tbuckley/cabot-search huggingface dataset:
Abstract 3844: K-Ras is required for maintaining survivin protein stability in human cancer cells harboring mutant but not wild type K-Ras
Authors: Awet Tecleab, Said M. Sebti
Journal: Cancer Research (2011)

Abstract The anti-apoptotic protein survivin is maintained at high levels in cancer cells relative to normal cells. The mechanism by which this occurs is ill-understood. Here we show in several human cancer cell lines including those derived from pancreatic, lung and ovarian cancers that knocking down K-Ras expression by siRNA results in decreased survivin levels in cancer cells harboring mutant but not wild type K-Ras. K-Ras knockdown decreases survivin mRNA and protein levels by 50% and 85%, respectively, suggesting that K-Ras regulates survivin transcription as well as protein stability. Consistent with this K-Ras knockdown decreases the levels of ectopically-expressed Myc-tagged survivin. Further support for the ability of K-Ras to regulate the protein stability of survivin is also supported by the fact that the proteasome inhibitor Velcade partially inhibits K-Ras siRNA from decreasing the levels of survivin. Taken together, the data suggest that K-Ras is a contributor to the maintenance of high levels of survivin in human cancer cells which harbor mutant but not wild type K-Ras. 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 3844. doi:10.1158/1538-7445.AM2011-3844
The vomeronasal organ and chemical sensitivity: a hypothesis.
Authors: Glenn J Greene, Howard M Kipen
Journal: Environmental Health Perspectives (2002)

Environmental exposures to very low levels of airborne chemicals are associated with adverse symptoms, often affecting multiple organ systems, in the phenomenon of chemical sensitivity (CS). Recent surveys suggest a significant prevalence of chemically sensitive subjects in the United States, but the mechanism linking exposure to symptoms remains unclear, despite the advancement of a variety of theoretical models. In many of these models, exposure of the nasal respiratory system to an airborne agent is the first step in the pathway leading to symptoms. In this article, we advance the hypothesis that interactions between environmental chemicals and the vomeronasal organ (VNO) may play a role in the etiology of CS. The VNO, a bilateral, tubular organ located in the nose, serves in animals as part of a sensitive chemosensory system; however, evidence suggesting that the VNO retains a functional role in the adult human is controversial. Reported characteristics of the human VNO relevant to CS, including location, prevalence, selective sensitivity to airborne chemical exposure, and capacity to produce systemic effects, are discussed within the context of this ongoing debate. Beyond relevance to CS, the demonstration of an active, adult VNO could have significant impact on environmental toxicology.
The role of the immune system in hexachlorobenzene-induced toxicity.
Authors: C C Michielsen, H van Loveren, J G Vos
Journal: Environmental Health Perspectives (1999)

Hexachlorobenzene (HCB) is a persistent environmental pollutant. The toxicity of HCB has been extensively studied after an accidental human poisoning in Turkey and more recently it has been shown that HCB has immunotoxic properties in laboratory animals and probably also in man. Oral exposure of rats to HCB showed stimulatory effects on spleen and lymph node weights and histology, increased serum IgM levels, and an enhancement of several parameters of immune function. Moreover, more recent studies indicate that HCB-induced effects in the rat may be related to autoimmunity. In Wistar rats exposed to HCB, IgM antibodies against several autoantigens were elevated; in the Lewis rat, HCB differently modulated two experimental models of autoimmune disease. Oral exposure of rats to HCB induces skin and lung pathology in the rat. Recently several studies have been conducted to investigate whether these skin and lung lesions can be related to HCB-induced immunomodulation, and these studies will be discussed in this review. HCB-induced skin and lung lesions probably have a different etiology; pronounced strain differences and correlation of skin lesions with immune parameters suggest a specific involvement of the immune system in HCB-induced skin lesions. The induction of lung lesions by HCB was thymus independent. Thymus-dependent T cells were not likely to be required for the induction of skin lesions, although T cells enhanced the rate of induction and the progression of the skin lesions. No deposition of autoantibodies was observed in nonlesional or lesional skin of HCB-treated rats. Therefore, we concluded that it is unlikely that the mechanism by which most allergic or autoimmunogenic chemicals work, i.e., by binding to macromolecules of the body and subsequent T- and B-cell activation, is involved in the HCB-induced immunopathology in the rat. Such a thymus-independent immunopathology is remarkable, as HCB strongly modulates T-cell-mediated immune parameters. This points at a very complex mechanism and possible involvement of multiple factors in the immunopathology of HCB.
Initial contact and subsequent adhesion of human neutrophils or monocytes to human aortic endothelial cells releases an endothelial intracellular calcium store.
Authors: R C Ziegelstein, S Corda, R Pili, A Passaniti, D Lefer, J L Zweier, A Fraticelli, M C Capogrossi
Journal: Circulation (1994)

Increases in both leukocyte and endothelial cytosolic free [Ca2+] may be involved in intercellular adhesion by regulating the affinity of surface adhesion molecules or by facilitating transendothelial leukocyte migration. The purpose of this study was to examine the effect of initial contact and subsequent adhesion of human neutrophils or monocytes on human aortic endothelial [Ca2+].Endothelial monolayers were loaded with the fluorescent Ca2+ indicator indo 1 and exposed to isolated human peripheral blood neutrophils or to a cultured human monocyte cell line. A rapid, fourfold to fivefold increase in endothelial cytosolic [Ca2+] occurred within seconds of leukocyte contact. No increase in endothelial [Ca2+] occurred on contact of 18.25-microns inert microspheres, isolated red blood cells, or suspensions of cultured human aortic endothelial cells. In experiments performed on monolayers grown in 1-mm2 capillary flow tubes, the increase in endothelial cytosolic [Ca2+] on initial leukocyte contact was found to be related to the subsequent resistance to leukocyte detachment during exposure to arterial levels of shear stress (13.4 dyne.cm-2). The increase in endothelial cytosolic [Ca2+] during leukocyte contact was not inhibited in Ca(2+)-free buffer but was abolished by prior depletion of an endoplasmic reticulum Ca2+ store by thapsigargin. Pretreatment of neutrophils with R15.7, a specific monoclonal antibody to the adhesion protein CD-18, inhibited the increase in endothelial cytosolic [Ca2+] on neutrophil contact.Initial contact leading to subsequent adhesion of human leukocytes to human aortic endothelial cells releases an endothelial intracellular Ca2+ store. This may, in part, be mediated by specific adhesion proteins and may in turn regulate the affinity of surface adhesion molecules or facilitate transendothelial migration of leukocytes.
Conflicts of interest in guideline panel members
Authors: E. A. M. Gale
Journal: BMJ (2011)

A change in the culture of medicine is needed; legislation is not enough

It has been said that “it is difficult to get a man to understand something when his salary depends upon his not understanding it,”1 and the medical profession has been slow to understand the importance of conflicts of interest. The linked study by Neuman and colleagues (doi:10.1136/bmj.d5621) reports the prevalence of financial conflicts among guideline panel members in the United States and Canada. Of the 14 guidelines considered, six came from government sponsored organisations, six from specialist or professional organisations, and two from private non-profit organisations; three were from Canada and the remainder from the US. Five (four government sponsored) guidelines provided no conflict of interest statement, but their participants had presumably been screened, because only four of 77 panellists seemed to have a conflict. Six of 12 named chairpersons had a conflict, as did 138 of the 211 panellists who provided a disclosure statement; 12 more failed to disclose an interest, and 10 others received research funding from industry. Only 61 (29%) had no potential financial ties.2

The guidelines in question related to the management of diabetes and hyperlipidaemia, …
New vectorcardiographic criteria for diagnosing right ventricular hypertrophy in mitral stenosis: comparison with electrocardiographic criteria.
Authors: C D Cowdery, G S Wagner, J W Starr, G Rogers, J C Greenfield
Journal: Circulation (1980)

Frank-lead vectorcardiograms (VCGs) and standard 12-lead electrocardiograms (ECGs) were analyzed to develop simple, linear, quantitative criteria for the diagnosis of right ventricular hypertrophy (RVH). The study subjects included a population with a definite RVH (84 patients with mitral stenosis proved by cardiac catheterization and pulmonary arterial systolic pressure &gt; 40 mm Hg) and a population with minimal likelihood of RVH (173 young, healthy volunteers and 151 normal subjects proved by cardiac catheterization). VCGs were evaluated to identify criteria that provided maximum sensitivity and at least a 95% specificity: the maximum QRS magnitude had to be &lt; 1.8 mV and either (1) the amplitude at -45 degrees (transverse plane) had to be &lt; 0.3 mV or (2) the maximum anterior amplitude plus the maximum rightward amplitude minus the amplitude at -45 degrees must be greater than or equal to 0.5 mV. Application of these criteria achieved 60% (50 of 84) sensitivity in patients with RVH, similar to that for previous VCG criteria but significantly better (p &lt; 0.01) than the best sensitivity with any ECG criteria (27%, 23 of 84). The specificity of the proposed criteria was 96% (310 of 324), significantly better (p &lt; 0.001) than the 78% specificity (252 of 324) of existing VCG criteria. Thus, linear measurements of the QRS complex displayed on the VCG identify 60% of patients with moderate-to-severe RVH and falsely indicate RVH in only 4% of normal subjects.
Once weekly rosuvastatin is useful in statin intolerance
Authors: D. Macaulay
Journal: BMJ (2012)

<h3>Background</h3> We report a case of a young male athlete who sustained a three column displaced teardrop fracture of the C5 vertebra due to a head-first impact in hockey, suffered neurapraxia, yet made full neurological recovery. This full recovery was in sharp contrast to multiple case series which reported permanent quadriplegia in the vast majority of teardrop fracture patients. We investigate the etiology and biomechanical mechanisms of injury. <h3>Methods</h3> Admission imaging revealed the teardrop fracture which consisted of: a frontal plane fracture which separated an anterior quadrilateral-shaped fragment from the posterior vertebral body; a vertical fracture of the posterior vertebral body in the sagittal plane; and incomplete fractures of the neural arch that initiated superiorly at the anterior aspect of the spinous process and left lamina adjacent to the superior facet. Epidural hematoma in the region of the C5 vertebra was observed in addition to disc and ligamentous disruptions at C4-5 and C5-6. Our patient was ultimately treated surgically with anterior fusion from C4 through C6 and subsequently with bilateral posterior fusion at C5-6. <h3>Results</h3> The injuries were caused by high-energy axial compression with the neck in a pre-flexed posture. The first fracture event consisted of the anterior vertebral body fragment being sheared off of the posterior fragment under the compression load due in part to the sagittal plane concavity of the C5 inferior endplate. The etiology of the vertical fracture of the posterior vertebral body fragment in the sagittal plane was consistent with a previously described hypothesis of the mechanistic injury events. First, the C4-5 disc height decreased under load which increased its hoop stress. Next, this increased hoop stress transferred lateral forces to the C5 uncinate processes which caused their outward expansion. Finally, the outward expansion of the uncinate processes caused the left and right sides of the vertebral body to split and spread. Evidence in support of this mechanistic event sequence was provided by the neural arch fractures which initiated superiorly, average angulation of the C5 uncinate processes, and similar well-established mechanisms causing vertical fractures at other spinal regions. <h3>Conclusions</h3> Our case study and analyses provide insight into the etiology of the specific teardrop fracture patterns observed clinically.
Laparoscopic study of peliosis hepatis and nodular transformation of the liver before and after renal transplantation: natural history and aetiology in follow-up cases
Authors: Satoru Izumi, Meiko Nishiuchi, Yoshio Kameda, Shunsuke Nagano, Takanobu Fukunishi, Takashi Kohro, Yoshitake Shinji
Journal: Journal of Hepatology (1994)
Brief Communication: Cardiovascular Screening Practices of Major North American Professional Sports Teams
Authors: Kevin M. Harris, Austin Sponsel, Adolph M. Hutter, Barry J. Maron
Journal: Annals of Internal Medicine (2006)

Background: Customary preparticipation screening strategies to detect heart disease in professional athletes have not been examined systematically. Objective: To describe the current preparticipation cardiovascular screening process for professional athletes. Design: Screening practices surveyed by questionnaire. Setting: The 122 major professional sports teams in North America. Participants: Athletic trainers and team physicians. Measurements: League recommendations for history taking and physical examination and noninvasive testing were compared with screening recommendations from an American Heart Association consensus panel. Results: All 122 teams have team physicians perform annual screening, including family and personal history taking (100%), physical examination (100%), and lipid panels (108 of 122 [89%]). Diagnostic testing by using electrocardiography was substantially more common (112 of 122 [92%]) than exercise testing and stress echocardiography (21 of 122 [17%]) or echocardiography (16 of 122 [13%]). League recommendations for history taking and physical examination were most complete for Major League Baseball and the National Hockey League, meeting 10 of 12 and 8 of 12 American Heart Association recommendations, respectively. The most comprehensive cardiovascular screening using echocardiography is confined to selected, elite professional basketball players. Limitations: Data were self-reported by team representatives. Conclusions: A variety of nonstandardized preparticipation screening strategies for the detection of cardiovascular disease, varying considerably in scope, constitute customary practice among professional sports teams.
Tibial Lesion in a Laotian Girl
Authors: Deborah L. Day
Journal: JAMA (1985)

<h3>History</h3> A 14-year-old Laotian girl presented with a history of persistent and increasing pain in the proximal segment of the left leg after being hit with a hockey stick one month before. Over the past several months, she had a 6.8- to 9.0-kg (15- to 20-lb) weight loss and had recently experienced lethargy and fever with temperature to 38.8 °C (102 °F). The patient had spent the first 12 years of life in Laos. While she was in Laos just prior to her arrival in the United States, a "lump" in the right side of her neck had been resected. Information covering the pathological interpretation of the sections obtained from the resected mass in the neck is withheld. Physical examination showed a cachectic Laotian girl with a tender, swollen left leg in its proximal segment. Cervical adenopathy and a 1.5×1.5-cm right supraclavicular mass were present. A roentgenogram of the left
Mandatory Premarital Rubella Serologic Testing in Colorado
Authors: Franklyn N. Judson
Journal: JAMA (1974)

On July 1, 1971, a Colorado law went into effect requiring a serologic test for rubella of each female marriage license applicant. During the first 18 months, 22,785 sera were processed; of these, 3,281 (14.4%) were negative (hemagglutination inhibition titer, &lt;10). The results provide an ongoing indicator of the immunity levels of Colorado women entering their childbearing years. Only 248 of 878 women reported to be seronegative during June and July 1972 could be located after marriage. Of 230 women who completed questionnaires, 95 (41%) had been immunized. Of 135 women not immunized, 39 (29%) had made plans to do so, 28 (21%) were pregnant, 34 (25%) were either sterile, using contraceptives, or otherwise avoiding pregnancy, and 34 (25%) gave other responses. (<i>JAMA</i>229:1200-1202, 1974)
A CONSIDERATION OF SPEECH DEFECTS.
Authors: JAMES M. BROWN
Journal: JAMA (1904)

In laryngologic practice attention is frequently directed to cases of defective speech, and it is hard to realize how so important a branch of medicine is almost wholly ignored by the profession. The treatment of these distressful ailments is left, with few exceptions, to the advertising quacks, each of whom has his separate guaranteed quick method, which, on investigation, has been proved unsuccessful. All forms of speech defects, known by various terms as dyslalia, magilalia, lallamania, balbuties and psellism, have been generally classified as stammering and stuttering, with the exception of lisping, which is the most difficult of speech defects to correct. Considerable ignorance of this subject prevails among those who have the care of children, and in children defects of speech are comparatively common. Speech defect is usually observed first between the ages of five and fifteen, and is productive of much distress, and often results seriously. The average
Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone
Authors: Vanesa C. Sanchez, Jorge Goldstein, Ronald C. Stuart, Virginia Hovanesian, Lihong Huo, Heike Munzberg, Theodore C. Friedman, Christian Bjorbaek, Eduardo A. Nillni
Journal: Journal of Clinical Investigation (2004)

Regulation of energy balance by leptin involves regulation of several neuropeptides, including thyrotropin-releasing hormone (TRH). Synthesized from a larger inactive precursor, its maturation requires proteolytic cleavage by prohormone convertases 1 and 2 (PC1 and PC2). Since this maturation in response to leptin requires prohormone processing, we hypothesized that leptin might regulate hypothalamic PC1 and PC2 expression, ultimately leading to coordinated processing of prohormones into mature peptides. Using hypothalamic neurons, we found that leptin stimulated PC1 and PC2 mRNA and protein expression and also increased PC1 and PC2 promoter activities in transfected 293T cells. Starvation of rats, leading to low serum leptin levels, decreased PC1 and PC2 gene and protein expression in the paraventricular nucleus (PVN) of the hypothalamus. Exogenous administration of leptin to fasted animals restored PC1 levels in the median eminence (ME) and the PVN to approximately the level found in fed control animals. Consistent with this regulation of PCs in the PVN, concentrations of TRH in the PVN and ME were substantially reduced in the fasted animals relative to the fed animals, and leptin reversed this decrease. Further analysis showed that proteolytic cleavage of pro–thyrotropin-releasing hormone (proTRH) at known PC cleavage sites was reduced by fasting and increased in animals given leptin. Combined, these findings suggest that leptin-dependent stimulation of hypothalamic TRH expression involves both activation of trh transcription and stimulation of PC1 and PC2 expression, which lead to enhanced processing of proTRH into mature TRH.
KRAS Mutations in Colorectal Cancer Patients in Serbia: 5 Years Experience of Central Testing
Authors: Jankovic Radmila, Brotto Ksenija, Malisic Emina, Krivokuca Ana, Cavic Milena, Jovanovic Katarina, Boljevic Ivana, Tanic Miljana, Radulovic Sinisa
Journal: Annals of Oncology (2014)
Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite
Authors: S. Vavricka, R. Tutuian, A. Imhof, S. Wildi, C. Gubler, H. Fruehauf, C. Ruef, A. Schoepfer, M. Fried
Journal: Endoscopy (2010)

Background and study aims: Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination.
Once Identified, Will High-Risk Families Make Life-style Changes, Lower Coronary Disease Rate?
Authors: Jody W. Zylke
Journal: JAMA (1987)

BLUE EYES or curly hair run in some families. In others, however, it's heart disease, and some new approaches to this problem are taking form.  Coronary heart disease occurring before age 55 years strikes only 3% to 8% of families in the general population. But it accounts for 40% to 60% of coronary deaths, according to Roger R. Williams, MD, professor of internal medicine, University of Utah School of Medicine, Salt Lake City.  In high-risk families, two or more first-degree relatives are afflicted. Currently healthy relatives of these people have a greater chance of someday developing coronary heart disease, perhaps five to ten times higher.  To obtain information on such families, Williams and associates have been working since 1976 on gathering pedigrees and tracking down medical records. They have collected and computerized genealogies of 1.2 million persons in four to six generations, obtained information from 140 000 death certificates, and