tbuckley/cabot-search huggingface dataset:
Combined Resistance and Aerobic Exercise Program Reverses Muscle Loss in Men Undergoing Androgen Suppression Therapy for Prostate Cancer Without Bone Metastases: A Randomized Controlled Trial
Authors: Daniel A. Galvão, Dennis R. Taaffe, Nigel Spry, David Joseph, Robert U. Newton
Journal: Journal of Clinical Oncology (2009)

Purpose Androgen suppression therapy (AST) results in musculoskeletal toxicity that reduces physical function and quality of life. This study examined the impact of a combined resistance and aerobic exercise program as a countermeasure to these AST-related toxicities. Patients and Methods Between 2007 and 2008, 57 patients with prostate cancer undergoing AST (commenced &gt; 2 months prior) were randomly assigned to a program of resistance and aerobic exercise (n = 29) or usual care (n = 28) for 12 weeks. Primary end points were whole body and regional lean mass. Secondary end points were muscle strength and function, cardiorespiratory capacity, blood biomarkers, and quality of life. Results Analysis of covariance was used to compare outcomes for groups at 12 weeks adjusted for baseline values and potential confounders. Patients undergoing exercise showed an increase in lean mass compared with usual care (total body, P = .047; upper limb, P &lt; .001; lower limb, P = .019) and similarly better muscle strength (P &lt; .01), 6-meter walk time (P = .024), and 6-meter backward walk time (P = .039). Exercise also improved several aspects of quality of life including general health (P = .022) and reduced fatigue (P = .021) and decreased levels of C-reactive protein (P = .008). There were no adverse events during the testing or exercise intervention program. Conclusion A relatively brief exposure to exercise significantly improved muscle mass, strength, physical function, and balance in hypogonadal men compared with normal care. The exercise regimen was well tolerated and could be recommended for patients undergoing AST as an effective countermeasure to these common treatment-related adverse effects.
High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells
Authors: Takuya Miyagi, M. Pilar Gil, Xin Wang, Jennifer Louten, Wen-Ming Chu, Christine A. Biron
Journal: The Journal of Experimental Medicine (2007)

The best-characterized type 1 interferon (IFN) signaling pathway depends on signal transducer and activator of transcription 1 (STAT1) and STAT2. The cytokines can, however, conditionally activate all STATs. Regulation of their access to particular signaling pathways is poorly understood. STAT4 is important for IFN-γ induction, and NK cells are major producers of this cytokine. We report that NK cells have high basal STAT4 levels and sensitivity to type 1 IFN–mediated STAT4 activation for IFN-γ production. Increases in STAT1, driven during viral infection by either type 1 IFN or IFN-γ, are associated with decreased STAT4 access. Both STAT1 and STAT2 are important for antiviral defense, but STAT1 has a unique role in protecting against sustained NK cell IFN-γ production and resulting disease. The regulation occurs with an NK cell type 1 IFN receptor switch from a STAT4 to a STAT1 association. Thus, a fundamental characteristic of NK cells is high STAT4 bound to the type 1 IFN receptor. The conditions of infection result in STAT1 induction with displacement of STAT4. These studies elucidate the critical role of STAT4 levels in predisposing selection of specific signaling pathways, define the biological importance of regulation within particular cell lineages, and provide mechanistic insights for how this is accomplished in vivo.
Right ventricular diastolic abnormalities in systemic sclerosis. Relation to left ventricular involvement and pulmonary hypertension
Authors: A. Giunta
Journal: Annals of the Rheumatic Diseases (2000)

To investigate right ventricular diastolic function in systemic sclerosis (SSc) and its relation to clinical features of the disease.Seventy seven unselected SSc patients and 33 healthy subjects were submitted to echocardiography and echo Doppler study to assess left and right systolic as well diastolic function and to estimate maximal arterial systolic pulmonary pressure (PAP). In addition, the patients were investigated to define the SSc subset and the extent of skin and internal organ involvement.An abnormal right ventricular filling, as expressed by an inverted tricuspidal (Tr) E/A ratio (Tr E/A ratio <1), was detected in 31 of the 77 SSc patients (40%) and in 0 of the 36 controls ( p<0.001 ). All the 31 patients with an inverted Tr E/A ratio were found to have a PAP > 30 mm Hg. Twenty resulted to have an inverted mitral (Mit) E/A ratio (Mit E/A ratio <1), indicating an abnormal left ventricular filling. In multiple regression analysis, Tr E/A ratio resulted to be independently correlated to both PAP (r= -0.35;p<0. 003) and Mit E/A ratio (r=0.39;p<0.001).This study points out an impaired right ventricular filling in a significant percentage of SSc patients whatever the subset. This alteration is independently correlated to both PAP and left ventricular filling abnormalities.
Autophagy Induced by Conventional Chemotherapy Mediates Tumor Cell Sensitivity to Immunotherapy
Authors: Rupal Ramakrishnan, Chun Huang, Hyun-Il Cho, Mark Lloyd, Joseph Johnson, Xiubao Ren, Soner Altiok, Daniel Sullivan, Jeffrey Weber, Esteban Celis, Dmitry I. Gabrilovich
Journal: Cancer Research (2012)

Autophagy attenuates the efficacy of conventional chemotherapy but its effects on immunotherapy have been little studied. Here, we report that chemotherapy renders tumor cells more susceptible to lysis by CTL in vivo. Moreover, bystander tumor cells that did not express antigen were killed by CTL. This effect was mediated by transient but dramatic upregulation of the mannose-6-phosphate receptor (MPR) on the tumor cell surface. Antitumor effects of combined treatment related to the kinetics of MPR upregulation and abrogation of this event abolished the combined effect of immunotherapy and chemotherapy. MPR accumulation on the tumor cell surface during chemotherapy was observed in different mouse tumor models and in patients with multiple myeloma. Notably, this effect was the result of redistribution of the receptor caused by chemotherapy-inducible autophagy. Together, our findings reveal one molecular mechanism through which the antitumor effects of conventional cancer chemotherapy and immunotherapy are realized.
TIMP-1 Deficiency Does Not Attenuate Interstitial Fibrosis in Obstructive Nephropathy
Authors: HEUNGSOO KIM, TAKASHI ODA, JESÚS LÓPEZ-GUISA, DIANE WING, DYLAN R. EDWARDS, PAUL D. SOLOWAY, ALLISON A. EDDY
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Progressive renal disease as a result of renal fibrosis is caused in part by an impairment of the proteolytic machinery that normally regulates matrix turnover. The goal of the present study was to determine whether genetic deficiency of tissue inhibitor of metalloproteinases-1 (TIMP-1) could attenuate interstitial fibrosis caused by unilateral ureteral obstruction (UUO). Groups of wild-type ( Timp-1 ) mice and TIMP-1—deficient ( timp-1 ) mice were killed after 3 and 14 d of UUO or sham operation. Timp-1 mRNA levels were significantly increased 37- and 19-fold in the wild-type mice 3 and 14 d, respectively, after UUO operation. Matrix metalloproteinase-9 (MMP-9) activity fell in all UUO groups but remained significantly higher in the timp-1 group compared with the Timp-1 group. The degree of interstitial fibrosis (kidney collagen content and percentage of tubulointerstitial area stained with picrosirius red and collagen III) was significantly increased 14 d after UUO operation, but there was no difference between the Timp-1 and timp-1 groups. Many features of the fibrogenic response were similar between the Timp-1 and timp-1 groups, including the number of myofibroblasts and the induction of genes encoding procollagen III, fibronectin, and transforming growth factor-β. After UUO operation, renal mRNA levels for Timp-3 and plasminogen activator inhibitor-1 were significantly higher in the TIMP-1—deficient mice. The results of this study show that elimination of TIMP-1 alone does not alter the severity of interstitial fibrosis. These findings may be due to compensation by other protease inhibitors such as TIMP-2, TIMP-3, and/or plasminogen activator inhibitor-1 or to the possibility that inhibition of intrinsic MMP activity does not constitute a profibrogenic event in the kidney.
Clinical Presentation of Patients with Ebola Virus Disease in Conakry, Guinea
Authors: Elhadj Ibrahima Bah, Marie Claire Lamah, Tom Fletcher, Shevin T. Jacob, David M. Brett-Major, Amadou Alpha Sall, Nahoko Shindo, William A. Fischer, Francois Lamontagne, Sow Mamadou Saliou, Daniel G. Bausch, Barry Moumié, Tim Jagatic, Armand Sprecher, James V. Lawler, Thierry Mayet, Frederique A. Jacquerioz, María F.Méndez Baggi, Constanza Vallenas, Christophe Clement, Simon Mardel, Ousmane Faye, Oumar Faye, Baré Soropogui, Nfaly Magassouba, Lamine Koivogui, Ruxandra Pinto, Robert A. Fowler
Journal: New England Journal of Medicine (2014)

In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date.From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors.Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007).Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.
Loop Diuretic Infusion Increases Thiazide-Sensitive Na+/Cl--Cotransporter Abundance
Authors: JOSEPH G. ABDALLAH, ROBERT W. SCHRIER, CHARLES EDELSTEIN, SUSAN D. JENNINGS, BRUCE WYSE, DAVID H. ELLISON
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Chronic infusion of loop diuretics into animals induces structural and functional changes in the distal nephron. These changes include increases in the activity of the thiazide-sensitive Na + /Cl - -cotransporter (NCC). The NCC was recently demonstrated to be an aldosterone-induced protein. These experiments were designed to test the hypotheses that chronic loop diuretic infusion, with replacement of NaCl losses, increases NCC protein abundance and that this effect results, in part, from stimulation by aldosterone. Sprague-Dawley rats received vehicle (group 1), furosemide (22 mg/100 g body wt per d) (group 2), or furosemide plus spironolactone (22 and 20 mg/100 g body wt per d, respectively) (group 3). Urine output was higher for groups 2 and 3 than for group 1 (151 ± 32, 149 ± 24, and 12 ± 4 ml, respectively; P &lt; 0.0001). Immunoblot analysis of NCC protein demonstrated that loop diuretics increased NCC protein abundance by nearly 100% (from 2562 ± 30 to 5248 ± 151 arbitrary units, P &lt; 0.01). Spironolactone decreased NCC protein abundance by 66% (to 3532 ± 113 units), compared with the furosemide-treated group ( P &lt; 0.005). Northern blot analysis of NCC mRNA demonstrated no significant effect of furosemide (NCC/glyceraldehyde-3-phosphate dehydrogenase ratios: group 1, 0.6 ± 0.12; group 2, 0.5 ± 0.05; P &gt; 0.05, NS) These results indicate that increased NCC activity during chronic loop diuretic infusion is associated with increases in NCC protein abundance. A portion of the furosemide effect can be prevented by blockade of mineralocorticoid receptors.
Genomic features of Bordetella parapertussis clades with distinct host species specificity.
Authors: Mary M Brinig, Karen B Register, Mark R Ackermann, David A Relman
Journal: Genome biology (2006)

Abstract Background The respiratory pathogen Bordetella parapertussis is a valuable model in which to study the complex phenotype of host specificity because of its unique two-species host range. One subset of strains, including the sequenced representative, causes whooping cough in humans, while other strains infect only sheep. The disease process in sheep is not well understood, nor are the genetic and transcriptional differences that might provide the basis for host specificity among ovine and human strains. Results We found 40 previously unknown genomic regions in an ovine strain of B. parapertussis using subtractive hybridization, including unique lipopolysaccharide genes. A microarray survey of the gene contents of 71 human and ovine strains revealed further differences, with 47 regions of difference distinguishing the host-restricted subgroups. In addition, sheep and human strains displayed distinct whole-genome transcript abundance profiles. We developed an animal model in which sheep were inoculated with a sheep strain, human strain, or mixture of the two. We found that the ovine strain persisted in the nasal cavity for 12 to 14 days, while the human strain colonized at lower levels and was no longer detected by 7 days post-inoculation. The ovine strain induced less granulocyte infiltration of the nasal mucosa. Conclusion Several factors may play a role in determining host range of B. parapertussis . Human- and ovine-associated strains have differences in content and sequence of genes encoding proteins that mediate host-pathogen contact, such as lipopolysaccharide and fimbriae, as well as variation in regulation of toxins, type III secretion genes, and other virulence-associated genes.
Air travel and COPD: A new algorithm for pre-flight evaluation
Authors: Anne Edvardsen, Aina Akerø, Carl Christian Christensen, Morten Ryg, Ole Henning Skjønsberg
Journal: European Respiratory Journal (2012)

The reduced pressure in the aircraft cabin may cause significant hypoxaemia and respiratory distress in patients with COPD. Simple and reliable methods for predicting need for supplemental oxygen during air travel have been requested.   Objective  To construct a pre-flight evaluation algorithm for COPD patients.   Methods  In this prospective, cross-sectional study of 100 COPD patients, sea level pulse oximetry at rest (SpO 2 SL ) and exercise desaturation (SpO 2  6MWT ) were used to evaluate whether the patient a) is fit to fly without further assessment, b) needs further evaluation with hypoxia-altitude simulation test (HAST) or c) should receive in-flight supplemental oxygen without further evaluation. HAST was used as reference method.   Results  An algorithm was constructed using a combination of SpO 2  SL  and SpO 2  6MWT . Categories for SpO 2  SL : >95%, 92-95%, and  2  6MWT  was calculated to 84%. Arterial oxygen pressure   Patients with SpO 2 SL  >95% combined with SpO 2  6MWT  ≥84% may travel by air without further assessment. Supplemental oxygen is recommended if SpO 2 SL  92-95% combined with SpO 2  6MWT   2 SL     Conclusions  The algorithm is a simple tool for pre-flight evaluation of COPD patients.
Relative sensitivity of fetal and newborn mice to induction of hapten-specific B cell tolerance.
Authors: B L Pike, T W Kay, G J Nossal
Journal: The Journal of Experimental Medicine (1980)

Mice were rendered tolerant to the hapten fluorescein (FLU) by a single injection of FLU-human gamma globulin (FLU5HGG) 2-3 d after birth or via the maternal circulation at 14.5 d of fetal life. After 7-9 d, the degree of functional nonresponsiveness induced in vivo among splenic FLU-specific B cells of tolerized mice was assessed by limiting-dilution analysis in vitro, and the serum levels of trace-labeled tolerogen were determined. When tolerogen was introduced before the appearance of any B cells, and was thus present during the pre-B to B cell transition stage, a concentration of 5.4 x 10(-13) M effectively silenced 50% of the clonable anti-FLU PFC precursors; but a similar reduction on newborns required a minimal tolerogen concentration of 1.3 x 10(-10) M, > 300-fold less than has previously been shown to equally affect adult B cells, but at least 240-fold more than in the in utero situation. Neonatally induced tolerance using a relatively high tolerogen dose lasted approximately 12 wk.
<i>NKX3.1</i> is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia
Authors: Sophie Kusy, Bastien Gerby, Nicolas Goardon, Nathalie Gault, Federica Ferri, Delphine Gérard, Florence Armstrong, Paola Ballerini, Jean-Michel Cayuela, André Baruchel, Françoise Pflumio, Paul-Henri Roméo
Journal: The Journal of Experimental Medicine (2010)

TAL1 (also known as SCL) is expressed in &amp;gt;40% of human T cell acute lymphoblastic leukemias (T-ALLs). TAL1 encodes a basic helix-loop-helix transcription factor that can interfere with the transcriptional activity of E2A and HEB during T cell leukemogenesis; however, the oncogenic pathways directly activated by TAL1 are not characterized. In this study, we show that, in human TAL1–expressing T-ALL cell lines, TAL1 directly activates NKX3.1, a tumor suppressor gene required for prostate stem cell maintenance. In human T-ALL cell lines, NKX3.1 gene activation is mediated by a TAL1–LMO–Ldb1 complex that is recruited by GATA-3 bound to an NKX3.1 gene promoter regulatory sequence. TAL1-induced NKX3.1 activation is associated with suppression of HP1-α (heterochromatin protein 1 α) binding and opening of chromatin on the NKX3.1 gene promoter. NKX3.1 is necessary for T-ALL proliferation, can partially restore proliferation in TAL1 knockdown cells, and directly regulates miR-17-92. In primary human TAL1-expressing leukemic cells, the NKX3.1 gene is expressed independently of the Notch pathway, and its inactivation impairs proliferation. Finally, TAL1 or NKX3.1 knockdown abrogates the ability of human T-ALL cells to efficiently induce leukemia development in mice. These results suggest that tumor suppressor or oncogenic activity of NKX3.1 depends on tissue expression.
Integrated Optical Coherence Tomography and Microscopy for <i>Ex Vivo</i> Multiscale Evaluation of Human Breast Tissues
Authors: Chao Zhou, David W. Cohen, Yihong Wang, Hsiang-Chieh Lee, Amy E. Mondelblatt, Tsung-Han Tsai, Aaron D. Aguirre, James G. Fujimoto, James L. Connolly
Journal: Cancer Research (2010)

Abstract Three-dimensional (3D) tissue imaging methods are expected to improve surgical management of cancer. In this study, we examined the feasibility of two 3D imaging technologies, optical coherence tomography (OCT) and optical coherence microscopy (OCM), to view human breast specimens based on intrinsic optical contrast. Specifically, we imaged 44 ex vivo breast specimens including 34 benign and 10 malignant lesions with an integrated OCT and OCM system developed in our laboratory. The system enabled 4-μm axial resolution (OCT and OCM) with 14-μm (OCT) and 2-μm (OCM) transverse resolutions, respectively. OCT and OCM images were compared with corresponding histologic sections to identify characteristic features from benign and malignant breast lesions at multiple resolution scales. OCT and OCM provide complimentary information about tissue microstructure, thus showing distinctive patterns for adipose tissue, fibrous stroma, breast lobules and ducts, cysts and microcysts, as well as in situ and invasive carcinomas. The 3D imaging capability of OCT and OCM provided complementary information to individual 2D images, thereby allowing tracking features from different levels to identify low-contrast structures that were difficult to appreciate from single images alone. Our results lay the foundation for future in vivo optical evaluation of breast tissues, using OCT and OCM, which has the potential to guide core needle biopsies, assess surgical margins, and evaluate nodal involvement in breast cancer. Cancer Res; 70(24); 10071–9. ©2010 AACR.
Organization and evolution of the alcohol dehydrogenase gene in Drosophila.
Authors: V H Cohn, G P Moore
Journal: Molecular Biology and Evolution (1988)

The alcohol dehydrogenase (A&) gene was isolated from Drosophila simulans and D. mauritiana, and the DNA sequence of a 4.6-kb region, containing the structural gene and flanking sequence, was determined for each.These sequences were compared with the Adh region of D. melanogaster to characterize changes that occur in the Drosophila genome during evolution and to identify conserved sequences of functional importance.Drosophila simulans and D. mauritiana Adh are organized in a manner similar to that of D. melanogaster Adh, including the presence of two promoters for the single Adh gene.This study identified conserved flanking elements that, in conjunction with other studies, suggest regions that may be involved in the control of Adh expression.Inter-and intraspecies comparisons revealed differences in the kinds of sequence changes that have accumulated.Sequence divergence in and around the Adh gene was used to assess inter-and intraspecies evolutionary relationships.Finally, there appears to be an unrelated structural gene located directly 3' of the Adh transcribed region.1.
A CASE OF XANTHOMA DIABETICORUM TREATED WITH A SULPHUR DERIVATIVE OF HISTIDINE (2-THIO-4 (OR 5)-AMINO-METHYL-GLYOXALINE).
Authors: J.E.R. McDONAGH
Journal: British Journal of Dermatology (1925)

Journal Article A CASE OF XANTHOMA DIABETICORUM TREATED WITH A SULPHUR DERIVATIVE OF HISTIDINE (2‐THIO‐4 (OR 5)‐AMINO‐METHYL‐GLYOXALINE). Get access J.E.R. McDONAGH, F.R.C.S. J.E.R. McDONAGH, F.R.C.S. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 1, 1 January 1925, Pages 30–33, https://doi.org/10.1111/j.1365-2133.1925.tb09216.x Published: 01 January 1925
Is the response to high pressure adjunct PTCA stent design specific? A sequential intravascular ultrasound study
Authors: A. Abizaid, T. Lefevre, A.J. Lansky, G.S. Mintz, B. Oljaca, M. Simon, P. Dumas, A.D. Pichard, R. Mehran, J.J. Popma, M.-C. Morice
Journal: Journal of the American College of Cardiology (1998)