tbuckley/cabot-search huggingface dataset:
Accessory Subunit KChIP2 Modulates the Cardiac L-Type Calcium Current
Authors: Morten B. Thomsen, Chaojian Wang, Nazira Özgen, Hong-Gang Wang, Michael R. Rosen, Geoffrey S. Pitt
Journal: Circulation Research (2009)

Complex modulation of voltage-gated Ca2+ currents through the interplay among Ca2+ channels and various Ca(2+)-binding proteins is increasingly being recognized. The K+ channel interacting protein 2 (KChIP2), originally identified as an auxiliary subunit for K(V)4.2 and a component of the transient outward K+ channel (I(to)), is a Ca(2+)-binding protein whose regulatory functions do not appear restricted to K(V)4.2. Consequently, we hypothesized that KChIP2 is a direct regulator of the cardiac L-type Ca2+ current (I(Ca,L)). We found that I(Ca,L) density from KChIP2(-/-) myocytes is reduced by 28% compared to I(Ca,L) recorded from wild-type myocytes (P<0.05). This reduction in current density results from loss of a direct effect on the Ca2+ channel current, as shown in a transfected cell line devoid of confounding cardiac ion currents. I(Ca,L) regulation by KChIP2 was independent of Ca2+ binding to KChIP2. Biochemical analysis suggested a direct interaction between KChIP2 and the Ca(V)1.2 alpha(1C) subunit N terminus. We found that KChIP2 binds to the N-terminal inhibitory module of alpha(1C) and augments I(Ca,L) current density without increasing Ca(V)1.2 protein expression or trafficking to the plasma membrane. We propose a model in which KChIP2 impedes the N-terminal inhibitory module of Ca(V)1.2, resulting in increased I(Ca,L). In the context of recent reports that KChIP2 modulates multiple K(V) and Na(V) currents, these results suggest that KChIP2 is a multimodal regulator of cardiac ionic currents.
THE "ADEQUATE RELAXATION INTERIM" FOLLOWING SUCCINYLCHOLINE ADMINISTRATION IN ELECTROSHOCKTHERAPY
Authors: CHARLES BUCKMAN, ARTHUR KRELL, IRVING PINSLEY, ARTHUR S. IMPASTATO, DAVID J. IMPASTATO
Journal: American Journal of Psychiatry (1960)

The foregoing investigation demonstrates that the SCC injection causes relaxation lasting for a variable time depending upon the EST technic used. With the classic AC treatment the interim begins 20 seconds following the appearance of perioral fasciculations and lasts for 20 seconds. With the PM-GM technic the interim begins in 10 seconds and lasts 70 seconds. After 40 seconds with the Standard Technic and 70 seconds with the PM-GM Technic, the degree of relaxation lessened and treatments given at this time or later are potentially capable of producing injury. It may therefore be concluded that with the Standard Technic, without using barbiturates and quickly injecting 15 mg. of SCC, one should not wait longer than 40 seconds after the onset of perioral fasciculations. To administer the grand mal with the PM-GM Technic it is apparently [see source pdf figure 2] safe to wait up to 70 seconds. We were surprised to discover that the double petit mal greatly prolonged the "adequate relaxation interim." A possible explanation for this might be that the petit mal application releases acetylcholine which re-enforces and prolongs the action of SCC. Further study to discover the actual reason why the petit mal re-enforces and prolongs the action of SCC, should be undertaken.
A Cluster of Olfactory Receptor Genes Linked to Frugivory in Bats
Authors: Sara Hayden, Michaël Bekaert, Alisha Goodbla, William J. Murphy, Liliana M. Dávalos, Emma C. Teeling
Journal: Molecular Biology and Evolution (2014)

Diversity of the mammalian olfactory receptor (OR) repertoire has been globally reshaped by niche specialization. However, little is known about the variability of the OR repertoire at a shallower evolutionary timeframe. The vast bat radiation exhibits an extraordinary variety of trophic and sensory specializations. Unlike other mammals, bats possess a unique and diverse OR gene repertoire. We elucidated whether the evolution of the OR gene repertoire can be linked to ecological niche specializations, such as sensory modalities and diet. The OR gene repertoires of 27 bat species spanning the chiropteran radiation were amplified and sequenced. For each species, intact and nonfunctional genes were assessed, and the OR gene abundances in each gene family were analyzed and compared. We identified a unique OR pattern linked to the frugivorous diet of New World fruit-eating bats and a similar convergent pattern in the Old World fruit-eating bats. Our results show a strong association between niche specialization and OR repertoire diversity even at a shallow evolutionary timeframe.
Routine Preventive Care and Cancer Surveillance in Long-Term Survivors of Colorectal Cancer: Results From National Surgical Adjuvant Breast and Bowel Project Protocol LTS-01
Authors: Hiroko Kunitake, Ping Zheng, Greg Yothers, Stephanie R. Land, Louis Fehrenbacher, Jeffrey K. Giguere, Lawrence Wickerham, Patricia A. Ganz, Clifford Y. Ko
Journal: Journal of Clinical Oncology (2010)

National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol LTS-01 examines routine preventive care and cancer surveillance in long-term colorectal cancer (CRC) survivors previously treated in NSABP adjuvant trials.Long-term CRC survivors (≥5 years) from five completed NSABP trials (Protocols C-05, C-06, C-07, R-02, and R-03) at 60 study sites were recruited and surveyed using preventive health care items from the National Health Interview Survey (NHIS). A 3:1 comparison cohort case-matched by age, sex, race, and education was created from the 2005 NHIS. Contingency tables and multivariate models were used to compare cohorts and determine predictors of preventive care and cancer surveillance.A total of 708 patients in protocol LTS-01 (681 patients with colon cancer, 27 patients with rectal cancer) completed the interview: 57.1% male, mean age 66.2 years (standard deviation=10.6), median survival 8 years. Patients in the LTS-01 protocol were more likely to have a usual source of health care (97.7% v 93.8%, P<.0001), have received a flu shot in the past 12 months (67.5% v 44.3%, P<.0001), and have undergone cancer screening by Pap smear (67.3% v 54.8%, P<.0001), mammogram (80.4% v 70.7%, P<.0001), and prostate-specific antigen test (84.5% v 74.5%, P<.0001) than patients in the NHIS cohort. For CRC surveillance, 96.5% of patients in protocol LTS-01 had a colonoscopy, 88.2% had a carcinoembryonic antigen test, and 66.4% had a computed tomography scan in the previous 5 years. Health insurance was the best predictor of cancer screening for all three methods (odds ratio=2.6 to 4.5). No factor was uniformly associated with CRC surveillance.This select population of long-term CRC survivors who participated in clinical trials achieved better routine preventive care and cancer screening than the general population and high rates of cancer surveillance.
Molecular Epidemiology of Cancer
Authors: Y.-C. Chen, D. J. Hunter
Journal: CA A Cancer Journal for Clinicians (2005)

Epidemiology is very successful in identifying environmental and lifestyle factors that increase or reduce risk of specific cancers, leading to cancer prevention strategies. However, the etiology of many types of cancer is still poorly understood, despite extensive use of questionnaires and interview-based approaches in conventional epidemiologic studies. The integration of molecular techniques into epidemiology studies may provide new insights and has been referred to as molecular epidemiology. For instance, our ability to make connections between lifestyle and cancer risk is limited by difficulty in accurately measuring exposure to many carcinogens—newer molecular markers of exposure may provide better information. The completion of the Human Genome Project gives us knowledge of the genetic variations that presumably underlie the fact that a family history of cancer is a risk factor for most cancer types. Some of this excess risk has been explained over the last decade by identification of mutations in genes that give rise to a very high familial risk. Molecular epidemiologists are searching for genes that may give rise to much smaller increases in individual risk, but account for much of the residual risk associated with family history. These genes may also interact with environment and lifestyle factors such that cancer risk is not equally elevated in all persons exposed to an environmental factor (but not genetically susceptible), or all gene carriers (but not exposed to the environmental factor). Molecular markers may help to differentiate tumors with the same histologic appearance into different etiologic subtypes. Finally, response to treatment may be determined by molecular subtypes of the tumor, or inherited variation in drug metabolism. Examples will be given of how use of molecular techniques is informative in epidemiological studies of cancer and is predicted to lead to improvements in cancer incidence, early detection, and mortality.
Emigration and immigration of mesenchymal cells: a multicultural airway wall
Authors: A.G. Stewart
Journal: European Respiratory Journal (2004)

The author's work cited herein was supported by grants from National Health and Medical Research Council (NHMRC) and GlaxoSmithKline (UK).

Chronic inflammatory disease is accompanied by structural changes that appear to relate to disease severity and duration, and are often considered to be poorly reversible, if at all. The processes underpinning the structural changes are varied, complex and not well understood. It is clear that these structural changes contribute to tissue dysfunction.

In asthma, remodelling comprises changes in all compartments of the airway wall, with the epithelium potentially orchestrating a persistent cycle of inflammatory injury and repair 1. The epithelium is thought to influence the underlying mesenchymal cell network through the release of transforming growth factor-β resulting in the activation of myofibroblasts that secrete excessive amounts of collagen and contribute to the burden of pro-inflammatory cytokines. Such changes in the superficial aspect of the airway recapitulate aspects of the pathogenesis of neointima formation, in which damage to the endothelium initiates a repair response that ultimately may compromise vessel function 2.

The most significant cellular component of the airway wall remodelling is an increase in the volume of airway smooth muscle (ASM), which is considered to play a dominant role in the consequences of the airway wall thickening for airway reactivity 3. The mechanisms of the increase in volume of ASM remain ill-defined despite extensive investigation over the last 15 yrs. Hyperplasia of ASM is well evidenced, but there is also evidence for a more limited hypertrophy 4, 5. The hyperplasia has been ascribed to proliferation in situ of ASM in response to growth factors and inflammatory mediators released during exacerbations of chronic asthma. Several investigations of antigen-induced …
Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study
Authors: Richard E Pratley, Michael A Nauck, Anthony H Barnett, Mark N Feinglos, Fernando Ovalle, Illana Harman-Boehm, June Ye, Rhona Scott, Susan Johnson, Murray Stewart, Julio Rosenstock
Journal: The Lancet Diabetes & Endocrinology (2014)
Diagnosis of X-linked Adrenal Hypoplasia Congenita by Mutation Analysis of the DAX1 Gene
Authors: Weiwen Guo
Journal: JAMA (1995)

<h3>Objective.</h3> —To develop a rapid diagnostic approach to individuals with the X-linked cytomegalic form of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to mutations in<i>DAX1</i>, a new member of the nuclear hormone receptor gene superfamily. <h3>Design.</h3> —Molecular genetic diagnostic investigations of individuals with AHC and their relatives included polymerase chain reaction amplification of<i>DAX1</i>for identification of intragenic mutations and fluorescence in situ hybridization with a cosmid containing the<i>DAX1</i>gene for evaluation of larger deletions. <h3>Participants.</h3> —Families that had males affected with AHC were evaluated for mutations involving the<i>DAX1</i>gene. <h3>Results.</h3> —<i>DAX1</i>mutations were identified in four families that had males affected with AHC. Two apparently independent pedigrees had an identical frame-shift mutation due to a single base pair deletion, and a third had a larger deletion involving the entire<i>DAX1</i>locus. The fourth family was evaluated by fluorescence in situ hybridization for prenatal diagnosis, and both the<i>DAX1</i>locus and the contiguous glycerol kinase region were deleted. <h3>Conclusions.</h3> —Molecular genetic and molecular cytogenetic techniques represent rapid and complementary approaches to the diagnosis of mutations in the<i>DAX1</i>gene responsible for AHC and the associated HH. Specific diagnosis of the cause of adrenal insufficiency in these boys permits anticipatory management of the HH and prenatal counseling for parents of the affected child and other members of their families. (<i>JAMA</i>. 1995;274:324-330)
Hepatitis C and B-cell lymphoma
Authors: N.C. Turner, G. Dusheiko, A. Jones
Journal: Annals of Oncology (2003)

<h2>Abstract</h2> The association between the hepatitis C virus and B-cell non-Hodgkin's lymphomas is controversial. We review the epidemiological evidence behind the association, and look at the reasons behind the variation in study findings. There is increasing evidence of the pathogenesis of hepatitis C-associated lymphoma. Treatment of the hepatitis C virus with antiviral therapy may lead to the regression of some low-grade lymphomas. The management of other hepatitis C-associated lymphomas is similar to that of conventional lymphoma, although viral reactivation and subsequent immune reconstitution hepatitis can complicate chemotherapy.
Epilation for Trachomatous Trichiasis and the Risk of Corneal Opacification
Authors: Saul N. Rajak, Esmael Habtamu, Helen A. Weiss, Amir Bedri, Teshome Gebre, Asrat Genet, Peng T. Khaw, Robin L. Bailey, David C.W. Mabey, Clare E. Gilbert, Paul M. Emerson, Matthew J. Burton
Journal: Ophthalmology (2011)

Eight million people have trachomatous trichiasis (TT). The World Health Organization (WHO) recommends entropion surgery for TT regardless of severity. However, epilation is widely practiced for treating minor TT (1-5 lashes touching the globe). We report the frequency and effectiveness of patient-initiated epilation and its relationship to corneal opacity.Cross-sectional baseline data of individuals recruited to 2 randomized, clinical trials.We included 2556 individuals (4310 eyes) with previously unoperated TT in ≥ 1 eye.A single ophthalmologist examined all participants for signs of trachoma using WHO grading systems with additional assessment of entropion grading, location and number of trichiatic lashes, and evidence of epilation. A questionnaire enquired about epilation practices.The association between epilation and degree of corneal opacity. Epilation practices of TT patients.Central corneal scarring was present in 1436 (33%) eyes. Entropion was absent/mild in 2328 (54%) eyes, moderate in 1259 (29.2%), and severe in 723 (16.8%). The median number of lashes touching the eye was 2 (interquartile range, 1-5; range, 0-133). There was clinical evidence of epilation in 3018 (70%) eyes, of which 738 (24%) were successfully epilated (no lashes touching globe). Epilation was performed frequently (at least monthly in 3311 [76.8%] eyes), by someone other than the patient (92.8%), and using locally made forceps (88.9%). Controlling for age and degree of entropion, successful epilation was associated with less corneal opacity (odds ratio [OR], 0.61; 95% confidence interval [CI]. 0.43-0.88; P = 0.007). The association was only significant in patients with severe entropion (OR, 0.07; 95% CI, 0.02-0.25; P<0.005).We found an association between successful epilation and less central corneal opacity. This indicates the importance of preventing eyelashes from touching the cornea, particularly in individuals with severe entropion. This is a cross-sectional study; therefore, a causative relationship cannot be concluded. However, the results suggest that among patients who decline or are unable to access surgery, and perhaps in minor TT where the management remains controversial, the provision of high-quality forceps and epilation training may be beneficial.The authors have no proprietary or commercial interest in any of the materials discussed in this article.
In vitro sensitization of thymocytes. Role of H-21 I region determinants and cell-free mixed leukocyte culture supernates in generation of cytotoxic responses.
Authors: M Sopori, A Bernstein, F H Bach
Journal: The Journal of Experimental Medicine (1978)

Stimulation of thymocytes in vitro by spleen cells differing for the entire H-2 complex leads to a significant proliferative response without a significant cell-mediated lympholysis (CML) response. Addition of soluble cell-free supernates (SF), (taken from a 7-day mixed leukocyte culture) enables these cultures to develop CML response. For optimal CML response, the SF has to be added within 48 h of onset of cultures. Although with spleen cells as responding cells, SF could quantitatively replace I-region different stimulating cells for generation of CML responses, with thymocytes as responding cells, stimulation with I-region cells appeared obligatory for the generation of CML responses. The implications of these findings are discussed.
Liver transplantation for hepatocellular carcinoma: The impact of human immunodeficiency virus infection
Authors: Eric Vibert, Jean-Charles Duclos-Vallée, Maria-Rosa Ghigna, Emir Hoti, Chady Salloum, Catherine Guettier, Denis Castaing, Didier Samuel, René Adam
Journal: Hepatology (2010)

Liver transplantation (LT) has become an accepted therapy for end-stage liver disease in human immunodeficiency virus-positive (HIV+) patients, but the specific results of LT for hepatocellular carcinoma (HCC) are unknown. Between 2003 and 2008, 21 HIV+ patients and 65 HIV- patients with HCC were listed for LT at a single institution. Patient characteristics and pathological features were analyzed. Univariate analysis for overall survival (OS) and recurrence-free survival (RFS) after LT was applied to identify the impact of HIV infection. HIV+ patients were younger than HIV- patients [median age: 48 (range = 41-63 years) versus 57 years (range = 37-72 years), P < 0.001] and had a higher alpha-fetoprotein (AFP) level [median AFP level: 16 (range = 3-7154 μg/L] versus 13 μg/L (range = 1-552 μg/L), P = 0.04]. There was a trend toward a higher dropout rate among HIV+ patients (5/21, 23%) versus HIV- patients (7/65, 10%, P = 0.08). Sixteen HIV+ patients and 58 HIV- patients underwent transplantation after median waiting times of 3.5 (range = 0.5-26 months) and 2.0 months (range = 0.5-24 months, P = 0.18), respectively. No significant difference was observed in the pathological features of HCC. With median follow-up times of 27 (range = 5-74 months) and 36 months (range = 3-82 months, P = 0.40), OS after LT at 1 and 3 years reached 81% and 74% in HIV+ patients and 93% and 85% in HIV- patients, respectively (P = 0.08). RFS rates at 1 and 3 years were 69% and 69% in HIV+ patients and 89% and 84% in HIV- patients, respectively (P = 0.09). In univariate analysis, HIV status did not emerge as a prognostic factor for OS or RFS.Because of a higher dropout rate among HIV+ patients, HIV infection impaired the results of LT for HCC on an intent-to-treat basis but had no significant impact on OS and RFS after LT.
Increased expression of mRNA encoding RANTES and MCP-3 in the bronchial mucosa in atopic asthma
Authors: N Powell, M Humbert, SR Durham, B Assoufi, AB Kay, CJ Corrigan
Journal: European Respiratory Journal (1996)

The selective recruitment of eosinophils into the mucosal lining of the airways is a prominent feature of atopic asthma, and is believed to be an important component in the disease pathogenesis. The precise stimuli responsible for the influx of eosinophils remain unclear. Using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique, the numbers of copies (relative to the "housekeeping" gene beta-actin) of messenger ribonucleic acid (mRNA) encoding the eosinophil-active chemotactic cytokines, the factor regulated upon activation in normal T-cells expressed and secreted (RANTES) and monocyte chemotactic protein-3 (MCP-3), was measured in bronchial biopsies from atopic asthmatic patients (n = 9), and compared with atopic nonasthmatic (n = 8) and nonatopic nonasthmatic (n = 8) control subjects. In addition, further biopsies from each subject were prepared for immunohistochemistry and the numbers of activated (EG2+) eosinophils measured. The expression of RANTES mRNA was significantly elevated in the atopic asthmatic group as compared to the atopic nonasthmatic controls (p = 0.013) and the nonatopic nonasthmatic controls (p = 0.007). Similarly, the expression of mRNA encoding MCP-3 was significantly elevated in the atopic asthmatic group, relative to the atopic nonasthmatic controls (p = 0.014) and the nonatopic nonasthmatic control group (p = 0.011). Elevated RANTES and MCP-3 mRNA expression was associated with significantly increased numbers of bronchial mucosal eosinophils in the atopic asthmatic patients as compared to the atopic nonasthmatic (p = 0.03) and nonatopic nonasthmatic (p = 0.006) control subjects. In conclusion, we have identified elevated expression of messenger ribonucleic acid encoding RANTES and monocyte chemotactic protein-3 in the bronchial mucosa of atopic asthmatic patients relative to controls. These findings are compatible with the hypothesis that eosinophil-active beta-chemokines play a role in the mechanism of eosinophil recruitment to the asthmatic bronchial mucosa.
Exposure of Humans to Lead
Authors: P B Hammond
Journal: The Annual Review of Pharmacology and Toxicology (1977)

Since 1972. several important reviews of lead toxicology have been published (1-3), as well as proceedings of two major conferences (4, 5). One of the reviews (I) was written specifically as a resource document for promulgating air lead standards. In a similar vein, the World Health Organization convened a task force in May 1975 to prepare a document which the member states could use in the establishment of national regulations pertaining to lead. Having participated in the preparation of both of these documents, it seems appropriate that this author should review the recent literature on lead that was most useful in assessing acceptable limits of human exposure. The focus of this review is on the transfer of lead from the environment into the human organism and on the major consequences thereof. Three target organ sys­ tems are generally acknowledged as being of major concern, the heme-hemoprotein system, the kidney, and the nervous system. Although the last-named system may ultimately prove to be the most critical, it is not dealt with in this review, because space is limited and because the subject is in a state of ferment. Hopefully, a sepa­ rate review of the effects of lead on the central and peripheral nervous system will be published soon.