk of IDDM in African-American and Hispanic Children in Chicago, 1985–1990
Authors: Rebecca B Lipton, Julie A Fivecoate
Journal: Diabetes Care (1995)

OBJECTIVE To determine the incidence of insulin-dependent diabetes mellitus (IDDM) among African-American and Hispanic children &amp;lt;18 years of age in the city of Chicago. These minority communities are large and heterogeneous with respect to socioeconomic status, length of time since migration, and place of origin, so that correlates of IDDM risk can be examined with precision. RESEARCH DESIGN AND METHODS Cases occurring during the years 1985–1990 were drawn from records at 37 hospitals in Cook County. African-American and Hispanic patients using insulin, residing within the city limits, and &amp;lt;18 years old at onset were included. Three secondary sources of cases were used: medical records of clinics associated with the Chicago Department of Health, a survey of unaffiliated neighborhood clinics, and lists of children attending diabetes camps. Overall ascertainment was estimated at 86%. RESULTS There were 413 new cases during this 6-year interval. The average incidence of IDDM was 12.0/100,000 annually among African-American males, 12.1 among African-American females, 9.1 among Hispanic males, and 10.2 among Hispanic females. Mean age at onset was 11.1, 11.0, 10.7, and 10.1 years for African-American males, African-American females, Hispanic males, and Hispanic females, respectively. Fewer cases occurred during the summer months. Diabetes among the first-degree relatives of children from both ethnic groups was commonly noted on the medical charts. CONCLUSIONS The incidence rates in Chicago fall near the upper limits of reports for both African-origin and Hispanic populations worldwide. The relatively early age at onset may point to an environmental factor associated with this high incidence of the disease. Further studies will provide valuable data on comorbid conditions, unusual diabetic syndromes, and family dynamics in childhood chronic disease.
Selective inhibition of the reverse transcription of duck hepatitis B virus by binding of 2?,3?-dideoxyguanosine 5?-triphosphate to the viral polymerase
Authors: A Y Howe, M J Robins, J S Wilson, D L Tyrrell
Journal: Hepatology (1996)

Hepatitis B virus (HBV) replication is mediated by the viral polymerase that possesses three functional domains: primer, DNA polymerase/reverse transcriptase, and RNase H. Using the Pekin duck as an animal model, we demonstrate a novel mechanism of inhibition of duck hepatitis B virus (DHBV) by 2,6-diaminopurine 2',3'-dideoxyriboside (ddDAPR), a prodrug of 2',3'-dideoxyguanosine (ddG). A selective and irreversible inhibition of DHBV DNA replication is found in ducklings treated with high doses of ddDAPR (20 to 50 mg/kg), but not with similar doses of 2',3'-dideoxycytidine (ddC). The inhibition mediated by ddDAPR occurs at a very early stage of the reverse transcription. Despite the inhibition of DHBV DNA replication by ddDAPR, the DNA polymerase and reverse transcriptase activities of the polymerase are found to remain active when tested on exogenous templates in activity gels. We have demonstrated direct binding of [alpha-32P]ddGTP to the DHBV polymerase expressed in an in vitro transcription and translation system. These results suggest that the binding of ddGTP to the polymerase blocks the initial DNA replication.
Novel Speckle-Tracking Radial Strain From Routine Black-and-White Echocardiographic Images to Quantify Dyssynchrony and Predict Response to Cardiac Resynchronization Therapy
Authors: Matthew S. Suffoletto, Kaoru Dohi, Maxime Cannesson, Samir Saba, John Gorcsan
Journal: Circulation (2006)

Background— Mechanical dyssynchrony is a potential means to predict response to cardiac resynchronization therapy (CRT). We hypothesized that novel echocardiographic image speckle tracking can quantify dyssynchrony and predict response to CRT. Methods and Results— Seventy-four subjects were studied: 64 heart failure patients undergoing CRT (aged 64±12 years, ejection fraction 26±6%, QRS duration 157±28 ms) and 10 normal controls. Speckle tracking applied to routine midventricular short-axis images calculated radial strain from multiple circumferential points averaged to 6 standard segments. Dyssynchrony from timing of speckle-tracking peak radial strain was correlated with tissue Doppler measures in 47 subjects ( r =0.94, P &lt;0.001; 95% CI 0.90 to 0.96). The ability of baseline speckle-tracking radial dyssynchrony (time difference in peak septal wall–to–posterior wall strain ≥130 ms) to predict response to CRT was then tested. It predicted an immediate increase in stroke volume in 48 patients studied the day after CRT with 91% sensitivity and 75% specificity. In 50 patients with long-term follow-up 8±5 months after CRT, baseline speckle-tracking radial dyssynchrony predicted a significant increase in ejection fraction with 89% sensitivity and 83% specificity. Patients in whom left ventricular lead position was concordant with the site of latest mechanical activation by speckle-tracking radial strain had an increase in ejection fraction from baseline to a greater degree (10±5%) than patients with discordant lead position (6±5%; P &lt;0.05). Conclusions— Speckle-tracking radial strain can quantify dyssynchrony and predict immediate and long-term response to CRT and has potential for clinical application.
Moderate Increase in <i>Mdr1a/1b</i> Expression Causes <i>In vivo</i> Resistance to Doxorubicin in a Mouse Model for Hereditary Breast Cancer
Authors: Marina Pajic, Jayasree K. Iyer, Ariena Kersbergen, Eline van der Burg, Anders O.H. Nygren, Jos Jonkers, Piet Borst, Sven Rottenberg
Journal: Cancer Research (2009)

We have found previously that acquired doxorubicin resistance in a genetically engineered mouse model for BRCA1-related breast cancer was associated with increased expression of the mouse multidrug resistance (Mdr1) genes, which encode the drug efflux transporter ATP-binding cassette B1/P-glycoprotein (P-gp). Here, we show that even moderate increases of Mdr1 expression (as low as 5-fold) are sufficient to cause doxorubicin resistance. These moderately elevated tumor P-gp levels are below those found in some normal tissues, such as the gut. The resistant phenotype could be completely reversed by the third-generation P-gp inhibitor tariquidar, which provides a useful strategy to circumvent this type of acquired doxorubicin resistance. The presence of MDR1A in drug-resistant tumors with a moderate increase in Mdr1a transcripts could be shown with a newly generated chicken antibody against a mouse P-gp peptide. Our data show the usefulness of realistic preclinical models to characterize levels of Mdr1 gene expression that are sufficient to cause resistance.
Selective depletion or blockade of Kupffer cells leads to enhanced and prolonged hepatic transgene expression using high-capacity adenoviral vectors
Authors: Gudrun Schiedner, Sabine Hertel, Marion Johnston, Volker Dries, Nico van Rooijen, Stefan Kochanek
Journal: Molecular Therapy (2003)

Tissue macrophages, in particular hepatic Kupffer cells (KCs), contribute to early inflammatory responses following adenoviral vector administration. This study evaluates the effect of selective and transient (3 days) depletion of KCs by a single injection of clodronate liposomes on the in vivo performance of high-capacity adenoviral (HC-Ad) vectors. In KC-depleted C57BL/6 and C3H mice increased and stabilized hAAT levels were observed following intravenous injection of HC-Ad vectors expressing human α-1 anti-trypsin (hAAT) either from the hAAT promoter or from the human cytomegalovirus promoter. Comparable increases in hAAT levels were obtained in mice preinjected with a transcriptionally silent HC-Ad vector. Interestingly, in the majority of animals of both strains depletion of KCs was sufficient to prevent the generation of anti-hAAT antibodies, resulting in prolonged transgene expression. Thus, short-term and selective depletion of hepatic macrophages at the same time significantly increased hepatic transgene expression and reduced the humoral immune response to the transgenic protein.
Treatment of NIDDM With Insulin Agonists or Substitutes
Authors: John A Galloway
Journal: Diabetes Care (1990)

Non-insulin-dependent diabetes mellitus (NIDDM) is a common disorder occurring in 3–6% of adults in most western populations. In the United States, 29% of patients with diabetes take insulin; of these, 76% have NIDDM. Insulin therapy is usually required at some time in NIDDM. Insulin therapy improves the abnormalities of NIDDM (reduced β-cell function, increased hepatic glucose production, reduced peripheral glucose disposal, lipid abnormalities). Insulin and sulfonylurea agents have comparable effects on mild forms of NIDDM, but for more severe forms, insulin is usually superior. Combination insulin-sulfonylurea treatment may improve the response to sulfonylureas, although long-term well-controlled trials have not been conducted. Short-term insulin treatment may restore response to sulfonylureas. Other promising treatments (human proinsulin, nasal insulin, somatostatin) have not shown any advantage over conventional insulin therapy. Insulin causes hypoglycemia and peripheral hyperinsulinemia. The hazards of hyperinsulinemia, e.g., weight gain and hypoglycemia, have been overstated, and questions about its atherogenic effects remain to be resolved. The effect of glycemic control on macro- and microvascular complications has not been established; however, maintaining fasting blood glucose levels of &amp;lt;6.7 mM may protect against progression of retinopathy, neuropathy, and nephropathy and reduce the severity of ischemic stroke. Dosage algorithms generally use intermediate- or long-acting insulin to control basal glycemia, with regular insulin added before meals if needed to control postprandial glycemia. Effective therapy depends on the patient being informed, cooperative, and willing to self-monitor blood glucose. Insulin treatment intermittency increases the risk for immune complications (resistance and allergy). Overall, patients with NIDDM can benefit from insulin therapy.