tbuckley/cabot-search huggingface dataset:
Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability
Authors: Jacob S. Lee, Cristina M. Tato, Barbara Joyce-Shaikh, Muhammet F. Gulen, Corinne Cayatte, Yi Chen, Wendy M. Blumenschein, Michael Judo, Gulesi Ayanoglu, Terrill K. McClanahan, Xiaoxia Li, Daniel J. Cua
Journal: Immunity (2015)
Primary Culture of Human Mammary Epithelial Cells Embedded in Collagen Gels&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: J Yang, R Guzman, J Richards, V Jentoft, M R DeVault, S R Wellings, S Nandi
Journal: JNCI Journal of the National Cancer Institute (1980)

Human mammary epithelial cells were dissociated from mastectomy tissues. The contaminating fibroblasts were removed by the use of Percoll density-gradient centrifugation, which utilizes the difference in buoyant densities between epithelial cells and fibroblasts. A preparation highly enriched for mammary epithelial cells was then embedded in collagen gel and cultured in Ham's F12 medium containing 12.5% horse serum, 2.5% fetal calf serum, 0.1 μg cholera toxin/ml, an extract prepared from human male urine (6 μg protein/ml), and a hormone combination of 10 μg insulin/ml, 10 μg human placental lactogen/ml, 1 μg aldosterone/ml, and 0.5 μg hydrocortisone/ml. Sustained growth leading to an increase of tenfold to thirtyfold in cell number over the initial value was accomplished in primary culture, and this growth was maintained even after passage to secondary culture. Deletion of either the urine extract or the hormone combination resulted in less than optimal growth. Subsequent studies showed that hydrocortisone alone could replace the hormone combination. In addition, urine extract could be replaced by extracts prepared from human kidneys or brains. The collagen gel system provides a reproducible and consistent method for sustained three-dimensional growth of mammary epithelial cells from human breast tissue in primary as well as passaged cultures.
Tuberculosis (TB) and young age
Authors: Maria Korzeniewska-Kosela
Journal: European Respiratory Journal (2014)

Aim: Comparison of TB features in children, adolescents and young adults.  Method: Data from TB Register were analyzed. Statistical significance (Si) was assessed with chi2 test.  Results: In total (IT) 10.1807 TB cases were notified from 2002 to 2013 in Poland including 341 cases below 5year of life (A); 313 aged 6 to 10 yrs (B), 654 aged 11 to 15 yrs (C); 2168 aged 16 to 20 yrs (D) and 3784 aged 21 to 25 yrs (E).  Pulmonary TB as the sole (91.5 % IT) was in similar proportion in A and B (35.2% and 33.5%). With age proportion rose to 88.6 % (Si). Pulmonary TB was culture confirmed (IT 63.7%) in 36.3% of A; 29.8 % of B; 50.7 % of C; 65.2% of D; 68.9 % of E (Si, except A v B). Smears were positive (IT 39,4%) in 17.4 % of A; 10.8 % of B; 19.3 % of C; 40.4 % of D(Si); 45.0 % of E (Si).  Solely extrapulmonary TB (IT 7.8%) occurred in 60.4 % of A; 63.6 % of B; 42.7% of C; 10.9% of D; 8.2% of E (Si, except A v B). Miliary TB was most often in B (2.2%); TB meningitis in A (2.6%). Isoniazid resistance and MDR-TB were most often in C (8.8% and 3.5%; IT 3.1 and 0.7%). Pleural TB (IT 3.2%) was in 2.0% of A; 6.7 % of B (Si); 7.6 % of C; 5.8% of D; 4.9 % of E.  Occurrence ofchest lymph nodes TB (IT-0,6%) decreased in consecutive groups from 42 % to 0.2%)(Si, except A v B).  In all groups except C, there were more males, most in E (54,8%) (67% in IT).  Defaulters (IT 8,8%) were 3.4 % in A; 2.4 % in B; 3.9 % in C; 5.3 % in D; 6.7% in E (Si).  Conclusion: Extrapulmonary TB predominates in children up to10 yrs. With age pulmonary TB continues to emerge. Young aged 21 to 25 yrs as the first have the TB characteristics similar to whole population of patients. Teenagers and young adults require concern because infectious TB, drug resistance and default are common in these groups.
Enhanced Risk Profiling of Implanted Defibrillator Shocks With Circulating SCN5A mRNA Splicing Variants
Authors: Ge Gao, Vikram Brahmanandam, Mihai Raicu, Lianzhi Gu, Li Zhou, Srinivasan Kasturirangan, Anish Shah, Smita I. Negi, Melissa R. Wood, Ankit A. Desai, Antone Tatooles, Alan Schwartz, Samuel C. Dudley
Journal: Journal of the American College of Cardiology (2014)
Vaccinations with RNA coding for tumor associated antigens in advanced RCC patients—A phase I/II study
Authors: S. M. Schmidt, M. Haentschel, M. R. Mueller, J. Wierecky, L. Kanz, O. Maksimovic, A. Stenzl, W. Brugger, S. Pascolo, P. Brossart
Journal: Journal of Clinical Oncology (2008)

3017 Background: RCC is recognized as an immunogenic tumor and several TAA are known to be widely expressed on RCC. In previous experiments intradermal vaccination of naked RNA in mice showed that this approach leads to expression of the corresponding protein and induction of a protective antitumor immunity. Methods: Based on these results we conducted a phase I/II trial to evaluate feasibility, safety and efficacy as well as immunological responses of RNA vaccination in patients with metastatic RCC. Vaccination was performed with mRNA encoding for TAA using 2 different treatment arms. Eligibility criteria included bidimensionally measurable lesions, age 18 to 79 years and a 6 week interval to last therapy. In vitro transcribed RNA was generated using plasmids coding for the TAA MUC1, CEA, Her-2/neu, telomerase, survivin and MAGE-1. Vaccinations were performed intradermally on days 1, 14, 28 and 42 in arm A and on days 0–3, 7–10, 28 and 42 in an intensified arm B. Subsequently vaccinations were repeated monthly until documented tumor progression. On the day following RNA vaccination GM-CSF was applicated s.c. Results: 30 patients aged 36 to 79 years were enrolled in this study, 14 in arm A and 16 in arm B. All patients had progressive disease and had received previous therapy. Treatment was well tolerated with no severe side effects. In arm A 1 patient showed tumor shrinkage of pulmonary metastasis. 42.9% of patients survived more than 24 months with a median survival of 15.1 months for the whole population. 7 of 14 patients showed stable disease (RECIST) at analysis on day 42. 85.7% of these patients survived more than 24 months (after first vaccination). In the intensified arm B tumor shrinkage was observed in 2 patients with 52.9% surviving more than 2 years. The median survival for the whole population was 20 months. 12 of 17 showed stable disease on d42. 90% of these patients survived more than 2 years (after first vaccination). In ongoing ELISPOT assays CD4+ and CD8+ T cell induction could be shown for several TAA. Furthermore, induced cyctotoxic T cells lysed HLA matched tumor cells in an antigen specific manner. Conclusions: This study demonstrates that vaccination with RNA coding for TAA can be effective in the treatment of RCC patients and induces clinical and immunological responses. No significant financial relationships to disclose.
Response Inhibition During Differential Reinforcement of Low Rates (DRL) Schedules May Be Sensitive to Low-Level Polychlorinated Biphenyl, Methylmercury, and Lead Exposure in Children
Authors: Paul W. Stewart, David M. Sargent, Jacqueline Reihman, Brooks B. Gump, Edward Lonky, Thomas Darvill, Heraline Hicks, James Pagano
Journal: Environmental Health Perspectives (2006)

Animal studies have shown that exposure to common, low-level environmental contaminants [e.g., polychlorinated biphenyls (PCBs), lead] causes excessive and inappropriate responding on intermittent reinforcement schedules. The Differential Reinforcement of Low Rates task (DRL) has been shown to be especially sensitive to low-level PCB exposure in monkeys.We investigated the relationships between prenatal PCB and postnatal Pb exposure performance on a DRL schedule in children. We predicted that a) prenatal PCB exposure would reduce interresponse times (IRTs) and reinforcements earned, and b) postnatal Pb exposure would reduce IRTs and reinforcements earned.We tested 167 children on a DRL20 (20 sec) reinforcement schedule, and recorded IRTs and the number of reinforced responses across the session. We measured prenatal PCB exposure (cord blood), methylmercury (MeHg) (maternal hair), and postnatal Pb exposure (venous blood), and > 50 potentially confounding variables.Results indicated impaired performance in children exposed to PCBs, MeHg, and Pb. Children prenatally exposed to PCBs responded excessively, with significantly lower IRTs and fewer reinforcers earned across the session. In addition, exposure to either MeHg or Pb predicted statistically significant impairments of a similar magnitude to those for PCBs, and the associated impairments of all three contaminants (PCB, MeHg, and Pb) were statistically independent of one another.These results, taken with animal literature, argue the high sensitivity of DRL performance to low-level PCB, MeHg, and Pb exposure. Future research should employ behavioral tasks in children, such as DRL, that have been demonstrably sensitive to low-level PCB, MeHg, and Pb exposure in animals.
Systematic Mutation Analysis of the Catechol <i>O</i>-Methyltransferase Gene as a Candidate Gene for Schizophrenia
Authors: Chia-Hsiang Chen, Yu-Ru Lee, Ming-Yi Chung, Fu-Chuan Wei, Farn-Jong Koong, Cheng-Kuang Shaw, Jih-I Yeh, Kwang-Jen Hsiao
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Catechol O-methyltransferase (COMT) is involved in the degradation of catecholamine neurotransmitters. Recent linkage studies of schizophrenia and molecular studies of velocardiofacial syndrome suggest that the COMT gene might be a candidate gene for schizophrenia. METHOD: The authors systematically searched for mutations and microdeletion of the COMT gene in 177 Chinese schizophrenic patients from Taiwan; 99 comparison subjects were also studied. RESULTS: Five molecular variants were identified: c.186C>T at exon 3, c.408C>G at exon 4, c.472G>A at exon 4, c.597G>A at exon 5, and c.821-827insC at the 3′ untranslated region. However, no differences in the genotype and haplotype frequencies of these molecular variants between the schizophrenic and comparison subjects were detected. Furthermore, no microdeletion was identified among the patients. CONCLUSIONS: These data suggest that the COMT gene does not play a major role in the pathogenesis of schizophrenia, and the genotypic overlap between schizophrenia and velocardiofacial syndrome was rare in this cohort.
Effect of supplementation with vitamin A or beta carotene on mortality related to pregnancy
Authors: K Vijayaraghavan, K. Krishnaswamy, H P S Sachdev, C. Ronsmans, O. Campbell, M. Collumbien, K. P West, J. Katz, S. Khatry
Journal: BMJ (1999)

A comparative study was conducted to examine the effects of vitamin A and B carotene supplementation on mortality risk during pregnancy.  Two groups (1 treatment and 1 control group) were formed to compare the effects.  The results showed that women who had consumed 80% of the intended quantity of vitamin A or vitamin B supplements during pregnancy reduced the risk of mortality by 40-50%.  Related risk for both vitamin A and B were not significant but were significant upon pooling.  Serum retinol levels in the B carotene and placebo groups were comparable but there was a significant difference between the vitamin A and placebo groups (p < 0.001).  In conclusion a much more detailed study is required before claims can be made that vitamin A and B carotene supplementation reduce mortality risk among pregnant women by as much as 40-50%.
Familial Risks of Tourette Syndrome and Chronic Tic Disorders
Authors: David Mataix-Cols, Kayoko Isomura, Ana Pérez-Vigil, Zheng Chang, Christian Rück, K. Johan Larsson, James F. Leckman, Eva Serlachius, Henrik Larsson, Paul Lichtenstein
Journal: JAMA Psychiatry (2015)

Tic disorders, including Tourette syndrome (TS) and chronic tic disorders (CTDs), are assumed to be strongly familial and heritable. Although gene-searching efforts are well under way, precise estimates of familial risk and heritability are lacking. Previous controlled family studies were small and typically conducted within specialist clinics, resulting in potential ascertainment biases. They were also underpowered to disentangle genetic from environmental factors that contribute to the observed familiality. Twin studies have been either very small or based on parent-reported tics in population-based (nonclinical) twin samples.To provide unbiased estimates of familial risk and heritability of tic disorders at the population level.In this population cohort, multigenerational family study, we used a validated algorithm to identify 4826 individuals diagnosed as having TS or CTDs (76.2% male) in the Swedish National Patient Register from January 1, 1969, through December 31, 2009.We studied risks for TS or CTDs in all biological relatives of probands compared with relatives of unaffected individuals (matched on a 1:10 ratio) from the general population. Structural equation modeling was used to estimate the heritability of tic disorders.The risk for tic disorders among relatives of probands with tic disorders increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives (odds ratio [OR], 18.69; 95% CI, 14.53-24.05) were significantly higher than for second-degree relatives (OR, 4.58; 95% CI, 3.22-6.52) and third-degree relatives (OR, 3.07; 95% CI, 2.08-4.51). First-degree relatives at similar genetic distances (eg, parents, siblings, and offspring) had similar risks for tic disorders despite different degrees of shared environment. The risks for full siblings (50% genetic similarity; OR, 17.68; 95% CI, 12.90-24.23) were significantly higher than those for maternal half siblings (25% genetic similarity; OR, 4.41; 95% CI, 2.24-8.67) despite similar environmental exposures. The heritability of tic disorders was estimated to be 0.77 (95% CI, 0.70-0.85). There were no differences in familial risk or heritability between male and female patients.Tic disorders, including TS and CTDs, cluster in families primarily because of genetic factors and appear to be among the most heritable neuropsychiatric conditions.
Mortality of bullous pemphigoid in Switzerland: a prospective study
Authors: B. Cortés, G. Marazza, L. Naldi, C. Combescure, L. Borradori
Journal: British Journal of Dermatology (2011)

Background Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and has been associated with a significant morbidity and an increased mortality rate. Objectives Our aims were: (i) to evaluate the mortality rate of BP in Swiss patients during the first 3 years after the diagnosis of BP, as the primary endpoint; and (ii) to compare this mortality rate with that of the general Swiss population and determine prognostics factors, as secondary endpoints. Methods All new cases of BP diagnosed in Switzerland between 1 January 2001 and 31 December 2002 were collected prospectively by means of a standardized data collection form. After collection of the data, the treating physicians were asked to specify the course and evolution of the disease. In total, 115 patients were included in our study. Results The 1‐, 2‐ and 3‐year probability of death were 20·9%, 28·0% and 38·8%, respectively. The mortality rate of patients with BP was three times higher than that of age‐ and sex‐matched members of the general Swiss population. Besides age, the presence of neurological diseases at diagnosis was associated with increased mortality in multivariate analysis. Conclusion This is the first prospective study analysing the mortality rate of BP in an entire country. The calculated mortalities are in the lower range of those reported in previous European studies. However, in line with the latter, our findings confirm a high case‐fatality rate for BP, with an increased 1‐year mortality rate compared with the expected mortality rate for age‐ and sex‐adjusted general population.
Late-breaking abstract: Determination of anaerobic threshold through different methodologies during ramp protocol in elderly healthy men
Authors: Michel Reis, Ross Arena, Danilo Berton, Adriano Barroco, Aparecida Catai, J. Alberto Neder, Audrey Borghi-Silva
Journal: European Respiratory Journal (2011)

For assessing the cardiopulmonary integration during aerobic exercise, anaerobic threshold (AT) has been an important index of performance. Additionally, the respiratory compensation threshold (RCT) has been useful for determining performance of quasi-maximum intensities (Wasserman et al., 1983). The aim of this study to identify the anaerobic threshold (AT) obtained from the V-slope method, visual inspection of oxihemoglobin (O2Hb) and deoxihemoglobin (HHb) curves and compare findings with the heteroscedastic (HS) method applied to VCO2, heart rate (HR) and HHb data. Fourteen healthy-men were subjected to cardiopulmonary testing (CPX) on a cycle-ergometer until physical exhaustion. Biological signals collected during CPX included: ventilatory variables; spectroscopy by NIRS; and HR by a cardiofrequencymeter. We observed temporal equivalence and similar values of power, VO2 (mL/min), VO2 (mL kg-1 min-1) and HR at AT by the detection methods performed. In addition, by the Bland-Altman plot (Fig. 1), HR confirmed the good agreement between the methods with biases between -1.3 and 3.5 bpm.

![Figure][1] 



In conclusion: (i) all detection methods were sensitive in identifying AT, including the HS applied to HR and (ii) the methods showed a good correlation in the identification of AT. Thus the results support the HR seems to be a valid parameter in determining the AT of the individuals in our study (Grants: FAPESP)

 [1]: pending:yes
Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis
Authors: Anna Baghdasaryan, Claudia D. Fuchs, Christoph H. Österreicher, Ursula J. Lemberger, Emina Halilbasic, Ingrid Påhlman, Hans Graffner, Elisabeth Krones, Peter Fickert, Annika Wahlström, Marcus Ståhlman, Gustav Paumgartner, Hanns-Ulrich Marschall, Michael Trauner
Journal: Journal of Hepatology (2015)

Approximately 95% of bile acids (BAs) excreted into bile are reabsorbed in the gut and circulate back to the liver for further biliary secretion. Therefore, pharmacological inhibition of the ileal apical sodium-dependent BA transporter (ASBT/SLC10A2) may protect against BA-mediated cholestatic liver and bile duct injury.Eight week old Mdr2(-/-) (Abcb4(-/-)) mice (model of cholestatic liver injury and sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) - a highly potent and selective ASBT inhibitor - or a chow diet. Liver injury was assessed biochemically and histologically after 4weeks of A4250 treatment. Expression profiles of genes involved in BA homeostasis, inflammation and fibrosis were assessed via RT-PCR from liver and ileum homogenates. Intestinal inflammation was assessed by RNA expression profiling and immunohistochemistry. Bile flow and composition, as well as biliary and fecal BA profiles were analyzed after 1week of ASBT inhibitor feeding.A4250 improved sclerosing cholangitis in Mdr2(-/-) mice and significantly reduced serum alanine aminotransferase, alkaline phosphatase and BAs levels, hepatic expression of pro-inflammatory (Tnf-α, Vcam1, Mcp-1) and pro-fibrogenic (Col1a1, Col1a2) genes and bile duct proliferation (mRNA and immunohistochemistry for cytokeratin 19 (CK19)). Furthermore, A4250 significantly reduced bile flow and biliary BA output, which correlated with reduced Bsep transcription, while Ntcp and Cyp7a1 were induced. Importantly A4250 significantly reduced biliary BA secretion but preserved HCO3(-) and biliary phospholipid secretion resulting in an increased HCO3(-)/BA and PL/BA ratio. In addition, A4250 profoundly increased fecal BA excretion without causing diarrhea and altered BA pool composition, resulting in diminished concentrations of primary BAs tauro-β-muricholic acid and taurocholic acid.Pharmacological ASBT inhibition attenuates cholestatic liver and bile duct injury by reducing biliary BA concentrations in mice.
Phase I/pharmacokinetic study of thioguanine administered as a 48-hour continuous intraperitoneal infusion.
Authors: S Zimm, S M Cleary, C N Horton, S B Howell
Journal: Journal of Clinical Oncology (1988)

Thioguanine (TG) is an antimetabolite with established antileukemic activity. The most pharmacologically rational manner of TG administration is continuous infusion. Intraperitoneal (IP) delivery of TG provides the opportunity to definitively test the concept of high-dose, long-term antimetabolite administration. The high systemic clearance and in vitro activity of TG against ovarian carcinoma suggested that it would be an excellent candidate for IP administration as a prolonged infusion. TG was administered as a 48-hour continuous IP infusion in this phase I/pharmacokinetic study. TG infusions were administered using a portable, programmable pump (Pancretec Provider Model 2000; Pancretec, Inc, San Diego). Twenty-five patients were treated. At a dose of 900 mg/m2/48 h, TG produced unacceptably severe myelosuppression. The dose-limiting toxicity was granulo-cytopenia. Other toxicities were mild: emesis, alopecia, skin rashes, and photosensitivity reactions. IP TG did not produce chemical peritonitis, hepatotoxicity, or mucositis. The pharmacokinetics of IP TG were determined in 16 patients. TG levels were measured by reverse-phase high-performance liquid chromatography (HPLC). At steady state, the mean peritoneal to plasma TG ratio was 1,800 at the maximum tolerated dose (MTD). Steady-state TG levels in the peritoneal cavity and plasma were 2 mmol/L and 1.1 mumol/L, respectively, at a dose of 744 mg/m2. The elimination half-life of TG from the peritoneal cavity was one hour. TG exhibited linear pharmacokinetics over the dosage range investigated. Encouraging clinical activity was seen with IP TG. There was one partial response (PR) and four minor responses (MR). TG can be safely administered by the IP route. The recommended dose for phase II testing is 744 mg/m2/48 h. IP TG has a favorable pharmacokinetic advantage and has demonstrated encouraging clinical activity. Further studies of IP TG infusions are warranted.
Different IgE recognition of mite allergen components in asthmatic and nonasthmatic children
Authors: Yvonne Resch, Sven Michel, Michael Kabesch, Christian Lupinek, Rudolf Valenta, Susanne Vrtala
Journal: Journal of Allergy and Clinical Immunology (2015)

House dust mites (HDMs) represent one of the most important inducers of respiratory allergies worldwide.We sought to investigate the IgE and IgG reactivity profiles to a comprehensive panel of HDM allergens in children with allergic asthma and to compare them with those of nonasthmatic atopic children.Sera from clinically well-characterized asthmatic children with HDM allergy (n = 105), nonasthmatic children (n = 53), and nonatopic nonasthmatic children (n = 53) were analyzed for IgE and IgG reactivity to a panel of 7 HDM allergens (nDer p 1, rDer p 2, rDer p 5, rDer p 7, rDer p 10, rDer p 21, and rDer p 23) by means of allergen microarray technology.Asthmatic children with HDM allergy more frequently showed an IgE response to each of the HDM allergens and recognized more allergens than nonasthmatic children with HDM allergy. Furthermore, IgE levels to certain HDM allergens (nDer p 1, P = .002; rDer p 2, P = .007; rDer p 5, P = .031; and rDer p 23, P < .001) were significantly higher in asthmatic children than in children without asthma. By contrast, fewer asthmatic children showed IgG reactivity to HDM allergens than nonasthmatic children, but allergen-specific IgG levels were comparable.The IgE and IgG reactivity profiles to HDM allergens, as well as IgE levels to certain allergen components, differed considerably between children with and without asthmatic symptoms caused by HDM allergy. In fact, asthmatic children were characterized by an expanded IgE repertoire regarding the numbers of recognized allergen components and by increased specific IgE levels.