tbuckley/cabot-search huggingface dataset:
6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death
Authors: Alison I Bernstein, Sean P Garrison, Gerard P Zambetti, Karen L O'Malley
Journal: Molecular Neurodegeneration (2011)

Abstract Background Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN), resulting in tremor, rigidity, and bradykinesia. Although the etiology is unknown, insight into the disease process comes from the dopamine (DA) derivative, 6-hydroxydopamine (6-OHDA), which produces PD-like symptoms. Studies show that 6-OHDA activates stress pathways, such as the unfolded protein response (UPR), triggers mitochondrial release of cytochrome-c, and activates caspases, such as caspase-3. Because the BH3-only protein, Puma ( p 53- u pregulated m ediator of a poptosis), is activated in response to UPR, it is thought to be a link between cell stress and apoptosis. Results To test the hypothesis that Puma serves such a role in 6-OHDA-mediated cell death, we compared the response of dopaminergic neurons from wild-type and Puma -null mice to 6-OHDA. Results indicate that Puma is required for 6-OHDA-induced cell death, in primary dissociated midbrain cultures as well as in vivo . In these cultures, 6-OHDA-induced DNA damage and p53 were required for 6-OHDA-induced cell death. In contrast, while 6-OHDA led to upregulation of UPR markers, loss of ATF3 did not protect against 6-OHDA. Conclusions Together, our results indicate that 6-OHDA-induced upregulation of Puma and cell death are independent of UPR. Instead, p53 and DNA damage repair pathways mediate 6-OHDA-induced toxicity.
Fluticasone propionate does not influence bone metabolism in contrast to beclomethasone dipropionate.
Authors: G P Bootsma, P N Dekhuijzen, J Festen, P G Mulder, L M Swinkels, C L van Herwaarden
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Inhaled corticosteroids (ICS) in dosages above 1,000 micrograms/d may influence parameters of bone metabolism. Fluticasone propionate (FP) is a new ICS with a higher clinical potency than beclomethasone dipropionate (BDP) combined with negligible oral bioavailability. The aim of this study was to evaluate the effects of FP and BDP in clinically equipotent dosages on indices of bone metabolism and morning cortisol. FP 750 micrograms/d and BDP 1,500 micrograms/d were compared in a randomized, double-blind, crossover study consisting of two 6-wk treatment periods, each preceded by a 3-wk single-blind placebo period. Twenty-one nonsmoking asthmatic completed the study. FP had the same effect on FEV1 and peak expiratory flow as the double dose of BDP. Both treatments did not change morning cortisol. BDP decreased both osteocalcin and procollagen type 1 carboxyterminal propeptide, indices of bone formation, significantly by 18.5 and 21.9%, respectively. In contrast, FP did not change any variable of bone formation. FP and BDP did not increase type 1 collagen carboxyterminal telopeptide and deoxypyridinoline crosslinks, both markers of bone resorption. In changes in parameters of bone metabolism indicate adverse effects on bone quality in the long term, FP may offer an advantage over BDP.
Skin test reactivity to 2 recombinant Aspergillus fumigatus allergens in A fumigatus–sensitized asthmatic subjects allows diagnostic separation of allergic bronchopulmonary aspergillosis from fungal sensitization
Authors: Stefanie Hemmann, Günter Menz, Chaim Ismail, Kurt Blaser, Reto Crameri
Journal: Journal of Allergy and Clinical Immunology (1999)
Multicentric reticulohistiocytosis and malignant disease
Authors: M. D. CATTERALL, J. E. WHITE
Journal: British Journal of Dermatology (1978)

Multicentric reticulohistiocytosis developed in a 45-year-old woman, who had a 3 year history of untreated breast carcinoma. A review of the literature revealed that malignant disease has been associated with 27% of reported cases. It is considered that, like adult dermatomyositis, the onset of multicentric reticulohistiocytosis should stimulate detailed investigation for an underlying neoplasm.
Maturation of the rat small intestine at weaning: changes in epithelial cell kinetics, bacterial flora, and mucosal immune activity.
Authors: A G Cummins, T W Steele, J T LaBrooy, D J Shearman
Journal: Gut (1988)

The relationship between maturation of the small intestine and change in mucosal immune activity was examined in the DA rat during the weaning period from 12 to 30 days. Two stages of jejunal maturation were observed: an initial stage of morphological development and crypt proliferation (days 12 to 22), followed by a period of stabilisation (days 24 to 30). By day 22 of the initial phase, villi increased principally in width but not in length, crypt length increased, and crypt cell production rate increased from 0.5 (day 12) to 11.1 (day 22) cells/crypt/hour. Various measures of mucosal immune activity showed a biphasic response. Up to days 20 to 22, the weight of the mesenteric lymph node increased seven-fold (p less than 0.0001), counts of jejunal eosinophils and goblet cells increased 3- (p less than 0.0001) and 19-fold (p less than 0.0001) respectively, and mean serum rat mucosal mast cell protease II, released from mucosal mast cells, increased from 24 (day 12) to 313 (day 22) ng/ml (p less than 0.0001). After day 22, mesenteric lymph node weight stabilised, eosinophil count stabilised and goblet cells decreased, serum rat mucosal mast cell protease II decreased three-fold (p less than 0.0001), and mean jejunal count of intraepithelial lymphocytes increased from 26 (day 22) to 54 (day 24) cells per mm of muscularis mucosae (p less than 0.0001), before stabilising. These results demonstrated a close association between maturation of the small intestine and change in activity of the mucosal immune system.
Inhibition of mediator release during the early reaction to antigen
Authors: Robert M. Naclerio
Journal: Journal of Allergy and Clinical Immunology (1992)

A nasal lavage model and a new jilter paper disk model have been used to measure biologic and physiologic responses to antigen challenge in patients with allergic rhinitis.Pretreatment of subjects with cetirizine reduced the number of sneezes induced by antigen challenge but did not signi$cantly reduce levels of histamine or prostaglandin D, in a double-blind, placebo-controlled trial with the lavage model.Pretreatment with 60 or 300 mg of terfenadine did signijicantly reduce levels of histamine, kinin, albumin, and TAME-esterase activity in a double-blind, placebo-controlled study with this model.Again with the nasal lavage model, u double-blind.placebo-controlled comparison of pretreatment with 60 mg of terfenadine or 10 mg of loratadine showed that both agents significantly reduced sneezing.Both drugs also lowered levels of antigen-induced histamine and TAME-esterase, but only terfenadine did so signi$cantly.In a double-blind, placebo-controlled study, the new disk method showed that terfenadine reduced sneezing but not nasal congestion in eight patients with allergic rhinitis.Terfenadine signi$cantly reduced the weight of nasal secretions on both sides of the nose and sign$cantly reduced histamine on the ipsilateral side.(
Midportion Achilles tendinosis and the plantaris tendon
Authors: Håkan Alfredson
Journal: British Journal of Sports Medicine (2011)

When re-operating patients with midportion Achilles tendinosis, having had a poor effect of ultrasound (US) and Doppler-guided scraping, the author found the involvement of the plantaris tendon to be a likely reason for the poor result. The aim of this study was to investigate the occurrence of a plantaris tendon in close relation to the Achilles tendon in consecutive patients with midportion Achilles tendinosis undergoing treatment with US and Doppler-guided scraping.This study includes 73 consecutive tendons with chronic painful midportion Achilles tendinosis, where US+Doppler examination showed thickening, irregular tendon structure, hypo-echoic regions, and localised high blood flow outside and inside the ventral Achilles midportion. The tendons were treated with US+Doppler-guided scraping, via a medial incision. If there was a plantaris tendon located in close relation to the medial Achilles, it was extirpated.An invaginated, or 'close by located', enlarged plantaris tendon was found in 58 of 73 (80%) tendons. Preliminary clinical results of the combined procedure, US + Doppler-guided surgical scraping and extirpation of the plantaris tendon, are very promising.A thickened plantaris tendon located in close relation to the medial Achilles seems common in patients with chronic painful midportion tendinosis. The role of the plantaris tendon in midportion Achilles tendinosis needs to be further evaluated and should be kept in mind when treating this condition.
State-related Changes in Upper Airway Caliber and Surrounding Soft-Tissue Structures in Normal Subjects
Authors: FRANK J. TRUDO, WARREN B. GEFTER, KEVIN C. WELCH, KRISHANU B. GUPTA, GREG MAISLIN, RICHARD J. SCHWAB
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

State-dependent changes in upper airway caliber were studied with magnetic resonance imaging (MRI) techniques. We hypothesized that changes in airway caliber during sleep in normal subjects would result from positional and dimensional changes in upper airway soft-tissue structures, including the lateral pharyngeal walls, tongue, and soft palate. We used MRI to study 15 normal subjects during wakefulness and sleep. Sleep was facilitated by one night of sleep deprivation prior to MRI. During sleep, the volume of the retropalatal (RP) airway was reduced by 19% (p = 0.03). The volume of the retroglossal (RG) airway was not significantly reduced during sleep, suggesting that the RP region may be more likely to collapse. The mean minimal cross-sectional airway area was reduced by 228% (p = 0.004) in the RP and by 22% (p = 0.02) in the RG region during sleep as compared with values in anatomically matched axial images during wakefulness. Airway anteroposterior (AP) and lateral dimensions were also significantly reduced in the RP region. Airway narrowing in the RP region was associated with a 7% increase in thickness of the lateral pharyngeal walls (p = 0.04). In nine subjects, sagittal data showed significant posterior displacement of the soft palate during sleep as compared with wakefulness. Multiple linear regression analyses indicated that reduction in the RP airway area during sleep resulted from posterior movement of the soft palate, thickening of the lateral pharyngeal walls, and an increase in tongue oblique distance. We conclude that the lateral pharyngeal walls play an important role in upper airway narrowing during sleep in normal subjects.
The Low Molecular Weight Cyclin E Isoforms Augment Angiogenesis and Metastasis of Human Melanoma Cells <i>In vivo</i>
Authors: Elise Bales, Lisa Mills, Nancy Milam, Mollianne McGahren-Murray, Debdutta Bandyopadhyay, Dahu Chen, Jon A. Reed, Nikolai Timchenko, Joost J. van den Oord, Menashe Bar-Eli, Khandan Keyomarsi, Estela E. Medrano
Journal: Cancer Research (2005)

Immunohistochemical analysis has consistently shown that cyclin E is up-regulated in human malignant melanomas in vivo. Here we analyzed such expression in more detail and show that cyclin E is overexpressed and present in low molecular weight (LMW) isoforms in metastatic melanoma and in a subset of primary invasive melanoma tumor tissues, but not in benign nevi. Human metastatic melanoma cell lines, but not normal melanocytes, also expressed the LMW cyclin E forms. The biological significance of these findings was established by showing that overexpression of two LMW cyclin E forms named cyclin E truncated 1 [cyclinE(T1)] and cyclin E truncated 2 [cyclinE(T2)] in a low tumorigenic and non-metastatic primary cutaneous melanoma cell line generated angiogenic tumors with prominent perineural invasion compared with full-length cyclin E. In addition, cyclin E(T1)- and cyclin E(T2)-expressing melanoma cells displayed a dramatic increase in the incidence and number of metastases in an experimental lung metastasis assay. Together, these results indicate that the LMW cyclin E forms are functional and likely act as regulators of human melanoma tumor progression and invasion.
Threat bias, not negativity bias, underpins differences in political ideology
Authors: Scott O. Lilienfeld, Robert D. Latzman
Journal: Behavioral and Brain Sciences (2014)

Abstract Although disparities in political ideology are rooted partly in dispositional differences, Hibbing et al.'s analysis paints with an overly broad brush. Research on the personality correlates of liberal–conservative differences points not to global differences in negativity bias, but to differences in threat bias, probably emanating from differences in fearfulness. This distinction bears implications for etiological research and persuasion efforts.
Plasminogen Kringle 5–Engineered Glioma Cells Block Migration of Tumor-Associated Macrophages and Suppress Tumor Vascularization and Progression
Authors: Sabrina R. Perri, Josephine Nalbantoglu, Borhane Annabi, Zafiro Koty, Laurence Lejeune, Moïra François, Marcos R. Di Falco, Richard Béliveau, Jacques Galipeau
Journal: Cancer Research (2005)

Abstract Angiostatin, a well-characterized angiostatic agent, is a proteolytic cleavage product of human plasminogen encompassing the first four kringle structures. The fifth kringle domain (K5) of human plasminogen is distinct from angiostatin and has been shown, on its own, to act as a potent endothelial cell inhibitor. We propose that tumor-targeted K5 cDNA expression may act as an effective therapeutic intervention as part of a cancer gene therapy strategy. In this study, we provide evidence that eukaryotically expressed His-tagged human K5 cDNA (hK5His) is exported extracellularly and maintains predicted disulfide bridging conformation in solution. Functionally, hK5His protein produced by retrovirally engineered human U87MG glioma cells suppresses in vitro migration of both human umbilical vein endothelial cells and human macrophages. Subcutaneous implantation of Matrigel-embedded hK5His-producing glioma cells in nonobese diabetic/severe combined immunodeficient mice reveals that hK5His induces a marked reduction in blood vessel formation and significantly suppresses the recruitment of tumor-infiltrating CD45+Mac3+Gr1− macrophages. Therapeutically, we show in a nude mouse orthotopic brain cancer model that tumor-targeted K5 expression is capable of effectively suppressing glioma growth and promotes significant long-term survival (&amp;gt;120 days) of test animals. These data suggest that plasminogen K5 acts as a novel two-pronged anticancer agent, mediating its inhibitory effect via its action on host-derived endothelial cells and tumor-associated macrophages, resulting in a potent, clinically relevant antitumor effect.
Phase II Study of Doxorubicin and Bevacizumab for Patients With Metastatic Soft-Tissue Sarcomas
Authors: David R. D'Adamo, Sibyl E. Anderson, Karen Albritton, Jennifer Yamada, Elyn Riedel, Kelly Scheu, Gary K. Schwartz, Helen Chen, Robert G. Maki
Journal: Journal of Clinical Oncology (2005)

To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS).Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2.A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related.The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.
Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study
Authors: Jin-Ping Zheng, Jian Kang, Shao-Guang Huang, Ping Chen, Wan-Zen Yao, Lan Yang, Chun-Xue Bai, Chang-Zheng Wang, Chen Wang, Bao-Yuan Chen, Yi Shi, Chun-Tao Liu, Ping Chen, Qiang Li, Zhen-Shan Wang, Yi-Jiang Huang, Zhi-Yang Luo, Fei-Peng Chen, Jian-Zhang Yuan, Ben-Tong Yuan, Hui-Ping Qian, Rong-Chang Zhi, Nan-Shan Zhong
Journal: The Lancet (2008)
A Functional Common Polymorphism in a Sp1 Recognition Site of the Epidermal Growth Factor Receptor Gene Promoter
Authors: Wanqing Liu, Federico Innocenti, Michael H. Wu, Apurva A. Desai, M. Eileen Dolan, Edwin H. Cook, Mark J. Ratain
Journal: Cancer Research (2005)

The epidermal growth factor receptor (EGFR) plays a prominent role in cell growth and development. Its regulation in humans is complex and incompletely understood. In this study, 12 new polymorphisms were discovered in the 5'-regulatory region of EGFR gene and 2 common single nucleotide polymorphisms (-216G/T and -191C/A) were found in the essential promoter area, one of which is located in a Sp1 recognition site (-216). Transient transfection in human cancer and primary cell lines showed significantly different promoter activity between the two most common haplotypes (-216G-191C and -216T-191C). The replacement of G by T at position -216 increases the promoter activity by 30%. A transient transfection assay in the Sp1-deficient cell line (Schneider cell line 2) showed a strong dependence of EGFR promoter activity on Sp1 and confirmed the effect of the aforementioned polymorphisms. Electrophoretic mobility shift assay also showed a significantly higher binding efficiency of nuclear protein or pure Sp1 protein to the T allele compared with the G allele. We then investigated the allelic imbalance of EGFR transcription in fibroblast cell lines with heterozygous genotype at -216G/T but C/C homozygous genotype at -191C/A. The expression of mRNA carrying T-C haplotype was significantly stronger compared with that of G-C haplotype (P < 0.02). Thus, we successfully showed that a common polymorphism in the EGFR promoter was associated with altered promoter activity and gene expression both in vitro and in vivo. Our findings have implications for cancer etiology and therapy and may also be relevant to the inherited susceptibility of other common diseases.
Neonatal lupus erythematosus. Report of serological and immunogenetic studies in twins discordant for congenital heart block
Authors: R.M. WATSON, J.N. SCHEEL, M. PETRI, J.S. KAN, T.T. PROVOST, H. RATRIE, N.A. CALLANI
Journal: British Journal of Dermatology (1994)

Journal Article Neonatal lupus erythematosus. Report of serological and immunogenetic studies in twins discordant for congenital heart block Get access R.M. WATSON, R.M. WATSON Department of Dermatology, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 212015, U.S.A. Dr M.Petri is supported by NIH grant R29 HL47080‐01. Search for other works by this author on: Oxford Academic Google Scholar J.N. SCHEEL, J.N. SCHEEL Division of Pediatric Cardiology, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 212015, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar M. PETRI, M. PETRI Division of Rheumatology, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 212015, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J.S. KAN, J.S. KAN Division of Pediatric Cardiology, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 212015, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar T.T. PROVOST, T.T. PROVOST Department of Dermatology, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 212015, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar H. III RATRIE, H. III RATRIE Department of Dermatology, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 212015, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar N.A. CALLANI N.A. CALLANI Department of Obstetrics and Gynecology, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 212015, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 3, 1 March 1994, Pages 342–348, https://doi.org/10.1111/j.1365-2133.1994.tb02931.x Published: 01 March 1994 Article history Accepted: 28 July 1993 Published: 01 March 1994
New guidelines are needed to manage heat stress in elite sports – The Fédération Internationale de Volleyball (FIVB) Heat Stress Monitoring Programme
Authors: Roald Bahr, Jonathan C Reeser
Journal: British Journal of Sports Medicine (2012)

There seems to be a discrepancy between the available heat stress guidelines and the actual risk of heat-related illness among professional beach volleyball players competing under hot and humid conditions.To monitor heat stress and record cases of heat-related medical forfeits on the Swatch FIVB Beach Volleyball World Tour.The FIVB Heat Stress Monitoring Protocol covered events on the FIVB Beach Volleyball World Tour and FIVB Beach Volleyball World Championships during the 2009, 2010 and 2011 seasons (51 events, most of these double gender). The protocol consisted of (1) measuring the Wet Bulb Globe Temperature (WBGT) on centre court prior to the start of every match, and (2) recording any heat-related medical forfeits during the tournament.Data were collected during 48 of 51 events. There were nine events where the peak WBGT exceeded the US Navy Black flag conditions of >32.3°C and an additional two events where the peak WBGT exceeded 31°C, (meeting Red flag conditions.) In two events, the average WBGT equalled at least 31°C. One case of a medical forfeit related to heat stress was recorded over the 3-year surveillance period: an athlete whose fluid balance was compromised from a 3-day bout of acute gastroenteritis.The incidence of significant heat illness among athletes competing on the FIVB Beach Volleyball World Tour appears to be quite low, even though weather conditions frequently result in a WBGT index >32°C. Currently available guidelines appear to be inadequate to fully assess the risk of heat stress and too conservative to inform safety decisions in professional beach volleyball.