tbuckley/cabot-search huggingface dataset:
α–Intercalated cells defend the urinary system from bacterial infection
Authors: Neal Paragas, Ritwij Kulkarni, Max Werth, Kai M. Schmidt-Ott, Catherine Forster, Rong Deng, Qingyin Zhang, Eugenia Singer, Alexander D. Klose, Tian Huai Shen, Kevin P. Francis, Sunetra Ray, Soundarapandian Vijayakumar, Samuel Seward, Mary E. Bovino, Katherine Xu, Yared Takabe, Fábio E. Amaral, Sumit Mohan, Rebecca Wax, Kaitlyn Corbin, Simone Sanna-Cherchi, Kiyoshi Mori, Lynne Johnson, Thomas Nickolas, Vivette D’Agati, Chyuan-Sheng Lin, Andong Qiu, Qais Al-Awqati, Adam J. Ratner, Jonathan Barasch
Journal: Journal of Clinical Investigation (2014)

α–Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC–dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system.
Dose–Response Characteristics during Long-Term Inhalation of Nitric Oxide in Patients with Severe Acute Respiratory Distress Syndrome
Authors: Herwig Gerlach, Didier Keh, Alexander Semmerow, Thilo Busch, Klaus Lewandowski, Dirk M. Pappert, Rolf Rossaint, Konrad J. Falke
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Inhaled nitric oxide (NO) improves systemic oxygenation (PaO2/FIO2) in adult patients with acute respiratory distress syndrome (ARDS). However, individual response varies, and previous trials demonstrated no outcome benefit. This prospective, randomized study in 40 ARDS patients analyzed dose-response (DR) characteristics during long-term inhaled NO. Patients were randomized for conventional therapy (control) or continuous treatment with 10 parts per million (ppm) inhaled NO until weaning was initiated. We measured DR curves of PaO2/FIO2 versus the inhaled NO dose at regular intervals. Before treatment (Day 0), peak improvement in PaO2/FIO2 was achieved at 10 ppm for both control and NO-treated patients. After 4 days, the DR curve of the NO-treated patients was left shifted with a peak response at 1 ppm. At higher doses (10 and 100 ppm), oxygenation deteriorated, and the response to inhaled NO disappeared in several patients. This effect was not observed in the control group. There was no effect of inhaled NO on duration of mechanical ventilation or stay at the intensive care unit. In conclusion, long-term inhaled NO with constant doses of 10 ppm leads to enhanced sensitivity after several days and does do not allow reduction of ventilation parameters. Hence, previous trials on therapy with inhaled NO in ARDS should be carefully interpreted, as they used constant NO concentrations, which may have become overdoses leading to deterioration of oxygenation after several days.
The Cost of Self-Monitoring of Blood Glucose Is an Important Factor Limiting Glycemic Control in Diabetic Patients
Authors: B.L. Gregoire Nyomba, Lori Berard, Liam J. Murphy
Journal: Diabetes Care (2002)

Maintenance of near normoglycemia can delay or prevent microvascular complications, but it cannot be carried out without a program of patient education, including self-monitoring of blood glucose (SMBG) (1,2). Motivation toward SMBG depends on several ill-defined factors, and there is no consensus on the effectiveness of SMBG in diabetes management (3–6).

We undertook a single-blinded, control-matched, longitudinal study of patients with insulin-requiring diabetes ( n = 62) to examine barriers to SMBG and determine whether eliminating the cost barrier would increase SMBG frequency and glycemic control. Eligibility criteria were insulin treatment with at least two injections/day for at least 1 year (1), HbA1c >120% of upper limit of normal (2), and recent diabetes education (3). The patients completed questionnaires reporting their habitual SMBG frequency, perceived barriers to SMBG, monthly income, and any private health insurance plans to verify …
Left Ventricular Systolic Unloading and Augmentation of Intracoronary Pressure and Doppler Flow During Enhanced External Counterpulsation
Authors: Andrew D. Michaels, Michel Accad, Thomas A. Ports, William Grossman
Journal: Circulation (2002)

Background— Enhanced external counterpulsation (EECP) is a noninvasive, pneumatic technique that provides beneficial effects for patients with chronic, symptomatic angina pectoris. However, the physiological effects of EECP have not been studied directly. We examined intracoronary and left ventricular hemodynamics in the cardiac catheterization laboratory during EECP. Methods and Results— Ten patients referred for diagnostic evaluation underwent left heart catheterization and coronary angiography from the radial artery. At baseline and then during EECP, central aortic pressure, intracoronary pressure, and intracoronary Doppler flow velocity were measured using a coronary catheter, a sensor-tipped high-fidelity pressure guidewire, and a Doppler flow guidewire, respectively. Similar to changes in aortic pressure, EECP resulted in a dramatic increase in diastolic (71±10 mm Hg at baseline to 137±21 mm Hg during EECP; +93%; P &lt;0.0001) and mean intracoronary pressures (88±9 to 102±16 mm Hg; +16%; P =0.006) with a decrease in systolic pressure (116±20 to 99±26 mm Hg; −15%; P =0.002). The intracoronary Doppler measure of average peak velocity increased from 11±5 cm/s at baseline to 23±5 cm/s during EECP (+109%; P =0.001). The TIMI frame count, a quantitative angiographic measure of coronary flow, showed a 28% increase in coronary flow during EECP compared with baseline ( P =0.001). Conclusions— EECP unequivocally and significantly increases diastolic and mean pressures and reduces systolic pressure in the central aorta and the coronary artery. Coronary artery flow, determined by both Doppler and angiographic techniques, is increased during EECP. The combined effects of systolic unloading and increased coronary perfusion pressure provide evidence that EECP may serve as a potential mechanical assist device.
Unilateral hyperlucent lung: the case for investigation.
Authors: S A McKenzie, D J Allison, M P Singh, S Godfrey
Journal: Thorax (1980)

Seventeen children with unilateral hyperlucent lungs were referred for investigation. Of the 11 who had a referring diagnosis of possible Macleod's syndrome only two were shown to have post-viral bronchiolitis. Three of the 11 had conditions that required surgical treatment and a further two with brochiectasis were treated medically. To avoid confusion we suggest that Macleod's syndrome is reserved exclusively for children with post-viral bronchiolitis. Radioisotopic regional lung function studies were useful in the investigation of the subjects from three points of view. Firstly, they distinguished children with primary perfusion abnormalities and normal ventilation, secondly, they defined the extent of altered respiratory function, and thirdly, they were able to distinguish compensatory emphysema from congenital lobar emphysema. As bronchography and bronchoscopy may be hazardous in small children with poor respiratory reserve, such regional studies may be useful in indicating which patients do not require further invasive investigation.
Acid fog and hospital visits for asthma: an epidemiological study
Authors: H Tanaka, S Honma, M Nishi, T Igarashi, S Teramoto, F Nishio, S Abe
Journal: European Respiratory Journal (1998)

The aim of this study was to elucidate the adverse respiratory effects of naturally occurring acid fog. In total, 102 adult asthmatic patients (44 nonatopic and 58 atopic) were studied for a 2 yr period (January 1992 to December 1993) in Kushiro, a city with only a small industrial area, located in the northern-most island in Japan. Fog occurred on 378 out of 731 days, and the acidity of the fog ranged from pH 3.32 to 6.91 (mean pH 4.95). The association between hospital visits for asthma and meteorological factors or air pollutants was investigated. In nonatopic patients, fog, high ozone and water vapour pressure, low day-to-day temperature differences, low concentrations of atmospheric NO and NO2 contributed significantly (p&lt;0.05) to increasing hospital visits. In atopic subjects, fog, high water vapour pressure, low levels of atmospheric NO2 and SO2 contributed significantly to hospital visits (p&lt;0.05). In Poisson regression analysis the remaining factors of significance (p&lt;0.01) for nonatopic asthma were fog and low NO and for atopic asthma were high water vapour pressure and low SO2 (p&lt;0.05). A weak but significant correlation was observed between the number of hospital visits and the mean pH of the foggy day (r=-0.38, p&lt;0.05) in nonatopic asthmatic patients, not in atopic asthma. On foggy days, gaseous air pollutant levels were significantly (p&lt;0.01) lower than on fog-free days. It was concluded that, naturally occurring acid fog may have a weak bronchoconstrictive effect which appears to be more influential in nonatopic asthmatic subjects than in atopic subjects.
Inefficacy of intravenous immunoglobulin in patients with low‐risk thrombotic thrombocytopenic purpura/hemolytic‐uremic syndrome
Authors: Guido Finazzi, Piero Bellavita, Anna Falanga, Piera Viero, Tiziano Barbui
Journal: American Journal of Hematology (1992)

Abstract Objective: To assess the efficacy of intravenous immunoglobulin (IVIG), in comparison with plasma exchange (PE), in the treatment of patients with thrombotic thrombocytopenic purpura/hemolytic‐uremic syndrome (TTP/HUS). © 1992 Wiley‐Liss, Inc. Design: Prospective, nonrandomized comparative study. Setting: Hematology department in a general hospital. Patients: 17 consecutive adult patients, six of them pregnant, with diagnosis of TTP/ HUS. Three had a severity score at diagnosis ≦4 and were treated with IVIG and 14 had a severity score of ≧5 and/or were pregnant and received PE. The response was evaluated after 5 days of therapy. Results: Complete remission was obtained in 0/3 cases treated with IVIG and 10/14 (71%) with PE (Fisher's exact test P = 0.05). Three patients died for widespread TTP‐HUS, and four had persistent disease. In three of the four resistant patients, complete remission was obtained by further PE but not by further IVIG. The overall remission rate was 76% (13/17). Conclusions: Our study does not confirm the utility of IVIG in the management of TTP‐HUS, as suggested by earlier single case reports. © 1992 Wiley‐Liss, Inc.
High-Dosage Ascorbic Acid Treatment in Charcot-Marie-Tooth Disease Type 1A
Authors: Richard A. Lewis
Journal: JAMA Neurology (2013)

No current medications improve neuropathy in subjects with Charcot-Marie-Tooth disease type 1A (CMT1A). Ascorbic acid (AA) treatment improved the neuropathy of a transgenic mouse model of CMT1A and is a potential therapy. A lower dosage (1.5 g/d) did not cause improvement in humans. It is unknown whether a higher dosage would prove more effective.To determine whether 4-g/d AA improves the neuropathy of subjects with CMT1A.A futility design to determine whether AA was unable to reduce worsening on the CMT Neuropathy Score (CMTNS) by at least 50% over a 2-year period relative to a natural history control group.Three referral centers with peripheral nerve clinics (Wayne State University, Johns Hopkins University, and University of Rochester).One hundred seventy-four subjects with CMT1A were assessed for eligibility; 48 did not meet eligibility criteria and 16 declined to participate. The remaining 110 subjects, aged 13 to 70 years, were randomly assigned in a double-masked fashion with 4:1 allocation to oral AA (87 subjects) or matching placebo (23 subjects). Sixty-nine subjects from the treatment group and 16 from the placebo group completed the study. Two subjects from the treatment group and 1 from the placebo group withdrew because of adverse effects.Oral AA (4 g/d) or matching placebo.Change from baseline to year 2 in the CMTNS, a validated composite impairment score for CMT.The mean 2-year change in the CMTNS was -0.21 for the AA group and -0.92 for the placebo group, both better than natural history (+1.33). This was well below 50% reduction of CMTNS worsening from natural history, so futility could not be declared (P > .99).Both treated patients and those receiving placebo performed better than natural history. It seems unlikely that our results support undertaking a larger trial of 4-g/d AA treatment in subjects with CMT1A.clinicaltrials.gov Identifier: NCT00484510.
Birth Weight and Prenatal Exposure to Polychlorinated Biphenyls (PCBs) and Dichlorodiphenyldichloroethylene (DDE): A Meta-analysis within 12 European Birth Cohorts
Authors: Eva Govarts, Mark Nieuwenhuijsen, Greet Schoeters, Ferran Ballester, Karolien Bloemen, Michiel de Boer, Cécile Chevrier, Merete Eggesbø, Mònica Guxens, Ursula Krämer, Juliette Legler, David Martínez, Lubica Palkovicova, Evridiki Patelarou, Ulrich Ranft, Arja Rautio, Maria Skaalum Petersen, Rémy Slama, Hein Stigum, Gunnar Toft, Tomas Trnovec, Stéphanie Vandentorren, Pál Weihe, Nynke Weisglas Kuperus, Michael Wilhelm, Jürgen Wittsiepe, Jens Peter Bonde
Journal: Environmental Health Perspectives (2011)

Objectives: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight.Methods: We used maternal and cord blood and breast milk samples of 7,990 women enrolled in 15 study populations from 12 European birth cohorts from 1990 through 2008. Using identical variable definitions, we performed for each cohort linear regression of birth weight on estimates of cord serum concentration of PCB-153 and p,p´-DDE adjusted for gestational age and a priori selected covariates. We obtained summary estimates by meta-analysis and performed analyses of interactions.Results: The median concentration of cord serum PCB-153 was 140 ng/L (range of cohort medians 20–484 ng/L) and that of p,p´-DDE was 528 ng/L (range of cohort medians 50–1,208 ng/L). Birth weight decreased with increasing cord serum concentration of PCB-153 after adjustment for potential confounders in 12 of 15 study populations. The meta-analysis including all cohorts indicated a birth weight decline of 150 g [95% confidence interval (CI): –250, –50 g] per 1-µg/L increase in PCB-153, an exposure contrast that is close to the range of exposures across the cohorts. A 1-µg/L increase in p,p´-DDE was associated with a 7-g decrease in birth weight (95% CI: –18, 4 g).Conclusions: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p´-DDE does not. The study adds to mounting evidence that low-level exposure to PCBs is inversely associated with fetal growth.
Clustering of cytokine genes on mouse chromosome 11.
Authors: S D Wilson, P R Billings, P D'Eustachio, R E Fournier, E Geissler, P A Lalley, P R Burd, D E Housman, B A Taylor, M E Dorf
Journal: The Journal of Experimental Medicine (1990)

The presence of positionally conserved amino acid residues suggests that the mouse proteins TCA3, P500, MIP1-alpha, MIP1-beta, and JE are members of a single gene family. These proteins are activation specific and can be expressed by both myeloid and lymphoid cells. MIP1-alpha/MIP1-beta and MCAF (the putative human homologue of JE) act as chemotactic and activating agents for neutrophils and macrophages, respectively. The functions of TCA3 and P500 are unknown. We have used interspecies somatic cell hybrids and recombinant inbred mouse strains to show that the genes encoding TCA3, MIP1-alpha, MIP1-beta, and JE (provisionally termed Tca3, Mip-1a, Mip-1b, and Sigje, respectively) map as a cluster on the distal portion of mouse chromosome 11 near the Hox-2 gene complex. DNA sequence analysis indicates that the P500 and TCA3 proteins are encoded by alternative splicing products of one genomic gene. Additionally, the genes encoding TCA3 and JE are found to be strikingly similar with respect to the positions of intron-exon boundaries. Together, these data support the model that the cytokines TCA3, P500, MIP1-alpha, MIP1-beta, and JE are encoded by a single cluster of related genes. The gene encoding IL-5 (Il-5), which acts as a T cell-replacing factor, a B cell growth factor, and an eosinophil differentiation factor, is also mapped to mouse chromosome 11.Il-5 maps approximately 25 cM proximal to the Tca-3 gene and appears tightly linked to a previously described gene cluster that includes Il-3, Il-4, and Csfgm. We discuss the potential relevance of the two cytokine gene clusters described here with particular attention to specific human hematologic malignancies associated with chromosomal aberrations at corresponding locations on human chromosomes 5 and 17.
Hemodynamics in transgenic mice with overexpression of atrial natriuretic factor.
Authors: R W Barbee, B D Perry, R N Ré, J P Murgo, L J Field
Journal: Circulation Research (1994)

The circulatory effects associated with lifelong plasma atrial natriuretic factor (ANF) elevation were examined by generating transgenic mice, which constitutively express a fusion gene consisting of the transthyretin promoter and the ANF structural gene. These mice have chronically elevated ANF levels as compared with their nontransgenic siblings. Transgenic animals exhibited immunoreactive ANF levels that were nearly fivefold higher than those measured in nontransgenic littermates. Systemic and regional hemodynamics and blood volumes were explored by using modifications of the reference microsphere and dilution techniques. Mean arterial pressure was reduced by 24 mm Hg, associated with a 27% reduction in total heart weight. This chronic reduction in blood pressure was due to a 21% reduction in total peripheral resistance, whereas cardiac output, stroke volume, and heart rate were not significantly altered, despite a 15% elevation in plasma volume. Transgenic mice displayed reductions of 35%, 33%, 32%, and 19% in muscle, skin, brain, and renal vascular resistance, respectively, whereas coronary and splanchnic resistances were not significantly altered. The findings complement earlier data from chronically infused normotensive mammals and suggest that these mice are an excellent model for investigating the effects of lifelong ANF elevation.
The role of microaerophilic colonic mucosal bacteria in de novo paediatric inflammatory bowel disease
Authors: R. Hansen, I. Mukhopadhya, R. K. Russell, W. M. Bisset, S. H. Berry, J. M. Thomson, E. M. El-Omar, G. L. Hold
Journal: Gut (2011)

<h3>Introduction</h3> <i>Helicobacter</i> species can initiate animal colitis similar to human ulcerative colitis (UC). <i>Campylobacter concisus</i> has been linked to paediatric Crohn9s disease (CD). Microaerophilic organisms such as <i>Helicobacter</i> and <i>Campylobacter</i> may be involved in the initiation of IBD. <h3>Methods</h3> Paediatric patients undergoing colonoscopy were recruited to two groups: those with a new diagnosis of IBD at their first presentation and controls with a macroscopically normal colon and no evidence of IBD on biopsy. All subjects were free from systemic antibiotics, steroids and immunosuppression for 3 months. 24 IBD patients and 26 controls were studied. The IBD cohort comprised 12 (50%) CD, 8 (33.3%) UC and 4 (16.7%) IBD unspecified (IBD-U) patients. 15 (62.5%) of the IBD and 20 (77.8%) of the control groups were male with median ages of 12.4 and 11.0 years, respectively. 5–6 Colonic mucosal biopsies were taken: in controls largely from the sigmoid/rectum and in IBD from the most distal inflamed site. 3 biopsies were stored at −80°C for subsequent DNA extraction and PCR. 1–2 biopsies were used for culture. 5 selective plates were used alongside blood agar. Cultures were incubated in microaerophilic conditions (Anoxomat) at 37°C. Plates were reviewed twice weekly for up to 1 month. Isolates deemed Gram-negative and microaerophilic underwent PCR of the 16S rRNA gene for phylogenetic identification. <h3>Results</h3> No <i>Helicobacter</i> were cultured. 3 <i>Campylobacter</i> spp. were isolated: <i>C concisus</i> from a subject with CD, <i>Campylobacter curvus</i> and <i>Campylobacter showae</i> from controls. <i>Sutterella wadsworthensis</i> was isolated from 13 subjects: 8 controls and 5 IBD. All biopsies were positive for bacterial DNA with universal primers. Nested PCR for <i>Helicobacter</i> genus was positive in 5 (10%) subjects, comprising 3 (12.5%) IBD and 2 (7.7%) controls. PCR for <i>Campylobacter</i> genus was positive in 38 (76%) subjects, comprising 19 (79.2%) IBD and 19 (73.1%) controls. Nested PCR for <i>C concisus</i> was positive in 25 (50%) subjects, comprising 14 (58.3%) IBD (8/12 CD, 3/8 UC and 3/4 IBD-U) and 11 (42.3%) controls. In response to frequent isolation of the organism, PCR for <i>S wadsworthensis</i> was positive in 48 (96%) subjects, comprising 23 (95.8%) IBD and 25 (96.2%) controls. <h3>Conclusion</h3> <i>Campylobacter</i> spp. and <i>Sutterella wadsworthensis</i> are commonly identified in the paediatric colon. <i>C concisus</i> appears more prevalent in CD although this was not significant. <i>Helicobacter</i> spp. are uncommon. PCR and culture methodology have revealed no significant distinction between the microaerophilic microbiota of paediatric IBD versus controls. It is unlikely that these organisms have a role in the initiation of paediatric IBD.
Short term effects of airborne pollen concentrations on asthma epidemic
Authors: A Tobias
Journal: Thorax (2003)

<b>Background:</b> Few studies have used time series to investigate the relationship between asthma attacks and aeroallergen levels on a daily basis. <b>Methods:</b> This study, based on time series analysis adjusting for meteorological factors and air pollution variables, assessed the short term effects of different types of allergenic pollen on asthma hospital emergencies in the metropolitan area of Madrid (Spain) for the period 1995–8. <b>Results:</b> Statistically significant associations were found for <i>Poaceae</i> pollen (lag of 3 days) and <i>Plantago</i> pollen (lag of 2 days), representing an increase in the range between the 99th and 95th percentiles of 17.1% (95% confidence interval (CI) 3.2 to 32.8) and 15.9% (95% CI 6.5 to 26.2) for <i>Poaceae</i> and <i>Plantago</i>, respectively. A positive association was also observed for <i>Urticaceae</i> (lag of 1 day) with an 8.4% increase (95% CI 2.8 to 14.4). <b>Conclusions:</b> There is an association between pollen levels and asthma related emergencies, independent of the effect of air pollutants. The marked relationship observed for <i>Poaceae</i> and <i>Plantago</i> pollens suggests their implication in the epidemic distribution of asthma during the period coinciding with their abrupt release into the environment.