tbuckley/cabot-search huggingface dataset:
Earlier Onset of Tumoral Angiogenesis in Matrix Metalloproteinase-19–Deficient Mice
Authors: Maud Jost, Alicia R. Folgueras, Françoise Frérart, Alberto M. Pendas, Silvia Blacher, Xavier Houard, Sarah Berndt, Carine Munaut, Didier Cataldo, Jesus Alvarez, Laurence Melen-Lamalle, Jean-Michel Foidart, Carlos López-Otín, Agnès Noël
Journal: Cancer Research (2006)

Abstract Among matrix metalloproteinases (MMP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19−/− mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP to improve anticancer strategies. (Cancer Res 2006; 66(10): 5234-41)
The Brain Renin-Angiotensin System Controls Divergent Efferent Mechanisms to Regulate Fluid and Energy Balance
Authors: Justin L. Grobe, Connie L. Grobe, Terry G. Beltz, Scott G. Westphal, Donald A. Morgan, Di Xu, Willem J. de Lange, Huiping Li, Koji Sakai, Daniel R. Thedens, Lisa A. Cassis, Kamal Rahmouni, Allyn L. Mark, Alan Kim Johnson, Curt D. Sigmund
Journal: Cell Metabolism (2010)
Adult-Type Soft Tissue Sarcomas in Pediatric-Age Patients: Experience at the Istituto Nazionale Tumori in Milan
Authors: Andrea Ferrari, Michela Casanova, Paola Collini, Cristina Meazza, Roberto Luksch, Maura Massimino, Graziella Cefalo, Monica Terenziani, Filippo Spreafico, Serena Catania, Lorenza Gandola, Alessandro Gronchi, Luigi Mariani, Franca Fossati-Bellani
Journal: Journal of Clinical Oncology (2005)

Nonrhabdomyosarcoma soft tissue sarcomas are a heterogeneous group of tumors for which optimal treatment remains controversial. We report on a large group of 182 patients younger than 18 years old treated at a single institution over a 25-year period.In this relatively homogeneous subgroup of adult-type histotypes, surgery was the mainstay of treatment; radiotherapy was administered to 73 patients, and chemotherapy was administered to 114 patients (70 received chemotherapy as adjuvant therapy).Overall survival at 5 years was 89% in patients who underwent complete resection at diagnosis, 79% in patients who had marginal resection, 52% in initially unresected patients, and 17% in patients with metastases at onset. Outcome was unsatisfactory in patients with large and high-grade tumors, even after gross resection; adjuvant chemotherapy seemed to improve the results in this group. Initially unresected patients who responded well to chemotherapy and subsequently underwent complete resection had an event-free survival rate of approximately 70%. The rate of response to chemotherapy was 58%.The identification of prognostic variables should enable risk-adapted therapies to be planned. Patients with initially unresectable disease and patients with resected large and high-grade tumors are at high risk of metastases and treatment failure. Although the limits of this retrospective analysis are self-evident, our data would suggest that intensive chemotherapy (with an ifosfamide-doxorubicin regimen) might have a more significant role in these patients than what is generally assumed.
Cardiac nuclear high mobility group box 1 prevents the development of cardiac hypertrophy and heart failure
Authors: Akira Funayama, Tetsuro Shishido, Shunsuke Netsu, Taro Narumi, Shinpei Kadowaki, Hiroki Takahashi, Takuya Miyamoto, Tetsu Watanabe, Chang-Hoon Woo, Jun-ichi Abe, Koichiro Kuwahara, Kazuwa Nakao, Yasuchika Takeishi, Isao Kubota
Journal: Cardiovascular Research (2013)

High mobility group box 1 (HMGB1) is an abundant and ubiquitous nuclear DNA-binding protein that has multiple functions dependent on its cellular location. HMGB1 binds to DNA, facilitating numerous nuclear functions including maintenance of genome stability, transcription, and repair. However, little is known about the effects of nuclear HMGB1 on cardiac hypertrophy and heart failure. The aim of this study was to examine whether nuclear HMGB1 plays a role in the development of cardiac hypertrophy induced by pressure overload. Analysis of human biopsy samples by immunohistochemistry showed decreased nuclear HMGB1 expression in failing hearts compared with normal hearts. Nuclear HMGB1 decreased in response to both endothelin-1 (ET-1) and angiotensin II (Ang II) stimulation in neonatal rat cardiomyocytes, where nuclear HMGB1 was acetylated and translocated to the cytoplasm. Overexpression of nuclear HMGB1 attenuated ET-1 induced cardiomyocyte hypertrophy. Thoracic transverse aortic constriction (TAC) was performed in transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) and wild-type (WT) mice. Cardiac hypertrophy after TAC was attenuated in HMGB1-Tg mice and the survival rate after TAC was higher in HMGB1-Tg mice than in WT mice. Induction of foetal cardiac genes was decreased in HMGB1-Tg mice compared with WT mice. Nuclear HMGB1 expression was preserved in HMGB1-Tg mice compared with WT mice and significantly attenuated DNA damage after TAC was attenuated in HMGB1-TG mice. These results suggest that the maintenance of stable nuclear HMGB1 levels prevents hypertrophy and heart failure by inhibiting DNA damage.
An Address ON GENERAL PRINCIPLES IN THE TREATMENT OF DISEASES OF THE HEART: Delivered at a Meeting of the Huddersfield Division of the Yorkshire Branch of the British Medical Association
Authors: J. Barr
Journal: BMJ (1909)

GENTLEMEN,-When I undertook to address a Yorkshire audience I at once thought it wise to select a which would appeal to their sense of practical and, rightly or wrongly, I considered that, even emotional race, no subject would be more likely to an attentive hearing than that of the treatment disease.Although you may not be very liable to disturbances of the heart, I believe the common affections of that organ are not at all uncommon in this kingdom, if I be rightly informed by a distinguished Yorkshire physician,
Long-Term Prognosis of Patients With Type B Aortic Intramural Hematoma
Authors: Shuichiro Kaji, Takashi Akasaka, Minako Katayama, Atsushi Yamamuro, Kenji Yamabe, Koichi Tamita, Maki Akiyama, Nozomi Watanabe, Kazuo Tanemoto, Shigefumi Morioka, Kiyoshi Yoshida
Journal: Circulation (2003)

Recent studies have shown an favorable short-term prognosis of patients with type A acute aortic intramural hematoma (IMH). The difference of aortic pathology may have a different impact on clinical course compared with classic aortic dissection (AD). The purpose of this study was to elucidate clinical features and long-term prognosis of patients with type A IMH.Clinical data were compared retrospectively between 30 patients with acute type A IMH (IMH group) and 101 patients with acute type A AD (AD group) who were admitted to our institutions from 1988 to 1998. In AD group, 72 patients underwent surgical repair and 29 patients were treated medically. All patients in IMH group were treated initially with supportive medical therapy. Thirteen patients who demonstrated progression to AD or increase in size of hematoma underwent timed surgical repair except for 1 patient. The overall in-hospital mortality rate in IMH group was significantly lower than that in AD group (7% and 34%, P=0.004). Follow-up periods were 56+/-37 (IMH group) and 60+/-42 months (AD group), which revealed 1 and 6 late deaths, respectively. The actuarial survival rates in IMH group were all 90% at 1, 2, and 5 years, which were significantly higher than those in AD group (67%, 66%, and 62%, respectively; P=0.004).Patients with type A IMH have better long-term prognosis than patients with AD.
Topical tacrolimus in granuloma annulare and necrobiosis lipoidica
Authors: W. Harth, R. Linse
Journal: British Journal of Dermatology (2004)

Journal Article Topical tacrolimus in granuloma annulare and necrobiosis lipoidica Get access W. Harth, W. Harth Hautklinik, Helios Klinikum Erfurt, Nordhäuserstrasse 74, 99089 Erfurt, Germany Search for other works by this author on: Oxford Academic Google Scholar R. Linse R. Linse Hautklinik, Helios Klinikum Erfurt, Nordhäuserstrasse 74, 99089 Erfurt, Germany R.Linse. E‐mail: rlinse@erfurt.helios‐kliniken.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 150, Issue 4, 1 April 2004, Pages 792–794, https://doi.org/10.1111/j.0007-0963.2004.05899.x Published: 01 April 2004
Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease
Authors: Jiaqi Yao, Daniel Ho, Noel Y. Calingasan, Nina H. Pipalia, Michael T. Lin, M. Flint Beal
Journal: The Journal of Experimental Medicine (2012)

There is extensive evidence that cholesterol and membrane lipids play a key role in Alzheimer disease (AD) pathogenesis. Cyclodextrins (CD) are cyclic oligosaccharide compounds widely used to bind cholesterol. Because CD exerts significant beneficial effects in Niemann-Pick type C disease, which shares neuropathological features with AD, we examined the effects of hydroxypropyl-β-CD (HP-β-CD) in cell and mouse models of AD. Cell membrane cholesterol accumulation was detected in N2a cells overexpressing Swedish mutant APP (SwN2a), and the level of membrane cholesterol was reduced by HP-β-CD treatment. HP-β-CD dramatically lowered the levels of Aβ42 in SwN2a cells, and the effects were persistent for 24 h after withdrawal. 4 mo of subcutaneous HP-β-CD administration significantly improved spatial learning and memory deficits in Tg19959 mice, diminished Aβ plaque deposition, and reduced tau immunoreactive dystrophic neurites. HP-β-CD lowered levels of Aβ42 in part by reducing β cleavage of the APP protein, and it also up-regulated the expression of genes involved in cholesterol transport and Aβ clearance. This is the first study to show neuroprotective effects of HP-β-CD in a transgenic mouse model of AD, both by reducing Aβ production and enhancing clearance mechanisms, which suggests a novel therapeutic strategy for AD.
Reduction of Transient Myocardial Ischemia With Pravastatin in Addition to the Conventional Treatment in Patients With Angina Pectoris
Authors: Ad J. van Boven, J. Wouter Jukema, Aeilko H. Zwinderman, Harry J.G.M. Crijns, Kong I. Lie, Albert V.G. Bruschke
Journal: Circulation (1996)

Background Lipid-lowering therapy reduces cardiac morbidity and mortality. Less is known about its potential anti-ischemic effect. Methods and Results In a 2-year prospective randomized placebo-controlled study, the effect of pravastatin 40 mg on transient myocardial ischemia was assessed. Forty-eight–hour ambulatory ECGs with continuous ST-segment analysis were performed in 768 male patients with stable angina pectoris, documented coronary artery disease, and serum cholesterol between 4 and 8 mmol/L (155 and 310 mg/dL). During the trial, patients received routine antianginal treatment. In the patients randomized to pravastatin, transient myocardial ischemia was present at baseline in 28% and after treatment in 19%; in the placebo group, it was found in 20% and 23% of the patients, respectively ( P =.021 for change in percentage between two treatment groups; odds ratio, 0.62; 95% CI, 0.41 to 0.93). Ischemic episodes decreased by 1.23±0.25 (SEM) episode with pravastatin and by 0.53±0.25 episode with placebo ( P =.047). Under pravastatin, the duration of ischemia decreased from 80±12 minutes to 42±10 minutes ( P =.017) and with placebo, from 60±13 minutes to 51±9 minutes ( P =.56). The total ischemic burden decreased from 41±5 to 22±5 mm·min in the pravastatin group ( P =.0058) and from 34±6 to 26±4 mm·min in the placebo group ( P =.24). Adjusted for independent risk factors for the occurrence of ischemia, the effect of pravastatin on the reduction of risk for ischemia remained statistically significant (odds ratio, 0.45; 95% CI, 0.22 to 0.91; P =.026). Conclusions In men with documented coronary artery disease and optimal antianginal therapy, pravastatin reduces transient myocardial ischemia. ( Circulation. 1996;94:1503-1505.)
Sensitive detection of circulating breast cancer cells by reverse-transcriptase polymerase chain reaction of maspin gene
Authors: M. Luppi, M. Morselli, E. Bandieri, M. Federico, R. Marasca, P. Barozzi, M.G. Ferrari, M. Savarino, A. Frassoldati, G. Torelli
Journal: Annals of Oncology (1996)
Null alleles of human complement C4. Evidence for pseudogenes at the C4A locus and for gene conversion at the C4B locus.
Authors: L Braun, P M Schneider, C M Giles, J Bertrams, C Rittner
Journal: The Journal of Experimental Medicine (1990)

The two genes for the C4A and C4B isotypes of the fourth component of human complement are located in the MHC class III region. Previous studies have demonstrated the unusual expression of C4 genes in the form of aberrant or duplicated haplotypes. Null alleles of C4A or C4B (AQ0 or BQ0) have been defined by the absence of gene products and occur at frequencies of 0.1-0.3. However, only some C4 null alleles are due to gene deletions, the remainder were thought to be nonexpressed genes. We have analyzed the C4 gene structure of 26 individuals lacking either C4A or C4B protein. The DNA of individuals with apparently nonexpressed C4 genes was tested for the presence of C4A- and C4B-specific sequences using restriction fragment analysis and isotype-specific oligonucleotide hybridization of DNA amplified by polymerase chain reaction. All nondeleted AQ0 allels had C4A-specific sequences and may thus be described as pseudogenes, whereas the nondeleted BQ0 alleles had C4A-instead of C4B-specific sequences. Gene conversion is the probable mechanism by which a C4A gene is found at the second C4 locus normally occupied by C4B genes.
Determining promoter location based on DNA structure first-principles calculations
Authors: J Ramon Goñi, Alberto Pérez, David Torrents, Modesto Orozco
Journal: Genome biology (2007)

A new method for the prediction of promoter regions based on atomic molecular dynamics simulations of small oligonucleotides has been developed. The method works independently of gene structure conservation and orthology and of the presence of detectable sequence features. Results obtained with our method confirm the existence of a hidden physical code that modulates genome expression.
Association Between Infant Breastfeeding and Overweight in Young Children
Authors: Mary L. Hediger
Journal: JAMA (2001)

It has been suggested that breastfeeding is protective against children becoming overweight, and that there is a dose-dependent effect of its duration.To determine whether breastfeeding and its duration are associated with a reduced risk of being overweight among young children in the United States.Data on infant feeding and child overweight status were taken from the third National Health and Nutrition Examination Survey (NHANES III), a cross-sectional health examination survey conducted from 1988-1994.Sample of 2685 US-born children between the ages of 3 and 5 years, with birth certificates, height and weight measures, and information on infant feeding.A body mass index (BMI) between the 85th and 94th percentile was considered at risk of overweight and a BMI in the 95th percentile or higher was considered being overweight.After adjusting for potential confounders, there was a reduced risk of being at risk of overweight for ever breastfed children (adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.41-0.96) compared with those never breastfed. There was no reduced risk of being overweight (AOR, 0.84; 95% CI, 0.62-1.13). There was no clear dose-dependent effect of the duration of full breastfeeding on being at risk of overweight or overweight and no threshold effect. The strongest predictor of child overweight status was the mother's concurrent weight. The rate of children being overweight nearly tripled with maternal overweight status (BMI, 25.0-29.9 kg/m(2); AOR, 2.95; 95% CI, 1.35-6.42) and more than quadrupled with maternal obesity status (BMI >/=30.0 kg/m(2); AOR, 4.34; 95% CI, 2.50-7.54).There are inconsistent associations among breastfeeding, its duration, and the risk of being overweight in young children. Breastfeeding continues to be strongly recommended, but may not be as effective as moderating familial factors, such as dietary habits and physical activity, in preventing children from becoming overweight.
Evidence for the Involvement of Double-Strand Breaks in Heat-Induced Cell Killing
Authors: Akihisa Takahashi, Hideki Matsumoto, Kosuke Nagayama, Mutsuko Kitano, Sayako Hirose, Hidenori Tanaka, Eiichiro Mori, Nobuhiro Yamakawa, Jun-ichi Yasumoto, Kazue Yuki, Ken Ohnishi, Takeo Ohnishi
Journal: Cancer Research (2004)

Abstract To identify critical events associated with heat-induced cell killing, we examined foci formation of γH2AX (histone H2AX phosphorylated at serine 139) in heat-treated cells. This assay is known to be quite sensitive and a specific indicator for the presence of double-strand breaks. We found that the number of γH2AX foci increased rapidly and reached a maximum 30 minutes after heat treatment, as well as after X-ray irradiation. When cells were heated at 41.5°C to 45.5°C, we observed a linear increase with time in the number of γH2AX foci. An inflection point at 42.5°C and the thermal activation energies above and below the inflection point were almost the same for cell killing and foci formation according to Arrhenius plot analysis. From these results, it is suggested that the number of γH2AX foci is correlated with the temperature dependence of cell killing. During periods when cells were exposed to heat, the cell cycle-dependent pattern of cell killing was the same as the cell cycle pattern of γH2AX foci formation. We also found that thermotolerance was due to a depression in the number of γH2AX foci formed after heating when the cells were pre-treated by heat. These findings suggest that cell killing might be associated with double-strand break formation via protein denaturation.
Expression of adhesion molecules on circulating polymorphonuclear leukocytes during orthotopic liver transplantation
Authors: Manfred Thiel, Swantje Imendörffer, Alexander Chouker, Jochen Groh, Josef Briegel, Matthias Anthuber, Hans J. Krämling, Karl E. Arfors, Klaus Peter, Konrad Messmer
Journal: Hepatology (1998)

After ischemia-reperfusion, polymorphonuclear leukocytes (PMNLs) become activated by inflammatory mediators, adhere to the vascular endothelium via the interaction of specific adhesion molecules, and cause tissue injury by the release of cytotoxic oxygen radicals and enzymes. Results obtained in animal experiments suggest a key role for PMNLs in ischemia-reperfusion injury of transplanted livers; therefore, we studied the expression of adhesion molecules on circulating PMNLs (beta2-integrins [CD18] and L-selectin [CD62L]) in 20 patients undergoing orthotopic liver transplantation (study group). To determine the effects of surgical trauma to the liver in the absence of ischemia and reperfusion, the expression of PMNL adhesion molecules was measured in 10 patients scheduled for elective partial liver resection without hepatic vascular exclusion (control group). Patients were classified as responders or nonresponders based on changes in the expression of adhesion molecules elicited by reperfusion. In the control group, all patients remained nonresponders, showing that surgical trauma of the liver alone does not cause activation of circulating PMNLs. In contrast, 8 of 20 patients in the study group were classified as responders. In responders, postoperative serum liver enzyme activities were significantly higher than in nonresponders, indicating that activation of PMNL was associated with damage to hepatocellular integrity. Because expression of adhesion molecules was already changed during surgery, monitoring of the expression of beta2-integrins and L-selectin on circulating PMNLs during orthotopic liver transplantation might be useful in prediction of early graft dysfunction.
Protein Profiling of Microdissected Prostate Tissue Links Growth Differentiation Factor 15 to Prostate Carcinogenesis
Authors: Peter K. Cheung, Bruce Woolcock, Hans Adomat, Margaret Sutcliffe, Terry C. Bainbridge, Edward C. Jones, Douglas Webber, Thomas Kinahan, Marianne Sadar, Martin E. Gleave, Juergen Vielkind
Journal: Cancer Research (2004)

Abstract Identification of proteomic alterations associated with early stages in the development of prostate cancer may facilitate understanding of progression of this highly variable disease. Matched normal, high-grade prostatic intraepithelial neoplasia (hPIN) and prostate cancer cells of predominantly Gleason grade 3 were procured by laser capture microdissection from serial sections obtained from snap-frozen samples dissected from 22 radical prostatectomy specimens. From these cells, protein profiles were generated by surface-enhanced laser desorption/ionization-time of flight mass spectrometry. A 24-kDa peak was observed at low or high intensity in profiles of prostate cancer cells in 19 of 27 lesions and at low intensity in 3 of 8 hPIN lesions but was not detectable in matched normal cells. SDS-PAGE analysis of prostate cancer and matched normal epithelium confirmed expression of a prostate cancer-specific 24-kDa protein. Mass spectrometry and protein data-based analysis identified the protein as the dimeric form of mature growth differentiation factor 15 (GDF15). The increased expression of mature GDF15 protein in prostate cancer cells cannot be explained on the basis of up-regulation of GDF15 mRNA because reverse transcription-PCR analysis showed similar amounts of transcript in normal, hPIN, and prostate cancer cells that were obtained by laser capture microdissection in the same set of serial sections from which the protein profiles were obtained. Our findings suggest that early prostate carcinogenesis is associated with expression of mature GDF15 protein.