tbuckley/cabot-search huggingface dataset:
Pulmonary vascular response patterns during exercise in interstitial lung disease
Authors: Luiza H. Degani-Costa, Barbara Levarge, Subba R. Digumarthy, Aaron S. Eisman, R. Scott Harris, Gregory D. Lewis
Journal: European Respiratory Journal (2015)

When overt pulmonary hypertension arises in interstitial lung disease (ILD), it contributes to exercise intolerance. We sought to determine the functional significance of abnormal pulmonary arterial pressure (PAP) responses to exercise in ILD. 27 ILD patients and 11 age-matched controls underwent invasive cardiopulmonary exercise testing (iCPET). Mean PAP (mPAP) was indexed to cardiac output ( Q ´ T ) during exercise, with a mPAP– Q ´ T slope ≥3 mmHg·min·L −1 defined as an abnormal pulmonary vascular response. All control subjects had mPAP– Q ´ T slopes &lt;3 mmHg·min·L −1 (mean± sem 1.5±0.1 mmHg·min·L −1 ). 15 ILD patients had mPAP– Q ´ T slopes ≥3 mmHg·min·L −1 (4.1±0.2 mmHg·min·L −1 ) and were labelled as having ILD plus pulmonary vascular dysfunction (PVD). Subjects without pulmonary hypertension and with mPAP– Q ´ T slopes &lt;3 mmHg·min·L −1 (1.9±0. 2 mmHg·min·L −1 ) were labelled as ILD minus PVD (n=12). ILD+PVD and ILD−PVD patients did not differ in terms of age, sex, body mass index, pulmonary function testing or degree of exercise oxygen desaturation. Peak oxygen consumption was lower in ILD+PVD than in ILD−PVD (13.0±0.9 versus 17±1.1 mL·kg −1 ·min −1 , p=0.012) and controls (19.8±1.7 mL·kg −1 ·min −1 , p=0.003). ILD+PVD patients had increased dead space volume ( V D )/tidal volume ( V T ) and minute ventilation/carbon dioxide production at the anaerobic threshold. In ILD, mPAP– Q ´ T slope ≥3 mmHg·min·L −1 is associated with lower peak oxygen consumption, increased V D / V T and inefficient ventilation. While noninvasive parameters were unable to predict those with abnormal pulmonary vascular responses to exercise, iCPET-derived mPAP– Q ´ T slope may aid in identifying physiologically significant, early pulmonary vascular disease in ILD.
Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm.
Authors: E J Small, N J Vogelzang
Journal: Journal of Clinical Oncology (1997)

PURPOSE To discuss the evolution of new concepts in the Use of second-line hormonal therapy for patients with progressive prostate cancer despite androgen deprivation. DESIGN Pertinent contemporary prostate-specific antigen (PSA)-based reports of the utility of secondary hormonal maneuvers after treatment with combined androgen blockade (CAB) were reviewed. RESULTS The use of PSA as an end point in hormonerefractory prostate cancer (HRPC) trials is more widely accepted, but still remains somewhat controversial. Using PSA as an end point, it is clear that a variety of secondary hormonal maneuvers can result in responses. Antiandrogen withdrawal is efficacious in approximately 20% of patients and can be observed with a variety of antiandrogens, including flutamide, bicalutamide, and megestrol acetate. A variety of regimens, including megestrol, bicalutamide, glucocorticoids, aminoglutethimide, and ketoconazole, retain activity (14% to 75% PSA response proportion) even in patients who have failed to respond to CAB and flutamide withdrawal. CONCLUSION Once CAB (suppression of gonadal and adrenal androgen) is undertaken, further hormonal maneuvers remain efficacious in some patients with progressive prostate cancer. Antiandrogen withdrawal is now a mandatory maneuver before proceeding to other regimens. It is clear that certain patients will continue to respond to hormonal maneuvers even after antiandrogen withdrawal. An understanding of the molecular basis of these responses may result in the development of a more targeted therapy in the future.
Mammary Tumors and Mammary Gland Development in Normal and EstrogenTreated F&lt;sub&gt;1&lt;/sub&gt; Hybrids of Strains C3H/J and RIII/An Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Flavia L. Richardson
Journal: JNCI Journal of the National Cancer Institute (1966)

A comparison of the rate of tumor development in F1 hybrids of reciprocal crosses between the high-mammary-tumor strains C3H/HeJ and RIII/AnJ showed that the mean tumor age was higher and the incidence of mammary tumors was lower in the F1 virgins with RIII mothers than in F1 virgins with C3H mothers. Pellets composed of 20 percent diethylstilbestrol and 80 percent cholesterol were implanted subcutaneously into male and female mice and removed after 8 weeks or left in for life. The mice used were F1 hybrids of C3H/J and RIII/An with the mammary-tumor agent and F1 hybrids of agent-free strains C3HeB and RlllfB. Less than half of the untreated F1 virgins born to agent-free C3H or agent-free RIII mothers developed mammary tumors and these occurred only in old animals. Virgins exposed to diethylstilbestrol pellets for 8 weeks developed a high percentage of mammary tumors whether or not the agent was present, but they occurred at a later age in agent-free females. The tumor incidence and mean tumor age in male and female hybrids with the agent were approximately the same as in male and female hybrids without the agent when the mice were treated for life with diethylstilbestrol. This indicates that in these hybrids the mammary-tumor agent is not an important factor in tumor formation if the animals are stimulated by exogenous estrogenic hormones for a long period. Wholemounts were made of mammary glands of all groups studied. Most of the mammary glands were fairly well developed in strain RIII/An virgin females and in virgin hybrids between strains C3H and RIII.
Role of maternal phenotype in asthma development in children
Authors: Liudmila Zhelenina, Maria Vakharlovskaya, Olga Lavrova, Tatiana Ivashchenko
Journal: European Respiratory Journal (2012)

Children born from mothers with bronchial asthma are the most vulnerable group for development of allergic diseases.  AME of study. We have done research into data obtained from 117 pregnant women with bronchial asthma and their children. The average age of mothers was 27,7±5,2 years. Most mothers developed the disease before the age of 16 (88 mothers; 75,2%); 29 mothers got ill when they were over 16 years of age (24.8%) (“child” and “adult” bronchial asthma respectively). We have researched medical data of 117 children born from these mothers: 64 boys (54.7%) and 53 girls (45.2%). Over 70% of the children reached the age of 7-9 by the end of the observation period. Children born by caesarean section developed bronchial asthma 1.5 times more often than children born naturally. Children who had been breastfed for over 4 months had significantly lower incidence of atopic dermatitis than children fed artificially (14% and 32.7% respectively; χ2-4,5042, p=0,033). Children born from mothers with “child” asthma phenotype more often developed bronchial asthma by the age of 7 (p=0.034, χ2=4,4929). Children born from mothers with “child” asthma phenotype run a 3-fold higher risk of developing bronchial asthma than those whose mothers had “adult” asthma phenotype (OR = 3,042[CI:1,013 – 9,132]).  Conclusion  The research has confirmed the significance of hereditary load, maternal asthma phenotype, mode of child delivery, and baby feeding for development of allergic diseases in children.
Validation of a Japanese version of the COPD diagnostic questionnaire in the general Asian population: The Hisayama study
Authors: Hiromasa Inoue, Go Tsukuya, Satoru Fukuyama, Yoichi Nakanishi, Takuya Samukawa, Takahiro Nakamura, Koichiro Matsumoto
Journal: European Respiratory Journal (2013)

Although COPD Population Screener (COPD-PS) questionnaire was developed in the United State as a screening tool to assess the likelihood of COPD, its validity is not clear in population-based study. This study determines the validity of the Japanese version of the COPD diagnostic questionnaire in the general Asian population.  This was an observational study of Japanese subjects living in the town of Hisayama in Fukuoka, Japan. All registered residents aged above 40 were solicited to participate in a town-wide health check-up including the completion of the COPD-PS and spirometry. Only subjects who had a FEV1/FVC of less than 0.7 were required to have a post-bronchodilator spirometry for further COPD evaluation. Subjects were classified into airway obstruction groups (none, pre-bronchodilator obstruction but not post, airflow obstruction). The sensitivity and specificity of the COPD-PS was assessed by logistic regression and cut-points evaluated for the best predictive threshold.  The COPD-PS was evaluated among a total of 2,468 subjects and was found to be acceptable for completion with little missing data. The overall area under the ROC curve for the continuous COPD-PS score was 0.735. A cut-point of 4-points is recommended, resulting in a sensitivity of 63.9% and specificity of 73.7% with an area under the receiver operating characteristic curve of 0.69. The positive predictive value was 17.3% and negative predictive value was 96.0%.  The COPD-PS appears to be an adequate measure for large scale screening of possible airflow obstruction requiring further testing with spirometry.
Abstract MP58: Vitamin D Consumption is Not Associated with Incident Heart Failure: the Physicians' Health Study
Authors: Jeremy Robbins, Andrew Petrone, J. Michael Gaziano, Luc Djousse
Journal: Circulation (2015)

Background: Previous research investigating the relationship between vitamin D supplementation and incident heart failure (HF) has yielded equivocal results. Limited research exists on the association of dietary vitamin D consumption and the risk of incident heart failure. Objective: We sought to test the hypothesis that vitamin D consumption is associated with a lower incidence of heart failure. Methods and Results: Using a validated food frequency questionnaire, we estimated dietary vitamin D consumption for 19,635 participants of the Physician’s Health Study who were free of HF at baseline. The mean age at baseline was 66.4 ± 9.2 years. Over a mean followup of 9.3 years, 858 cases of incident HF were captured using an annual follow-up questionnaire with validation in a subsample. From the multivariable Cox regression model, hazard ratios (95% CI) of incident HF were 1.0 (reference), 1.49 (1.17 to 1.89), 1.37 (1.07 to 1.75), 1.34 (1.02 to 1.75), and 1.28 (0.94 to 1.75) from lowest to highest quintile of calorie-adjusted vitamin D, respectively, after adjusting for age, BMI, smoking, alcohol, exercise, multivitamin use, fruits and vegetables, chocolate, and breakfast cereal consumption, atrial fibrillation, and valvular heart disease (p for linear trend = 0.71). Conclusions: In this prospective study of male health professionals, dietary vitamin D consumption is associated with a higher risk of HF.
Subarachnoid Haemorrhage-Can We Do Better?
Authors: S R D Johnston, A Hammond, L Griffiths, R Greenwood, C R A Clarke
Journal: Journal of the Royal Society of Medicine (1989)

Patients with subarachnoid haemorrhage often have warning symptoms which are unrecognized. Specific neurological signs such as cranial nerve palsies due to aneurysm expansion may occur. Sudden and severe 'out-of-the-blue' headache following minor haemorrhage may be misinterpreted as migraine. Focal neurological signs from secondary ischaemia may be misinterpreted as thromboembolic events. Computed tomography (CT) head scans can be misleading especially if performed too late.
Lung cancer in women: Is it different?
Authors: David Bravo, Patricia Sobradillo, Olatz Llaguno, Laura Tomás, Marta Inchausti, Julia Amaranta García, Jose Luis Lobo
Journal: European Respiratory Journal (2014)

BACKGROUND  Lung cancer is the fourth most frequent cancer in women after breast, colorectal and cervix cancer. Nowadays, lung cancer is the first cause of death due to cancer in women. The differences between sexes are decreasing.  The aim of the study was to analyze the differences in frequency, clinical characteristics and survival rates in lung cancer between men and women in our hospital.  METHODS  A retrospective and descriptive study was performed. All consecutive patients with a primary lung cancer diagnosis presented in the lung cancer committee from September 2011 to October 2013 were included. Variables analyzed included data on clinical presentation, functional parameters, diagnostic test, treatment and prognosis. Variables are described as percentage, mean and standard deviation. The chi-squared and Mann-Whitney tests were used to compare variables. Survival analysis was performed using Kaplan-Meyer graphics. A p  RESULTS  A total of 202 patients were included. Average age was 64.5 years old (+/-10.3), 44 of them were women (21.8%), only 7.9% (16 patients) were never smokers, 19.3% had had a previous cancer and 32.7% of them had a COPD diagnosis. The most common way of presentation was a casual finding (31.7% of all cases) and in the symptomatic group the cough was the most frequent symptom (22.8%). During follow up 85 patients died (42.1%). In the survival analysis there were not significant statistics differences between men and women.  CONCLUSIONS  Prevalence of lung cancer was 22%.  There were no significant differences between men and women according to presentation, clinical characteristics and survival. There were differences in smoking habits, previous neoplasic history and the histologic results.
Transfer of Immunity to Sarcoma I Homografts in Newborn Mice2
Authors: Mang-So Tsoi, Russell S. Weiser, Seikichi Tokuda
Journal: JNCI Journal of the National Cancer Institute (1965)

Immunity to Sarcoma I (Sal) was readily transferred to newborn C57BL/6Ks mice from mothers that had been either actively immunized with live tumor or passively immunized with hyperimmune serum or hyperimmune cell-free ascitic fluid containing anti-Sal antibody. The transfer of immunity to the newborn was most effectively demonstrated with a low challenge dose of 1,000 tumor cells given intraperitoneally. Foster-nursing experiments indicated that the immunity of the newborn offspring of immune mothers was acquired principally via the lacteal route. The development of Sal tumors was also prevented when the hyperimmune serum or ascitic fluid was introduced directly into newborn mice. These results indicated that acquired maternal immunity transmitted to the newborn results from humoral antibody. Adult C57BL/6Ks mice rendered immunologically incompetent by X irradiation were likewise protected by hyperimmune serum against small challenge doses of tumor cells. Serum and cell-free ascitic fluid derived from these animals during primary rejection of Sarcoma I gave much less protection to newborn mice than serum or cell-free ascitic fluid taken from hyperimmunized mice.
Preclinical assessment of gene expression and proteomic profiles promoted by the novel antiandrogen BMS-641988, bicalutamide and castration.
Authors: Ricardo M. Attar, Aaron J. Balog, Jing Chen, Shen-Jue Chen, Mark Curran, Mary-Ellen Cvijic, Janet Dell-John, Joseph E. Dinchuk, Gennaro Dito, Ashok R. Dongre, William R. Foster, Aiqing He, Ching-Ping Ho, Donald Jackson, Maria N. Jure-Kunkel, Anne C. Lewin, Cheryl A. Rizzo, Douglas M. Robinson, Mark E. Salvati, Liang Schweizer, Thomas E. Spires, Gregory D. Vite, Michael Woo, Li-An Xu, Marco Gottardis
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5345 

Complete androgen ablation (LHRH agonists and antiandrogens) is the gold standard treatment for metastatic prostate cancer. BMS-641988 is a recently identified novel antiandrogen with superior potency and efficacy compared to bicalutamide (Casodex®, AstraZenceca). Global mechanistic similarities and differences between the two antiandrogens and castration were assessed by gene and protein expression in two different in vivo systems. In the first noted, the gene expression profiles of CWR22 human prostate tumors implanted into mice treated with a) vehicle, b) BMS-641988, c) bicalutamide, and d) castration, were analyzed by Affymetrix and QT-RT-PCR after 1, 2, and 7 days of treatment. These studies show that BMS-641988 treatment promotes an expression profile more similar to castration than bicalutamide, especially at days 2 and 7. Several genes previously reported to be regulated by the androgen receptor such as IGBP3, AR, FKBP5, and NKX3-1, were also identified in this experiment. The second in vivo model consisted of mature male rats treated for 14 days with each antiandrogen or castration. At the end of the study serum and ventral prostates were collected and subject to proteomic analysis. At the same dose, the serum profiles of castrated rats were more similar to BMS641988 than to bicalutamide. In addition, there were a substantially larger number of peptides showing a positive dose dependence with BMS-641988 than with bicalutamide. Together with the pharmacological profile these differences in global gene and protein expression suggest differences between BMS-641988 from bicalutamide and support BMS-641988 as a new clinical candidate.
Phase I trial of O6-benzylguanine for patients undergoing surgery for malignant glioma.
Authors: H S Friedman, D M Kokkinakis, J Pluda, A H Friedman, I Cokgor, M M Haglund, D M Ashley, J Rich, M E Dolan, A E Pegg, R C Moschel, R E McLendon, T Kerby, J E Herndon, D D Bigner, S C Schold
Journal: Journal of Clinical Oncology (1998)

PURPOSE The major mechanism of resistance to alkylnitrosourea therapy is the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which removes chlorethylation or methylation damage from the O6-position of guanine. O6-benzylguanine (O6-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial to define the presurgical dose required for depletion of tumor AGT activity in patients with malignant glioma. MATERIALS AND METHODS Patients were to be treated 18 hours before craniotomy with intravenous doses that ranged between 40 and 100 mg/m2 given over 1 hour. Resected tumor was snap-frozen in liquid nitrogen and AGT activity analyzed by high-pressure liquid chromatography (HPLC). Up to 13 patients were treated at a specific dose of O6-BG, with a target end point of &gt; or = 11 of 13 patients with undetectable tumor AGT levels (&lt; 10 fmol/mg protein). RESULTS Thirty patients with malignant gliomas were enrolled, with 11 of 11 patients treated at 100 mg/m2 O6-BG demonstrating tumor AGT levels less than 10 fmol/mg protein. No toxicity was noted in any patient treated. CONCLUSION These results indicate that 100 mg/m2 of O6-BG can maintain tumor AGT levels less than 10 fmol/mg protein for at least 18 hours after treatment, a time interval in which bis(2-chloroethyl)nitrosourea (BCNU)-induced chloroethyl adducts are fully converted into interstrand cross-links. A 100-mg/m2 dose of O6-BG will be used in combination with BCNU in another phase I trial designed to determine the maximal-tolerated dose of BCNU.
Susceptibility of Human Cell Lines to Feline Leukemia Virus and Feline Sarcoma Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J Azocar, M Essex
Journal: JNCI Journal of the National Cancer Institute (1979)

The susceptibility of human fibroblasts and human lymphoid cell lines to feline leukemia virus (FeLV) and feline sarcoma virus (FeSV) was investigated. Human cells were highly sensitive to infection by FeLV subgroups B and C and FeSV but resistant to infection by FeLV subgroup A. The cells became infected, produced infectious virus, and displayed no differences in morphology or viability. T-cell lines appeared to be more sensitive to FeLV and FeSV infection and to produce more virus than did autochthonous B-cells. B-cell lines with membrane IgG appeared more resistant to infection than did those with no membrane IgG.
Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during <i>Mycobacterium tuberculosis</i> infection
Authors: Egidio Torrado, Jeffrey J. Fountain, Mingfeng Liao, Michael Tighe, William W. Reiley, Rachel P. Lai, Graeme Meintjes, John E. Pearl, Xinchun Chen, Daniel E. Zak, Ethan G. Thompson, Alan Aderem, Nico Ghilardi, Alejandra Solache, K. Kai McKinstry, Tara M. Strutt, Robert J. Wilkinson, Susan L. Swain, Andrea M. Cooper
Journal: The Journal of Experimental Medicine (2015)

CD4+ T cells mediate protection against Mycobacterium tuberculosis (Mtb); however, the phenotype of protective T cells is undefined, thereby confounding vaccination efforts. IL-27 is highly expressed during human tuberculosis (TB), and absence of IL-27R (Il27ra) specifically on T cells results in increased protection. IL-27R deficiency during chronic Mtb infection does not impact antigen-specific CD4+ T cell number but maintains programmed death-1 (PD-1), CD69, and CD127 expression while reducing T-bet and killer cell lectin-like receptor G1 (KLRG1) expression. Furthermore, T-bet haploinsufficiency results in failure to generate KLRG1+, antigen-specific CD4+ T cells, and in improved protection. T cells in Il27ra−/− mice accumulate preferentially in the lung parenchyma within close proximity to Mtb, and antigen-specific CD4+ T cells lacking IL-27R are intrinsically more fit than intact T cells and maintain IL-2 production. Improved fitness of IL-27R–deficient T cells is not associated with increased proliferation but with decreased expression of cell death–associated markers. Therefore, during Mtb infection, IL-27R acts intrinsically on T cells to limit protection and reduce fitness, whereas the IL-27R–deficient environment alters the phenotype and location of T cells. The significant expression of IL-27 in TB and the negative influence of IL-27R on T cell function demonstrate the pathway by which this cytokine/receptor pair is detrimental in TB.
Association of Child Poverty, Brain Development, and Academic Achievement
Authors: Nicole L. Hair, Jamie L. Hanson, Barbara L. Wolfe, Seth D. Pollak
Journal: JAMA Pediatrics (2015)

Children living in poverty generally perform poorly in school, with markedly lower standardized test scores and lower educational attainment. The longer children live in poverty, the greater their academic deficits. These patterns persist to adulthood, contributing to lifetime-reduced occupational attainment.
ERICA (evaluating the role of inflammation in chronic airways disease): Extrapulmonary manifestations of COPD
Authors: Divya Mohan, Carmel McEniery, Nicola Gale, Jonathan Fuld, Charlotte Bolton, William MacNee, Peter Calverley, Ruth Tal-Singer, Ian Wilkinson, Michael Polkey, John Cockcroft
Journal: European Respiratory Journal (2013)

Introduction   ERICA is a longitudinal study investigating the significance of cardiovascular (CV) and skeletal muscle (SM) manifestations of COPD and fibrinogen in relation to death/admission. This midpoint analysis asks whether the CV & SM manifestations represent the same patient subsets.   Method   We measured blood pressure (BP), spirometry, fibrinogen, 6 min walk distance (6MW), quadriceps maximal voluntary contraction force (MVC), and aortic pulse wave velocity (PWV). We defined CV manifestation as PWV>10m/s (EHJ 2010;31: 2338) and SM weakness as MVC/BMI ratio   Results   Table 1 presents data from the first 318 of a planned 800 patients, grouped according to presence of CV and/or SM manifestations, with Group 1 (SM) N=95, Group 2 (CV & SM) N=80, Group 3 (neither CV/SM) N=78 and Group 4 (CV) N=65 (Fig 1).   Conclusion Analysis of data from COPD patients enrolled in ERICA thus far suggests that there are distinct CV and SM subsets.