tbuckley/cabot-search huggingface dataset:
Acellular Normal and Fibrotic Human Lung Matrices as a Culture System for <i>In Vitro</i> Investigation
Authors: Adam J. Booth, Ryan Hadley, Ashley M. Cornett, Alyssa A. Dreffs, Stephanie A. Matthes, Jessica L. Tsui, Kevin Weiss, Jeffrey C. Horowitz, Vincent F. Fiore, Thomas H. Barker, Bethany B. Moore, Fernando J. Martinez, Laura E. Niklason, Eric S. White
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Extracellular matrix (ECM) is a dynamic tissue that contributes to organ integrity and function, and its regulation of cell phenotype is a major aspect of cell biology. However, standard in vitro culture approaches are of unclear physiologic relevance because they do not mimic the compositional, architectural, or distensible nature of a living organ. In the lung, fibroblasts exist in ECM-rich interstitial spaces and are key effectors of lung fibrogenesis.Objectives: To better address how ECM influences fibroblast phenotype in a disease-specific manner, we developed a culture system using acellular human normal and fibrotic lungs.Methods: Decellularization was achieved using treatment with detergents, salts, and DNase. The resultant matrices can be sectioned as uniform slices within which cells were cultured.Measurements and Main Results: We report that the decellularization process effectively removes cellular and nuclear material while retaining native dimensionality and stiffness of lung tissue. We demonstrate that lung fibroblasts reseeded into acellular lung matrices can be subsequently assayed using conventional protocols; in this manner we show that fibrotic matrices clearly promote transforming growth factor-β–independent myofibroblast differentiation compared with normal matrices. Furthermore, comprehensive analysis of acellular matrix ECM details significant compositional differences between normal and fibrotic lungs, paving the way for further study of novel hypotheses.Conclusions: This methodology is expected to allow investigation of important ECM-based hypotheses in human tissues and permits future scientific exploration in an organ- and disease-specific manner.
Cryptorchidism and Maternal Alcohol Consumption during Pregnancy
Authors: Ida N. Damgaard, Tina K. Jensen, Jørgen H. Petersen, Niels E. Skakkebæk, Jorma Toppari, Katharina M. Main
Journal: Environmental Health Perspectives (2006)

Prenatal exposure to alcohol can adversely affect the fetus. We investigated the association between maternal alcohol consumption during pregnancy and cryptorchidism (undescended testis) among newborn boys.We examined 2,496 boys in a prospective Danish-Finnish birth cohort study for cryptorchidism at birth (cryptorchid/healthy: 128/2,368) and at 3 months of age (33/2,215). Quantitative information on alcohol consumption (average weekly consumption of wine, beer, and spirits and number of binge episodes), smoking, and caffeine intake was obtained by questionnaire and/or interview once during the third trimester of pregnancy, before the outcome of the pregnancy was known. For a subgroup (n = 465), information on alcohol consumption was obtained twice during pregnancy by interviews.We investigated maternal alcohol consumption both as a continuous variable and categorized. The odds for cryptorchidism increased with increasing weekly alcohol consumption. After adjustment for confounders (country, smoking, caffeine intake, binge episodes, social class, maternal age, parity, maturity, and birth weight) the odds remained significant for women with a weekly consumption of five or more alcoholic drinks (odds ratio = 3.10; 95% confidence interval, 1.05-9.10).Regular alcohol intake during pregnancy appears to increase the risk of congenital cryptorchidism in boys. The mechanisms for this association are unknown. Counseling of pregnant women with regard to alcohol consumption should also consider this new finding.
Osteocytes Regulate Primary Lymphoid Organs and Fat Metabolism
Authors: Mari Sato, Noboru Asada, Yuko Kawano, Kanako Wakahashi, Kentaro Minagawa, Hiroki Kawano, Akiko Sada, Kyoji Ikeda, Toshimitsu Matsui, Yoshio Katayama
Journal: Cell Metabolism (2013)
Frequency of Pulmonary Thromboembolism in Man
Authors: David G. Freiman, Joe Suyemoto, Stanford Wessler
Journal: New England Journal of Medicine (1965)

RECOGNITION of the magnitude of the problem of pulmonary embolism in man requires reliable data concerning its incidence. Unfortunately, most of the available statistics on incidence are based on routine post-mortem examinations in which the pulmonary arteries are rarely inspected adequately.We were stimulated to examine the frequency of human pulmonary embolism found at autopsy as a result of observations in an experimental investigation of pulmonary embolism in dogs.1 , 2 While studying the fate of experimentally induced autologous peripheral venous thrombi released to the pulmonary circulation, we repeatedly noted that some of the residua observed weeks to months after the embolic . . .
What Can We Expect From the 1993 International Conference on AIDS?
Authors: Jonathan M. Mann
Journal: JAMA (1993)

From June 6 through 11, 1993, more than 10000 people will attend the Ninth International Conference on AIDS, held this year in Berlin, Germany. This enormous meeting, ninth of an annual series, is unique among international health gatherings. Not only has the organization and "culture" of successive meetings evolved considerably, but each year's international AIDS conference has strongly influenced our view of the pandemic. The first two meetings, in Atlanta, Ga (1985), and Paris, France (1986), were organized as classic medical gatherings, with the traditional array of large plenary lectures and many smaller, abstract-driven sessions. Yet, they also firmly established the global scope of the epidemic, which was fundamental for launching of the World Health Organization's global AIDS strategy in 1986. The next year, in Washington, DC, politics forcefully (and permanently) entered the conference, as demonstrations outside and inside the meeting rooms expressed growing frustration among AIDS activists with the
Rarity of mineral fibre pleurisy among persons exposed to Finnish anthophyllite and with low risk of mesothelioma.
Authors: G Hillerdal, A Zitting, A H van Assendelft, T Kuusela
Journal: Thorax (1984)

Endemic pleural plaques are reported from many parts of the world. In Central Europe and in Finland no connection with malignant mesotheliomas has been found, whereas this tumour is often encountered in areas in Turkey where endemic plaques also occur. There seem, however, to be differences in the radiological appearances found in these areas. In the present study chest radiographs of 317 persons with pleural plaques from the endemic area of Finland were scrutinized. It was found that 4.7% showed a blunted costophrenic angle unilaterally and 0.9% bilaterally. The prevalence of sequelae of pleurisy is statistically very highly significantly lower than in people with pleural plaques in Turkey. As the risk of mesothelioma appears to be low in Finland, the results are in accordance with the hypothesis that the risk of mesothelioma in a given population is higher if in that population there is a high incidence of benign asbestos pleurisy.
The antiviral drug selected hepatitis B virus rtA181T/sW172* mutant has a dominant negative secretion defect and alters the typical profile of viral rebound
Authors: Nadia Warner, Stephen Locarnini
Journal: Hepatology (2008)

The hepatitis B virus (HBV) mutation that encodes rtA181T is selected in the viral polymerase during antiviral drug therapy and can also encode a stop codon in the overlapping surface gene at amino acid 172 (sW172*) resulting in truncation of the last 55 amino acids of the C-terminal hydrophobic region of the surface proteins. This mutation is usually detected as a mixed population with wild-type HBV. In vitro analysis revealed that the rtA181T/sW172* variant is not only defective in secretion of viral particles causing intracellular retention of surface proteins, it also has a dominant negative effect on virion but not subviral particle secretion when coexpressed with the wild type. This dominant negative effect was attributed to the truncated S protein alone. Furthermore, these truncated surface proteins were less glycosylated, and the truncated L protein was able to support virion secretion. Examination of sequential HBV DNA levels in patients failing lamivudine or adefovir therapy where only the rtA181T change was detected via polymerase chain reaction sequencing revealed that viral load rebound did not occur or was not as large as usually observed with drug-resistant HBV. Conclusion: The rtA181T/sW172* variant has a secretory defect and exerts a dominant negative effect on wild-type HBV virion secretion. The selection of rtA181T/sW172* reduced the typical extent of virological breakthrough, resulting in a missed diagnosis of drug resistance if viral load was used as the only criterion for drug failure, necessitating HBV polymerase chain reaction sequencing or other genotypic methods to diagnose antiviral drug resistance in these cases. (HEPATOLOGY 2008.)
Comparison between sodium cromoglycate (MDI: metered‐dose inhaler) and beclomethasone dipropionate (MDI) in treatment of adult patients with mild to moderate bronchial asthma A double‐blind, double‐dummy randomized, parallel‐group study
Authors: P. Faurschou, J. Bing, G. Edman, A.‐M. Engel
Journal: Allergy (1994)

This study compared the efficacy and tolerability of sodium cromoglycate (SC) and beclomethasone dipropionate (BDP) in adult patients with bronchial asthma inadequately treated with bronchodilators alone. The study was a double‐blind, randomized, double‐dummy, parallel‐group study. Patients with mild to moderate symptomatic asthma, inadequately treated with bronchodilators only, were, after a 2–week run‐in (base‐line) period, randomized to 8 weeks of treatment with either SC 10 mg four times daily or BDP 100 μg four times daily. Salbutamol metered‐dose inhaler was given as relief medication. A total of 37 patients were randomized for treatment, 19 patients in the SC group and 18 patients in the BD group. Efficacy and safety were determined by daily record card data: morning and evening peak‐expiratory‐flow rates (PEER), daytime and nighttime asthma symptom scores, and rescue salbutamol use. At clinic visits, FEV 1 and FVC were measured, as were the physician's and the patient's assessment of the medication at the end of the study. The safety and tolerability of the trial medication were assessed by monitoring adverse events throughout the study. A clinically and statistically significant improvement of the asthma in FEV 1 , symptom scores, rescue medication, and global opinion of efficacy was observed, and both groups provided equivalent efficacy. The morning PEFR as well as the evening PEFR for both groups improved, but was statistically significant only for the BDP group (M‐PEFR). Both drugs were well tolerated with only a few minor adverse events. This trial shows that SC and BDP are equally effective anti‐inflammatory treatments for mild to moderate bronchial asthma in adults.
Impaired Decision-Making Ability in Subjects With Alzheimer’s Disease and Willingness to Participate in Research
Authors: Scott Y.H. Kim, Christopher Cox, Eric D. Caine
Journal: American Journal of Psychiatry (2002)

Ethical concerns persist over research participation of decisionally impaired persons, such as those suffering from Alzheimer's disease. Such persons may be poor judges of the burdens and risks of specific research protocols. Since even decisionally incapacitated persons cannot be enrolled in studies against their objection, their preferences convey important ethical information. The authors examined the effects of cognitive and decisional impairment on willingness to participate in research among persons with Alzheimer's disease.Cognitive status, decision-making ability, and willingness to participate in four hypothetical research protocols of varying risk/benefit profiles were measured in 34 subjects with mild to mild/moderate Alzheimer's disease and 14 healthy elderly comparison subjects. Univariate and multivariate methods were used to analyze the effects of impairment in cognitive and decision-making abilities on willingness to participate in research.There were no differences in willingness to participate found between the Alzheimer's and the healthy comparison subjects for three of the four hypothetical protocols. In both groups, willingness declined as risk increased. Within the Alzheimer's disease group, the presence of greater decisional impairment tended to predict less willingness to participate in research, even after adjusting for cognitive impairment, gender, and education.Persons with decisional impairment due to Alzheimer's disease are as a group able to distinguish between research protocols of varying risk/benefit profiles. Because declining decision-making abilities may predict declining willingness to participate in research, informed consent procedures for Alzheimer's disease research should be sensitive to this possibility.
Is endothelin-1 a mediator in asthma?
Authors: D W Hay, P J Henry, R G Goldie
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

There is a growing understanding of the effects and potential pathophysiological role of the ETs in asthma and several of the criteria required to strongly implicate ET-1 as a mediator in this disease have been fulfilled. However, some of the information is preliminary, equivocal and requires confirmation. Furthermore, the most important and most difficult criteria, the clinical testing of potent and selective ET receptor antagonists in these diseases has not been conducted and will probably not be completed for several years. A critical area of research continues to be the elucidation and classification of the ET receptor subtypes mediating the diverse effects of ET-1 in the lung. The unequivocal determination of the pathophysiological role of the ETs in asthma awaits the results of clinical trials with appropriate compounds. Only after these results will we know whether ET-1 has fulfilled its promise as a key player in lung pathophysiology, rather than being added to the list of purported important mediators with unfulfilled expectations.
Medical Care of the Adolescent: A Textbook Concerning the Medical Care and Understanding of Adolescents Themselves and of Their Disorders
Authors: William P. Barba
Journal: JAMA (1960)

The stated purpose of this book is, "to discuss those ailments which are common in adolescence or which present some peculiarity during that period of life" and "to emphasize the importance of taking adolescents themselves, their characteristics, their hopes and fears into account, and of treating them not just their illnesses." The format is excellent and conducive to pleasant reading. References are given at the conclusion of each chapter. The index is complete. The length of the book is, if anything, inadequate for the material covered. The first four chapters, dealing with the general means and methods of evaluating the adolescent, should be invaluable to one inexperienced with this age group. These contain helpful points for those with wide experience. The remaining chapters dealing with specific ailments, with several notable exceptions, suffer somewhat by the limitations of space. The effort to be brief and concise has resulted in a degree
Low‐dose subcutaneous erythropoietin in continuous ambulatory peritoneal dialysis
Authors: C. Rotellar, M. J. Mazzoni, W. F. Mosher, M. Aminrazavi, A. Bauer, T. A. Rakowski, G. E. Schreiner, J. F. Winchester
Journal: American Journal of Hematology (1991)

We evaluated changes in hematocrit in patients on continuous ambulatory peritoneal dialysis (CAPD) before and after the administration of erythropoietin (EPO). Thirty-five patients were evaluated at the beginning of treatment with CAPD and after an average of 3.5 years on CAPD; mean hematocrit (Hct) rose from 25.4 +/- 5.4% to 28.1 +/- 6.7% (P less than 0.001). In the period before EPO administration 11 patients required a total of 44 transfusions (one patient needed 23 transfusions). Fifteen patients were started on subcutaneous erythropoietin 3,000 units 3 times a week and were followed for a mean period of 6.3 months. Hct rose from 23.8 +/- 1.8% to 25.2 +/- 2.4% (P less than 0.01) within the first 2 weeks and up to 27.5 +/- 3.7% (P less than 0.01) in the fourth week. By the eighth week the target Hct (30 to 35%) was reached. During the next 5 months the EPO doses were adjusted to each patient's needs ranging between 2,000 U per week to 4,000 U 3 times per week. Mild hypertension was the only side effect seen in some of the patients. In conclusion low dose subcutaneous EPO is effective in managing the anemia of patients on CAPD with only minor side effects.
Expression of Class III β-Tubulin Is Predictive of Patient Outcome in Patients with Non–Small Cell Lung Cancer Receiving Vinorelbine-Based Chemotherapy
Authors: Pascal Sève, Sylvie Isaac, Olivier Trédan, Pierre-Jean Souquet, Yves Pachéco, Maurice Pérol, Laurence Lafanéchère, Aurélie Penet, Eva-Laure Peiller, Charles Dumontet
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC). Experimental Design: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. Results: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III β-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III β-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Δ2 α-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II β-tubulin, class III β-tubulin, and Δ2 α-tubulin levels, confirmed that class III β-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). Conclusions: These findings suggest that a high level of expression of class III β-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.
<i>In Vivo</i> Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K–AKT Signaling at Endosomes
Authors: Chen Li Chew, Andrea Lunardi, Federico Gulluni, Daniel T. Ruan, Ming Chen, Leonardo Salmena, Michiya Nishino, Antonella Papa, Christopher Ng, Jacqueline Fung, John G. Clohessy, Junko Sasaki, Takehiko Sasaki, Roderick T. Bronson, Emilio Hirsch, Pier Paolo Pandolfi
Journal: Cancer Discovery (2015)

The phosphatases PTEN and INPP4B have been proposed to act as tumor suppressors by antagonizing PI3K-AKT signaling and are frequently dysregulated in human cancer. Although PTEN has been extensively studied, little is known about the underlying mechanisms by which INPP4B exerts its tumor-suppressive function and its role in tumorigenesis in vivo. Here, we show that a partial or complete loss of Inpp4b morphs benign thyroid adenoma lesions in Pten heterozygous mice into lethal and metastatic follicular-like thyroid cancer (FTC). Importantly, analyses of human thyroid cancer cell lines and specimens reveal INPP4B downregulation in FTC. Mechanistically, we find that INPP4B, but not PTEN, is enriched in the early endosomes of thyroid cancer cells, where it selectively inhibits AKT2 activation and in turn tumor proliferation and anchorage-independent growth. We therefore identify INPP4B as a novel tumor suppressor in FTC oncogenesis and metastasis through localized regulation of the PI3K-AKT pathway at the endosomes.Although both PTEN and INPP4B can inhibit PI3K-AKT signaling through their lipid phosphatase activities, here we demonstrate lack of an epistatic relationship between the two tumor suppressors. Instead, the qualitative regulation of PI3K-AKT2 signaling by INPP4B provides a mechanism for their cooperation in suppressing thyroid tumorigenesis and metastasis.
Adipose tissue levels of organochlorine pesticides and polychlorinated biphenyls and risk of non-Hodgkin's lymphoma.
Authors: Penelope J E Quintana, Ralph J Delfino, Susan Korrick, Argyrios Ziogas, Frederick W Kutz, Ellen L Jones, Francine Laden, Eric Garshick
Journal: Environmental Health Perspectives (2004)

In this nested case-control study we examined the relationship between non-Hodgkin's lymphoma (NHL) and organochlorine pesticide exposure. We used a data set originally collected between 1969 and 1983 in the U.S. Environmental Protection Agency National Human Adipose Tissue Survey. Adipose samples were randomly collected from cadavers and surgical patients, and levels of organochlorine pesticide residues were determined. From the original study population, 175 NHL cases were identified and matched to 481 controls; 173 controls were selected from accident victims, and 308 from cases with a diagnosis of myocardial infarction. Cases and controls were mainly from cadavers (&gt; 96%) and were matched on sex, age, region of residence within the United States, and race/ethnicity. Conditional logistic regression showed the organochlorine pesticide residue heptachlor epoxide to be significantly associated with NHL [compared with the lowest quartile: third quartile odds ratio (OR) = 1.82, 95% confidence interval (CI), 1.01-3.28; fourth quartile OR = 3.41, 95% CI, 1.89-6.16]. The highest quartile level of dieldrin was also associated with elevated NHL risk (OR = 2.70; 95% CI, 1.58-4.61), as were higher levels of oxychlordane, p,p'-DDE [p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], and ss-benzene hexachloride (ORs = 1.79, 1.99, and 2.47, respectively). The p-values for trends for these associations were significant. In models containing pairs of pesticides, only heptachlor epoxide and dieldrin remained significantly associated with risk of NHL. Limitations of this study include collection of samples after diagnosis and a lack of information on variables affecting organochlorine levels such as diet, occupation, and body mass index. Given the persistence of pesticides in the environment, these findings are still relevant today.
Calf blood flow and oxygen carriage after reversal of polycythaemia secondary to hypoxic lung disease.
Authors: P J Wallis, M C Apps, A C Newland, D W Empey
Journal: Thorax (1986)

Reduction of packed cell volume has been recommended as a therapeutic procedure in patients with polycythaemia secondary to hypoxic lung disease. We have investigated the effects of this policy on blood flow and oxygen carriage to the calf in 12 such patients. Packed cell volume was decreased from 0.61 to 0.51 (mean) by isovolaemic haemodilution on a cell separator, with significant reductions in blood viscosity at high and low shear rates. Resting calf blood flow was unchanged but peak flow during reactive hyperaemia increased by 17% and 21% one and seven days after the procedure. Oxygen carriage to the calf at rest was initially unchanged but had fallen by 20% at seven days. During reactive hyperaemia oxygen carriage was not impaired by the reduction in packed cell volume since the rise in blood flow offset any reduction in arterial oxygen content. This study has shown that when blood flow is stressed during reactive hyperaemia oxygen carriage is not compromised by a therapeutic reduction in packed cell volume.