tbuckley/cabot-search huggingface dataset:
Anisotropic Isolation by Distance: The Main Orientations of Human Genetic Differentiation
Authors: Flora Jay, Per Sjödin, Mattias Jakobsson, Michael G.B. Blum
Journal: Molecular Biology and Evolution (2012)

Genetic differentiation among human populations is greatly influenced by geography due to the accumulation of local allele frequency differences. However, little is known about the possibly different increment of genetic differentiation along the different geographical axes (north–south, east–west, etc.). Here, we provide new methods to examine the asymmetrical patterns of genetic differentiation. We analyzed genome-wide polymorphism data from populations in Africa (n = 29), Asia (n = 26), America (n = 9), and Europe (n = 38), and we found that the major orientations of genetic differentiation are north–south in Europe and Africa, and east–west in Asia, but no preferential orientation was found in the Americas. Additionally, we showed that the localization of the individual geographic origins based on single nucleotide polymorphism data was not equally precise along all orientations. Confirming our findings, we obtained that, in each continent, the orientation along which the precision is maximal corresponds to the orientation of maximum differentiation. Our results have implications for interpreting human genetic variation in terms of isolation by distance and spatial range expansion processes. In Europe, for instance, the precise northnorthwest–southsoutheast axis of main European differentiation cannot be explained by a simple Neolithic demic diffusion model without admixture with the local populations because in that case the orientation of greatest differentiation should be perpendicular to the direction of expansion. In addition to humans, anisotropic analyses can guide the description of genetic differentiation for other organisms and provide information on expansions of invasive species or the processes of plant dispersal.
NOTE ON A SUCCESSFUL METHOD FOR THE EXTERMINATION OF VERMIN INFESTING TROOPS
Authors: S. M. Copeman
Journal: BMJ (1915)

S8HMAPNEL WOUND OF SPNEI M-RDICAL JOURNAAL 247 grow, but did not become thinner, and he Tst all sexual desire.-His urine was scaiity, but normal.Jn spite of rest in bed, and an exceptionally ample diet, he continued to lose weight; thyroid gland m-nde liim worse, but large doses of opium and bromide relieved the excitement, and his weiglht became almost stationary.On June 18th, 1911, hie weighed 127 lb.; lhe was givenI 1:-gaaiu of dried para- thlyroid gland four tiunes daily, and touir days later lie dis- continued the opium and bromlide.He gained 6.) lb. in thie first four days, 12 lb.the next five days, and 28.lb. in the first nineteen days.Simultaneously all his symptoms disappeared, and in a montlh hie w%Yas well.He continued
Mesenchymal Stem Cell Carriers Protect Oncolytic Measles Viruses from Antibody Neutralization in an Orthotopic Ovarian Cancer Therapy Model
Authors: Emily K. Mader, Yoshihiro Maeyama, Yi Lin, Greg W. Butler, Holly M. Russell, Evanthia Galanis, Stephen J. Russell, Allan B. Dietz, Kah-Whye Peng
Journal: Clinical Cancer Research (2009)

Preexisting antiviral antibodies in cancer patients can quickly neutralize oncolytic measles virus (MV) and decrease its antitumor potency. In contrast to "naked" viruses, cell-associated viruses are protected from antibody neutralization. Hence, we hypothesized that measles virotherapy of ovarian cancer in measles-immune mice might be superior if MV-infected mesenchymal stem cell (MSC) carriers are used.Antimeasles antibodies titers in ovarian cancer patients were determined. The protection of MV by MSC from antimeasles antibodies, the in vivo biodistribution profiles, and tumor infiltration capability of MSC were determined. Measles-naïve or immune tumor-bearing mice were treated with naked virus or MSC-associated virus and mice survivals were compared.MSC transferred MV infection to target cells via cell-to-cell heterofusion and induced syncytia formation in the presence of high titers of antimeasles antibody, at levels that completely inactivated naked virus. Athymic mice bearing i.p. human SKOV3ip.1 ovarian tumor xenografts passively immunized with measles-immune human serum were treated with saline, naked MV, or MV-infected MSC. Bioluminescent and fluorescent imaging data indicated that i.p. administered MSC localized to peritoneal tumors, infiltrated into the tumor parenchyma, and transferred virus infection to tumors in measles naïve and passively immunized mice. Survival of the measles-immune mice was significantly enhanced by treatment with MV-infected MSC. In contrast, survivals of passively immunized mice were not prolonged by treatment with naked virus or uninfected MSC.MSC should be used as carriers of MV for intraperitoneal virotherapy in measles-immune ovarian cancer patients.
Development of heart failure following isoproterenol administration in the rat: role of the renin–angiotensin system
Authors: D Grimm
Journal: Cardiovascular Research (1998)

Objective: High dosages of catecholamines induce cardiomyocyte necrosis and interstitial fibrosis in rats. We investigated whether this initial damage is followed by the development of heart failure and assessed the particular role of the renin–angiotensin system using ramipril. Methods and Results: Following the administration of 0 mg or 150 mg isoproterenol/kg 6 groups of Wistar rats were followed for 2 or 16 weeks: Sham, isoproterenol, isoproterenol+ramipril. Isoproterenol induced significant increases of echocardiographically measured left ventricular end-diastolic posterior wall thickness and dimension, whereas ramipril treatment significantly attenuated these changes. Left ventricular end-diastolic pressure was markedly increased in isoproterenol-treated rats and normalized following ramipril. Isoproterenol rats were further characterized by hormonal activations including transient elevations of plasma renin activity, aldosterone and cardiac angiotensin converting enzyme activity. Histomorphological characterization of isoproterenol-treated hearts demonstrated cardiomyocyte necrosis and reparative fibrosis. Ramipril treatment only slightly reduced the amount of necrosis as well as the expression of extracellular matrix proteins. Conclusions: In rats, a toxic dosage of isoproterenol caused characteristic myocardial damage that subsequently resulted in mild heart failure. Ramipril administration following isoproterenol was highly effective to attenuate hemodynamic and hormonal alterations as well as the development of left ventricular hypertrophy, but had only little influence on the expression of extracellular matrix proteins. Since angiotensin converting enzyme inhibition had no impact on the initial myocardial injury, the development of heart failure in this model seems to require functional integrity of the renin–angiotensin system.
Pulmonary studies using positron emission tomography
Authors: CG Rhodes, JM Hughes
Journal: European Respiratory Journal (1995)

The detailed investigation of regional differences in lung function at a local level began when suitable gamma-ray emitting isotopes and focused external radiation detectors (especially the Anger gamma-camera) became available. A major recent advance has been the development of positron emission tomography (PET), which provides a powerful combination of highly accurate tomographic reconstruction of radioisotope concentration with a potentially unlimited list of biological compounds to be labelled with the positron emitting isotopes of oxygen, carbon and fluorine. Early studies using PET focused on the inhalation of 11CO (or C15O) and 19Ne gases and the intravenous injection of 13N in saline and H215O for the measurement of relatively simple aspects of regional lung function, such as tissue, blood and gas volumes, blood flow, ventilation and ventilation/perfusion (V'A/Q'). More recent work has been directed towards the more challenging areas of regional endothelial permeability, carbohydrate utilization, enzyme and receptor binding assays, and in vivo pharmacokinetics. The short physical half-lives of the isotopes (17 s to 2 h) and the noninvasive nature of PET allows serial measurements to be made on patients (within the constraints of permitted radiation doses) to assess the effect of physiological and therapeutic interventions.
The long-term outcomes of radiosurgery for intracranial hemangioblastomas
Authors: S. Hanakita, T. Koga, M. Shin, S. Takayanagi, A. Mukasa, M. Tago, H. Igaki, N. Saito
Journal: Neuro-Oncology (2013)

Optimal timing in the treatment of intracranial hemangioblastoma (HB) remains controversial, particularly for patients of von Hippel–Lindau disease (VHL) with multiple small lesions. We evaluated efficacy of stereotactic radiosurgery (SRS) for intracranial HB based on the longer follow-up data with a larger number of patients and lesions. Twenty-one patients (11 men, 10 women) initially underwent SRS for 57 intracranial HBs. Seven patients had sporadic lesions and 14 had VHL-related lesions. During the follow-up, 40 lesions were additionally treated in VHL patients in 10 SRS treatments. Thus, a total of 97 lesions were included in this study. Median tumor volume was 0.13 cm3 (range, 0.004–9.5 cm3), and median margin dose was 18 Gy (range, 14–20 Gy). Median duration of follow-up was 96 months (range, 3–235 mo) after initial SRS treatment. Ten tumors in 7 patients showed progression after SRS. Actuarial tumor control rates after SRS at 5 and 10 years were 94% and 80%, respectively. Factors associated with longer control were solid lesion (P = .03), smaller volume (P = .01), and lesions associated with VHL (P = .0005) in univariate analysis. Five- and 10-year tumor control rates were 67% and 44% for sporadic patients and 97% and 83% for VHL patients. SRS could be offered as an effective treatment for small, solid, and VHL-associated HBs. If the tumors show apparent enlargement in size or can possibly become symptomatic along with a slight increase in size, SRS should be recommended before they present with the clinical symptoms.
Skin and soft tissue infections in intercontinental travellers and the import of multi-resistant Staphylococcus aureus to Europe
Authors: D. Nurjadi, B. Friedrich-Jänicke, J. Schäfer, P.J.J. Van Genderen, A. Goorhuis, A. Perignon, A. Neumayr, A. Mueller, A. Kantele, M. Schunk, J. Gascon, A. Stich, C. Hatz, E. Caumes, M.P. Grobusch, R. Fleck, F.P. Mockenhaupt, P. Zanger
Journal: Clinical Microbiology and Infection (2015)
The role of interleukin-17 during acute rejection after lung transplantation
Authors: B. M. Vanaudenaerde, L. J. Dupont, W. A. Wuyts, E. K. Verbeken, I. Meyts, D. M. Bullens, E. Dilissen, L. Luyts, D. E. Van Raemdonck, G. M. Verleden
Journal: European Respiratory Journal (2006)

Acute rejection (AR) is an important complication that can occur after lung transplantation and constitutes a risk factor for bronchiolitis obliterans syndrome, which is characterised by a neutrophilic airway inflammation. The specific aim of this study was to investigate the role of interleukin (IL)-17, which promotes chemotaxis of neutrophils by inducing IL-8 production, in AR. Cell differentials, mRNA and protein levels were quantified in bronchoalveolar lavages (BALs) taken from patients at 28 and 90 days after lung transplantation. The patient's rejection status was assessed by transbronchial biopsy. An AR was found in nine out of the 26 patients examined, 28 days after transplantation. The number of BAL neutrophils and lymphocytes were increased in these patients. IL-17 mRNA and protein levels in the BAL were increased in patients with AR. Analysis of BAL obtained at day 90 after transplantation, demonstrated that the increase in IL-17 had disappeared, whereas the increase in neutrophils and lymphocytes persisted. These data showed that interleukin-17 is temporarily upregulated in bronchoalveolar lavage during acute rejection. The number of lymphocytes and neutrophils are increased in bronchoalveolar lavage during acute rejection and may persist up to 2 months after acute rejection. These findings suggest that interleukin-17 is important in the pathophysiology of acute lung rejection.
Effect of Ethics Consultations on Nonbeneficial Life-Sustaining Treatments in the Intensive Care Setting
Authors: Lawrence J. Schneiderman, Todd Gilmer, Holly D. Teetzel, Daniel O. Dugan, Jeffrey Blustein, Ronald Cranford, Kathleen B. Briggs, Glen I. Komatsu, Paula Goodman-Crews, Felicia Cohn, Ernlé W. D. Young
Journal: JAMA (2003)

ContextEthics consultations increasingly are being used to resolve conflicts about life-sustaining interventions, but few studies have reported their outcomes.ObjectiveTo investigate whether ethics consultations in the intensive care setting reduce the use of life-sustaining treatments delivered to patients who ultimately did not survive to hospital discharge, as well as the reactions to the consultations of physicians, nurses, and patients/surrogates.DesignProspective, multicenter, randomized controlled trial from November 2000 to December 2002.SettingAdult intensive care units (ICUs) of 7 US hospitals representing a spectrum of institutional characteristics.PatientsFive hundred fifty-one patients in whom value-related treatment conflicts arose during the course of treatment.InterventionsPatients were randomly assigned either to an intervention (ethics consultation offered) (n = 278) or to usual care (n = 273).Main Outcome MeasuresThe primary outcomes were ICU days and life-sustaining treatments in those patients who did not survive to hospital discharge. We examined the same measures in those who did survive to discharge and also compared the overall mortality rates of the intervention and usual care groups. We also interviewed physicians and nurses and patients/surrogates about their views of the ethics consultation.ResultsThe intervention and usual-care groups showed no difference in mortality. However, ethics consultations were associated with reductions in hospital (−2.95 days, P = .01) and ICU (−1.44 days, P = .03) days and life-sustaining treatments (−1.7 days with ventilation, P = .03) in those patients who ultimately did not survive to discharge. The majority (87%) of physicians, nurses, and patients/surrogates agreed that ethics consultations in the ICU were helpful in addressing treatment conflicts.ConclusionEthics consultations were useful in resolving conflicts that may have inappropriately prolonged nonbeneficial or unwanted treatments in the ICU.
Use of Bronchoalveolar Lavage Semiquantitative Cultures in Cystic Fibrosis
Authors: ROBERT P. BAUGHMAN, DEBORAH A. KEETON, CARLOS PEREZ, ROBERT W. WILMOTT
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To assess bronchoalveolar lavage (BAL) in adult CF patients with respiratory symptoms, we studied BAL fluid (BALF) culture results from 28 bronchoscopies in 11 patients. Patients were asked to provide sputum for culture. All but two patients were receiving antibiotics at the time of bronchoscopy, with 13 bronchoscopies done on patients who had been receiving antibiotics for more than 10 d. Gram stain of the BALF was positive in 18 cases. In all but one BALF, > 10,000 colony-forming units per milliliter (cfu/ml) BALF of one or more pathogens was identified. The final case grew Burkholderia cepacia, which was not grown in the sputum. In only six cases (21%) were the sputum and BALF culture results the same. Prior to 11 bronchoscopies, the sputum was not adequate. The remaining 11 cases either had different pathogens in the BAL (six cases), or had some but not all of the BALF pathogens in the sputum. BALF cultures changed therapy in 13 (48%) of cases. Semiquantitative culture of BALF was a useful diagnostic tool in CF in patients in whom empiric therapy failed.
Effects of pollen extract upon adolescent swimmers.
Authors: R. J. Maughan, S. P. Evans
Journal: British Journal of Sports Medicine (1982)

Many competitive sportsmen in this country regularly use pollen extract as a dietary supplement in the belief that it can lead to an improvement in performance. We have investigated the effects of a six-week course of pollen extract administration on a variety of physiological parameters in a group (n = 20) of adolescent swimmers. At the time of the study, all subjects were training on a daily basis. During the course of the study, maximum oxygen uptake increased in both the treatment group and the placebo group, no difference between the response of the two groups being observed. Vital capacity showed a significant increase in the treatment group, but not in the placebo group. The results indicate that no positive benefit was obtained from the use of pollen supplementation. However, the number of training days missed due to upper respiratory tract infections was much less in the pollen treatment group (4 days) than in the placebo group (27 days). In a study of longer duration, this difference could lead to an improved performance by the pollen treatment group due to fewer interruptions to training.
Evaluating processes underlying the predictive value of baseline erosions for future radiological damage in early rheumatoid arthritis
Authors: Jessica A B van Nies, Hanna W van Steenbergen, Annemarie Krabben, Wouter Stomp, Tom W J Huizinga, Monique Reijnierse, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Baseline erosions are characteristic for rheumatoid arthritis (RA) and predictive for a severe disease course. The mechanisms leading to baseline erosions being a strong predictor for radiological progression are unknown. We aimed to increase this understanding by mediation analyses in an observational cohort and a cross-sectional MRI study. <h3>Methods</h3> 3256 hands and feet radiographs of 653 early RA patients assessed during 7 years of disease were scored using the Sharp–van der Heijde method. Mediation models and multivariate regression analyses were used to explore the association between baseline erosions, other predictors and radiological damage over time. 603 joints (MCP2-5 and MTP1-5) of 67 RA patients underwent 1.5 T MRI at baseline. Data on MRI inflammation were compared with clinical inflammation and baseline radiological erosions. <h3>Results</h3> Patients with baseline erosions had, at any point in time during 7 years, 3.45 times more joint damage than patients without erosions (p&lt;0.001, 95% CI 3.00 to 3.98). Baseline erosions were an independent predictor and not a mediator between symptom duration, systemic or local clinical inflammation (erythrocyte sedimentation rate (ESR), swollen joint count (SJC)) or autoantibodies (anti-citrullinated-peptide antibodies, rheumatoid factor) and radiological damage. Subclinical MRI inflammation was studied in relation to erosions, revealing that 83% of the non-swollen joints with baseline erosions had subclinical MRI inflammation compared with 25% of the non-swollen joints without baseline erosions (OR 15.2 95% CI 3.1 to 102.1). The association between MRI inflammation and baseline erosions was independent of symptom duration, ESR, SJC and autoantibodies. <h3>Conclusions</h3> Baseline erosions are a predictor for future joint damage, independent of known predictors as time, autoantibodies or clinical measurable inflammation. Subclinical inflammation is suggested as an underlying mechanism.
The Novel <i>p21</i> Polymorphism <i>p21G251A</i> Is Associated with Locally Advanced Breast Cancer
Authors: Vidar Staalesen, Stian Knappskog, Ranjan Chrisanthar, Silje H. Nordgard, Erik Løkkevik, Gun Anker, Bjørn Østenstad, Steinar Lundgren, Terje Risberg, Ingvil Mjaaland, Inger Torhild Gram, Vessela N. Kristensen, Anne-Lise Børresen-Dale, Johan Richard Lillehaug, Per Eystein Lønning
Journal: Clinical Cancer Research (2006)

Abstract Purpose: p21 is a main effector of growth arrest induced by p53. In addition, a second transcript from the same gene (p21B) has been linked to apoptosis. We previously analyzed p21 status in breast cancer and reported two novel polymorphisms of the p21 gene. In the present study, we present a larger study designed to explore a possible association between these novel polymorphisms and breast cancer. Experimental Design: The p21/p21B polymorphisms were analyzed in 507 breast cancer patients and 1,017 healthy individuals using cDNA or genomic DNA from tumor and/or blood samples. Results: We detected five polymorphisms of the p21 gene. Three of these polymorphisms are earlier reported by others, whereas two were reported for the first time in a recent study by us. The presence of the A allele of the p21G251A polymorphism was observed more frequently among patients with primary stage III breast cancer (4.5%) compared with stage I and II tumors (1.5%) and healthy female controls (1.4%; P = 0.007, comparing the three groups; P = 0.0049 and P = 0.0057, comparing locally advanced to stage I/II and healthy controls, or to healthy controls alone, respectively). The allele frequencies of the remaining four polymorphisms were evenly distributed among patients and healthy individuals. Discussion: The finding of an association between locally advanced breast cancer and one particular polymorphism of the p21 gene suggests this polymorphism to be related to tumor behavior, including enhanced growth rate. If confirmed in other studies, this may add significant information to our understanding of the biology as well as of the clinical behaviour of locally advanced breast cancers.
Histone deacetylase–mediated transcriptional activation reduces proviral loads in HTLV-1–associated myelopathy/tropical spastic paraparesis patients
Authors: Agnès Lezin, Nicolas Gillet, Stéphane Olindo, Aïssatou Signaté, Nathalie Grandvaux, Olivier Verlaeten, Gildas Belrose, Marcelo de Carvalho Bittencourt, John Hiscott, Becca Asquith, Arsène Burny, Didier Smadja, Raymond Césaire, Luc Willems
Journal: Blood (2007)
Lower Gene Expression for KCNS3 Potassium Channel Subunit in Parvalbumin-Containing Neurons in the Prefrontal Cortex in Schizophrenia
Authors: Danko Georgiev, Dominique Arion, John F. Enwright, Mitsuru Kikuchi, Yoshio Minabe, John P. Corradi, David A. Lewis, Takanori Hashimoto
Journal: American Journal of Psychiatry (2013)

Objective In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent in parvalbumin-containing neurons. Parvalbumin neurons selectively express KCNS3, the gene encoding the Kv9.3 potassium channel α-subunit. Kv9.3 subunits are present in voltage-gated potassium channels that contribute to the precise detection of coincident excitatory synaptic inputs to parvalbumin neurons. This distinctive feature of parvalbumin neurons appears important for the synchronization of cortical neural networks in γ-oscillations. Because impaired prefrontal cortical γ-oscillations are thought to underlie the cognitive impairments in schizophrenia, the authors investigated whether KCNS3 mRNA levels are altered in the prefrontal cortex of schizophrenia subjects. Method KCNS3 mRNA expression was evaluated by in situ hybridization in 22 matched pairs of schizophrenia and comparison subjects and by microarray analyses of pooled samples of individually dissected neurons that were labeled with Vicia villosa agglutinin (VVA), a parvalbumin neuron-selective marker, in a separate cohort of 14 pairs. Effects of chronic antipsychotic treatments on KCNS3 expression were tested in the prefrontal cortex of antipsychotic-exposed monkeys. Results By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower. By microarray, KCNS3 mRNA levels were lower by 40% in VVA-labeled neurons from schizophrenia subjects. KCNS3 mRNA levels were not altered in antipsychotic-exposed monkeys. Conclusions These findings reveal lower KCNS3 expression in prefrontal cortical parvalbumin neurons in schizophrenia, providing a molecular basis for compromised detection of coincident synaptic inputs to parvalbumin neurons that could contribute to altered γ-oscillations and impaired cognition in schizophrenia.