tbuckley/cabot-search huggingface dataset:
<i>Helicobacter pylori</i> independent chronological change in gastric acid secretion in the Japanese
Authors: Y Kinoshita, C Kawanami, K Kishi, H Nakata, Y Seino, T Chiba
Journal: Gut (1997)

Background —Gastric acid secretion in Japanese subjects decreases with aging. One of the possible causative mechanisms of this attenuated acid secretion is speculated to be a Helicobacter pylori induced chronic gastritis. The infection rate of this microorganism has decreased recently in Japan. Aims —To investigate whether gastric acid secretion has altered over the past 20 years, and if so, what the influence of H pylori infection might be in the Japanese population. Subjects and methods —Gastric acid secretion, serum gastrin and pepsinogen I and II concentrations, and H pylori infection were determined in 110 Japanese subjects in both the 1970s and 1990s. Results —Basal acid output as well as maximal acid output have greatly increased over the past 20 years, not only in individuals with H pylori infection but also in those without infection. Furthermore, subjects with H pylori infection tended to show decreased gastric acid secretion in comparison with those without infection, particularly in geriatric subjects. There was a positive correlation between gastric acid secretion and serum pepsinogen I concentrations. Conclusions —In Japan, both basal and stimulated gastric acid secretion have increased over the past 20 years; some unknown factors other than the decrease in H pylori infection may play an important role in this phenomenon.
Propeptide levels of type III and type I procollagen in the serum and bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis
Authors: L Lammi, V Kinnula, S Lahde, J Risteli, P Paakko, E Lakari, L Ryhanen
Journal: European Respiratory Journal (1997)

No single test is available to reliably assess the activity or prognosis of pulmonary sarcoidosis. In this study, we have evaluated two procollagen markers, aminoterminal propeptide of type III procollagen (PIIINP) and carboxyterminal propeptide of type I procollagen (PICP) in serum and bronchoalveolar lavage fluid (BALF) and compared them to other disease markers of pulmonary sarcoidosis, such as serum level of angiotensin converting enzyme (S-ACE) or serum interleukin-2 receptor (S-IL-2R). Bronchoalveolar lavage was performed in 40 sarcoidosis patients without (stages 0-I) and 20 patients with lung parenchymal involvement (stages II-III), as well as in 17 controls. Serum (S)- and BALF-PIIINP and PICP, S-ACE, S-IL-2R, BALF-albumin, BALF-lymphocytes and mast cells were determined in these patients. BALF-PIIINP was clearly and S-PIIINP slightly elevated in sarcoidosis compared to the controls. Similarly BALF-PICP, but not S-PICP, was significantly higher in sarcoidosis. BALF-PIIINP, but not BALF-PICP correlated with S-ACE and S-IL-2R levels. Patients with lung parenchymal disease had higher S-ACE and BALF-PIIINP, but neither S-IL-2R, S-PIIINP nor S- or BALF-PICP were elevated. S-PIIINP and S-IL-2R but not S-ACE were higher in symptomatic than nonsymptomatic patients. Symptomatic patients with parenchymal disease had elevated BALF-PIIINP whereas in the symptomatic nonparenchymal group S-PIIINP was elevated. In conclusion, this is the first study to evaluate carboxyterminal propeptide of type I procollagen in sarcoidosis and showed elevated levels in bronchoalveolar lavage fluid. In contrast to the levels of bronchoalveolar lavage fluid aminoterminal propeptide of type III procollagen, levels of carboxyterminal propeptide of type I procollagen did not correlate with serum level of angiotensin converting enzyme and serum interleukin-2 receptor levels, suggesting that carboxyterminal propeptide of type I procollagen may be less suitable disease marker in sarcoidosis than aminoterminal propeptide of type III procollagen. However, the role of carboxyterminal propeptide of type I procollagen as an indicator of fibrogenesis must be further studied.
ENVIRONMENTAL RISK FACTORS AND FEMALE BREAST CANCER
Authors: Francine Laden, David J. Hunter
Journal: Annual Review of Public Health (1998)

The increasing incidence of breast cancer in the United States and the international variation in risk have led to speculation that environmental risk factors are an important cause of breast cancer. We review the epidemiologic evidence on the breast cancer risk associated with ambient environmental exposures experienced passively by the US population, and discuss the difficulties associated with measurement of specific exposures in environmental studies. We review geographic variation of breast cancer rates in the United States, and exposure to organochlorines, ionizing and electromagnetic radiation, and passive smoking. Results are inconclusive but do not support a major role of environmental risk factors in the etiology of breast cancer.
Evaluating guidelines on continuation of anti-tumour necrosis factor treatment after 3 months: clinical effectiveness and costs of observed care and different alternative strategies
Authors: W Kievit, J Fransen, E M Adang, H H Kuper, T L Jansen, C M A De Gendt, D J R A M De Rooij, H L M Brus, M A F J van de Laar, P C L M Van Riel
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To study the adherence of rheumatologists to the Dutch guidelines for anti-tumour necrosis factor alpha (TNF-α) treatment. The secondary objective was to evaluate alternatives to the present guidelines with regard to the percentage of responders and costs. <h3>Methods:</h3> The response (&gt;1.2 DAS28 decrease) in patients who started on anti-TNF-α treatment for the first time was evaluated at 3 and 6 months after initiation. How many patients continued or discontinued their initial anti-TNF-α treatment was evaluated. Possible alternative guidelines were evaluated by means of a decision tree, with regard to the expected percentage of successfully (responders) and unsuccessfully treated patients and expected costs. <h3>Results:</h3> At 3 months 56% (N = 306) and 44% (N = 233) of all 539 evaluable patients were classified as responders or non-responders, respectively. Despite the guidelines, most (81%) (N = 189) of the non-responders continued treatment. 37% of the non-responders who continued anti-TNF-α treatment were eventually classified as responders at 6 months. Decision analytical modelling showed that with equal expected costs all alternative strategies would result in more responders than according to theoretical full adherence with the guidelines. “Continuation in case of partial response” had the best trade-off between successfully treated patients (64%) and unsuccessfully treated patients (17%). <h3>Conclusion:</h3> There was suboptimal adherence to the Dutch guidelines for treatment with anti-TNF-α for rheumatoid arthritis patients. This seemed to be justified by the fact that a delayed response up to 6 months was shown. If treatment is continued despite a non-response at 3 months, this is only recommended in patients with at least a partial response (at least 0.6 DAS28 improvement).
Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana
Authors: Marianna K. Baum, Adriana Campa, Shenghan Lai, Sabrina Sales Martinez, Lesedi Tsalaile, Patricia Burns, Mansour Farahani, Yinghui Li, Erik van Widenfelt, John Bryan Page, Hermann Bussmann, Wafaie W. Fawzi, Sikhulele Moyo, Joseph Makhema, Ibou Thior, Myron Essex, Richard Marlink
Journal: JAMA (2013)

Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive.
Relation between Cord Blood Mercury Levels and Early Child Development in a World Trade Center Cohort
Authors: Sally Ann Lederman, Robert L. Jones, Kathleen L. Caldwell, Virginia Rauh, Stephen E. Sheets, Deliang Tang, Sheila Viswanathan, Mark Becker, Janet L. Stein, Richard Y. Wang, Frederica P. Perera
Journal: Environmental Health Perspectives (2008)

This study was designed to determine whether prenatal mercury exposure, including potential releases from the World Trade Center (WTC) disaster, adversely affects fetal growth and child development.We determined maternal and umbilical cord blood total mercury of nonsmoking women who delivered at term in lower Manhattan after 11 September 2001, and measured birth outcomes and child development.Levels of total mercury in cord and maternal blood were not significantly higher for women who resided or worked within 1 or 2 miles of the WTC in the month after 11 September, compared with women who lived and worked farther away. Average cord mercury levels were more than twice maternal levels, and both were elevated in women who reported eating fish/seafood during pregnancy. Regression analyses showed no significant association between (ln) cord or maternal blood total mercury and birth outcomes. Log cord mercury was inversely associated with the Bayley Scales of Infant Development psychomotor score [Psychomotor Development Index (PDI)] at 36 months (b = -4.2, p = 0.007) and with Performance (b = -3.4, p = 0.023), Verbal (b = -2.9, p = 0.023), and Full IQ scores (b = -3.8, p = 0.002) on the Wechsler Preschool and Primary Scale of Intelligence, Revised (WPPSI-R), at 48 months, after controlling for fish/seafood consumption and other confounders. Fish/seafood consumption during pregnancy was significantly associated with a 5.6- to 9.9-point increase in 36-month PDI, and 48-month Verbal and Full IQ scores.Blood mercury was not significantly raised in women living or working close to the WTC site in the weeks after 11 September 2001. Higher cord blood mercury was associated with reductions in developmental scores at 36 and 48 months, after adjusting for the positive effects of fish/seafood consumption during pregnancy.
Identifying the hepatic organic anion transporter: One of many?
Authors: Steven A. Weinman
Journal: Hepatology (1994)

Using expression cloning in Xenopus laevis oocytes, we have isolated a cDNA encoding a rat liver organic anion-transporting polypeptide (oatp). The cloned oatp mediated Na + -independent uptake of sulfobromophthalein (BSP) which was Cl − -dependent in the presence of bovine serum albumin (BSA) at low BSP concentrations (e.g., 2 μM). Addition of increasing amounts of BSA had no effects on the maximal velocity of initial BSP uptake, but it increased the K m value from 1.5 μM (no BSA) to 24 μM (BSA/BSP molar ratio, 3.7) and 35 μM (BSA/BSP ratio, 18.4). In addition to BSP, the cloned oatp also mediated Na + -independent uptake of conjugated (taurocholate) and unconjugated (cholate) bile acids. Sequence analysis of the cDNA revealed an open reading frame of 2010 nucleotides coding for a protein of 670 amino acids (calculated molecular mass, 74 kDa) with four possible N-linked glycosylation sites and 10 putative transmembrane domains. Translation experiments in vitro indicated that the transporter was indeed glycosylated and that its polypeptide backbone had an apparent molecular mass of 59 kDa. Northern blot analysis with the cloned probe revealed crossreactivity with several mRNA species from rat liver, kidney, brain, lung, skeletal muscle, and proximal colon as well as from liver tissues of mouse and rabbit, but not of skate (Raja erinacea) and human.
TP53 R72P polymorphism modulates DNA methylation in hepatocellular carcinoma
Authors: Khadija Rebbani, Agnès Marchio, Sayeh Ezzikouri, Rajaa Afifi, Mostafa Kandil, Olfa Bahri, Henda Triki, Abdellah Essaid El Feydi, Anne Dejean, Soumaya Benjelloun, Pascal Pineau
Journal: Molecular Cancer (2015)

Hepatocellular carcinoma (HCC) is characterized by widespread epidemiological and molecular heterogeneity. Previous work showed that in the western part of North Africa, a region of low incidence of HCC, mutations are scarce for this tumor type. As epigenetic changes are considered possible surrogates to mutations in human cancers, we decided, thus, to characterize DNA methylation in HCC from North-African patients. A set of 11 loci was investigated in a series of 45 tumor specimens using methylation-specific and combined-bisulfite restriction assay PCR. Results obtained on clinical samples were subsequently validated in liver cancer cell lines. DNA methylation at tumor suppressor loci is significantly higher in samples displaying chromosome instability. More importantly, DNA methylation was significantly higher in Arg/Arg when compared to Pro/Pro genotype carriers at codon 72 rs1042522 of TP53 (65% vs 20% methylated loci, p = 0.0006), a polymorphism already known to affect somatic mutation rate in human carcinomas. In vitro experiments in cell lines indicated that enzymes controlling DNA methylation were differentially regulated by codon 72 Arg or Pro isoforms of p53. Furthermore, the Arg72-carrying version of p53 was shown to re-methylate DNA more rapidly than the pro-harboring isoform. Finally, Pro-carrying cell lines were shown to be significantly more resistant to decitabine treatment (two-fold, p = 0.005). Our data suggest that Arg72Pro polymorphism in a WT p53 context may act as a primary driver of epigenetic changes in HCC. It suggests, in addition, that rs1042522 genotype may predict sensitivity to epigenetic-targeted therapy. This model of liver tumorigenesis that associates low penetrance genetic predisposition to epigenetic changes emerges from a region of low HCC incidence and it may, therefore, apply essentially to population living in similar areas. Surveys on populations submitted to highly mutagenic conditions as perinatally-acquired chronic hepatitis B or aflatoxin B1 exposure remained to be conducted to validate our observations as a general model.
Phase III Study of Doxorubicin/Cyclophosphamide With Concomitant Versus Sequential Docetaxel As Adjuvant Treatment in Patients With Human Epidermal Growth Factor Receptor 2–Normal, Node-Positive Breast Cancer: BCIRG-005 Trial
Authors: Wolfgang Eiermann, Tadeusz Pienkowski, John Crown, Saeed Sadeghi, Miguel Martin, Arlene Chan, Mansoor Saleh, Sandeep Sehdev, Louise Provencher, Vladimir Semiglazov, Michael Press, Guido Sauter, Mary-Ann Lindsay, Alessandro Riva, Marc Buyse, Philippe Drevot, Henry Taupin, John R. Mackey
Journal: Journal of Clinical Oncology (2011)

Purpose Anthracyclines, taxanes, and alkylating agents are among the most active agents in treatment of adjuvant breast cancer (BC), but the optimal schedule for their administration is unknown. We performed an adjuvant trial to compare the sequential regimen of doxorubicin with cyclophosphamide (AC) followed by docetaxel (ie, AC&gt;T) with the combination regimen of TAC. Patients and Methods Women with node-positive, human epidermal growth factor receptor 2–nonamplified, operable BC were stratified by number of axillary nodes and hormone receptor status and were randomly assigned to adjuvant chemotherapy with six cycles of TAC (75/50/500 mg/m 2 every 3 weeks) or four cycles of AC (60/600 mg/m 2 every 3 weeks) followed by four doses of docetaxel at 100 mg/m 2 every 3 weeks (AC&gt;T). After completion of chemotherapy, radiation therapy was given as indicated, and patients with hormone receptor (HR) –positive disease received adjuvant hormonal therapy with tamoxifen and/or aromatase inhibitors. Results In 30 months, 3,298 patients were enrolled (n = 1,649 in each arm). The major baseline characteristics were well balanced between the groups. At a median follow-up of 65 months, estimated 5-year disease-free survival rates were 79% in both groups (log-rank P = .98; hazard ratio [HR], 1.0; 95%CI, 0.86 to 1.16), and 5-year overall survival rates for both arms were 88% and 89%, respectively (log-rank P = .37; HR, 0.91; 95% CI, 0.75 to 1.11). TAC was associated with more febrile neutropenia and thrombocytopenia, and AC&gt;T was associated with more sensory neuropathy, nail changes, and myalgia. The incidence of neutropenic infection was similar in both groups. Conclusion The sequential and combination regimens incorporating three drugs were equally effective but differed in toxicity profile.
Phthalate Esters and Their Effect on the Liver
Authors: Agneta E. Ganning, Ulf Brunk, Gustav Dallner
Journal: Hepatology (1984)

The advantageous properties of polyvinyl chloride plastics make these materials indispensable at all levels of human life, and there is no reason to believe that the upward trend of their use will change. One third of most polyvinyl chloride plastics consists of plasticizers, mostly phthalate esters, which may migrate out contaminating our environment and consequently our bodies. Experimental results indicate that chronic exposure to phthalic esters may be responsible for a number of adverse health effects. Phthalates change the structure and function of the liver in a profound manner by inducing peroxisomes, mitochondria and enzymes which participate in fatty acid transport and β-oxidation. Prolonged administration of phthalate esters, in doses comparable to those occurring in human exposures, seems to have an accumulative effect on the liver. Liver biopsies taken from dialysis patients show peroxisome proliferation which again warn of the possibility that human health may be influenced by plasticizers.
Effect of ventricular extrasystoles on idioventricular rhythm in patients with complete heart block
Authors: B. M. KENNELLY, G. K. LANE
Journal: Cardiovascular Research (1978)

Idioventricular rate, QRS width, site of block and responses to premature ventricular stimulation were studied in 23 patients with chronic complete heart block in an attempt to distinguish patients liable to syncopal attacks. Seven patients were asymptomatic, five gave a history of presyncope and 11 of syncope. Although the mean idioventricular rate of the nine patients in the narrow QRS group (39.7 per min) was significantly faster than that of the 14 patients in the wide QRS group (35.3 per min; P <0.05), the rate did not distinguish symptomatic patients within either the narrow or the wide QRS groups. His bundle studies of the site of block and the effect of single and paired right ventricular stimulation upon idioventricular rhythm were also unhelpful. The response of the return cycle to increasingly premature ventricular extrasystoles, however, proved more complex than was anticipated.
Effect of 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene on Production and Action of Gamma Interferon&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: K A Golemboski, D K DeLor, U N Streips, G Sonnenfeld
Journal: JNCI Journal of the National Cancer Institute (1982)

Spleens were removed from Swiss Webster mice, and cultures of spleen cells were prepared. Gamma (ty pe II immune) interferon (IFN) production was induced in these cells by addition of the purified protein form of phytohemagglutinin (PHA-P) to the cultures. When 7,12-dimethylbenz[a]anthracene (DMBA) was added to the cultures either before or after addition of PHA-P, the production of gamma IFN was inhibited. The degree of inhibition was greater when the cells were treated with DMBA before addition of PHA-P. In experiments to determine the effects of DMBA on the antivirus activity of previously prepared gamma IFN preparations, DMBA was either added to target cells before the addition of exogenous gamma IFN or mixed together with exogenous gamma IFN. In both cases. the antivirus activity of this exogenous gamma IFN was not affected. These data suggest that DMBA treatment can inhibit the production but not the antivirus activity of murine gamma IFN.
Vandetanib for the Treatment of Symptomatic or Progressive Medullary Thyroid Cancer in Patients with Unresectable Locally Advanced or Metastatic Disease: U.S. Food and Drug Administration Drug Approval Summary
Authors: Katherine Thornton, Geoffrey Kim, V. Ellen Maher, Somesh Chattopadhyay, Shenghui Tang, Young Jin Moon, Pengfei Song, Anshu Marathe, Suchitra Balakrishnan, Hao Zhu, Christine Garnett, Qi Liu, Brian Booth, Brenda Gehrke, Robert Dorsam, Leigh Verbois, Debasis Ghosh, Wendy Wilson, John Duan, Haripada Sarker, Sarah Pope Miksinski, Lisa Skarupa, Amna Ibrahim, Robert Justice, Anthony Murgo, Richard Pazdur
Journal: Clinical Cancer Research (2012)

On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa tablets; AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first drug approved for this indication, and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other endpoints included evaluation of overall survival and objective response rate. The PFS analysis showed a marked improvement for patients randomized to vandetanib (hazard ratio = 0.35; 95% confidence interval, 0.24-0.53; P < 0.0001). The objective response rate for the vandetanib arm was 44% compared with 1% for the placebo arm. The most common grade 3 and 4 toxicities (>5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in PFS. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease.
Specific T Cell Frequency and Cytokine Expression Profile Do Not Correlate with Protection against Tuberculosis after Bacillus Calmette-Guérin Vaccination of Newborns
Authors: Benjamin M. N. Kagina, Brian Abel, Thomas J. Scriba, Elizabeth J. Hughes, Alana Keyser, Andreia Soares, Hoyam Gamieldien, Mzwandile Sidibana, Mark Hatherill, Sebastian Gelderbloem, Hassan Mahomed, Anthony Hawkridge, Gregory Hussey, Gilla Kaplan, Willem A. Hanekom
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Immunogenicity of new tuberculosis (TB) vaccines is commonly assessed by measuring the frequency and cytokine expression profile of T cells.
CO<sub>2</sub> Rebreathing during BiPAP® Ventilatory Assistance
Authors: Gary T. Ferguson, Mary Gilmartin
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

BiPAP® ventilatory assistance can increase minute ventilation and reduce respiratory effort, but does not always reduce PaCO2. We studied the effects of BiPAP ventilatory assistance on PaCO2 and examined specific mechanisms whereby BiPAP ventilatory assistance may not lower PaCO2. BiPAP ventilatory assistance using a non-rebreather valve and volume cycled ventilation at similar settings produced significantly lower PaCO2 than BiPAP ventilatory assistance using a standard exhalation device. The failure of PaCO2 to fall with the standard exhalation device was due to exhalation past the exhalation device into the ventilator tubing, subsequent rebreathing of the exhaled gases, and an increase in dead space ventilation. Use of other fixed-resistance exhalation devices also resulted in exhalation back into the ventilator tubing. Use of a new plateau exhalation device or a non-rebreather valve eliminated CO2 rebreathing and its effect on dead space ventilation. Changing exhalation devices had no significant effect on BiPAP pressure generation or sensing capabilities. Our results indicate that the use of a standard exhalation device during BiPAP ventilatory assistance causes CO2 rebreathing, which can blunt any effect of BiPAP on PaCO2. Use of an appropriate alternative exhalation device can eliminate this problem.