tbuckley/cabot-search huggingface dataset:
Heritability of Anxiety Sensitivity: A Twin Study
Authors: Murray B. Stein, Kerry L. Jang, W. John Livesley
Journal: American Journal of Psychiatry (1999)

In attempting to explain the familial predisposition to panic disorder, most studies have focused on the heritability of physiologic characteristics (e.g., CO2 sensitivity). A heretofore unexplored possibility is that a psychological characteristic that predisposes to panic-anxiety sensitivity-might be inherited. In this study, the authors examined the heritability of anxiety sensitivity through use of a twin group.Scores on the Anxiety Sensitivity Index were examined in a group of 179 monozygotic and 158 dizygotic twin pairs. Biometrical model fitting was conducted through use of standard statistical methods.Broad heritability estimate of the Anxiety Sensitivity Index as a unifactorial construct was 45%. Additive genetic effects and unique environmental effects emerged as the primary influences on anxiety sensitivity. There was no evidence of genetic discontinuity between normal and extreme scores on the Anxiety Sensitivity Index.This study suggests that one psychological risk factor for the development of panic disorder-anxiety sensitivity-may have a heritable component. As such, anxiety sensitivity should be considered in future research on the heritability of panic disorder.
Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort.
Authors: Gertrud S Berkowitz, Josephine Obel, Elena Deych, Robert Lapinski, James Godbold, Zhisong Liu, Philip J Landrigan, Mary S Wolff
Journal: Environmental Health Perspectives (2002)

Evidence is growing that indoor pesticide exposure is of considerable magnitude in the United States and that pesticide concentrations may be especially high in urban areas. Of particular concern is exposure of pregnant women because animal data suggest that exposure to pesticides during pregnancy and early life may impair neurodevelopment in the offspring. To investigate the relationship between prenatal exposure to indoor pesticides and infant growth and development, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. This article provides data on pesticide exposure based on questionnaire items and analysis of maternal urinary metabolite levels among 386 women. Both the questionnaire and laboratory data revealed that exposure to indoor pesticides was considerable. The proportion of women estimated from questionnaire data as having been exposed during pregnancy to indoor pesticides (approximately 70%) was somewhat lower than the 80-90% of American households who reportedly used pesticides in previous surveys, but some of the latter surveys included both indoor and outdoor pesticide use. Urinary metabolite levels of 3,5,6-trichloro-2-pyridinol (TCPy; median = 11.3 micro g/g creatinine), phenoxybenzoic acid (PBA; median =19.3 micro g/g creatinine), and pentachlorophenol (PCP; median =7.3 micro g/g creatinine) were higher than those reported in other studies of adults in the United States. Furthermore, no associations were evident between the pesticide questionnaire data and the urinary metabolites. Assessments of sociodemographic and building characteristics with questionnaire data and the metabolite levels revealed no consistent trends. Significant temporal variations were observed for urinary PBA but not TCPy or PCP. The temporal variations for PBA were consistent with seasonal spraying of pyrethroid pesticides. These data underscore the need to assess the potentially adverse effects of pesticide exposure on fetuses and infants and the importance of finding alternative methods for pest management to reduce pesticide exposures.
Efficacy and safety of a carbon-dioxide ablative fractional resurfacing device for treatment of atrophic acne scars in Asians
Authors: Woraphong Manuskiatti, Daranporn Triwongwaranat, Supenya Varothai, Sasima Eimpunth, Rungsima Wanitphakdeedecha
Journal: Journal of the American Academy of Dermatology (2010)
Current burden of sudden cardiac death: Multiple source surveillance versus retrospective death certificate-based review in a large U.S. community
Authors: Sumeet S. Chugh, Jonathan Jui, Karen Gunson, Eric C. Stecker, Benjamin T. John, Barbara Thompson, Nasreen Ilias, Catherine Vickers, Vivek Dogra, Mohamud Daya, Jack Kron, Zhi-Jie Zheng, George Mensah, John McAnulty
Journal: Journal of the American College of Cardiology (2004)
Inherited incomplete deficiency of the fourth component of complement (C4) determined by a gene not linked to human histocompatibility leukocyte antigens.
Authors: W A Muir, S Hedrick, C A Alper, O D Ratnoff, B Schacter, J J Wisnieski
Journal: Journal of Clinical Investigation (1984)

We have studied a family in which the proband had systemic lupus erythematosus and selective incomplete deficiency of the fourth component of complement (C4) (2-5% of the normal level). An additional six healthy family members also had low C4 levels (2.4-24.1% of normal) but no evidence of lupus. This form of inherited C4 deficiency differs from that in previously reported families in that inheritance was autosomal dominant (rather than recessive), C4 levels were markedly reduced (but not undetectable), and there was no linkage to HLA, BF, or C4 structural loci, all known to be within the major histocompatibility complex.
BLOOD PLASMA PROTEIN REGENERATION AS INFLUENCED BY INFECTION, DIGESTIVE DISTURBANCES, THYROID, AND FOOD PROTEINS
Authors: S. C. Madden, P. M. Winslow, J. W. Rowland, G. H. Whipple
Journal: The Journal of Experimental Medicine (1937)

When blood plasma proteins are depleted by bleeding, with return of washed red cells (plasmapheresis), it is possible to bring dogs to a steady state of low plasma protein in the circulation and a uniform plasma protein production on a basal diet. Such dogs become test subjects by which the effect of various factors on plasma protein regeneration can be measured. Dogs previously the subjects of plasmapheresis, during long rest periods appear to increase their stores of plasma protein building materials and their blood plasma protein concentrations above former normal levels. A sterile abscess (turpentine) induces a marked reduction in plasma protein regeneration in these test dogs consuming an ample basal diet. The sharp reduction during the initial 24 hours may in part reflect an extravasation of plasma protein into the injured tissue but there also appears to develop a true disturbance of the mechanism which produces plasma proteins. Digestive disturbances interfere seriously with plasma protein production. Whereas large quantities of live yeast upset digestion and form no plasma protein, autoclaved yeast is well utilized, having a potency ratio of 4.4. Amino acids have been tested inadequately. A mixture of cystine, glutamic acid, and glycine does seem to have a definite effect upon protein metabolism and plasma protein production. Iron, under the conditions of these experiments, does not influence the output of plasma proteins. Liver extract (parenteral) is also inert. The proteins of red blood cells when added to the diet are poorly utilized for plasma protein formation and show a potency ratio of only 10.1. Kidney protein added to the kidney basal diet shows a potency ratio of about 5 as compared with 4.6 for that basal diet. A digest of beef stomach and rice polishings shows a potency ratio of about 7.9. Dried powdered serum shows a potency ratio of 3.5, which is much less than fresh serum (2.6). Powdered thyroid fed in doses sufficient to accelerate body metabolism shows no distinct effect upon plasma protein production not attributable to the protein in the thyroid powder itself. Long periods (25 to 30 weeks) of plasma depletion and basal diet intake remove much protein from body fluids and tissues. Associated with this protein depletion the dog loses its appetite and may vomit some food. There is loss of hair, a tendency to skin ulceration, and a distinct lowering of resistance to infection. The plasma protein output may fall to fasting levels in spite of food intake sufficient to maintain weight. We believe this condition to be a deficiency state related to severe depletion of the essential protein matrix of the body cells.
Dysregulated Osteoclastogenesis Is Related to Natural Killer T Cell Dysfunction in Rheumatoid Arthritis
Authors: Hye‐Mi Jin, Seung‐Jung Kee, Young‐Nan Cho, Jeong‐Hwa Kang, Moon‐Ju Kim, Hyun‐Ju Jung, Ki‐Jeong Park, Tae‐Jong Kim, Sang‐Il Lee, Hyuck Choi, Jeong‐Tae Koh, Nacksung Kim, Yong‐Wook Park
Journal: Arthritis & Rheumatology (2015)

To investigate the role played by natural killer T (NKT) cells in osteoclastogenesis and their effects on inflammatory bone destruction.Patients with rheumatoid arthritis (RA) (n = 25) and healthy controls (n = 12) were enrolled in this study. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells (PBMCs) in the presence of macrophage colony-stimulating factor and RANKL. PBMCs were cultured in vitro with α-galactosylceramide (αGalCer), and proliferation indices of NKT cells were estimated by flow cytometry. In vivo effects of αGalCer-stimulated NKT cells on inflammation and bone destruction were determined in mice with collagen-induced arthritis.In vitro osteoclastogenesis was found to be significantly inhibited by αGalCer in healthy controls but not in RA patients. Proliferative responses of NKT cells and STAT-1 phosphorylation in monocytes in response to αGalCer were impaired in RA patients. Notably, αGalCer-stimulated NKT cells inhibited osteoclastogenesis mainly via interferon-γ production in a cytokine-dependent manner (not by cell-cell contact) and down-regulated osteoclast-associated genes. Mice treated with αGalCer showed less severe arthritis and reduced bone destruction. Moreover, proinflammatory cytokine expression in arthritic joints was found to be reduced by αGalCer treatment.This study primarily demonstrates that αGalCer-stimulated NKT cells have a regulatory effect on osteoclastogenesis and a protective effect against inflammatory bone destruction. However, it also shows that these effects of αGalCer are diminished in RA patients and that this is related to NKT cell dysfunction. These findings provide important information for those searching for novel therapeutic strategies to prevent bone destruction in RA.
End-points and clinical trial design in pulmonary arterial hypertension: have we made progress?
Authors: A. J. Peacock, R. Naeije, N. Galiè, L. Rubin
Journal: European Respiratory Journal (2009)

There is enormous interest in the treatment of pulmonary arterial hypertension (PAH), so it is appropriate to consider the design of trials of new therapies and the end-points to be measured when trying to decide whether or not a therapy is effective. In May 2003, the first meeting devoted solely to the discussion of end-points and trial design in PAH was held in Gleneagles, UK. At that time, most of the randomised controlled trials in PAH had used 6-min walking distance and/or resting haemodynamics as their primary end-points. The present article considers the progress that has been made since 2003. It deals with aspects of clinical trial design (such as noninferiority, superiority and withdrawal trials), considers end-points used in previous and current studies (such as 6-min walking distance, time to clinical worsening, haemodynamics, imaging and plasma brain natriuretic peptide), and considers what end-points might be used in the future. The second end-points meeting was held in Turnberry, UK, in June 2007. It had a similar format to the first meeting. Much of what is presented here is a summary of the workshops from that meeting. An attempt has been made to both summarise the current state of end-points and trial design and suggest new ways in which they could be improved. The present article forms one of a series being published in the European Respiratory Journal on pulmonary hypertension.
Contribution of Androgen Deprivation Therapy to Elevated Osteoclast Activity in Men with Metastatic Prostate Cancer
Authors: M. Dror Michaelson, Rose M. Marujo, Matthew R. Smith
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Biochemical markers of both osteoblast and osteoclast activity are elevated in men with osteoblastic metastases from prostate cancer. Androgen deprivation therapy (ADT), the mainstay of therapy for advanced prostate cancer, increases markers of osteoblast and osteoclast activity, even in the absence of bone metastases. Little is known about the relative contributions of ADT and skeletal metastases to elevated bone turnover in men with prostate cancer. Experimental Design: To evaluate the relative contributions of ADT and skeletal metastases to osteoblast and osteoclast activity, we performed a cross-sectional study in three groups of men with advanced prostate cancer: (a) hormone-naïve men without bone metastases; (b) castrate men without bone metastases; and (c) castrate men with bone metastases. The primary study end points were serum levels of bone-specific alkaline phosphatase (BSAP), a marker of osteoblast activity, and N-telopeptide (NTX), a marker of osteoclast activity. Results: Serum levels of both BSAP and NTX were significantly higher in groups of castrate men (groups 2 and 3) than in hormone-naïve men (group 1; P &amp;lt; 0.01 for all comparisons). Among castrate men, serum BSAP was significantly higher in men with bone metastases than in men without bone metastases (P = 0.01). In contrast, serum levels of NTX were similar in groups 2 and 3 (P = 0.33). Conclusions: The unintended effects of ADT on the skeleton are sufficient to explain increased osteoclast activity in castrate men with bone metastases. These results may have important implications for the optimal timing and schedule of osteoclast-targeted therapy in men with advanced prostate cancer.
Optimizing Adjuvant Endocrine Therapy in Postmenopausal Women With Early-Stage Breast Cancer: A Decision Analysis
Authors: Rinaa S. Punglia, Karen M. Kuntz, Eric P. Winer, Jane C. Weeks, Harold J. Burstein
Journal: Journal of Clinical Oncology (2005)

Purpose The optimal adjuvant endocrine strategy for postmenopausal breast cancer is unknown. Options include the antiestrogen tamoxifen, estrogen deprivation with aromatase inhibitors, and sequential therapy with tamoxifen and then an aromatase inhibitor. Methods We developed Markov models to simulate 10-year disease-free survival among postmenopausal women with hormone receptor–positive breast cancer. The treatment strategies analyzed were 5 years of tamoxifen alone, 5 years of an aromatase inhibitor alone, and sequential treatment consisting of tamoxifen with cross over to an aromatase inhibitor at 2.5 or 5 years. Risk estimates were derived from reported randomized clinical trials. Results Sequential therapy with tamoxifen followed by cross over to an aromatase inhibitor at 2.5 years yielded a modest improvement in disease-free survival compared with planned aromatase inhibitor monotherapy. At 10 years, the cross-over strategy yielded absolute disease-free survival rates of 83.7% and 67.6% for node-negative and node-positive patients, respectively, compared with 82.6% and 65.5%, respectively, for aromatase inhibitor monotherapy, which is a 6% relative risk reduction. Sequential therapy improved disease-free survival estimates by year 6 after treatment initiation. Later cross over from tamoxifen to an aromatase inhibitor at 5 years did not further improve 10-year disease-free survival estimates. Sensitivity analyses suggest that sequential treatment strategies optimized 10-year disease-free and distant disease–free survival independent of the degree of the beneficial carryover effect after aromatase inhibitor therapy or the ratio of local to distant tumor recurrence. Conclusion Modeling estimates suggest that sequential adjuvant therapy with tamoxifen followed by an aromatase inhibitor after 2.5 years yields improved outcomes compared with either drug alone or cross-over treatment after 5 years of tamoxifen.
In vitro generation of mechanically functional cartilage grafts based on adult human stem cells and 3D-woven poly(ɛ-caprolactone) scaffolds
Authors: Piia K. Valonen, Franklin T. Moutos, Akihiko Kusanagi, Matteo G. Moretti, Brian O. Diekman, Jean F. Welter, Arnold I. Caplan, Farshid Guilak, Lisa E. Freed
Journal: Biomaterials (2010)
Long-lived immature dendritic cells mediated by TRANCE-RANK interaction
Authors: Isabelle Cremer, Marie-Caroline Dieu-Nosjean, Sylvie Maréchal, Colette Dezutter-Dambuyant, Sarah Goddard, David Adams, Nathalie Winter, Christine Menetrier-Caux, Catherine Sautès-Fridman, Wolf H. Fridman, Chris G. F. Mueller
Journal: Blood (2002)
Hepatitis C: looking at a virus that hasn't been seen.
Authors: L R Overby
Journal: Gut (1993)

Hepatitis C (HCV) is the first virus to be discovered by molecular cloning without direct use of biological or biophysical methods. HCV was first recognised in 1974 as non-A, non-B (NANB) hepatitis resulting from blood transfusions. It took almost 15 years to identify it successfully--by detecting a clone in a library of cDNA prepared from the nucleic acids extracted from plasma known to be infectious for chimpanzees. The clone was derived from a positive-sense RNA of about 10,000 nucleotides, with a long open reading frame encoding for a polyprotein of about 3000 amino acids. The structure of the RNA and the encoded polyprotein had properties similar to known flaviviruses and pestiviruses. Functions of viral proteins produced by proteolytic cleavage of the polyprotein are estimated by analogy with known viruses of similar genomic organisation. Each of the HCV proteins has been produced in recombinant organisms and used as an antigen in immunoassays to investigate serological responses during the course of infection. Seroconversions to both structural and non-structural antigens are observed during the course of disease but typical diagnostic serological patterns have not yet evolved. Immunoassays for HCV antibodies reacting with recombinant antigens are used widely for screening blood donations and for studying the epidemiology of HCV infection. Comparisons of the nucleic acid sequences from different isolates of HCV have shown considerable variability throughout the genome. The importance of this genomic heterogeneity will be a challenging problem for the future.
A Computer Simulation Model of Diabetes Progression, Quality of Life, and Cost
Authors: Honghong Zhou, Deanna J.M. Isaman, Shari Messinger, Morton B. Brown, Ronald Klein, Michael Brandle, William H. Herman
Journal: Diabetes Care (2005)

OBJECTIVE—To develop and validate a comprehensive computer simulation model to assess the impact of screening, prevention, and treatment strategies on type 2 diabetes and its complications, comorbidities, quality of life, and cost. RESEARCH DESIGN AND METHODS—The incidence of type 2 diabetes and its complications and comorbidities were derived from population-based epidemiologic studies and randomized, controlled clinical trials. Health utility scores were derived for patients with type 2 diabetes using the Quality of Well Being–Self-Administered. Direct medical costs were derived for managed care patients with type 2 diabetes using paid insurance claims. Monte Carlo techniques were used to implement a semi-Markov model. Performance of the model was assessed using baseline and 4- and 10-year follow-up data from the older-onset diabetic population studied in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). RESULTS—Applying the model to the baseline WESDR population with type 2 diabetes, we predicted mortality to be 51% at 10 years. The prevalences of stroke and myocardial infarction were predicted to be 18 and 19% at 10 years. The prevalences of nonproliferative diabetic retinopathy, proliferative retinopathy, and macular edema were predicted to be 45, 16, and 18%, respectively; the prevalences of microalbuminuria, proteinuria, and end-stage renal disease were predicted to be 19, 39, and 3%, respectively; and the prevalences of clinical neuropathy and amputation were predicted to be 52 and 5%, respectively, at 10 years. Over 10 years, average undiscounted total direct medical costs were estimated to be $53,000 per person. Among survivors, the average utility score was estimated to be 0.56 at 10 years. CONCLUSIONS—Our computer simulation model accurately predicted survival and the cardiovascular, microvascular, and neuropathic complications observed in the WESDR cohort with type 2 diabetes over 10 years. The model can be used to predict the progression of diabetes and its complications, comorbidities, quality of life, and cost and to assess the relative effectiveness, cost-effectiveness, and cost-utility of alternative strategies for the prevention and treatment of type 2 diabetes.
Congenital broncho-oesophageal fistula associated with tracheal agenesis.
Authors: A Parameswaran, H Krishnaswami, A Walter
Journal: Thorax (1983)

tracheobronchial tree from the floor of the foregutleads to various combinations ofatresia andfistula formation. Someofthese occurwithsufficient frequency toallow classification; the rare variations pose puzzlingproblems of morphogenesis. Therarity ofthemalformation presented hereprompted this report. Casereport A maleinfant wasbornafter 37weeksofanuncomplicated fourth pregnancy toa21-year-old womanwhose previous obstetric history included oneabortion andone stillbirth. Theinfant wasdelivered byspontaneous breech anddidnotbreathe orcryatbirth. Hewasintubated andintermittent positive-pressure respiration wasgiven, butspontaneous respiration wasnever established. Theinitial heart rateof50beats/min gradually declined andthe infant wasdeclared dead40minutes after birth. A tracheo-oesophageal
Prevalence and clonality of Burkholderia cepacia complex genomovars in UK patients with cystic fibrosis referred for lung transplantation
Authors: A De Soyza
Journal: Thorax (2004)

It has previously been reported that patients infected with Burkholderia cenocepacia (genomovar III) before lung transplantation have a poorer outcome than those with other B. cepacia complex infections.An extensive study was conducted to determine the prevalence and clonality of B. cepacia complex genomovars isolated from patients referred for transplant assessment between 1989 to the present and, where appropriate, whether strain type was related to transplant outcome.Isolates from 29 patients were identified as B. cepacia complex organisms by molecular analysis. Thirteen patients (45%) were infected with the highly transmissible ET-12 strain of B. cenocepacia recA lineage III-A, while all remaining patients were infected with genetically unique B. cenocepacia, B. multivorans, and B. vietnamiensis strains. All previously reported deaths following transplantation were associated with ET-12 infection.The ET-12 strain is the predominant cause of B. cenocepacia infections in patients with cystic fibrosis referred to our pulmonary transplant centre and is associated with poor transplant outcomes using standard treatment regimens.