tbuckley/cabot-search huggingface dataset:
Gene Transfer of Dominant-Negative Mutants of Extracellular Signal–Regulated Kinase and c-Jun NH2-Terminal Kinase Prevents Neointimal Formation in Balloon-Injured Rat Artery
Authors: Yasukatsu Izumi, Shokei Kim, Masashi Namba, Hideo Yasumoto, Hitoshi Miyazaki, Masaaki Hoshiga, Yasufumi Kaneda, Ryuichi Morishita, Yumei Zhan, Hiroshi Iwao
Journal: Circulation Research (2001)

We previously reported that extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), belonging to mitogen-activated protein kinases, are rapidly activated in balloon-injured artery. Therefore, we examined the role of these kinase activations in neointimal formation by using an in vivo gene transfer technique. We made the dominant-negative mutants of ERK (DN-ERK) and JNK (DN-JNK) to specifically inhibit endogenous ERK and JNK activation, respectively. Before balloon injury, these mutants were transfected into rat carotid artery using the hemagglutinating virus of Japan liposome method. In vivo transfection of DN-ERK and DN-JNK significantly suppressed the activation of ERK and JNK, respectively, after balloon injury, confirming successful expression of the transfected genes. Neointimal formation at 14 and 28 days after injury was prevented by gene transfer of DN-ERK or DN-JNK. Furthermore, bromodeoxyuridine labeling index and total cell-counting analysis at 7 days showed that either DN-ERK or DN-JNK remarkably suppressed smooth muscle cell (SMC) proliferation in both the intima and the media after injury. Gene transfer of wild-type ERK (W-ERK) or JNK (W-JNK) significantly enhanced neointimal hyperplasia at 14 days after injury. Furthermore, DN-ERK and DN-JNK significantly suppressed serum-induced SMC proliferation in vitro. We obtained the first evidence that in vivo gene transfer of DN-ERK or DN-JNK prevented neointimal formation in balloon-injured artery by inhibiting SMC proliferation. Thus, ERK and JNK activation triggers SMC proliferation, leading to neointimal formation. These kinases may be the new therapeutic targets for prevention of vascular diseases.
Lead, Mercury, and Arsenic in US- and Indian-Manufactured Ayurvedic Medicines Sold via the Internet
Authors: Robert B Saper, Russell S Phillips, Anusha Sehgal, Nadia Khouri, Roger B Davis, Janet Paquin, Venkatesh Thuppil, Stefanos N Kales
Journal: JAMA (2008)

<h3>Context</h3>Lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be present due to the practice of rasa shastra (combining herbs with metals, minerals, and gems). Whether toxic metals are present in both US- and Indian-manufactured Ayurvedic medicines is unknown.<h3>Objectives</h3>To determine the prevalence of Ayurvedic medicines available via the Internet containing detectable lead, mercury, or arsenic and to compare the prevalence of toxic metals in US- vs Indian-manufactured medicines and between rasa shastra and non–rasa shastra medicines.<h3>Design</h3>A search using 5 Internet search engines and the search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda, indicated for oral use, and available for sale. From 673 identified products, 230 Ayurvedic medicines were randomly selected for purchase in August-October 2005. Country of manufacturer/Web site supplier, rasa shastra status, and claims of Good Manufacturing Practices were recorded. Metal concentrations were measured using x-ray fluorescence spectroscopy.<h3>Main Outcome Measures</h3>Prevalence of medicines with detectable toxic metals in the entire sample and stratified by country of manufacture and rasa shastra status.<h3>Results</h3>One hundred ninety-three of the 230 requested medicines were received and analyzed. The prevalence of metal-containing products was 20.7% (95% confidence interval [CI], 15.2%-27.1%). The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%-30.4%) compared with 19.5% (95% CI, 11.3%-30.1%) in Indian products (P = .86). Rasa shastra compared with non–rasa shastra medicines had a greater prevalence of metals (40.6% vs 17.1%; P = .007) and higher median concentrations of lead (11.5 μg/g vs 7.0 μg/g; P = .03) and mercury (20 800 μg/g vs 34.5 μg/g; P = .04). Among the metal-containing products, 95% were sold by US Web sites and 75% claimed Good Manufacturing Practices. All metal-containing products exceeded 1 or more standards for acceptable daily intake of toxic metals.<h3>Conclusion</h3>One-fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain detectable lead, mercury, or arsenic.
Anthony Robert Trickett
Authors: P. Kettle
Journal: BMJ (2013)

Anthony Robert Trickett (“Tony”) always threw himself into everything he did. After practising for a few years in Pembrokeshire he became singlehanded GP to the island of Hoy in Orkney, where he spent the rest of his life, going part time in 2000 and retiring five5 years later. He was a wise and skilful GP, compassionate, and committed …
Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders. Implications for lymphomagenesis.
Authors: P G Pelicci, D M Knowles, Z A Arlin, R Wieczorek, P Luciw, D Dina, C Basilico, R Dalla-Favera
Journal: The Journal of Experimental Medicine (1986)

AIDS (acquired immune deficiency syndrome) and ARC (AIDS-related complex) are associated with a spectrum of lymphoproliferative disorders ranging from lymphadenopathy syndrome (LAS), an apparently benign polyclonal lymphoid hyperplasia, to B cell non-Hodgkin's lymphoma (B-NHL), i.e., malignant, presumably monoclonal B cell proliferations. To gain insight into the process of lymphomagenesis in AIDS and to investigate a possible pathogenetic relationship between LAS and NHL, we investigated the clonality of the B or T lymphoid populations by Ig or T beta gene rearrangement analysis, the presence of rearrangements involving the c-myc oncogene locus, and the presence of human immunodeficiency virus (HIV) sequences in both LAS and B-NHL biopsies. Our data indicate that multiple clonal B cell expansions are present in a significant percentage of LAS (approximately 20%) and B-NHL (60%) biopsies. c-myc rearrangements/translocations are detectable in 9 of our 10 NHLs, but not in any of the LAS cases. However, only one of the B cell clones, identified by Ig gene rearrangements carries a c-myc gene rearrangement, suggesting that only one clone carries the genetic abnormality associated with malignant B cell lymphoma. Furthermore, the frequency of detection of c-myc rearrangements in AIDS-associated NHLs of both Burkitt and non-Burkitt type suggest that the biological alterations present in AIDS favor the development of lymphomas carrying activated c-myc oncogenes. Finally, our data show that HIV DNA sequences are not detectable in LAS nor in NHL B cell clones, suggesting that HIV does not play a direct role in NHL development. Taken together, these observations suggest a model of multistep lymphomagenesis in AIDS in which LAS would represent a predisposing condition to NHL. Immunosuppression and EBV infection present in LAS can favor the expansion of B cell clones, which in turn may increase the probability of occurrence of c-myc rearrangements leading to malignant transformation.
Relaxed Observance of Traditional Marriage Rules Allows Social Connectivity without Loss of Genetic Diversity
Authors: Elsa G. Guillot, Martin L. Hazelton, Tatiana M. Karafet, J. Stephen Lansing, Herawati Sudoyo, Murray P. Cox
Journal: Molecular Biology and Evolution (2015)

Marriage rules, the community prescriptions that dictate who an individual can or cannot marry, are extremely diverse and universally present in traditional societies. A major focus of research in the early decades of modern anthropology, marriage rules impose social and economic forces that help structure societies and forge connections between them. However, in those early anthropological studies, the biological benefits or disadvantages of marriage rules could not be determined. We revisit this question by applying a novel simulation framework and genome-wide data to explore the effects of Asymmetric Prescriptive Alliance, an elaborate set of marriage rules that has been a focus of research for many anthropologists. Simulations show that strict adherence to these marriage rules reduces genetic diversity on the autosomes, X chromosome and mitochondrial DNA, but relaxed compliance produces genetic diversity similar to random mating. Genome-wide data from the Indonesian community of Rindi, one of the early study populations for Asymmetric Prescriptive Alliance, are more consistent with relaxed compliance than strict adherence. We therefore suggest that, in practice, marriage rules are treated with sufficient flexibility to allow social connectivity without significant degradation of biological diversity.
Sodium, Blood Pressure, and Cardiovascular Disease
Authors: Paul K. Whelton, Lawrence J. Appel, Ralph L. Sacco, Cheryl A.M. Anderson, Elliott M. Antman, Norman Campbell, Sandra B. Dunbar, Edward D. Frohlich, John E. Hall, Mariell Jessup, Darwin R. Labarthe, Graham A. MacGregor, Frank M. Sacks, Jeremiah Stamler, Dorothea K. Vafiadis, Linda V. Van Horn
Journal: Circulation (2012)

Recent reports of selected observational studies and a meta-analysis have stirred controversy and have become the impetus for calls to abandon recommendations for reduced sodium intake by the US general population. A detailed review of these studies documents substantial methodological concerns that limit the usefulness of these studies in setting, much less reversing, dietary recommendations. Indeed, the evidence base supporting recommendations for reduced sodium intake in the general population remains robust and persuasive. The American Heart Association is committed to improving the health of all Americans through implementation of national goals for health promotion and disease prevention, including its recommendation to reduce dietary sodium intake to <1500 mg/d.
Thymic stromal lymphopoietin links keratinocytes and dendritic cell–derived IL-23 in patients with psoriasis
Authors: Elisabetta Volpe, Lucia Pattarini, Carolina Martinez-Cingolani, Stephan Meller, Marie-Helene Donnadieu, Sofia I. Bogiatzi, Maria I. Fernandez, Maxime Touzot, Jean-Christophe Bichet, Fabien Reyal, Maria Paola Paronetto, Andrea Chiricozzi, Sergio Chimenti, Francesca Nasorri, Andrea Cavani, Andreas Kislat, Bernhard Homey, Vassili Soumelis
Journal: Journal of Allergy and Clinical Immunology (2014)
In what way may race, ethnicity or culture influence asthma outcomes?
Authors: M R PARTRIDGE
Journal: Thorax (2000)

In a civilised society it is important that all those in need of health care should have equal access to it and benefit equally from that which is available. There have been some suggestions that asthma outcomes in the UK for those of South Asian origin may be less good than for the rest of the population. This is a subject confounded by generalisations and by statements which are often based on minimal evidence. Caution is needed in comparing local and national studies and studies done many years apart.

There are two key questions regarding asthma and ethnic minority groups, especially Asians. (1) Does the prevalence of asthma vary between ethnic minorities such as South Asians living in the UK? (2) Are the outcomes for asthma care worse for these groups and, if so, why and how do we improve the situation?

The first question is not the main purpose of this editorial but in the USA physician diagnosed asthma has been reported to affect 13.4% of black children and 9.7% of white children.1Black children with asthma have also been reported to have significantly greater restrictions of activity, fewer contacts with doctors, and to be admitted to hospital more frequently than white children with asthma.2 In parallel with this increased suffering among African American children is an increased adult mortality due to asthma, and the death rate has been reported to be rising more quickly in African Americans than white Americans.3 

African Americans constitute approximately 12% of the US population. In the UK ethnic minority groups represent 6.4% of the population and the single largest subgroups are those who came originally from India, Pakistan, and Bangladesh (either directly or via Africa) who represent 3.0% of the total population. (These are subsequently referred to collectively as South …
Sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies.
Authors: W Richter, T Mertens, B Schoel, P Muir, A Ritzkowsky, W A Scherbaum, B O Boehm
Journal: The Journal of Experimental Medicine (1994)

Molecular mimicry between viral antigens and host proteins was often suggested to be involved in induction of autoimmune diseases. In type 1 diabetes where pancreatic beta cells are destroyed by autoimmune phenomena, a linear sequence homology between a major autoantigen, glutamate decarboxylase (GAD), and the 2C protein of coxsackie B4 was identified. In addition, a sequence homology between GAD and the mycobacterial heat shock protein 60 was described and the suggestions were made that molecular mimicry between GAD, coxsackievirus B4-2C protein, and/or heat shock protein 60 (hsp60) may be actively involved in an autoimmune reaction towards the pancreatic beta-cells. Our group was the first to isolate human monoclonal autoantibodies to GAD (MICA 1-6) from a patient with newly diagnosed type 1 diabetes. The MICA allowed a detailed characterization of the diabetes associated self-epitopes in GAD and represent a set of GAD autoantibodies present in sera from patients with type 1 diabetes. Using deletion mutants of GAD we demonstrated that the regions of GAD covering the homology sequences to coxsackievirus B4 and to the hsp60 were absolutely required for binding of the MICA to GAD. We now designed an antibody-based analysis to ask whether molecular mimicry between GAD and coxsackie B4-2C or hsp60 is relevant in type 1 diabetes. Since part of the MICA recognize conformational epitopes, they allow to test for conformational molecular mimicry in viruses that have been incriminated in the development of type 1 diabetes. Our data reveal no crossreactivity between the diabetes associated GAD epitopes defined by the MICA and hsp60, rubellavirus, cytomegalovirus, and coxsackie B1-B6 virus antigens. Neither coxsackie B4-specific antibodies in sera from normal individuals nor GAD-positive sera from patients with type 1 diabetes indicated a crossreactivity between coxsackie B4-2C and GAD. Although the regions in GAD homologous to coxsackie B4-2C and hsp60 represented parts of GAD indispensible for binding of diabetes associated autoantibodies they did not mediate a crossreactivity of autoantibodies between GAD and these two proteins. No evidence for molecular mimicry between GAD and a whole panel of foreign antigens was detected by autoantibodies in type 1 diabetes.
Effects of Gonadal Steroids in Women With a History of Postpartum Depression
Authors: Miki Bloch, Peter J. Schmidt, Merry Danaceau, Jean Murphy, Lynnette Nieman, David R. Rubinow
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression.METHOD: The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women—eight with and eight without a history of postpartum depression—with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales.RESULTS: Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline.CONCLUSIONS: The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.
Norepinephrine Inhibition of Mesenchymal Stem Cell and Chondrogenic Progenitor Cell Chondrogenesis and Acceleration of Chondrogenic Hypertrophy
Authors: Zsuzsa Jenei‐Lanzl, Susanne Grässel, Georg Pongratz, Frieder Kees, Nicolai Miosge, Peter Angele, Rainer H. Straub
Journal: Arthritis & Rheumatology (2014)

Objective Mesenchymal progenitor cell chondrogenesis is the biologic platform for the generation or regeneration of cartilage, but the external influence of the sympathetic nervous system on this process is not yet known. Sympathetic nerve fibers are present in articular tissue, and the sympathetic nervous system influences the musculoskeletal system by, for example, increasing osteoclastogenesis. This study was initiated to explore the role of the sympathetic neurotransmitter norepinephrine (NE) in mesenchymal stem cell (MSC)–dependent and cartilage progenitor cell (CPC)–dependent chondrogenesis. Methods Using human MSCs or CPCs, chondrogenic differentiation was induced in the presence of NE, the specific β‐adrenergic receptor (β‐AR) agonist isoproterenol, and the specific β‐AR antagonist nadolol. We studied sympathetic nerve fibers, tyrosine hydroxylase (TH) expression, catecholamine biosynthesis, and synovial fluid levels in human joints, as well as cartilage‐specific matrix deposition during differentiation. Results TH+ sympathetic nerve fibers were present in the synovial tissue, meniscus, and subchondral bone marrow. In addition, synovial fluid from patients with knee trauma demonstrated high concentrations of NE. During MSC or CPC chondrogenesis, β‐AR were expressed. Chondrogenic aggregates treated with NE or isoproterenol synthesized lower amounts of type II collagen and glycosaminoglycans. NE and isoproterenol treatment dose‐dependently increased the levels of cartilage hypertrophy markers (type X collagen and matrix metalloproteinase 13). Nadolol reversed the inhibition of chondrogenesis and the up‐regulation of cartilage hypertrophy. Conclusion Our findings demonstrate NE‐dependent inhibition of chondrogenesis and acceleration of hypertrophic differentiation. By inhibiting cartilage repair, these sympathetic influences can be important after joint trauma. These findings may be a basis for novel neurochondrogenic therapeutic options.
Does polysomnography predict post-operative respiratory complications after adeno-tonsillectomy?
Authors: Surendran Thavagnanam, Saou Yinn Cheong, Anna Marie Nathan, Anura Manuel, Jessie De Bruyne
Journal: European Respiratory Journal (2014)

Polysomnography (PSG) assesses the severity of obstructive sleep apneoa (OSA) and has traditionally been used to predict respiratory complications after adenotonsillectomy. In our centre, availability of a paediatric intensive care bed (PICU) for close post-operative monitoring is mandatory before adenotonsillectomies are performed in children with severe OSA. This has resulted in long waiting lists and cancellation of surgery.  Aim: To determine if PSGs predict post-operative respiratory complications following adenotonsillectomy in children with severe OSA.  Methodology: We performed a retrospective review of 107 children aged three to eighteen years with clinical suspicion of OSA and who underwent an overnight PSG. The PSGs were graded as per the 2007 American Academy of Sleep Medicine guidelines.  Results: Overall, the median AHI was 4 (0 to 164) events/hour and the mean post-operative hospital stay was 2 days (SD=1). Out of 35 children with severe OSA, half had nadir SpO2 of less than 80% and an AHI greater than 24 events/hour. Fifteen of these children underwent surgery and none of them had any post-operative respiratory complications. All of the children recovered well post-operatively and needed no further support upon discharge.  Conclusion: PSGs may not predict post-operative respiratory complications in children with OSA.
Effect of Carvedilol on the Morbidity of Patients With Severe Chronic Heart Failure
Authors: Milton Packer, Michael B. Fowler, Ellen B. Roecker, Andrew J.S. Coats, Hugo A. Katus, Henry Krum, Paul Mohacsi, Jean L. Rouleau, Michal Tendera, Christoph Staiger, Terry L. Holcslaw, Ildiko Amann-Zalan, David L. DeMets
Journal: Circulation (2002)

Background— β-Blocking agents improve functional status and reduce morbidity in mild-to-moderate heart failure, but it is not known whether they produce such benefits in severe heart failure. Methods and Results— We randomly assigned 2289 patients with symptoms of heart failure at rest or on minimal exertion and with an ejection fraction &lt;25% (but not volume-overloaded) to double-blind treatment with either placebo (n=1133) or carvedilol (n=1156) for an average of 10.4 months. Carvedilol reduced the combined risk of death or hospitalization for a cardiovascular reason by 27% ( P =0.00002) and the combined risk of death or hospitalization for heart failure by 31% ( P =0.000004). Patients in the carvedilol group also spent 27% fewer days in the hospital for any reason ( P =0.0005) and 40% fewer days in the hospital for heart failure ( P &lt;0.0001). These differences were as a result of both a decrease in the number of hospitalizations and a shorter duration of each admission. More patients felt improved and fewer patients felt worse in the carvedilol group than in the placebo group after 6 months of maintenance therapy ( P =0.0009). Carvedilol-treated patients were also less likely than placebo-treated patients to experience a serious adverse event ( P =0.002), especially worsening heart failure, sudden death, cardiogenic shock, or ventricular tachycardia. Conclusion— In euvolemic patients with symptoms at rest or on minimal exertion, the addition of carvedilol to conventional therapy ameliorates the severity of heart failure and reduces the risk of clinical deterioration, hospitalization, and other serious adverse clinical events.