tbuckley/cabot-search huggingface dataset:
Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction
Authors: Guillermina Girardi, Dmitry Yarilin, Joshua M. Thurman, V. Michael Holers, Jane E. Salmon
Journal: The Journal of Experimental Medicine (2006)

Immune mechanisms have been implicated in placental dysfunction in patients with recurrent miscarriages and intrauterine growth restriction (IUGR), but the mediators are undefined. Here we show that complement activation, particularly C5a, is a required intermediary event in the pathogenesis of placental and fetal injury in an antibody-independent mouse model of spontaneous miscarriage and IUGR, and that complement activation causes dysregulation of the angiogenic factors required for normal placental development. Pregnancies complicated by miscarriage or growth restriction were characterized by inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor 1 (sVEGFR-1, also known as sFlt-1; a potent anti-angiogenic molecule), and defective placental development. Inhibition of complement activation in vivo blocked the increase in sVEGFR-1 and rescued pregnancies. In vitro stimulation of monocytes with products of the complement cascade directly triggered release of sVEGFR-1, which sequesters VEGF. These studies provide the first evidence linking the complement system to angiogenic factor imbalance associated with placental dysfunction, and identify a new effector of immune-triggered pregnancy complications.
What did Doppler monitoring study show?
Authors: R. J. T. Wilson
Journal: BMJ (2011)

I have long championed so called haemodynamic optimisation in high risk surgery, having published a randomised controlled trial in the BMJ in 1999.1 I have used oesophageal Doppler monitoring many hundreds of times, and still do occasionally.

I was therefore interested in the article by Kuper and colleagues, but I don’t know what to believe from this piece of work, which …
Caveolae as Organizers of Pharmacologically Relevant Signal Transduction Molecules
Authors: Hemal H. Patel, Fiona Murray, Paul A. Insel
Journal: The Annual Review of Pharmacology and Toxicology (2007)

Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations of the plasma membrane that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N and C termini, palmitolylation sites, and a scaffolding domain that facilitates interaction and organization of signaling molecules so as to help provide coordinated and efficient signal transduction. Such signaling components include upstream entities (e.g., G protein-coupled receptors (GPCRs), receptor tyrosine kinases, and steroid hormone receptors) and downstream components (e.g., heterotrimeric and low-molecular-weight G proteins, effector enzymes, and ion channels). Diseases associated with aberrant signaling may result in altered localization or expression of signaling proteins in caveolae. Caveolin-knockout mice have numerous abnormalities, some of which may reflect the impact of total body knockout throughout the life span. This review provides a general overview of caveolins and caveolae, signaling molecules that localize to caveolae, the role of caveolae/caveolin in cardiac and pulmonary pathophysiology, pharmacologic implications of caveolar localization of signaling molecules, and the possibility that caveolae might serve as a therapeutic target.
Increased Oxidative Stress in the Nucleus Caused by Nox4 Mediates Oxidation of HDAC4 and Cardiac Hypertrophy
Authors: Shouji Matsushima, Junya Kuroda, Tetsuro Ago, Peiyong Zhai, Ji Yeon Park, Lai-Hua Xie, Bin Tian, Junichi Sadoshima
Journal: Circulation Research (2012)

Oxidation of cysteine residues in class II histone deacetylases (HDACs), including HDAC4, causes nuclear exit, thereby inducing cardiac hypertrophy. The cellular source of reactive oxygen species responsible for oxidation of HDAC4 remains unknown.We investigated whether nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4), a major nicotinamide adenine dinucleotide phosphate oxidase, mediates cysteine oxidation of HDAC4.Phenylephrine (100 μmol/L), an α1 adrenergic agonist, induced upregulation of Nox4 (1.5-fold; P<0.05) within 5 minutes, accompanied by increases in O(2)(-) (3.5-fold; P<0.01) from the nuclear membrane and nuclear exit of HDAC4 in cardiomyocytes. Knockdown of Nox4, but not Nox2, attenuated O(2)(-) production in the nucleus and prevented phenylephrine-induced oxidation and nuclear exit of HDAC4. After continuous infusion of phenylephrine (20 mg/kg per day) for 14 days, wild-type and cardiac-specific Nox4 knockout mice exhibited similar aortic pressures. Left ventricular weight/tibial length (5.7±0.2 versus 6.4±0.2 mg/mm; P<0.05) and cardiomyocytes cross-sectional area (223±13 versus 258±12 μm(2); P<0.05) were significantly smaller in cardiac-specific Nox4 knockout than in wild-type mice. Nuclear O(2)(-)production in the heart was significantly lower in cardiac-specific Nox4 knockout than in wild-type mice (4116±314 versus 7057±1710 relative light unit; P<0.05), and cysteine oxidation of HDAC4 was decreased. HDAC4 oxidation and cardiac hypertrophy were also attenuated in cardiac-specific Nox4 knockout mice 2 weeks after transverse aortic constriction.Nox4 plays an essential role in mediating cysteine oxidation and nuclear exit of HDAC4, thereby mediating cardiac hypertrophy in response to phenylephrine and pressure overload.
A family with complement factor D deficiency
Authors: Douwe H. Biesma, André J. Hannema, Heleen van Velzen-Blad, Leontine Mulder, Rob van Zwieten, Irma Kluijt, Dirk Roos
Journal: Journal of Clinical Investigation (2001)

A complement factor D deficiency was found in a young woman who had experienced a serious Neisseria meningitidis infection, in a deceased family member with a history of meningitis, and in three relatives without a history of serious infections. The patient and these three relatives showed a normal activity of the classical complement pathway, but a very low activity of the alternative complement pathway and a very low capacity to opsonize Escherichia coli and N. meningitidis (isolated from the patient) for phagocytosis by normal human neutrophils. The alternative pathway-dependent hemolytic activity and the opsonizing capacity of these sera were restored by addition of purified factor D. The family had a high degree of consanguinity, and several other family members exhibited decreased levels of factor D. The gene encoding factor D was found to contain a point mutation that changed the TCG codon for serine 42 into a TAG stop codon. This mutation was found in both alleles of the five completely factor D–deficient family members and in one allele of 21 other members of the same family who had decreased or low-normal factor D levels in their serum. The gene sequence of the signal peptide of human factor D was also identified. Our report is the first, to our knowledge, to document a Factor D gene mutation. The mode of inheritance of factor D deficiency is autosomal recessive, in accordance with the localization of the Factor D gene on chromosome 19. Increased susceptibility for infections in individuals with a partial factor D deficiency is unlikely.
Demographic and disease-related predictors of abnormal lung function in patients with established inflammatory polyarthritis and a comparison with the general population
Authors: Suzanne M M Verstappen, Mark Lunt, Robert N Luben, Jackie Chipping, Tarnya Marshall, Kay-Tee Khaw, Nick Wareham, William G Dixon, Ian N Bruce, Deborah P M Symmons
Journal: Annals of the Rheumatic Diseases (2012)

To identify demographic and clinical predictors of obstructive lung disease (OLD) and restrictive lung disease (RLD) in patients with established inflammatory polyarthritis (IP) and to compare the prevalence of respiratory symptoms in patients with IP and the general population.A total of 421 patients with IP underwent a spirometry test 15 years after inclusion in the Norfolk Arthritis Register (NOAR). Logistic regression analyses were performed to assess the predictive ability of demographic and clinical characteristics obtained at inclusion in NOAR and to assess their association with OLD or RLD at 15 years (age- and gender-adjusted). In addition, the prevalence of OLD and RLD was compared with a matched population (1:4) of people participating in the European Prospective Investigation of Cancer-Norfolk, a representative sample of the general population in Norfolk, UK.In this IP population, current smoking was the strongest predictor for OLD and functional disability for RLD. In the comparison study, 11.6% had OLD in the IP population and 4.9% in the general population (adjOR 2.01, 95% CI 1.26 to 3.22). The prevalence of RLD was not statistically different between the IP population and the general population (14.6% vs 17.5%; adjOR 0.76, 95% CI 0.53 to 1.10).OLD, but not RLD, is more prevalent in the IP population than in the general population. Functional disability is especially associated with RLD whereas smoking is associated with OLD. The latter finding, and the known association between smoking and a poor disease prognosis, underlines the importance of smoking cessation in patients with IP.
Cost-Effectiveness of Human Papillomavirus Vaccination and Cervical Cancer Screening in Women Older Than 30 Years in the United States
Authors: Jane J. Kim
Journal: Annals of Internal Medicine (2009)

Background: Women older than 30 years are the main beneficiaries of improved cervical cancer screening with human papillomavirus (HPV) DNA testing. The role of vaccination against HPV types 16 and 18, which is recommended routinely for preadolescent girls, is unclear in this age group. Objective: To assess the health and economic outcomes of HPV vaccination in older U.S. women. Design: Cost-effectiveness analysis with an empirically calibrated model. Data Sources: Published literature. Target Population: U.S. women aged 35 to 45 years. Time Horizon: Lifetime. Perspective: Societal. Intervention: HPV vaccination added to screening strategies that differ by test (cytology or HPV DNA testing), frequency, and start age versus screening alone. Outcome Measures: Incremental cost-effectiveness ratios (2006 U.S. dollars per quality-adjusted life-year [QALY] gained). Results of Base-Case Analysis: In the context of annual or biennial screening, HPV vaccination of women aged 35 to 45 years ranged from $116 950 to $272 350 per QALY for cytology with HPV DNA testing for triage of equivocal results and from $193 690 to $381 590 per QALY for combined cytology and HPV DNA testing, depending on age and screening frequency. Results of Sensitivity Analysis: The probability of HPV vaccination being cost-effective for women aged 35 to 45 years was 0% with annual or biennial screening and less than 5% with triennial screening, at thresholds considered good value for money. Limitation: The natural history of the disease and the efficacy of the vaccine in older women are uncertain. Conclusion: Given currently available information, the effectiveness of HPV vaccination for women older than 30 years who are screened seems to be small. Compared with current screening that uses sensitive HPV DNA testing, HPV vaccination is associated with less attractive cost-effectiveness ratios in this population than those for other, well-accepted interventions in the United States. Primary Funding Source: National Cancer Institute, Centers for Disease Control and Prevention, and the American Cancer Society.
Evaluation of a Self-Administered Oral Glucose Tolerance Test
Authors: M. Angelyn Bethel, Hermione C. Price, Harald Sourij, Sarah White, Ruth L. Coleman, Arne Ring, Irene E.C. Kennedy, Lynne Tucker, Rury R. Holman
Journal: Diabetes Care (2013)

To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting.Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink.The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order.Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.
Stereotactic body radiation therapy and CTLA-4 blockade as a novel therapy for advanced melanoma
Authors: Christina Twyman, Andrew Rech, Ramesh Rengan, Robert Vonderheide, Andy Minn
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Ipilumimab, which is a monoclonal antibody to the inhibitory T-cell receptor CTLA-4, has been shown to improve survival in patients with metastatic melanoma; however, the response rate was only 10%, necessitating the need to develop ways to improve treatment. Anecdotal evidence
Mental Trauma Lingers in Tsunami’s Wake
Authors: Tracy Hampton
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits.
Authors: X J Girerd, A T Hirsch, J P Cooke, V J Dzau, M A Creager
Journal: Circulation Research (1990)

Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that L-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous L-arginine contributes to the modulation of vascular smooth muscle tone in vivo is still controversial. In hypercholesterolemia, resistance vessels do not relax normally in response to pharmacological stimuli that release endothelium-derived relaxing factor; bioassay experiments have suggested that impaired synthesis or release of endothelium-derived relaxing factor accounts, in part, for this blunted relaxation. We hypothesized that hypercholesterolemia reduces arginine metabolism and thereby impairs endothelium-derived relaxing factor synthesis. Accordingly, we designed a study to determine whether exogenous L-arginine could augment endothelium-dependent vasodilation of hind limb resistance vessels in anesthetized cholesterol-fed rabbits. Femoral blood flow was recorded with an electromagnetic flow probe in 16 cholesterol-fed and 12 control rabbits. The hind limb vasodilator responses to incremental intra-arterial infusions of acetylcholine (0.3-9.0 micrograms/kg/min) and nitroprusside (0.3-9.0 micrograms/kg/min) were studied before and during intravenous administration of L-arginine (10 mg/kg/min), D-arginine (10 mg/kg/min), or saline. The vasodilator response to acetylcholine was impaired in cholesterol-fed rabbits as compared with control rabbits. L-Arginine augmented vasodilation to acetylcholine in cholesterol-fed but not in control rabbits. L-Arginine did not alter the effect of nitroprusside in either group. Neither saline nor D-arginine changed the response to either acetylcholine or nitroprusside. Our data demonstrate that exogenous L-arginine normalizes the endothelium-dependent vasodilation of hind limb resistance vessels in cholesterol-fed rabbits.
Evolutionary Origins of Transcription Factor Binding Site Clusters
Authors: Xin He, Thyago S.P.C. Duque, Saurabh Sinha
Journal: Molecular Biology and Evolution (2011)

Empirical studies have revealed that regulatory DNA sequences such as enhancers or promoters often harbor multiple binding sites for the same transcription factor. Such "homotypic site clustering" has been hypothesized as arising out of functional requirements of the sequences. Here, we propose an alternative explanation of this phenomenon that multisite enhancers are common because they are favored by evolutionary sampling of the genotype–phenotype landscape. To test this hypothesis, we developed a new computational framework specialized for population genetic simulations of enhancer evolution. It uses a thermodynamics-based model of enhancer function, integrating information from strong as well as weak binding sites, to determine the strength of selection. Using this framework, we found that even when simpler genotypes exist for a desired strength of regulation, relatively complex genotypes (enhancers with more sites) are more readily reached by the simulated evolutionary process. We show that there are more ways to "build" a fit genotype with many weak sites than with a few strong sites, and this is why evolution finds complex genotypes more often. Our claims are consistent with an empirical analysis of binding site content in enhancers characterized in Drosophila melanogaster and their orthologs in other Drosophila species. We also characterized a subtle but significant difference between genotypes likely to be sampled by evolution and equally fit genotypes one would obtain by uniform sampling of the fitness landscape, that is, an "evolutionary signature" in enhancer sequences. Finally, we investigated potential effects of other factors, such as rugged fitness landscapes, short local duplications, and noise characteristics of enhancers, on the emergence of homotypic site clustering.
The nature of complications following liver biopsy in transplant patients with Roux-en-Y choledochojejunostomy
Authors: Joseph S. Galati, Howard P. Monsour, Jeremiah P. Donovan, Rowen K. Zetterman, Daniel F. Schafer, Alan N. Langnas, Byers W. Shaw, Michael F. Sorrell
Journal: Hepatology (1994)

Liver biopsy is an important diagnostic tool in the management of patients following orthotopic liver transplant. We evaluated complications following percutaneous liver biopsy in a group of liver transplant patients who had Roux-en-Y choledochojejunostomies fashioned as part of their biliary reconstruction during liver transplantation. Complications were divided into two major groups: septic complications (including fever, symptomatic bacteremia, cholangitis, infected hematoma and hypotension related to sepsis) and bleeding (defined as hypotension requiring volume expansion greater than 500 cm3 or blood transfusion, hemothorax, intrahepatic or peritoneal hemorrhage and hemobilia occurring within 1 wk of liver biopsy). One hundred ninety-two biopsies were performed in 46 patients with choledochojejunostomies, and 118 biopsies were carried out in an age- and sex-matched control group of patients with choledochocholedochostomy biliary anastomosis. There were no septic complications in the choledochojejunostomy patients and one (0.32%) septic complication in the choledochocholedochostomy patients (NS). Eight bleeding complications occurred (2.6%) in eight patients (8.3%). Five (2.6%) occurred in five (10.8%) of the choledochojejunostomy patients, vs. three (2.5%) in three (6.5%) choledochocholedochostomy patients (NS). None of the bleeding complications required surgical intervention or was fatal. We conclude that liver biopsy in posttransplant patients with Roux-en-Y choledochojejunostomies is a safe procedure and that the incidences of complications were similar in our two groups. The negligible incidence of septic complications in the choledochojejunostomy patients does not appear to warrant the administration of prophylactic antibiotics, as has been previously suggested.
Sister chromatid exchange frequencies in patients with scleroderma and their relatives.
Authors: R G Palmer, R S Pereira, C J Dore, A M Denman
Journal: Annals of the Rheumatic Diseases (1986)

Sister chromatid exchange (SCE) analysis is a sensitive measure of chromosome damage induced by many agents which damage DNA. These agents have been reported to be present in the serum of patients with scleroderma. Chromosome aberrations are thought to be more common in cells of these patients and their relatives than in cells of controls. We have observed that the SCE frequencies in blood lymphocytes of patients with scleroderma and their relatives do not differ from those of controls.
Protein A immunoadsorption: a novel and effective adjuvant treatment of severe pemphigus
Authors: E. Schmidt, E. Klinker, A. Opitz, S. Herzog, C. Sitaru, M. Goebeler, B. Mansouri Taleghoni, E-B. Brocker, D. Zillikens
Journal: British Journal of Dermatology (2003)

Journal Article Protein A immunoadsorption: a novel and effective adjuvant treatment of severe pemphigus Get access E. Schmidt, E. Schmidt Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar E. Klinker, E. Klinker Transfusion Medicine and Immunohematology, University of Würzburg, Josef‐Schneider‐Str. 2, 97080 Würzburg, Germany Search for other works by this author on: Oxford Academic Google Scholar A. Opitz, A. Opitz Transfusion Medicine and Immunohematology, University of Würzburg, Josef‐Schneider‐Str. 2, 97080 Würzburg, Germany Search for other works by this author on: Oxford Academic Google Scholar S. Herzog, S. Herzog Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar C. Sitaru, C. Sitaru Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar M. Goebeler, M. Goebeler Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar B. Mansouri Taleghoni, B. Mansouri Taleghoni Division of Transfusion Medicine, Central Haematological Laboratory, University Clinics, Inselspital, Berne, Switzerland Search for other works by this author on: Oxford Academic Google Scholar E‐B. Bröcker, E‐B. Bröcker Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar D. Zillikens D. Zillikens Departments of Dermatology and Dr Detlef Zillikens. E‐mail: zillikens‐d.derma@mail.uni‐wuerzburg.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 6, 1 June 2003, Pages 1222–1229, https://doi.org/10.1046/j.1365-2133.2003.05302.x Published: 01 June 2003 Article history Accepted: 09 October 2002 Published: 01 June 2003