tbuckley/cabot-search huggingface dataset:
Letter Regarding Article by von Lewinski et al, “Insulin Causes [Ca <sup>2+</sup> ] <sub>i</sub> -Dependent and [Ca <sup>2+</sup> ] <sub>i</sub> -Independent Positive Inotropic Effects in Failing Human Myocardium”
Authors: Chih-Hsueng Hsu, Cheng-I Lin, Jeng Wei
Journal: Circulation (2005)
Effect of dexamethasone on acute respiratory distress syndrome induced by the H5N1 virus in mice
Authors: T. Xu, J. Qiao, L. Zhao, G. He, K. Li, J. Wang, Y. Tian, H. Wang
Journal: European Respiratory Journal (2009)

Glucocorticoids are widely used in the treatment of different inflammatory diseases. The present study was performed to investigate the effect of dexamethasone (DEX) on acute respiratory distress syndrome (ARDS) induced by the H5N1 viral infection in mice. BALB/c mice, 6-8 weeks old, were divided into three groups with 80 mice in each. The infected group and the DEX-treated infected group were inoculated intranasally with 1 x 10(2) 50% mouse infectious dose of A/Chicken/Hebei/108/2002 (H5N1) viruses, with daily intraperitoneal injections of PBS, or 2.5 mg.kg(-1) DEX at days 3-14 post inoculation, respectively. The control group received noninfectious allantoic fluid and a daily intraperitoneal injection of PBS. In H5N1-infected mice, DEX treatment did not improve the mortality (17 out of 20 versus 16 out of 20 deaths in the DEX-treated infected group versus the infected group), and did not alleviate clinical signs, including weight loss, decreased food intake and inactivity. There was no significant amelioration of the hypoxaemia and ARDS-associated pathological changes in DEX-treated infected mice, as assessed by blood gas analysis and histological score. Furthermore, DEX therapy did not inhibit inflammatory cellular infiltration and cytokine release (interleukin-6 and tumour necrosis factor-alpha) in bronchoalveolar lavage fluid induced by the H5N1 infection. In conclusion, dexamethasone treatment (2.5 mg.kg(-1)) from days 3-14 post inoculation has no beneficial effect on acute respiratory distress syndrome caused by the H5N1 infection in mice.
ELEMENTARY BODIES OF VACCINIA FROM INFECTED CHORIO-ALLANTOIC MEMBRANES OF DEVELOPING CHICK EMBRYOS
Authors: Joseph E. Smadel, M. J. Wall
Journal: The Journal of Experimental Medicine (1937)

By a method of differential centrifugation and tryptic digestion suspensions of elementary bodies have been prepared from chorioallantoic membranes of chick embryos infected with vaccine virus. The infective titer of the final suspension of elementary bodies was usually the same as that of the original tissue emulsion. Elementary bodies from infected chick membranes were agglutinated as well by antivaccinal serum obtained from different mammalian species as were bodies prepared from inoculated rabbit skin. Seitz filtrates of infected chick material contained soluble precipitable substances of vaccinia; these filtrates and filtrates from infected rabbit skin, respectively, reacted equally well with rabbit serum which contained either L or S antibodies.
Metabolomics: the final frontier?
Authors: Timothy D Veenstra
Journal: Genome Medicine (2012)

e connection between genomics, proteomics and metabolomics is evident in even the most simplistic of scientific models.Genes give rise to mRNA.Proteins are translated from mRNA and then proceed to carry out a myriad of functions within the cell, including the metabolism of small molecules such as glucose and adenosine triphosphate.Not that many years ago, scientists used to study the 'big 4' biomolecules under the guise of genes, transcripts, protein and metabolites.e last decade of biomedical research, however, has been witness to the growth of the 'omics' industries.Genomics, trans criptomics and proteomics have become core technologies within almost every major academic or industrial research program around the world.What was missing was the final piece of the omics puzzle: metabolomics.
Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis
Authors: Vicente Arroyo, Richard Moreau, Rajiv Jalan, Pere Ginès
Journal: Journal of Hepatology (2015)

Acute-on-chronic liver failure (ACLF) is a recently recognized syndrome characterized by acute decompensation (AD) of cirrhosis and organ/system failure(s) (organ failure: liver, kidney, brain, coagulation, circulation and/or respiration) and extremely poor survival (28-day mortality rate 30-40%). ACLF occurs in relatively young patients. It is especially frequent in alcoholic- and untreated hepatitis B associated-cirrhosis, in addition it is related to bacterial infections and active alcoholism, although in 40% of cases no precipitating event can be identified. It may develop at any time during the course of the disease in the patient (from compensated to long-standing cirrhosis). The development of ACLF occurs in the setting of a systemic inflammation, the severity of which correlates with the number of organ failures and mortality. Systemic inflammation may cause ACLF through complex mechanisms including an exaggerated inflammatory response and systemic oxidative stress to pathogen- or danger/damage-associated molecular patterns (immunopathology) and/or alteration of tissue homeostasis to inflammation caused either by the pathogen itself or through a dysfunction of tissue tolerance. A scoring system composed of three scores (CLIF-C OFs, CLIF-C AD, and CLIF-C ACLFs) specifically designed for patients with AD, with and without ACLF, allows a step-wise algorithm for a rational indication of therapy. The management of ACLF should be carried out in enhanced or intensive care units. Current therapeutic measures comprise the treatment for associated complications, organ failures support and liver transplantation.
Bronchoscopic and high resolution CT findings in children with chronic wet cough
Authors: Konstantinos Douros, Efthymia Alexopoulou, Aggeliki Nicopoulou, Michael Anthracopoulos, Panayiotis Yiallouros, Andrew Fretzayas, Polixeni Nicolaidou, Kostas Priftis
Journal: European Respiratory Journal (2011)

Background:  Chronic wet cough strongly suggests endobronchial infection which, if left untreated, may progress to bronchiectasis. Our aim was to compare the effectiveness of chest high-resolution CT (HRCT) and flexible bronchoscopy (FB) in detecting airway abnormalities in children with chronic wet cough and to explore the association between radiological and bronchoscopic/bronchoalveolar lavage (BAL) findings.   Methods:  We retrospectively evaluated 93 children (0.6-16.4 years) with wet cough for more than 6 weeks referred to a specialized center and deemed unlikely to have asthma. All patients were submitted to hematological investigations, chest x-ray(s), HRCT, and FB/BAL. HRCTs were scored with the Bhalla method and bronchoscopic findings of bronchitis were grouped into 5 grades of severity.   Results:  Positive HRCT were found in 70 (75.2%) patients, respectively (p=0.76). A positive correlation was found between Bhalla score and duration of cough (p=0.23, p=0.028). FB/BAL was superior to HRCT in detecting abnormalities (p   Conclusions:  HRCT detected airway wall thickening and bronchiectasis and the severity of the findings correlated positively with the length of clinical symptoms and the intensity of neutrophilic inflammation in the airways. However, HRCT was less sensitive than FB/BAL in detecting airway abnormalities. The two modalities should be considered complementary in the evaluation of prolonged wet cough.
Can flare be predicted in DMARD treated RA patients in remission, and is it important? A cohort study
Authors: Benazir Saleem, Andrew K Brown, Mark Quinn, Zunaid Karim, Elizabeth M A Hensor, Philip Conaghan, Charles Peterfy, Richard J Wakefield, Paul Emery
Journal: Annals of the Rheumatic Diseases (2012)

The treatment target for patients with rheumatoid arthritis (RA) is remission. Imaging techniques and remission criteria may identify patients at risk of flare and associated consequences. This study aimed to determine the clinical, functional and imaging associations of disease flare in patients with RA in remission and any effect on long-term outcomes.RA patients in clinical remission as determined by their treating rheumatologist were assessed using clinical, remission criteria, imaging, functional and quality of life measures over 12 months. Flare was defined as any increase in disease activity requiring a change in therapy.26% of patients (24/93) in remission experienced a flare within 1 year. Fulfilment of remission criteria was not associated with a reduced likelihood of flare. Increased baseline ultrasound power Doppler (PD) activity (unadjusted OR (95% CI) 4.08 (1.26 to 13.19), p=0.014) and functional disability (Health Assessment Questionnaire Disability Index (HAQ-DI) per 0.1 unit1.27 (1.07 to 1.52), p=0.006) were independently associated with risk of flare. Patients who had a flare had significantly worse long-term clinical (Disease Activity Score 28; mean (95% CI) 2.90 (2.55 to 3.24) vs 2.26 (2.06 to 2.46), p=0.002) and functional outcomes (HAQ-DI; 0.412 (0.344 to 0.481) vs 0.322 (0.282 to 0.362), p=0.029) at 12 months compared with patients in sustained remission.The presence of PD activity was the most accurate determinant of flare in RA patients in remission. Flare was associated with worse clinical and functional outcomes. These results suggest ultrasound could form an important part of remission assessment in RA.
Researching New Methods of Screening for Adverse Pregnancy Outcome: Lessons from Pre-eclampsia
Authors: Gordon C. S. Smith
Journal: PLoS Medicine (2012)

Screening low-risk women for the risk of adverse pregnancy outcome, such as pre-eclampsia, is still largely based on clinical assessment, due to negative trials of new methods. The author argues that previous studies have weaknesses in their design and have focused on preterm pre-eclampsia despite the lack of clearly effective interventions to improve outcome.
Thyroid Cancer Rates and 131I Doses From Nevada Atmospheric Nuclear Bomb Tests
Authors: E. S. Gilbert, R. Tarone, E. Ron, A. Bouville
Journal: JNCI Journal of the National Cancer Institute (1998)

We examined data on death from thyroid cancer across the continental United States and data on incidence from selected areas of the country for evidence of an association between this disease and exposure to radioactive iodine (131I) from nuclear tests in Nevada in the 1950s.Analyses involving 4602 thyroid cancer deaths (1957-1994) and 12 657 incident cases of thyroid cancer (1973-1994) were performed. Excess relative risks (ERRs) per Gray (Gy) of radiation were estimated by relating age-, calendar year-, sex-, and county-specific rates to estimates of dose to the thyroid that take age at exposure into account.Analyses of cumulative dose yielded negative ERRs that were not statistically significant. An association was suggested for dose received by children under 1 year of age for both mortality data (ERR per Gy = 10.6; 95% confidence interval [CI] = -1.1 to 29) and incidence data (ERR per Gy = 2.4; 95% CI = -0.5 to 5.6); no association was found for dose received at older ages. For mortality data, but not incidence data, there was an elevated ERR in the 1950-1959 birth cohort of 12.0 (95% CI = 2.8 to 31) per Gy.Risk of thyroid cancer from exposure to 131I from atmospheric nuclear tests did not increase with cumulative dose or dose received at ages 1-15 years, but associations were suggested for individuals exposed under 1 year of age and for those in the 1950-1959 birth cohort. The absence of increased risk from dose received at ages 1-15 years is not consistent with studies of children exposed to external radiation sources. This inconsistency may result from the limitations and biases inherent in ecologic studies, including the error introduced when studying a mobile population. These problems preclude making a quantitative estimate of risk due to exposure; however, given such limitations, it is perhaps remarkable that any evidence of the effects of 131I emerges from this study.
Antagonism of ghrelin receptor reduces food intake and body weight gain in mice
Authors: A Asakawa
Journal: Gut (2003)

Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R), is an appetite stimulatory signal from the stomach with structural resemblance to motilin. We examined the effects of the gastric peptide ghrelin and GHS-R antagonists on energy balance and glycaemic control in mice.Body weight, fat mass, glucose, insulin, and gene expression of leptin, adiponectin, and resistin in white adipose tissue (WAT) were measured after repeated administrations of ghrelin under a high fat diet. Gastric ghrelin gene expression was assessed by northern blot analysis. Energy intake and gastric emptying were measured after administration of GHS-R antagonists. Repeated administration of GHS-R antagonist was continued for six days in ob/ob obese mice.Ghrelin induced remarkable adiposity and worsened glycaemic control under a high fat diet. Pair feeding inhibited this effect. Ghrelin elevated leptin mRNA expression and reduced resistin mRNA expression. Gastric ghrelin mRNA expression during fasting was increased by a high fat diet. GHS-R antagonists decreased energy intake in lean mice, in mice with diet induced obesity, and in ob/ob obese mice; it also reduced the rate of gastric emptying. Repeated administration of GHS-R antagonist decreased body weight gain and improved glycaemic control in ob/ob obese mice.Ghrelin appears to be closely related to excess weight gain, adiposity, and insulin resistance, particularly under a high fat diet and in the dynamic stage. Gastric peptide ghrelin and GHS-R may be promising therapeutic targets not only for anorexia-cachexia but also for obesity and type 2 diabetes, which are becoming increasingly prevalent worldwide.
AT1 Receptors in the Collecting Duct Directly Modulate the Concentration of Urine
Authors: Johannes Stegbauer, Susan B. Gurley, Matthew A. Sparks, Magdalena Woznowski, Donald E. Kohan, Ming Yan, Ruediger W. Lehrich, Thomas M. Coffman
Journal: Journal of the American Society of Nephrology (2011)

Mice lacking AT(1) angiotensin receptors have an impaired capacity to concentrate the urine, but the underlying mechanism is unknown. To determine whether direct actions of AT(1) receptors in epithelial cells of the collecting duct regulate water reabsorption, we used Cre-Loxp technology to specifically eliminate AT(1A) receptors from the collecting duct in mice (CD-KOs). Although levels of AT(1A) receptor mRNA in the inner medulla of CD-KO mice were significantly reduced, their kidneys appeared structurally normal. Under basal conditions, plasma and urine osmolalities and urine volumes were similar between CD-KO mice and controls. The increase in urine osmolality in response to water deprivation or vasopressin administration, however, was consistently attenuated in CD-KO mice. Similarly, levels of aquaporin-2 protein in inner and outer medulla after water deprivation were significantly lower in CD-KO mice compared with controls, despite its normal localization to the apical membrane. In summary, these results demonstrate that AT(1A) receptors in epithelial cells of the collecting duct directly modulate aquaporin-2 levels and contribute to the concentration of urine.
Cortisol and Alzheimer's disease, I: Basal studies
Authors: K L Davis, B M Davis, B S Greenwald, R C Mohs, A A Mathé, C A Johns, T B Horvath
Journal: American Journal of Psychiatry (1986)

Patients with Alzheimer's disease and nondemented elderly control subjects participated in studies of cortisol secretion during sleep and at 9:00 a.m. and were given dexamethasone suppression tests (DSTs) and lumbar punctures. Nocturnal and 9:00 a.m. cortisol concentrations were significantly higher in the demented patients. CSF MHPG negatively correlated with mean nocturnal cortisol. The most severely demented patients had the highest 9:00 a.m. and mean nocturnal cortisol concentrations. DST results did not distinguish samples with substantially different nocturnal cortisol concentrations. These results suggest that measurements of basal plasma cortisol concentrations and dexamethasone suppression provide different information but support the notion of somewhat higher than normal cortisol concentrations in Alzheimer's disease patients.
Correlation between effects of hydralazine on force and on the adenyl cyclase system of ventricular myocardium in dogs and cats
Authors: B. RABINOWITZ, W. W PARMLEY, Y. HAR-ZAHAV, E. ELAZAR, S. BLUMLEIN, R. NERINSKY, H. N NEUFELD
Journal: Cardiovascular Research (1986)

Hydralazine is a potent arteriolar dilator, which increases cardiac output in patients with heart failure. Previous studies suggested that these beneficial effects might be due in part to a positive inotropic effect. The present study further investigated the effect of hydralazine on myocardial contractility and adenyl cyclase activity. In isolated cat papillary muscles, bath concentrations of hydralazine up to 10−4 mol·litre−1 did not alter force development, whereas 10−3 mol·litre−1 hydralazine increased isometric force by 31%. This effect was blocked by 10−6 mol·litre−1 propranolol and was absent after catecholamine depletion produced by previous reserpine treatment. In canine ventricular myocardium hydralazine in all concentrations used (10−7 to 1(T−3 mol·litre−1) increased control adenyl cyclase activity. This increase was statistically significant in 10−6 to 10−3 mol·litre−1concentrations, reaching a maximum of 69.5% at 10−4 mol·litre−1. In cat ventricular myocardium 10−6 to 10−3 mol·litre−1 hydralazine increased the cyclic AMP production, although to a lesser magnitude than that in canine tissue. Hydralazine 10−5 mol·litre−1 produced a 37.8% increase, and the maximum effect of 45.2% occurred at 10−3 mol·litre−1. The positive effects of hydralazine were completely abolished by the addition of propranolol in dogs as well as in cats. Thus the adenyl cyclase stimulation induced by hydralazine is mediated through the beta receptor. Although there is quantitative dissociation concerning the effective dose on force compared with the effective dose on the adenylate cyclase system, the overall data produce the evidence for an adrenergic mechanism that might be responsible for inotropic stimulation.
Platelets Take Up the Monoclonal Antibody Bevacizumab
Authors: Henk M.W. Verheul, Martijn P.J. Lolkema, David Z. Qian, Yvonne H.A. Hilkes, Eleni Liapi, Jan-Willem N. Akkerman, Roberto Pili, Emile E. Voest
Journal: Clinical Cancer Research (2007)

One of the key factors that promotes angiogenesis is vascular endothelial growth factor (VEGF). Platelets are the main source of VEGF in blood and contribute to angiogenesis by release of growth factors, including VEGF, from their alpha-granules on activation. The monoclonal antibody bevacizumab blocks VEGF in the blood of patients within hours after administration. Platelets are known to endocytose plasma proteins including immunoglobulins. We tested the hypothesis that platelets take up bevacizumab.Fluorescence-activated cell sorting analysis, immunofluorescence imaging, and Western blotting were used to study uptake and release of bevacizumab by platelets in vitro and in vivo. The angiogenic activity of platelets preincubated with bevacizumab was studied in endothelial proliferation assays. Finally, we determined whether treatment with bevacizumab neutralizes VEGF in platelets from cancer patients.We found that platelets are able to take up bevacizumab. Activation of platelets preincubated with bevacizumab resulted in release of the antibody and release of VEGF neutralized by bevacizumab. Immunofluorescence microscopy revealed that FITC-labeled bevacizumab and P-selectin colocalize, indicating alpha-granule localization. In addition, bevacizumab uptake inhibited platelet-induced human endothelial cell proliferation. In in vivo rabbit experiments, FITC-labeled bevacizumab was present in platelets after 2 h and up to 2 weeks following i.v. administration. Finally, we found that platelets take up bevacizumab in patients receiving bevacizumab treatment. Within 8 h after bevacizumab administration, platelet VEGF was almost completely neutralized due to this uptake.These studies show that bevacizumab is taken up by platelets and may explain its clinical effect on wound healing and tumor growth.
Seroepidemiology and Molecular Epidemiology of Kaposi's Sarcoma-Associated Herpesvirus Among Jewish Population Groups in Israel
Authors: B. Davidovici, I. Karakis, D. Bourboulia, S. Ariad, J.-C. Zong, D. Benharroch, N. Dupin, R. Weiss, G. Hayward, B. Sarov, C. Boshoff
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: The incidence of classic Kaposi's sarcoma among Jews in Israel is among the highest in the developed world. Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is causally linked to Kaposi's sarcoma. Very little is known about the prevalence of KSHV in the Middle East or about the modes of transmission in Mediterranean countries. Methods: From 1992 through 1995, sera were obtained from 1648 adults who had tested positive for hepatitis B virus (HBV) surface antigen 20 years earlier at blood donations; sera were also obtained from 2403 of their family members. All sera were tested for anti-KSHV antibodies with the use of an indirect immunofluorescence assay. To analyze the effects of various factors on the risk of KSHV infection for both the HBV-positive cohort and their families, logistic regression for cluster data and generalized estimating equations were used. All statistical tests were two-sided. Results: Among family members, the seroprevalence of antibodies against KSHV was 9.9% (95% confidence interval [CI] = 8.7% to 11.1%); among the former blood donors who had tested positive for hepatitis B, it was 22% (95% CI = 19.9% to 24.1%). Overall, the best predictor of KSHV status was the place of birth. The most important risk factors found for both husband and wife to test KSHV positive were their own places of birth and their spouse's seropositivity. For a child to test positive, the most important risk factor was maternal seropositivity. Conclusions: The crude prevalence rate of KSHV among the Jewish population in Israel is 9.9%. Important routes of KSHV transmission in the families studied are spouse to spouse and mother to child. The presence of KSHV in Jews in Israel of all ethnic origins and their high incidence of reported Kaposi's sarcoma suggest that KSHV was introduced into the Jewish population prior to the major Diaspora.
Cyclin D1 Kinase Activity Is Required for the Self-Renewal of Mammary Stem and Progenitor Cells that Are Targets of MMTV-ErbB2 Tumorigenesis
Authors: Rinath Jeselsohn, Nelson E. Brown, Lisa Arendt, Ina Klebba, Miaofen G. Hu, Charlotte Kuperwasser, Philip W. Hinds
Journal: Cancer Cell (2010)