tbuckley/cabot-search huggingface dataset:
Wild type (wt) p53 suppresses soft tissue sarcoma (STS) invasion by inhibiting matrix metalloproteinase-9 (MMP-9) expression and activity
Authors: Dina Lev, Maochang Zhan, Dihua Yu, Juehui Liu, Parimal Das, Menghong Sun, Jonathan Hannay, Raphael Pollock
Journal: Cancer Research (2006)

4364   Introduction: MMP-9 plays an established role in tumor invasion and metastasis; however, the regulation of MMP-9 activity has not been fully determined. P53 mutations are the most common molecular alteration in STS, a hematogenous rather than lymphatic-disseminating tumor, and so we tested whether (1) MMP-9 expression and activity is increased due to p53 mutation, and (2) whether reintroduction of wt p53 could inhibit this increased MMP-9 activity. Methods: We created temperature-sensitive p53 mutants in SKLMS-1, a human leiomyosarcoma cell line bearing mut p53. These were used to test the effect of p53 mut on MMP9 protein levels (western blot), mRNA expression (northern blot), and activity (zymography). MMP-9 status was also examined in human STS tumor samples by immunohistochemistry (IHC) and also in human mut p53 STS xenografts grown in nude mice transfected with adenovirus p53 (Adp53) or empty vector controls. . Results: Using the temperature-sensitive p53 mutants, we found that MMP-9 activity as measured by zymography was significantly lower at 32°C (wt p53 status) than at 38°C (mut p53 status). Likewise, MMP-9 protein and mRNA was inhibited at 32°C compared to 38°C. MMP-9 protein expression was measured in 13 STS samples using IHC; 10/13 samples with strong MMP-9 expression developed metastases whereas 0/3 STS samples lacking MMP-9 expression developed metastases. MMP-9 expression in Adp53 transfectants growing as xenografts had markedly decreased MMP-9 expressions compared with those treated with empty vector controls. Conclusions: mut p53 status in STS results in increased MMP-9 protein and mRNA expression. MMP-9 expression in STS specimens correlates with the likelihood of developing metastasis. Reintroduction of wt p53 into mut p53 STS xenografts resulted in markedly decreased MMP-9 expression. Future therapy seeking to directly or indirectly modulate MMP-9 activity in STS may decrease metastasis, thereby improving survival in this devastating malignancy.
Abstract 14798: Right Atrial Function as Prognostic factor in Patients with Pulmonary Hypertension
Authors: Yuko Fukuda, Hidekazu Tanaka, Yoshiki Motoji, Keiko Ryo, Hiroki Matsuzoe, Keiko Hatazawa, Yutaka Hatani, Kumiko Dokuni, Hiromi Toki, Hiroyuki Shimoura, Junichi Ooka, Hiroyuki Sano, Takuma Sawa, Yasuhide Mochizuki, Kazuhiro Tatsumi, Kensuke Matsumoto, Noriaki Emoto, Ken-ichi Hirata
Journal: Circulation (2014)

Background: The development of right ventricular (RV) dysfunction in patients with pulmonary hypertension (PH) has been associated with adverse outcomes. Right atrial (RA) function could be a prognostic factors as well as RV function, but non-invasive evaluation of RA function is limited. Our objective was thus to test the hypothesis that RA function was associated with hemodynamic parameters of RV performance in PH patients. Methods: Eighty PH patients with mean pulmonary artery pressure (PAP) of 40±11mmHg (all≥25mmHg) were recruited in this study. RA function was assessed by using two-dimensional speckle-tracking strain from RV-focused apical 4-chamber view. RA strain was calculated with the reference point set at the P wave, which enabled the recognition of peak negative (RAneg), positive strain (RAposi), and the sum of those values (RAtotal), corresponding to RA contractile, conduit, and reservoir function, respectively. All patients underwent right-heart catheterization for measurement of mean PAP and pulmonary vascular resistance (PVR). Results: RAneg (r=0.24 and p=0.03), RAposi (r=0.31 and p=0.01) and RAtotal (r=0.35 and p=0.001) were significantly correlated with mean PAP. In addition, RAposi (r=0.41 and p&lt;0.001) and RAtotal (r=0.44 and p&lt;0.001) were also correlated with PVR. Conclusions: Non-invasively assessed RA strains were associated with mean PAP and PVR. RA strain may be of a valuable additive factor for the management of PH patients, and thus have potential clinical applications.
HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages
Authors: S. Swingler, A. Mann, J.-M. Jacqué, B. Brichacek, V.G. Sasseville, K. Williams, A.A. Lackner, E.N. Janoff, R. Wang, D. Fisher, M. Stevenson
Journal: Nature Medicine (1999)
Lineage-Specific Chimerism Monitoring Using Flow Cytometry with Anti HLA-Antibodies in Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Bo Hyun Kim, Seongsoo Jang, Yu-jin Lee, Nuree Park, Young-Uk Cho, Chan-Jeoung Park, Eun-Seok Choi, Jin-Kyung Seo, Seong-Uk Lee, Kyung-Nam Koh, Ho Joon Im, Jong Jin Seo
Journal: Blood (2014)
Comparison of prevalence of childhood asthma in two different African-American communities in Columbus area. A pilot study
Authors: Shahid Sheikh, Kevin Morris, Karen McCoy
Journal: European Respiratory Journal (2011)

Asthma prevalence is on the rise and children in minority communities have the highest prevalence.   Objective:  Pilot study done at Mission Day School (private elementary school) and at New Salem Baptist Church (urban inner city neighborhood) in Columbus, OH, to understand asthma prevalence in two communities with same racial but different socio-economic status. All children were African Americans.   Methods:  Asthma screening was done using validated “Easy Breathing Survey (Hall CB  et al . J Pediatr 2001;139:267-72) with 4 questions. A positive response to any of the 4 questions has 94% sensitivity for asthma and specificity [% (95%CI)] of each question between 66% - 86%.   Results:  Questionnaire was sent to 105 families at both places. Fifty four families at school and 53 families at church completed the survey. Comparing data from school and church revealed median age 7 and 9 years, M:F 28:26 and 27:26, family history of asthma 24 and 27, known asthma triggers in 16 and 18 children respectively. Nine (16%) children at both sites had previous diagnosis of asthma and among them, 8 at school and all nine at church still had positive responses to survey. Additional 27 children at school and 26 at church responded positively to questions on survey though none of them had a previous diagnosis of asthma and about one third of them at both sites had required acute care for asthma within a year.   Conclusions:  Asthma prevalence is high in African American community irrespective of their socio-economic status. In the majority, symptoms are not well controlled. More than half of children at both sites had positive survey suggesting that they might have undiagnosed asthma.
30 years experience of plasmapheresis using in complex treatment of pulmonary sarcoidosis (PS)
Authors: Olga Baranova, Valerii Voinov, Olga Baklanova
Journal: European Respiratory Journal (2014)

Aim:  To estimate of plasmapheresis (P) efficiency in patients (pts) with PS.  M ethods.  The retrospective analysis of clinical, radiologic, functional, laboratory data was performed after 10 years observation of pts with PS. The 1 st  group (58 pts) was subjected to P, the 2 nd  group (54 pts) did not receive P .  Glucocorticosteroid (GCS) treatment was administered according to ATS\ERS recommendations. Serum samples were tested for TNF-ag, IL-10,RAIL, and TGF-b1 by ELISA before and after the plasmapheresis. 37 healthy volunteers were examined as a control group. P was used in 6 months. Bone Mineral Density (BMD) was measured by DEXA.   Results.  After directly P decrease (pl0.05) in proinflammatory cytokines levels: TNF-a, IFN-g and increase (pl0.05) in IL-10,RAIL, and TGF-b1 were revealed, that explains the pathogenetic mechanisms of therapeutic action of P. After 10 years clinical improvement in 40 (68.9%) pts  of 1 st  group and only 21 pts (38.8%) of 2 nd  group was observed. We found tendency to improvement of average values PFTs in pts receiving P. In 1 st  group favorable course was observed in 38 pts (65 %), relapsing – in 11 (19%), stable – in 5 (9 %), progressive – in 4 pts (7%). In 2 nd  group favorable course was observed in 24 pts (45 %), relapsing – in 18 (33%), stable – 4 (7%), progressive – 8 pts (15%). P has been found to maintain improvement and stable remission with low-dose GCS therapy. BMD decreased significantly more often than subjects in 2 nd  group (OR=3.87, pl0.01).   Conclusion.  This investigation showed that plasmapheresis effectiveness in complex treatment of PS pts leads to improvement and stabilization of pathologic process and permits to decrease dose of GCS in some cases.
Microbiological and molecular characteristics of carbapenemase-producing Klebsiella pneumoniae endemic in a tertiary Greek hospital during 2004-2010
Authors: A Zagorianou, E Sianou, E Iosifidis, V Dimou, E Protonotariou, S Miyakis, E Roilides, D Sofianou
Journal: Eurosurveillance (2012)

We report 570 carbapenemase-producing Klebsiella pneumoniae (CPKP) clinical isolates in a 1,040-bed Greek tertiary hospital during 2004 to 2010. The first CPKP (VIM-producing) was isolated in September 2004. Despite initial containment, VIM producers have become endemic since 2006. KPC-producing K. pneumoniae was first isolated in August 2007 from a patient who came from Israel, spread rapidly, and outcompeted VIM. Overall, 267 (47%) VIM-producing and 301 (53%) KPC-producing strains were isolated, including 141 (24.7%) from patients with bacteraemia. Two isolates carrying both VIM and KPC were isolated in two consecutive months in 2009, but not since. The prevalence of CPKP increased from 0% in 2003 to 38.3% in 2010 (p&lt;0.0001). All genotyped KPC producers harboured bla KPC-2 and belonged to two clones, among which the hyperepidemic Greek clone, related to those from the United States and Israel, predominated. Most metallo-beta-lactamase (MBL) producers carried the bla VIM-1 gene and belonged to several clones, whereas all but one isolate with bla VIM-12 were clustered within a five-month period, arising from one clone. Resistance to non-beta-lactam antibiotics was also increased among CPKP. They were almost invariably resistant to ciprofloxacin and trimethoprim-sulfamethoxazole. Resistance to colistin increased from 3.5% (4/115) in 2008 to 20.8% (25/120) in 2010, and resistance to tigecycline also increased. Following reinforcement of infection control measures, prevalence of CPKP (mainly KPC) has been reduced since mid-2009 (from 46% in 2009 to 38.3% in 2010). In view of the exhaustion of available therapies, investment in infection control resources and optimal antibiotic use is urgently required.
A transgenic mouse model for analyzing the role of topoisomerase II in mediating the pharmacological effects of dexrazoxane.
Authors: Morten Grauslund, Annemette V. Thougaard, Annette Füchtbauer, Kenneth F. Hofland, Peter Hjorth, Seppo Langer, Peter B. Jensen, Lars H. Jensen, Ernst-Martin Füchtbauer, Maxwell Sehested
Journal: Cancer Research (2006)

5521   Topoisomerase II (topo II) is required to maintain DNA topology during various DNA metabolic processes and is also an important molecular target in cancer therapy. Drugs acting on topo II can be divided in two groups; “poisons” like the anthracyclines daunorubicin and doxorubicin which lead to DNA double strand breaks, and “catalytic inhibitors” such as dexrazoxane (ICRF-187) that inhibit topo II without creating DNA strand breaks at pharmacologically relevant concentrations. Clinically dexrazoxane is used to prevent anthracyline-mediated cardiotoxicity, and has also shown activity as an antidote in accidental anthracycline extravasation. Furthermore, dexrazoxane antagonizes etoposide-induced myelosuppression in the mouse allowing for increased etoposide dosing and improved targeting of brain tumors. Although it is well established that dexrazoxane targets topo II  in vitro , the role of topo II in mediating these  in vivo  effects of dexrazoxane remains elusive. We have introduced a point mutation (Y165S) in the topo II α gene in mice predicted to abrogate dexrazoxane binding  in vivo . The Y165S mutation was chosen on the basis of biochemical studies with recombinant Y165S protein which was previously shown to lack dexrazoxane binding. This mutant protein exhibits wild-type levels of DNA strand passage activity at saturating ATP levels, but has reduced ATP hydrolysis. By homologous recombination a targeting vector containing the Y165S mutation was integrated in embryonic stem cells (ES cells) at the topo II α loci. Correctly targeted ES cell clones were isolated, used for blastocyst injection, and mice with germline transmission obtained. When crossing heterozygous mice, no homozygous mutants were born. The homozygous mutant embryos die after day 7 of the embryonic development, but they are smaller in size than wild type and heterozygous embryos, indicating that the Y165S mutant allele is lethal during the late part of embryonic development when homozygous. On the other hand, no differences in size, mortality and life span were observed between heterozygous mutant mice and their wild type siblings. Clonogenic assays using heterozygous ES cells and bone marrow cells isolated from heterozygous mice showed that these cells are highly resistant to dexrazoxane. No resistance to other topoisomerase inhibitors such as daunorubicin, etoposide and camptothecin were seen. We are currently testing dexrazoxane-mediated effects on extravasation, myelosuppression and cardiotoxicity in Y165S/wt mice to elucidate the functional role of topo II α.
Engraftment syndrome after allogeneic hematopoietic cell transplantation in adults
Authors: Aazim K. Omer, Haesook T. Kim, Bhargavi Yalamarti, Steven L. McAfee, Bimalangshu R. Dey, Karen K. Ballen, Eyal Attar, Yi‐Bin Chen, Thomas R. Spitzer
Journal: American Journal of Hematology (2014)

We performed a retrospective study of the engraftment syndrome (ES) as defined by the Spitzer Criteria in adult patients undergoing allogeneic hematopoietic cell transplantation (HCT) for various hematological malignancies at a single institution, over a decade, and analyzed its relationship to acute GVHD; 217 patients underwent either myeloablative (38.7%) or reduced intensity (61.3%) HCT; 22.1% met the criteria for ES. Acute GVHD prophylaxis (P = 0.006) and transplants prior to 2006 (P < 0.0001) were significantly associated with a risk of ES in univariable analysis. Early aGVHD within 4 weeks of engraftment was significantly more common in the ES compared to the non ES cohort (21 vs. 8.3% respectively, P = 0.02). ES did not predict for future GVHD, as at day +180, the cumulative incidences of grades II-IV aGVHD (31 vs. 23%, P = 0.19) and of chronic GVHD at 2 years of engraftment (42 vs. 36%, P = 0.28) were not significantly different between the ES and non ES groups, respectively. No significant differences in NRM, overall survival and progression-free survival were observed between the two groups. Although predictive of early aGVHD, ES occurred independently of GVHD in 79% of the patients. Survival outcomes should be evaluated in a larger randomized study to investigate if there is a correlation with ES.
Tramadol Abuse and Dependence Among Physicians
Authors: Gregory E. Skipper, Carol Fletcher, Rosei Rocha-Judd, David Brase
Journal: JAMA (2004)

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Abstract 3701: Vitamin D Deficiency is Associated With Myalgias in Hyperlipidemic Subjects Taking Statins
Authors: P. Barton Duell, William E Connor
Journal: Circulation (2008)

Myalgias are a frequent symptom among patients taking statins, but it is sometimes uncertain whether myalgias are drug-related. Since vitamin D deficiency is common in the general population, and can be associated with reversible myalgias, we hypothesized that vitamin D deficiency may contribute to symptoms in some patients. This hypothesis was tested in 99 patients referred to our tertiary care academic Lipid Disorders Clinic with a diagnosis of hyperlipidemia. Mean age 58.7 ± 11.6 yr (range 20 – 84), 43% men, mean serum 25-hydroxy vitamin D (vit D) level 26.7 ± 12.5 ng/ml (range 5– 64). Statin-associated myalgias were present in 38.8% of patients. Patients with statin-associated myalgias were the same age as patients without myalgias (59.3 ± 10.4 vs 58.4 ± 12.3, P=NS), but had 32% lower mean vit D (20.5 ± 10.0 vs 30.1 ± 12.5 ng/ml, P=0.0003) and trended toward being female (68% vs 49%, P=0.095). Vit D was similar in men and women (24.3 ± 10.1 vs 28.8 ± 14.0, P=0.09). In the entire cohort, vit D deficiency was prevalent: 62.6% were &lt; 30 ng/ml; 31.9% were &lt; 20 ng/ml. Patients with myalgias were more likely to have vit D &lt; 30 ng/ml (81.3% vs 52.5%, P &lt; 0.01) and &lt; 20 ng/ml (62.5% vs 18.6%, P &lt; 0.01). Among patients with vit D &lt; 20 ng/ml, 62.1% had statin-associated myalgias vs 17.6% of patients with vit D ≥ 30 (P&lt;0.01). About 1/3 of patients reported fewer statin-associated myalgias after unblinded treatment with high dose ergocalciferol for 8 –12 weeks, but most subjects also changed to a different statin. In summary, (1) vit D deficiency is common in this group of patients referred for hyperlipidemia, (2) mild and severe vit D deficiency were significantly more common among patients with statin-associated myalgias; mean vit D level was 32% lower, (3) vit D &lt; 20 was associated with 4-fold higher rates of myalgias vs vit D ≥ 30, (4) reduced myalgias were anecdotally related to treatment with vit D in some patients. In conclusion, vit D deficiency appears to be prevalent among patients with hyperlipidemia, but is significantly more likely among patients with statin-associated myalgias. It is possible that vit D deficiency potentiates statin-induced myalgias, or may cause drug-unrelated myalgias in a subset of statin-treated patients. Further studies are required to elucidate these relationships.
Abstract 17535: Incremental Risk Stratification for Diabetic Patients Undergoing Nuclear Exercise Stress Testing by Exercise Capacity, % Heart-Rate Reserve Achieved, and Heart-Rate Recovery
Authors: Vishal Y Parikh, Boris Arbit, Babak Azarbal, Sean Hayes, Heidi Gransar, Daniel S Berman
Journal: Circulation (2014)

Introduction:  Diabetes mellitus (DM) and Exercise (Ex) capacity (EC), chronotropic incompetence, measured by the % heart rate (HR) reserve achieved (%HR-reserve), and abnormal HR-recovery are known predictors of all-cause mortality (ACM). We examined the prognostic relationship of these three Ex variables for predicting ACM in diabetic patients (pts) undergoing Ex myocardial perfusion SPECT (MPS).   Methods:  We studied 11,218 pts with no valvular disease and not on beta-blockers who underwent Ex MPS and were followed up for ACM for 3.2 ± 2.2 yrs. EC ≤ 7 METS was considered low. For %HR-reserve [(peak HR - rest HR) x 100/(220-age-rest HR)],    Results:  There were 1223 patients with DM. 445 patients died in the entire study. SSS, %HR-reserve, HR-recovery, EC, and DM status were all independent predictors of ACM (p 0.05). DM and non-DM pts had significant increase in annualized ACM with addition of Ex abnormalities in normal and abnormal SSS groups (all p≤ 0.05).   Conclusion:  In both DM and non-DM pts undergoing MPS, exercise variables of EC, %HR-reserve, and HR-recovery improve risk stratification for ACM. The presence of diabetes increases the risk of ACM for pts with normal MPS, but not for pts with abnormal MPS.
Competing effects of hypokalemia and hydrochlororothiazide treatment on regression of Cornell product left ventricular hypertrophy in hypertensive patients : implications for the development of potassium-sparing diuretics
Authors: Peter M Okin, Sverre Kjeldsen, Lars H Lindholm, Björn Dahlöf, Richard B Devereux
Journal: Circulation (2009)

Background: Hydrochlorothiazide (HCTZ) treatment is associated with blood pressure reduction and regression of left ventricular hypertrophy (LVH). HCTZ is also associated with hypokalemia (hypoK),  ...
HEPATITIS B IMMUNE GLOBULIN (HBIG) EFFICACY IN THE INTERRUPTION OF PERINATAL TRANSMISSION OF HEPATITIS B VIRUS CARRIER STATE
Authors: R. Palmer Beasley, Chia-Chin Lin, Kwei-Yu Wang, Fon-Jou Hsieh, Lu-Yu Hwang, CladdE. Stevens, Tsu-Shen Sun, Wolf Szmuness
Journal: The Lancet (1981)
Doctors warn of the dangers of trepanning
Authors: Roger Dobson
Journal: BMJ (2000)

Doctors have warned about the dangers of trepanning after the launch of several websites promoting the “do it yourself” surgery and the case of a Gloucestershire woman who drilled a 2 cm diameter hole in her skull.

Concern has been expressed about the growing interest in trepanning for a several conditions, including depression and the chronic fatigue syndrome. Concern is also growing about the increasing promotion of trepanning, including videos, T …
Abstract 2685: Regulation of Ras stability via inhibition of Wnt/β-catenin pathway as a potential therapeutic strategy to treat colorectal cancers
Authors: Pu-Hyeon Cha, Yong-Hee Cho, Woo-Jeong Jeong, Hyun-Yi Kim, Kang-Yell Choi
Journal: Cancer Research (2014)

Abstract Ras is a well-characterized proto-oncogene, and its various mutations contribute to transformation and tumorigenesis in a wide variety of human cancers. Although the GTP/GDP loading switch is known as a major regulatory mechanism of Ras, other mechanisms affecting Ras activity are poorly understood. Here, we report a mechanism for controlling Ras activity by regulating its degradation and describe this regulatory mechanism in the suppression of cellular transformation and tumors induced by Ras mutations. We found that negative regulators of Wnt/β-catenin signaling contributed to the polyubiquitin-dependent degradation of Ras following phosphorylation by glycogen synthase kinase 3β (GSK3β) and subsequent recruitment of β-TrCP-E3 ligase. We found a positive association between tumorigenesis and Ras stabilization due to the aberrant activation of Wnt/β-catenin signaling. Our results indicate an essential role for phosphorylation and degradation of Ras and suppression of Ras-induced transformation via the Wnt/β-catenin pathway and provide insight into the role of this novel regulatory mechanism for Ras in tumorigenesis of colorectal cancers (CRCs). Because both Ras and Wnt/β-catenin pathways are frequently activated in CRCs, these results suggest that the regulation of Ras stability through inhibition of the Wnt/β-catenin pathway could be an ideal therapeutic approach for treatment of CRC. Citation Format: Pu-Hyeon Cha, Yong-Hee Cho, Woo-Jeong Jeong, Hyun-Yi Kim, Kang-Yell Choi. Regulation of Ras stability via inhibition of Wnt/β-catenin pathway as a potential therapeutic strategy to treat colorectal cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2685. doi:10.1158/1538-7445.AM2014-2685