Hypoxia-inducible factor-1alpha (HIF-1alpha) is a key transcriptional mediator that coordinates the expression of various genes involved in tumorigenesis in response to changes in oxygen tension. The stability of HIF-1alpha protein is determined by oxygen-dependent prolyl hydroxylation, which is required for binding of the von Hippel-Lindau protein (VHL), the recognition component of an E3 ubiquitin ligase that targets HIF-1alpha for ubiquitination and degradation. Here, we demonstrate that PLD2 protein itself interacts with HIF-1alpha, prolyl hydroxylase (PHD) and VHL to promote degradation of HIF-1alpha via the proteasomal pathway independent of lipase activity. PLD2 increases PHD2-mediated hydroxylation of HIF-1alpha by increasing the interaction of HIF-1alpha with PHD2. Moreover, PLD2 promotes VHL-dependent HIF-1alpha degradation by accelerating the association between VHL and HIF-1alpha. The interaction of the pleckstrin homology domain of PLD2 with HIF-1alpha also promoted degradation of HIF-1alpha and decreased expression of its target genes. These results indicate that PLD2 negatively regulates the stability of HIF-1alpha through the dynamic assembly of HIF-1alpha, PHD2 and VHL.
Cell Line ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Phospholipase D/*metabolism ; Prolyl Hydroxylases/metabolism ; Proteasome Endopeptidase Complex/*metabolism ; *Protein Interaction Maps ; Proteolysis ; Ubiquitin-Protein Ligases/metabolism ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism

PURPOSE: Evidence suggests that some patients with breast cancer experience cognitive difficulties following chemotherapy. This longitudinal study was done to examine the prevalence of cognitive impairment and trajectory of cognitive function over time in women with breast cancer, who received adjuvant chemotherapy. METHODS: Participants were 137 patients with breast cancer. They completed neuropsychological tests and the Functional Assessment of Cancer Therapy-Cognitive Function before adjuvant therapy (pretest), toward the end of adjuvant therapy (posttest), and 6 months after the completion of adjuvant therapy (follow-up test). Of the patients, 91 were treated with adjuvant chemotherapy and 46 patients who did not receive chemotherapy made up the comparison group. A reliable-change index and repeated-measure ANOVA were used for statistical analyses. RESULTS: At the posttest point, over 30% of patients showed complex cognitive impairment and reported greater difficulty in subjective cognitive function. At the follow-up test point, 22.0% of patients exhibited complex cognitive impairment and 30.8% of patients complained of subjective cognitive impairment. Repeated-measure ANOVA showed significant decreases after receiving chemotherapy followed by small improvements 6 months after the completion of chemotherapy in cognitive domains of change for attention and concentration, memory, executive function, and subjective cognitive function. CONCLUSION: These results suggest that chemotherapy in patients with breast cancer may be associated with objective and subjective cognitive impairments. Further studies are needed to explore the potential risk factors and predictor of chemotherapy-related cognitive changes. Also nursing interventions for prevention and intervention of cognitive impairments should be developed and tested.
Adult ; Analysis of Variance ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Attention/drug effects ; Breast Neoplasms/*drug therapy ; Chemotherapy, Adjuvant ; Cognitive Dysfunction/epidemiology/*etiology ; Female ; Humans ; Longitudinal Studies ; Memory/drug effects ; Middle Aged

Cervical pregnancy is a rare form of ectopic gestation in which the blastocyst implants in the cervical mucosa below the histologic cervical os. Because of the serious vaginal bleeding, hysterectomy was usually done in the management of cervical pregnancy. Howerver, conservative treatment is desirable for women who want to be pregnancy in the future. Methotrexate has been utilized recently for conservative management of cervical pregnancy. We report a case of cervical pregnancy which was treated succesfully with intramuscular methotrexate injection.
Blastocyst ; Female ; Humans ; Hysterectomy ; Methotrexate* ; Mucous Membrane ; Pregnancy* ; Uterine Hemorrhage

No abstract available.
Mitral Valve Stenosis*

BACKGROUND: The gastroepiploic artery is not only an alternative graft but also may be considered an important primary graft for coronary revascularization. However, the long-term patency of the gastroepiploic arterial graft is yet to be determined and the incidence of perioperative spasm and long-term patency of a coronary graft may be affected by the properties of the graft response to certain vasoactive substances. The reactivity of the gastroepiploic artery to vasoactive substances has not been studied extensively and the results of the studies are contradictory. MATERIAL AND METHOD: This study was designed to test the reactivity of human gastroepiploic artery to four constrictors and four relaxants. The middle sections of the human gastroepiploic arteries were collected from the patients undergoing gastrectomy and the arterial rings with intact endothelium were suspended in organ baths for isometric tension recording. RESULT: Epinephrine, norepinephrine, and potassium chloride induced the maximum constriction to higher forces (7.0+/-1.1g, 6.6+/-0.9g, and 6.5+/-1.1g) than 5-hydroxytryptamine did (3.8+/-1.7g, p<0.05). Nitroprusside and histamine induced almost full relaxation in the gastroepiploic arteries preconstricted with norepinephrine. There was no significant difference between two relaxants regarding maximum relaxation force. Acetylcholine induced the maximum relaxation to weaker force when compared with nitroprusside and histamine (p<0.05), and isoproterenol was the weakest of the relaxants (p<0.05 compared with acetylcholine). CONCLUSION: The gastroepiploic artery has a strong capacity of endothelium-dependent relaxation which could have an important influence on long-term patency. The gastroepiploic artery exhibits a potent contractility to catecholamines and the enhanced contractility may facilitate vasospasm in the presence of high circulating levels of catecholamines. Nitroprusside, a potent relaxant in gastroepiploic artery, might be beneficial for the treatment of gastroepiploic arterial graft spasm. The gastroepiploic arterial graft with intact endothelium may respond weakly to beta-adrenoceptor agonist and 5-hydroxytryptamine.
Acetylcholine ; Baths ; Catecholamines ; Constriction ; Endothelium ; Epinephrine ; Gastrectomy ; Gastroepiploic Artery* ; Histamine ; Humans* ; Incidence ; Isoproterenol ; Nitroprusside ; Norepinephrine ; Potassium Chloride ; Relaxation ; Serotonin ; Spasm ; Transplants

PURPOSE: The purpose of this study was to determine the prevalence of distress and to investigate the related problems in breast cancer patients at the end of primary treatment. METHODS: A sample of 118 participants was recruited among outpatients who had successfully completed primary treatment of breast cancer. Data were collected between July, 2013 and October, 2014 using the Distress Thermometer (DT) scale and problem lists. Descriptive statistics and logistic regression analysis were used to analyze data. RESULTS: Among the 118 patients that participated in this study, 34 patients (28.8%) suffered from elevated distress using the previously validated cut point > or =4 for the DT. Problems most frequently encountered were fatigue (68.8%), worry (59.3%), appearance (51.7%) and memory/concentration (48.3%). Multivariate logistic regression analysis revealed that depression (OR=9.55), worry (OR=8.34), fatigue (OR=8.19) and age (OR=1.14) were independent predictors for elevated distress scores. CONCLUSION: Utilizing the DT, onethird of breast cancer patients screened met criteria for distress at the end of the primary treatment. Breast cancer patients with depression, worry, fatigue and older age should be targeted for distress screening and management.
Breast Neoplasms* ; Breast* ; Depression ; Fatigue ; Humans ; Logistic Models ; Mass Screening ; Outpatients ; Prevalence ; Survivors ; Thermometers

Pacemaker-mediated tachycardia (PMT) is a well-known complication of dual-chamber pacemaker with atrioventricular sensing and pacing (DDD) or atrial synchronous, ventricular demand pacemaker (VDD). PMT usually starts with sensing a retrograde P waves linked to ventricular extrasystole with retrograde ventriculoatrial conduction and forms reentrant or circus movement tachycardia with the pacemaker itself as an antegrade limb and the conducting tissue of the heart as a retrograde limb. Recently, a number of pacemaker manufactures have incorporated in their devices a variety of relatively complex algorithms to prevent PMT. Despite these measures, PMT may still occur because of inappropriate programming or unpredictable variations of ventri-culoatrial conduction. We report two cases of PMT in 78 year-old man and 60 year-old man who received DDD type pacemakers due to sick sinus syndrome, and a case of PMT in 69 year-old man who had suffered complete heart block and received a VDD type pacemaker. In these cases, we investigate symptoms, mechanism of PMT, programed parameters of pacemaker and treatments of PMT.
Aged ; Dichlorodiphenyldichloroethane ; Extremities ; Heart ; Heart Block ; Humans ; Middle Aged ; Sick Sinus Syndrome ; Tachycardia* ; Ventricular Premature Complexes

Phytosphingosine-1-phosphate (PhS1P) was found to stimulate an intracellular calcium increase via phospholipase C but not pertussis toxin (PTX)- sensitive G-proteins in L2071 mouse fibroblasts. PhS1P also activated ERK and p38 kinase, and these activations by PhS1P were inhibited by PTX. Moreover, PhS1P stimulated the chemotactic migration of L2071 cells via PTX-sensitive Gi protein(s). In addition, the PhS1P-induced chemotactic migration of L2071 cells was also dramatically inhibited by LY294002 and SB203580 (inhibitors of phosphoinositide 3-kinase and p38 kinase, respectively). L2071 cells are known to express four S1P receptors, i.e., S1P1, S1P2, S1P3, and S1P4, and pretreatment with an S1P1 and S1P3 antagonist (VPC 23019) did not affect on PhS1P-induced chemotaxis. This study demonstrates that PhS1P stimulates at least two different signaling cascades, one is a PTX-insensitive but phospholipase C dependent intracellular calcium increase, and the other is a PTX-sensitive chemotactic migration mediated by phosphoinositide 3-kinase and p38 kinase.
1-Phosphatidylinositol 3-Kinase/metabolism ; Animals ; Calcium Signaling/drug effects ; Chemotaxis/*drug effects ; Estrenes/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibroblasts/*cytology/*drug effects ; GTP-Binding Proteins/*metabolism ; Gene Expression Regulation/drug effects ; Humans ; Mice ; Pertussis Toxin/*pharmacology ; Phosphorylation/drug effects ; Pyrrolidinones/pharmacology ; RNA, Messenger/genetics/metabolism ; Receptors, Lysosphingolipid/genetics/metabolism ; Sphingosine/*analogs & derivatives/pharmacology ; p38 Mitogen-Activated Protein Kinases/metabolism

Accurate diagnosis of gastric intestinal metaplasia is important; however, conventional endoscopy is known to be an unreliable modality for diagnosing gastric intestinal metaplasia (IM). The aims of the study were to evaluate the interobserver variation in diagnosing IM by high-definition (HD) endoscopy and the diagnostic accuracy of this modality for IM among experienced and inexperienced endoscopists. Selected 50 cases, taken with HD endoscopy, were sent for a diagnostic inquiry of gastric IM through visual inspection to five experienced and five inexperienced endoscopists. The interobserver agreement between endoscopists was evaluated to verify the diagnostic reliability of HD endoscopy in diagnosing IM, and the diagnostic accuracy, sensitivity, and specificity were evaluated for validity of HD endoscopy in diagnosing IM. Interobserver agreement among the experienced endoscopists was "poor" (kappa = 0.38) and it was also "poor" (kappa = 0.33) among the inexperienced endoscopists. The diagnostic accuracy of the experienced endoscopists was superior to that of the inexperienced endoscopists (P = 0.003). Since diagnosis through visual inspection is unreliable in the diagnosis of IM, all suspicious areas for gastric IM should be considered to be biopsied. Furthermore, endoscopic experience and education are needed to raise the diagnostic accuracy of gastric IM.
Adult ; Aged ; Endoscopy, Gastrointestinal ; Female ; Humans ; Intestinal Mucosa/*pathology ; Male ; Metaplasia/*diagnosis/epidemiology ; Middle Aged ; Observer Variation ; Physicians ; Stomach/*pathology

No abstract available.
Nitric Oxide* ; Paclitaxel* ; Urinary Bladder Neoplasms* ; Urinary Bladder*