tbuckley/cabot-search huggingface dataset:
Changes in neurokinin A (NKA) airway responsiveness with inhaled frusemide in asthma
Authors: N. Crimi, G. Prosperini, I. Ciamarra, C. Mastruzzo, S. Magri, R. Polosa
Journal: Thorax (1997)

BACKGROUND: Inhaled frusemide exerts a protective effect against bronchoconstriction induced by several indirect stimuli in asthma which could be due to interference of airway nerves. A randomised, double blind, placebo controlled study was performed to investigate the effect of the potent loop diuretic, frusemide, administered by inhalation on the bronchoconstrictor response to neurokinin A (NKA) and histamine in 11 asthmatic subjects. METHODS: Subjects attended the laboratory on four separate occasions to receive nebulised frusemide (40 mg) or matched placebo 10 minutes prior to bronchial challenge with NKA and histamine in a randomised, double blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and responsiveness to the agonists was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). RESULTS: Compared with placebo, inhaled frusemide reduced the airway responsiveness to NKA in all the subjects studied, the geometric mean (range) values for PC20NKA increasing significantly (p &lt; 0.001) from 130.3 (35.8-378.8) to 419.9 (126.5-1000) micrograms/ml after placebo and frusemide, respectively. Moreover, a small but significant change in airway responsiveness to histamine was recorded after frusemide, their geometric mean (range) PC20 values being 0.58 (0.12-3.80) and 1.04 (0.28-4.33) mg/ml after placebo and frusemide, respectively. CONCLUSIONS: The decrease in airway responsiveness to NKA after administration of frusemide by inhalation suggests that this drug may interfere with the activation of neurotransmission in human asthma.
Retrotransposition as a Source of New Promoters
Authors: K. Okamura, K. Nakai
Journal: Molecular Biology and Evolution (2008)

The fact that promoters are essential for the function of all genes presents the basis of the general idea that retrotranspositions give rise to processed pseudogenes. However, recent studies have demonstrated that some retrotransposed genes are transcriptionally active. Because promoters are not thought to be retrotransposed along with exonic sequences, these transcriptionally active genes must have acquired a functional promoter by mechanisms that are yet to be determined. Hence, comparison between a retrotransposed gene and its source gene appears to provide a unique opportunity to investigate the promoter creation for a new gene. Here, we identified 29 gene pairs in the human genome, consisting of a functional retrotransposed gene and its parental gene, and compared their respective promoters. In more than half of these cases, we unexpectedly found that a large part of the core promoter had been transcribed, reverse transcribed, and then integrated to be operative at the transposed locus. This observation can be ascribed to the recent discovery that transcription start sites tend to be interspersed rather than situated at 1 specific site. This propensity could confer retrotransposability to promoters per se. Accordingly, the retrotransposability can explain the genesis of some alternative promoters.
Exercise and human collateralization: an angiographic and scintigraphic assessment.
Authors: A J Nolewajka, W J Kostuk, P A Rechnitzer, D A Cunningham
Journal: Circulation (1979)

The effect of exercise on the development of intercoronary collaterals and on left ventricular function is controversial. Twenty male patients (mean age 48 years, range 36-54 years) who had suffered an acute myocardial infarction were randomly allocated to an exercise group (10 patients) and a control group (10 patients). Both groups underwent coronary angiography, left ventricular function studies and myocardial perfusion studies with labeled microspheres, before and after the 7-month experimental period. Both groups had similar extent of disease as measured angiographically and both had mild progression of disease. Neither group showed changes in extent of callateralization, myocardial perfusion or left ventricular function. The exercise group had a significant increase in anginal threshold and a significant (p less than 0.01) decrease in heart rate at a given work load. Exercise, therefore, does not appear to affect progression of disease, myocardial perfusion, extent of collateralization, or left ventricular function in patients with coronary artery disease.
Effects of Flow Triggering on Breathing Effort During Partial Ventilatory Support
Authors: PIERRE ASLANIAN, SOUHAIL EL ATROUS, DANIEL ISABEY, ELISABETH VALENTE, DANIELLA CORSI, ALAIN HARF, FRANÇOIS LEMAIRE, LAURENT BROCHARD
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The effects of flow triggering (FT) as compared with pressure triggering (PT) on breathing effort have been the focus of several studies, and discrepant results have been reported. In the initial part of our study, a lung model was used to quantify triggering effort (airway pressure–time product, PTPaw) for a range of sensitivity settings in nine new-generation ventilators. A ventilator providing both FT and PT was then used to compare these systems during pressure-support (PSV) and volume-targeted assist-control ventilation (ACV) in eight ventilator-dependent patients, using sensitivity settings (2 L/min for FT and − 2 cm H2O for PT) that had proven significantly different in the initial bench study. Indexes of effort included the esophageal and transdiaphragmatic pressure–time products and inspiratory work of breathing per minute (PTPes/min, PTPdi/min, and Wi/min, respectively). The experimental study revealed significant differences between ventilators in PTPaw at commonly used settings. In two of three ventilators featuring both systems, PTPaw was significantly lower with FT than PT (p < 0.001). In the clinical study, FT as compared with PT, was associated with reductions in all indexes of breathing effort during PSV: 16 ± 6% (p < 0.001), 13 ± 10% (p < 0.01), and 14 ± 12% (p < 0.05) for PTPdi/min, PTPes/min, and Wi/min, respectively. By contrast, no differences were found when FT was used during ACV. Although FT reduced triggering effort in both modes (p < 0.001), the effects observed during the post-trigger phase differed, and explained the discrepant results between the two modes. We conclude that FT more effectively reduces breathing effort when used in conjunction with a pressure-targeted mode than with a volume-targeted mode, especially when flow delivery is close to or below demand.
Reduced Gas Transfer at Rest and during Exercise in School-age Survivors of Bronchopulmonary Dysplasia
Authors: SARA H. MITCHELL, W. GERALD TEAGUE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

School-age children who survive bronchopulmonary dysplasia (BPD) may have a permanent reduction in alveolar surface area that could limit gas transfer both at rest and during exercise. To test this hypothesis, 10 survivors of BPD, 10 children born prematurely without BPD, and 10 healthy children born at term, 6 to 9 yr of age, underwent treadmill exercise studies. During a three-phase protocol we measured intrabreath acetylene (C2H2) and carbon monoxide (CO) transfer, pulmonary function, and SaO2 . Both at rest and during exercise, C2H2 transfer corrected for body surface area was lower in survivors of BPD than it was in children born prematurely without BPD or children born at term. With exercise the transfer of both gases increased sharply over resting values in children born prematurely and at term. In survivors of BPD C2H2 transfer with exercise did increase, but not as much as it did in control subjects, and corrected CO transfer did not change at all. In survivors of BPD and children born prematurely, FEV1 fell during recovery from exercise, but this did not correlate with C2H2 transfer or Dl CO/Va. Thus, soluble gas transfer at rest and during acute exercise is reduced in children who survive BPD. This is likely explained either by long-term derangements in lung structure or residual right ventricular dysfunction affecting cardiac output.
Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda
Authors: Jonathan Mermin, John Lule, John Paul Ekwaru, Samuel Malamba, Robert Downing, Ray Ransom, Frank Kaharuza, David Culver, Francis Kizito, Rebecca Bunnell, Aminah Kigozi, Damalie Nakanjako, Winnie Wafula, Robert Quick
Journal: The Lancet (2004)
Real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia using junctional region specific TaqMan probes
Authors: MJ Pongers-Willemse, OJHM Verhagen, GJM Tibbe, AJM Wijkhuijs, V de Haas, E Roovers, CE van der Schoot, JJM van Dongen
Journal: Leukemia (1998)
Weber-Cockayne type of epidermolysis bullosa simplex associated with a novel mutation in keratin 5 and amyloid deposits
Authors: Y-Y. Chiang, S-C. Chao, W-Y. Chen, W-R. Lee, K-H. Wang
Journal: British Journal of Dermatology (2008)

Journal Article Weber–Cockayne type of epidermolysis bullosa simplex associated with a novel mutation in keratin 5 and amyloid deposits Get access Y‐Y. Chiang, Y‐Y. Chiang Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar S‐C. Chao, S‐C. Chao Department of Dermatology, National Cheng‐Kung University Hospital, Tainan, Taiwan Search for other works by this author on: Oxford Academic Google Scholar W‐Y. Chen, W‐Y. Chen Pathology, Taipei Medical University–Wan Fang Hospital, Taipei, Taiwan Search for other works by this author on: Oxford Academic Google Scholar W‐R. Lee, W‐R. Lee Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan Search for other works by this author on: Oxford Academic Google Scholar K‐H. Wang K‐H. Wang Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan Correspondence: Kuo‐Hsien Wang. E‐mail: khwang@tmu.edu.tw Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 6, 1 December 2008, Pages 1370–1372, https://doi.org/10.1111/j.1365-2133.2008.08801.x Published: 01 December 2008
Clinicopathologic Predictors of Sentinel Lymph Node Metastasis in Thin Melanoma
Authors: Dale Han, Jonathan S. Zager, Yu Shyr, Heidi Chen, Lynne D. Berry, Sanjana Iyengar, Mia Djulbegovic, Jaimie L. Weber, Suroosh S. Marzban, Vernon K. Sondak, Jane L. Messina, John T. Vetto, Richard L. White, Barbara Pockaj, Nicola Mozzillo, Kim James Charney, Eli Avisar, Robert Krouse, Mohammed Kashani-Sabet, Stanley P. Leong
Journal: Journal of Clinical Oncology (2013)

Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma.Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome.SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas < 0.75 mm had positive SLN rates of < 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P = .001).Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, and ulceration significantly predict SLN disease in thin melanoma. Most SLN metastases (86.2%) occur in melanomas ≥ 0.75 mm, with 6.3% of these patients having SLN disease, whereas in melanomas < 0.75 mm, SLN metastasis rates are < 5%. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas ≥ 0.75 mm, but further study is needed to define indications for SLNB in melanomas < 0.75 mm.
Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups
Authors: B.G. Haffty, D.H. Choi, S. Goyal, A. Silber, K. Ranieri, E. Matloff, M.H. Lee, M. Nissenblatt, D. Toppmeyer, M.S. Moran
Journal: Annals of Oncology (2009)
Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature
Authors: Latifa Karim, Haruko Takeda, Li Lin, Tom Druet, Juan A C Arias, Denis Baurain, Nadine Cambisano, Stephen R Davis, Frédéric Farnir, Bernard Grisart, Bevin L Harris, Mike D Keehan, Mathew D Littlejohn, Richard J Spelman, Michel Georges, Wouter Coppieters
Journal: Nature Genetics (2011)
Association of Substance Use Disorders With Childhood Trauma but not African Genetic Heritage in an African American Cohort
Authors: Francesca Ducci, Alec Roy, Pei-Hong Shen, Qiaoping Yuan, Nicole P. Yuan, Colin A. Hodgkinson, Lynn R. Goldman, David Goldman
Journal: American Journal of Psychiatry (2009)

Objective: Genetic variation influences differential vulnerability to addiction within populations. However, it remains unclear whether differences in frequencies of vulnerability alleles contribute to disparities between populations and to what extent ancestry correlates with differential exposure to environmental risk factors, including poverty and trauma. Method: The authors used 186 ancestry-informative markers to measure African ancestry in 407 addicts and 457 comparison subjects self-identified as African Americans. The reference group was 1,051 individuals from the Human Genome Diversity Cell Line Panel, which includes 51 diverse populations representing most worldwide genetic diversity. Results: African Americans varied in degrees of African, European, Middle Eastern, and Central Asian genetic heritage. The overall level of African ancestry was actually smaller among cocaine, opiate, and alcohol addicts (proportion=0.76–0.78) than nonaddicted African American comparison subjects (proportion=0.81). African ancestry was associated with living in impoverished neighborhoods, a factor previously associated with risk. There was no association between African ancestry and exposure to childhood abuse or neglect, a factor that strongly predicted all types of addictions. Conclusions: These results suggest that African genetic heritage does not increase the likelihood of genetic risk for addictions. They highlight the complex interrelation between genetic ancestry and social, economic, and environmental conditions and the strong relation of those factors to addiction. Studies of epidemiological samples characterized for genetic ancestry and social, psychological, demographic, economic, cultural, and historical factors are needed to better disentangle the effects of genetic and environmental factors underlying interpopulation differences in vulnerability to addiction and other health disparities.
An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria
Authors: Jaan-Olle Andressoo, James R. Mitchell, Jan de Wit, Deborah Hoogstraten, Marcel Volker, Wendy Toussaint, Ewoud Speksnijder, Rudolph B. Beems, Harry van Steeg, Judith Jans, Chris I. de Zeeuw, Nicolaas G.J. Jaspers, Anja Raams, Alan R. Lehmann, Wim Vermeulen, Jan H.J. Hoeijmakers, Gijsbertus T.J. van der Horst
Journal: Cancer Cell (2006)
Poverty and tuberculosis: is it truly a simple inverse linear correlation?
Authors: B. J. Marais, A. C. Hesseling, M. F. Cotton
Journal: European Respiratory Journal (2009)

disease or aged ,18 yrs or other reasons.The 311 study patients were interviewed 3.7¡1.88yrs (maximum range 1.1-6.3yrs) after the diagnosis.In total, 190 (61%, 95% confidence interval (CI) 55-67) patients confirmed a smoking history (active or former) at the time of pulmonary embolism, of whom 94 (30%, 95% CI 25-36) patients were actively smoking.Out of these 94 patients, 32 (35%, 95% CI 25-45) had successfully quit smoking in the first year following the diagnosis.Overall, only two (0.64%, 95% CI 0.08-2.3)patients started smoking after the diagnosis of pulmonary embolism.The percentage of quitters was not associated with age in the pulmonary embolism cohort.Analysis of the control group showed that of the 117,100 population controls randomly selected between 2001 and 2007, 71,614 (61%, 95% CI 60-61%) were current or former smokers and 34,177 (29%, 95% CI 28-30%) were active smokers.There were no significant differences between the fraction of (active) smokers between the patients at the time of the pulmonary embolism and the controls (odds ratio (OR) 1.05, 95% CI 0.82-1.34).According to the registry, 4-5% (maximum) of the smokers were able to successfully quit yearly.If 5% was assumed, successful smoking cessation occurred in 1,709 of the 34,177 active smokers, which is significantly lower compared with the patient cohort (p,0.001;OR 10.3, 95% CI 6.88-15.4).
Toll-interacting protein (Tollip) negatively regulates pressure overload-induced ventricular hypertrophy in mice
Authors: Yi Liu, Xiao-Li Jiang, Yu Liu, Ding-Sheng Jiang, Yan Zhang, Rui Zhang, Yingjie Chen, Qinglin Yang, Xiao-Dong Zhang, Guo-Chang Fan, Hongliang Li
Journal: Cardiovascular Research (2013)

Toll-interacting protein (Tollip) is a critical regulator of the Toll-like receptor-mediated signalling pathway. However, the role of Tollip in chronic pressure overload-induced cardiac hypertrophy remains unclear. This study aimed to determine the functional significance of Tollip in the regulation of aortic banding-induced cardiac remodelling and its underlying mechanisms.First, we observed that Tollip was down-regulated in human failing hearts and murine hypertrophic hearts, as determined by western blotting and RT-PCR. Using cultured neonatal rat cardiomyocytes, we found that adenovirus vector-mediated overexpression of Tollip limited angiotensin II-induced cell hypertrophy; whereas knockdown of Tollip by shRNA exhibited the opposite effects. We then generated a transgenic (TG) mouse model with cardiac specific-overexpression of Tollip and subjected them to aortic banding (AB) for 8 weeks. When compared with AB-treated wild-type mouse hearts, Tollip-TGs showed a significant attenuation of cardiac hypertrophy, fibrosis, and dysfunction, as measured by echocardiography, immune-staining, and molecular/biochemical analysis. Conversely, a global Tollip-knockout mouse model revealed an aggravated cardiac hypertrophy and accelerated maladaptation to chronic pressure overloading. Mechanistically, we discovered that Tollip interacted with AKT and suppressed its downstream signalling pathway. Pre-activation of AKT in cardiomyocytes largely offset the Tollip-elicited anti-hypertrophic effects.Our results provide the first evidence that Tollip serves as a negative regulator of pathological cardiac hypertrophy by blocking the AKT signalling pathway.
Genetic association between factor V Leiden and coeliac disease
Authors: T Mari, A Zullo, C Hassan, L Di Giulio, S Morini
Journal: Gut (2006)

We identified a family in which a previously unknown genetic association between coeliac disease (CD) and mutation of factor V (factor V Leiden) occurred. The index case was a young woman who abruptly presented with severe ascites due to Budd-Chiari syndrome. At endoscopy, she presented with a scalloped duodenal mucosa suggestive of CD, further confirmed by histology and serological tests. Haematological assessment unveiled the mutation of factor V due to the Arg506 …
THE DIET IN ALBUMINURIA.A CLINICAL-EXPERIMENTAL STUDY.
Authors: HEINRICH STERN
Journal: JAMA (1906)

Albuminuria is nothing but a symptom of disease. The cause of the symptom may be anterenal, renal or postrenal, and may be due to structural change or to pathologic function. Postrenal albuminuria, an admixture of various adventitious proteid substances with the urine after this has left the renal tubules, does not come within the scope of the subject under consideration. In the case of anterenal or renal causes, it is the albumin of the serum, or rather albumin having passed through the circulation which has found its way into the urine. We are perfectly justified in accepting anterenal factors of albuminuria when we are confronted with a large albumin output without corresponding kidney lesion as shown by the presence of goodly amounts of tubular epithelium. We may yet go a step further and maintain that native serum albumin occurring in normal amounts can not be eliminated, even by a structurally
Ethnic Neutropenia and Treatment Delay in African American Women Undergoing Chemotherapy for Early-Stage Breast Cancer
Authors: Dawn Hershman, Mitchell Weinberg, Zachary Rosner, Karenza Alexis, Amy Tiersten, Victor R Grann, Andrea Troxel, Alfred I Neugut
Journal: JNCI Journal of the National Cancer Institute (2003)

Disparities in breast cancer survival have been observed between African American and white women. There are also known differences in mean baseline white blood cell (WBC) count among racial and ethnic groups. If the WBC count falls below conventionally defined treatment thresholds for patients undergoing adjuvant chemotherapy, reduced doses or treatment delays may occur, which could lead to race-based differences in treatment duration. We used the tumor registry at Columbia-Presbyterian Medical Center to identify 1178 women with newly diagnosed stage I and II breast cancer from whom we collected base-line information for 73 African American women and 126 age- and tumor stage–matched white women. Of these women, 43 African American and 93 white women underwent adjuvant chemotherapy. African American women had statistically significantly lower WBC counts than white women at diagnosis (6.2 × 109/L for African American women versus 7.4 × 109/L for white women, difference = 1.2, 95% confidence interval [CI] = 0.2 to 1.2; P = .02) and after treatment (5.3 × 109/L for African American women versus 6.4 × 109/L for white women, difference = 1.1, 95% CI = 0.2 to 2.5; P = .03). Overall, African American women required a statistically significantly longer duration of treatment than white women (19 weeks versus 15 weeks, respectively, difference = 4 weeks, 95% CI = 0.5 to 7.2 weeks; P = .03). The lower baseline WBC counts and longer duration of treatment for early-stage breast cancer in African American women compared with those in white women result in lower dose intensity of treatment for African American women, possibly contributing to observed racial differences in breast cancer survival.