tbuckley/cabot-search huggingface dataset:
Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity.
Authors: R I Lehrer, A Barton, K A Daher, S S Harwig, T Ganz, M E Selsted
Journal: Journal of Clinical Investigation (1989)

Defensins are small, cysteine-rich antimicrobial peptides that are abundant in human, rabbit, and guinea pig neutrophils (PMN). Three defensins (human neutrophil peptide defensin [HNP]-1, HNP-2, and HNP-3) constitute between 30 and 50% of the total protein in azurophil granules of human PMN. We examined the mechanism of HNP-mediated bactericidal activity against Escherichia coli ML-35 (i-, y-, z+) and its pBR322-transformed derivative, E. coli ML-35p. Under conditions that supported bactericidal activity, HNP-1 sequentially permeabilized the outer membrane (OM) and inner membrane (IM) of E. coli. Coincident with these events, bacterial synthesis of DNA, RNA, and protein ceased and the colony count fell. Although these events were closely coupled under standard assay conditions, OM permeabilization was partially dissociated from IM permeabilization when experiments were performed with E. coli that had been plasmolyzed by mannitol. Under such conditions, the rate and extent of bacterial death more closely paralled loss of IM integrity than OM permeabilization. Electron microscopy of E. coli that had been killed by defensins revealed the presence of striking electron-dense deposits in the periplasmic space and affixed to the OM. Overall, these studies show that HNP-mediated bactericidal activity against E. coli ML-35 is associated with sequential permeabilization of the OM and IM, and that inner membrane permeabilization appears to be the lethal event.
Notch signalling in smooth muscle cells during development and disease
Authors: C. Fouillade, M. Monet-Lepretre, C. Baron-Menguy, A. Joutel
Journal: Cardiovascular Research (2012)

The Notch signalling pathway is a highly conserved cell–cell signalling mechanism that plays a central role in the development and maturation of most vertebrate organs. In vertebrates, Notch receptors, several ligands, and components of the downstream signalling machinery are expressed in the vessel. Over the past decade, numerous studies have highlighted the critical role of the Notch pathway in the vasculature. The goal of this review is to summarize our current understanding of the contribution of Notch signalling in smooth muscle cells to vascular development and physiology. We further discuss the growing clinical importance of this pathway in human pathological conditions involving the vasculature, namely cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Alagille syndrome, and pulmonary arterial hypertension.
Emergence, origin, and function of neutrophil–dendritic cell hybrids in experimentally induced inflammatory lesions in mice
Authors: Shuo Geng, Hironori Matsushima, Takashi Okamoto, Yi Yao, Ran Lu, Kristen Page, Robert M. Blumenthal, Nicole L. Ward, Toru Miyazaki, Akira Takashima
Journal: Blood (2013)
The Firearm Fatality Reporting System
Authors: Stephen P. Teret, Garen J. Wintemute, Peter L. Beilenson
Journal: JAMA (1992)

RECOMMENDATION: [R]equire that firearm injuries, in addition to being reportable to the police, be reportable to health departments. Place greater emphasis on coding the type of firearm on the death certificate. Develop a national fatal firearm injury reporting system, comparable to FARS [Fatal Accident Reporting System], with sufficient data for documenting the firearm problem and designing prevention strategies. —from<i>Cost of Injury in the United States</i><sup>1</sup> Firearms are the vehicle of death for approximately 34 000 people each year in the United States. The estimated lifetime costs for firearm injuries that occurred in 1985 will be $14.4 billion.<sup>1</sup>Firearm policy, as expressed most often through legislation, is in part health policy. For groups such as young African-American males, for whom almost half of all deaths are caused by gunfire,<sup>2</sup>gun policy may be more influential to their health status than any other form of health policy. But
Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease
Authors: Shigeru Shibata, Miki Nagase, Shigetaka Yoshida, Wakako Kawarazaki, Hidetake Kurihara, Hirotoshi Tanaka, Jun Miyoshi, Yoshimi Takai, Toshiro Fujita
Journal: Nature Medicine (2008)
Growth Hormone Therapy in Critically Ill Patients
Authors: Robert Demling
Journal: New England Journal of Medicine (1999)

In this issue of the Journal, Takala et al.1 report an increase in mortality among critically ill patients treated with growth hormone. This finding is of major importance and will generate considerable debate. The results of the two well-designed, multicenter trials described by Takala et al. call into question the safety of growth hormone therapy in critically ill patients. Previous studies showed that growth hormone in such patients was beneficial or at least did not differ from placebo.We need to compare these two excellent studies carefully with previous trials in order to explain the difference in results. In the . . .
Frequent Recovery of HIV-1 From Genital Herpes Simplex Virus Lesions in HIV-1–Infected Men
Authors: Timothy Schacker, Alexander J. Ryncarz, James Goddard, Kurt Diem, Mary Shaughnessy, Lawrence Corey
Journal: JAMA (1998)

Genital ulcer disease has been epidemiologically linked as a risk factor in the transmission of the human immunodeficiency virus 1 (HIV-1). While herpes simplex virus 2 (HSV-2) is the most common cause of genital ulcers, no study has systematically evaluated the frequency or titer of HIV-1 virus in HSV-2 lesions.To compare lesional HIV-1 RNA levels during and after genital HSV-2 reactivation and to evaluate the frequency, titer, and duration of HIV-1 RNA shedding in lesions due to HSV-2.Convenience sample.Sexually transmitted disease research clinic at the University of Washington, Seattle.Twelve HIV-infected men with a history of symptomatic HSV-2 infection who underwent daily sampling of genital lesions for HIV-1 RNA by polymerase chain reaction assay and HSV-2 by culture.Detection of lesional HIV RNA and HSV-2.HIV-1 RNA was detected from lesional swabs in 25 of 26 consecutively studied HSV-2 episodes and on 67% of days in which genital lesions were noted. The HIV-1 RNA titers in lesional swabs exceeded 10000 copies/mL of swab sample in 75% of samples (range, 2.2-3.2 x 10(5) copies/mL of swab sample). HIV-1 RNA in genital lesion swabs was seen in persons with high and low titers of plasma HIV-1 RNA and was not associated with plasma HIV-1 RNA levels.HIV-1 virions can consistently be detected in genital ulcers caused by HSV-2, which suggests that genital herpes infection likely increases the efficiency of the sexual transmission of HIV-1.
Abstract 652: <i>GPX3</i> promoter hypermethylation predicts platinum sensitivity in colorectal cancer cells.
Authors: Lorraine Pelosof, Sashidhar Yerram, Nilofer Azad, James Herman
Journal: Cancer Research (2013)

Abstract An estimated 52,000 people will die from colorectal cancer (CRC) in 2012 in the U.S. Unfortunately, these tumors do not respond uniformly to the available chemotherapeutic agents and molecular heterogeneity in these tumors is an important factor in determining their sensitivity to the different agents. Epigenetic regulation of gene expression is a critical determinant of normal and tumor cellular phenotypes. By combining tumors’ epigenetic alterations with existing knowledge of drugs’ mechanisms, specific DNA methylation alterations can serve as predictive biomarkers for the efficacy of particular chemotherapeutic agents which can then direct patients’ treatments for improved outcomes. The glutathione peroxidase family of enzymes is a critical cellular antioxidant system and increased glutathione peroxidase activity has been linked to platinum resistance in tumors such as prostate and ovarian cancer. Using methylation-specific PCR (MSP), we demonstrate that the glutathione peroxidase 3 (GPX3) promoter is hypermethylated in six of nine colorectal cancer cell lines and those lines with methylated GPX3 have significantly decreased GPX3 mRNA expression by real-time polymerase chain reaction (RT-PCR). Importantly, the cisplatin IC50 for the CRC cell lines with methylated GPX3 and thus lower GPX3 expression ranges between 2.5 and 6 micromolar compared to 15-50 micromolar in the cell lines with unmethylated GPX3. Initial studies demonstrate similar findings with oxaliplatin. We also examined primary colorectal cancer xenografts and find that 11 of 42 (26%) have GPX3 promoter hypermethylation, with reduction in GPX3 expression also demonstrated for methylated tumors. Analysis is underway to assess the impact that methylated GPX3 has on these primary tumor samples’ sensitivity to platinum agents. To further define the importance of GPX3 promoter hypermethylation in platinum sensitivity, experiments using azacitidine to demethylate GPX3 in cells with methylated GPX3 will be used to determine if increased platinum sensitivity can be restored. Our studies suggest that epigenetically silenced GPX3 may serve as a valuable predictive biomarker for platinum agent sensitivity. Citation Format: Lorraine Pelosof, Sashidhar Yerram, Nilofer Azad, James Herman. GPX3 promoter hypermethylation predicts platinum sensitivity in colorectal cancer cells. [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 652. doi:10.1158/1538-7445.AM2013-652
The gene transfection properties of a lipophosphoramidate derivative with two phytanyl chains
Authors: Mattias F. Lindberg, Nathalie Carmoy, Tony Le Gall, Aurore Fraix, Mathieu Berchel, Christophe Lorilleux, Hélène Couthon-Gourvès, Pascale Bellaud, Alain Fautrel, Paul-Alain Jaffrès, Pierre Lehn, Tristan Montier
Journal: Biomaterials (2012)
Training of the Medical Technologist
Authors: Elinor Judd
Journal: New England Journal of Medicine (1951)

IN 1928 the American Society of Clinical Pathologists established the registry examination. Until 1933 any medical technologist in the field was eligible for registration. Until 1938 one year of college with certain minimal sciences was required. Until 1948 two years of college study including courses in certain sciences constituted the eligibility requirement for examination. In 1948 an additional year in an approved school of medical technologists — that is, one year of rotating laboratory internship — was added to these standards. A third year of college is now forecast in a United States Department of Labor report on employment outlook. . . .
Enhancement of bone–titanium integration profile with UV-photofunctionalized titanium in a gap healing model
Authors: Takeshi Ueno, Masahiro Yamada, Takeo Suzuki, Hajime Minamikawa, Naoko Sato, Norio Hori, Kazuo Takeuchi, Masami Hattori, Takahiro Ogawa
Journal: Biomaterials (2009)
CEA for monitoring colon cancer
Authors: A. M. Cohen
Journal: JAMA (1994)

To the Editor.  —Moertel and colleagues 1 are unable to see the trees for the forest. The incremental overall survival benefit in patients with elevated CEA levels in their cohort of patients is slightly less than 1%. However, a larger group of patients actually benefited in that they underwent potentially curative reoperation, particularly hepatic resection.  Probable outcomes in the operative treatment of hepatic metastases from colorectal cancer should be related to patient subsets. There are approximately 150 000 new colorectal cancer patients per year, patients with early cancers and synchronous metastases are excluded, and so there are about 100 000 patients to be followed up. One half of these cancers will recur (50 000); one third of these will have only liver disease (17 000) 2 ; one third of these will have resectable hepatic metastases (5500) 3 ; and one third of these will be cured (1850). 4,5 Hence, the incremental
Genetic and environmental influences on symptomatic gallstone disease: A Swedish study of 43,141 twin pairs
Authors: Despina Katsika, Andrej Grjibovski, Curt Einarsson, Frank Lammert, Paul Lichtenstein, Hanns‐Ulrich Marschall
Journal: Hepatology (2005)

The contribution of hereditary and environmental factors to the pathogenesis of symptomatic gallstone disease is still unclear. We estimated the relative importance of genetic and environmental factors by analyzing a large population of twins. For this purpose, the Swedish Twin Registry was linked with the Swedish inpatient-discharge and causes of death registries for symptomatic gallstone disease and gallstone surgery–related diagnoses in 43,141 twin pairs born between 1900 and 1958. Concordance rates, correlations, and odds ratios were calculated for males, females, monozygotic, and dizygotic twins, respectively, as well as for twin pairs of opposite sex. Structural equation modeling techniques were used to estimate the contributions of genetic effects as well as shared and non-shared environmental factors to the development of symptomatic gallstone disease. We found that concordances and correlations were higher in monozygotic compared with dizygotic twins, both for males and females. Of note, there were no significant sex differences in heritability. In the full model, genetic effects accounted for 25% (95% CI, 9%–40%), shared environmental effects for 13% (95% CI, 1%–25%), and unique environmental effects for 62% (95% CI, 56%–68%) of the phenotypic variance among twins. In conclusion, our results show heritability to be a major susceptibility factor for symptomatic gallstone disease, consistent with results from previous, much smaller studies. (HEPATOLOGY 2005.)
Myelodysplastic syndromes: 2011 update on diagnosis, risk‐stratification, and management
Authors: Guillermo Garcia‐Manero
Journal: American Journal of Hematology (2011)

The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male and in individuals with prior exposure to cytotoxic therapy.Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, or molecular genetics is complementary but not diagnostic. RISK-STRATIFICATION: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics. The most commonly used system is the International Prognostic Scoring System. This score divides patients into a lower risk subset (low and intermediate-1) and a higher risk subset (int-2 and high). Other more modern systems have been developed that allow more precise risk calculation.Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts and more recently cytogenetic profile. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia, and a chromosome 5 alteration. 5-azacitidine and decitabine have activity in higher risk MDS. 5-azacitidine has been shown to improve survival in higher risk MDS. Additional supportive care measures may include the use of prophylactic antibiotics and iron chelation.At the present time, there are no approved interventions for patients with progressive or refractory disease particularly after hypomethylating based therapy. Options include cytarabine-based therapy, transplantation, and participation on a clinical trial.
Abstract 3319: Cell cycle regulation of glioblastoma progression by cord blood stem cells is mediated by downregulation of cyclin D1
Authors: Kiran Kumar Velpula, Venkata Ramesh Dasari, Andrew J. Tsung, Christopher S. Gondi, Jeffrey D. Klopfenstein, Sanjeeva Mohanam, Jasti S. Rao
Journal: Cancer Research (2011)

Abstract Normal progression of the cell cycle requires sequential expression of cyclins. Rapid induction of cyclin D1 and its associated binding with cyclin-dependent kinases, in the presence or absence of mitogenic signals, is considered a rate-limiting step during cell cycle progression through the G1 phase. In the present study, human umbilical cord blood stem cells (hUCBSC) co-cultured with glioblastoma cells (U251 and 5310) not only induced G0-G1 phase arrest, but also reduced the number of cells at the S and G2-M phases of the cell cycle. Western and FACS analyses of cell cycle regulatory proteins showed decreased expression levels upon treatment with hUCBSC. Co-localization experiments under in vivo conditions in nude mice brain xenografts with cyclin D1 and CD81 antibodies demonstrated decreased expression of cyclin D1 in the presence of hUCBSC. Treatment with hUCBSC decreased expression of the cyclin D1 and CDK4 complex as well as cyclin D1 and CDK6 complexes. However, there was no significant change in the CDK4 and CDK6 complex. Our results indicate that hUCBSC can attenuate uncontrolled cell cycle progression of glioma cells by downregulating the expression levels of cyclin D1 and its partner kinases CDK4 and CDK6 at the cell cycle level. Our data elucidate a model to regulate glioma cell cycle progression in which hUCBSC act to control cyclin D1 induction and its partner kinases, CDK4 and CDK6, by mediating cell cycle arrest via G0-G1 arrest. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3319. doi:10.1158/1538-7445.AM2011-3319
Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid–dependent, persistent asthma☆☆☆★★★
Authors: Gail Shapiro, Louis Mendelson, Michael J. Kraemer, Mario Cruz-Rivera, Karen Walton-Bowen, Joseph A. Smith
Journal: Journal of Allergy and Clinical Immunology (1998)
Perception of changes in wall tension of the proximal stomach in humans
Authors: H Piessevaux, J Tack, A Wilmer, B Coulie, A Geubel, J Janssens
Journal: Gut (2001)

Hypersensitivity to distension of the stomach is a frequent finding in functional dyspepsia. During gastric distension studies both wall tension and elongation are increased.We wished to distinguish changes in wall tension from changes in elongation in the genesis of perception of mechanical stimuli originating from the proximal stomach in healthy subjects.Twenty six volunteers were studied using gastric barostat and antroduodenal manometry. In 14 subjects, stepwise isobaric and isovolumetric distensions were performed before and during erythromycin infusion. In all volunteers, on a separate occasion, phasic contractions of the proximal stomach were detected as intraballoon pressure increases during fixed volume inflation. These contractions were matched with perception changes during two 10 minute periods, before and during administration of erythromycin.Erythromycin significantly lowered the perception and discomfort thresholds during stepwise gastric distension. During fixed volume inflation, erythromycin increased the number and amplitude of fundic contractions and enhanced their perception from 51.1 (7.4)% to 64.0 (4.7)%. The proportion of perception score increases coinciding with fundic contractions increased from 47.3 (0.7)% to 81.5 (0.5)%. The amplitude of correctly identified isolated fundic pressure waves was higher compared with non-identified waves.These results support the hypothesis that changes in gastric wall tension may be involved in the genesis of symptoms originating from the stomach.
CLINICAL IMPACT OF RELATIONSHIP BETWEEN ANKLE-BRACHIAL INDEX AND CORONARY ARTERY LESION COMPLEXITY : A SUBANALYSIS OF THE SHINANO-REGISTRY
Authors: Naoto Hashizume, Takashi Miura, Yusuke Miyashita, Kentaro Shimada, Masanori Kobayashi, Hiroyuki Nakajima, Hikaru Kimura, Takahiro Sakai, Hiroshi Akanuma, Eiichiro Mawatari, Toshio Sato, Shoji Hotta, Uichi Ikeda
Journal: Journal of the American College of Cardiology (2014)
Incidence, Predictors, and Outcomes of Aortic Regurgitation After Transcatheter Aortic Valve Replacement
Authors: Ganesh Athappan, Eshan Patvardhan, E. Murat Tuzcu, Lars Georg Svensson, Pedro A. Lemos, Chiara Fraccaro, Giuseppe Tarantini, Jan-Malte Sinning, Georg Nickenig, Davide Capodanno, Corrado Tamburino, Azeem Latib, Antonio Colombo, Samir R. Kapadia
Journal: Journal of the American College of Cardiology (2013)
Heterogeneous myocardial fluorodeoxyglucose uptake is associated with nonuniform left ventricular function in patients with hypertrophic cardiomyopathy
Authors: Pasquale Perrone-Filardi, Simone Maurea, Liisa-Maria Voipio-Pulkki, Stephen L. Bacharach, Vasken Dilsizian, Beate H.B. Scheffknecht, Joseph A. Frank, Robert O. Bonow
Journal: Journal of the American College of Cardiology (1991)
Limitations in the Feasibility of Pulmonary Embolectomy
Authors: RAY W. GIFFORD, LAURENCE K. GROVES
Journal: Circulation (1969)

Of 101 patients who had major pulmonary emboli confirmed at autopsy, 44 died within 1 hour of the onset of symptoms; 26 had no abrupt change in the clinical course to indicate the presence of emboli; and three died while they were under anesthesia. Of the 28 patients who survived for more than 1 hour after onset of symptoms, seven had incurable malignant lesions, four were unconscious with irreversible brain damage, six were too ill from other diseases to undergo embolectomy, and the diagnosis was not suspected for five. Consequently, of the 101 patients only six would have been selected to undergo pulmonary embolectomy. Only by increasing our diagnostic acumen and by obtaining pulmonary angiograms as soon as possible after onset of symptoms can this salvage rate be improved.