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.
Nitric Oxide* ; Paclitaxel* ; Urinary Bladder Neoplasms* ; Urinary Bladder*

Natural products have long been major sources of pharmaceutical products in medicine. We have undertaken a series of studies designed to characterize the pharmacologic profiles of natural products used to treat psychotic illnesses in Korean traditional medicine. In our previous screening assays, we found that three of plant extracts (Coptidis j, Citrus u, and Phellodendron a) contain active components which show relatively potent binding to alpha-2 adrenoceptors. The present study is to explore pharmacologic activities of extracts as agonism or antagonism by G-protein modulations in radioligand receptor binding study. We have found that two extracts(Coptidis j and Phellodendron a) contain active ingredients which have antagonistic properties to alpha-2 adrenoceptors, whereas one plant extract (Citrus u) has agonistic properties. The demonstration of three plant extracts used to treat psychotic illnesses in Korea may help in the elucidation or their pharmacologic characteristics and provide insights for the development of new psychotropic drugs.
Biological Products* ; Citrus ; Felodipine ; GTP-Binding Proteins ; Korea ; Mass Screening ; Medicine, Korean Traditional ; Medicine, Traditional ; Pharmaceutical Preparations ; Phellodendron ; Plant Extracts ; Plants ; Psychotropic Drugs ; Receptors, Adrenergic

OBJECTIVE: Conization is used for diagnosis and treatment of cervical neoplasia. Our purpose of this investigation is to determine the efficacy of loop conization for the treatment of cervical dysplasia and the significance of the clinical and histological factors used to predict residual dysplasia after loop conization. METHODS: We reviewed the charts of patients who were received conization and subsequently total hysterectomy at Kangnam St Mary Hospital during 1989 and 2000. Logistic regression and Chi-square test were used for analysis. RESULTS: Total 257 patients were included. The mean age of the patients was 44.7 years. Of these patients, 87 (33.8%) had residual disease in the hysterectomy specimens. Age, the involvement of cut surface of endocervix and exocervix, severity and extent of the lesion, and scattering lesion were associated with the residual disease. But preoperative HPV infection, which is known as the cause of cervical neoplasia was not associated with the residual disease. CONCLUSION: When the high risk factors are present, the validity of conservative treatment should be considered and more careful follow up with pap smear, HPV test and colposcopy is necessary. Because about one thirds of patient has residual disease after conization, LEEP conization should be used for diagnosis of cervical neoplasia rather than treatment.
Colposcopy ; Conization* ; Diagnosis ; Follow-Up Studies ; Humans ; Hysterectomy ; Logistic Models ; Risk Factors*

OBJECTIVES: This study was performed to identify genes regulated by electroconvulsive shock (ECS) and to observe the pattern of expression of genes according to different developmental stages and brain regions. METHODS: ECS(130V, 0.5 sec) was given to male Sprague-Dawley rats with age of postnatal day 7 and 21(P7, P21 respectively). After screening genes regulated by ECS with mRNA differential display-PCR(DD-PCR), we selected one clone among them and observed the induction of this gene after ECS by time-dependent Northern blot analysis of rat brain of P7, P21 and adult rat cortex and hippocampus. RESULTS: By DD-PCR method, we have identified four clones whose expression was regulated by ECS. Among them, one(CP 10-2) was proved to be a new gene by sequencing and BLAST search. Its expression was increased after ECS in P7, P21, and adult rat brain. The expression of CP 10-2 reached peak level at 180 minutes after ECS in P7 rat brain, but was further increased until 360 minutes after ECS in P21 and adult rat brain. CONCLUSION: In this study, a new gene was identified in rat brain which showed up-regulated expression in response to ECS. Cloning and characterization of this new gene would be helpful to elucidate the effect of ECS in rat brain.
Adult ; Animals ; Blotting, Northern ; Brain* ; Clone Cells ; Cloning, Organism ; Electroshock* ; Hippocampus ; Humans ; Male ; Mass Screening ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger

No abstract available.
Adrenal Glands* ; Ganglioneuroma* ; Hyperplasia*

Tracheal intubation for general anesthesia is usually performed using a rigid laryngoscope and reguires the mandible to be opened with forward and upward traction of the patient's jaw which may at times result in the inadvertant injury to temporomandibular joint(TMJ). The injury may include internal derangement, dislocation and hematoma of TMJ; subsequent intraarticular adhesion formation ; dislocation of the meniscus, and rarely auriculotemporal nerve damage from traumatic TMJ dislocation. We studied in 200 patients the size of mouth opening during intubation, the change of mouth opening by tracheal intubation evaluated after operation, and any TMJ disorder arising after tracheal intubation. The results were as follows; 1) The mean size of mouth opening before operation was 42.7+/-7.0 and 40.6+/-6.2mm in male and female patients, respectively. 2) The mean size of mouth opening during intubation was 24.7+/-2.6 and 23.4+/-2.7mm in male and female patients, respectively. When vecuronium was used to prevent fasciculation, the mean was 24.3+/-3.1 and 25.2+/-2.0mm in male and female patients, respectively. 3) One week following operation The mean size of mouth opening one week postoperation was 48.3+/-8.9 and 42.2+/-6.3mm in male and female patients, respectively. When vecuronium was used to prevent fasciculation, the mean size of mouth opening was 55.5+/-5.3 and 43.2+/-6.2mm in male and female patients, respectively. 4) Five patients complained of discomfort around TMJ after tracheal intubation. It seems that upward 45 mandibule lifting by laryngoscope caused trauma to TMJs.
Anesthesia, General ; Dislocations ; Fasciculation ; Female ; Hematoma ; Humans ; Intubation ; Intubation, Intratracheal* ; Jaw ; Laryngoscopes ; Lifting ; Male ; Mandible ; Mouth ; Temporomandibular Joint Disorders ; Temporomandibular Joint* ; Traction ; Vecuronium Bromide

No abstract available.
Breast Neoplasms* ; Breast* ; Diagnosis*