Negative feedback regulation of Wnt signaling by Gbetagamma-mediated reduction of Dishevelled

Wnt signaling is known to be important for diverse embryonic and post-natal cellular events and be regulated by the proteins Dishevelled and Axin. Although Dishevelled is activated by Wnt and involved in signal transduction, it is not clear how Dishevelled-mediated signaling is turned off. We report that guanine nucleotide binding protein beta 2 (Gnb2; Gbeta2) bound to Axin and Gbeta2 inhibited Wnt mediated reporter activity. The inhibition involved reduction of the level of Dishevelled, and the Gbeta2gamma2 mediated reduction of Dishevelled was countered by increased expression of Axin. Consistent with these effects in HEK293T cells, injection of Gbeta2gamma2 into Xenopus embryos inhibited the formation of secondary axes induced either by XWnt8 or Dishevelled, but not by beta-catenin. The DEP domain of Dishevelled is necessary for both interaction with Gbeta2gamma2 and subsequent degradation of Dishevelled via the lysosomal pathway. Signaling induced by Gbeta2gamma2 is required because a mutant of Gbeta2, Gbeta2 (W332A) with lower signaling activity, had reduced ability to downregulate the level of Dishevelled. Activation of Wnt signaling by either of two methods, increased Frizzled signaling or transient transfection of Wnt, also led to increased degradation of Dishevelled and the induced Dishevelled loss is dependent on Gbeta1 and Gbeta2. Other studies with agents that interfere with PLC action and calcium signaling suggested that loss of Dishevelled is mediated through the following pathway: Wnt/Frizzled-->Gbetagamma-->PLC-->Ca+2/PKC signaling. Together the evidence suggests a novel negative feedback mechanism in which Gbeta2gamma2 inhibits Wnt signaling by degradation of Dishevelled.

The Development of Behavioral Modification Program on Weight Reduction in Overweight Patients taking Atypical Antipsychotics: Preliminary Study

OBJECTS: SThe authors developed a behavioral modification program for overweight outpatients with schizophrenia and bipolar disorder who had been treated with atypical antipsychotics, and evaluated the applicability of this program to outpatients. METHODS: Two men and nine women who had been treated with atypical antipsychotics and who had gained at least 5 percent of their pre-treatment body weight for 10 weeks, attended a behavioral modification program. The patients' weight, body mass index and the diet-activity scale were assessed and were compared with those of a matched comparison group who did not attend the behavioral modification program. RESULTS: The body weight of patients who attended the behavioral modification program reduced with statistical significance. The treatment group showed significant improvement in diet-related items but not in activity-related items of the diet-activity scale. CONCLUSIONS: This study suggested the applicability of a behavioral modification program on weight reduction to overweight patients taking atypical antipsychotics for the first time in Korea. Additional large scale studies are needed to validate the effectiveness of this program.

Sexuality and its influential factors in old women

BACKGROUND: Although sexuality in old women is important for the quality of life, that has been overlooked due to social indifference. Because the studies for sexuality in old women were lack in Korea, we surveyed sexuality and its influential factors in old women. METHODS: From March to July 2000, we surveyed 115 old women over 60 years with 22 items of questionnaire. Data was gathered through written responses to the questionnaire and one to one interview between doctor and subject. Statistical analysis was done with SPSS ver10.0/PC and its significance was tested by chi square(p<0.05). RESULTS: Mean age of 115 women is 64.84+/-4.54year. There are 80 cases(69.6%) that thought sexuality is important in old women. Sexuality and sexual interest get gradually decreased by aging. Marital state, age of husband, family structure, economic state, sexual interest are statistically significant as the influential factors of sexuality(p<0.05). Sexual satisfaction comes out 35.7%. Age, marital state, family structure, job, economic state, subjective health state, current medication, sexual interest are statistically signifiant as the influential factors of sexual satisfaction(p<0.05). The reasons of decreased sexuality is due to aging process(47.8%), no partner(17.4%), partner problem(14.8%), physical illness(10.4%) and decreased libido. CONCLUSION: We conclude that sexuality in old women is important. Its influential factors are marital state, age of husband, family structure, economic state, sexual interest. Age, marital state, family structure, job, economic state, subjective health state, current medication, sexual interest are statistically signifiant as the influential factors of sexual satisfaction.

Intrapleural chemotherapy with cisplatin and cytarabine in the management of malignant pleural effusion / 대한내과학회지

BACKGROUND: Maligant pleural effusions are common and significant problems in patient with advanced malignancies. In comparison with traditional sclerosing agent, intrapleural chemotherapy has a potential advantage of treating the underlying malignancy in addition to providing local control of th effusion. This study evaluated efficacy of intrapleural chemotherapy with cisplatin and cytarabine in the management of malignant pleural effusion from lung cancer and others. METHODS: 29 patients with pathology-proven malignant pleural effusion were prospectively analyzed to estimate the effect of intrapleural chemotherapy. A single dose of cisplatin 100mg/m plus cytarabine 1200mg/m in the 250ml normal saline were instilled into the pleural space via a chest tube and drained 4 hours later. Patients were evaluated for toxicity and response at 24hours, 1st, 2nd, 3rd week, and monthly interval. No recurrence of the effusion was considered a complete response(CR). Partial responses (PR) was defined as a 75% or greater decrease in the amount of effusion on serial chest radiographs. RESULTS: The overall response rate(CR plus PR) was 93.1% (27 of 29 patients). The median length of response was 7.5 months. Among 17 patients who were assessable until they died, 14 patients(82%) maintained complete response at the last follow-up. One patient experienced reversible grade 4 myelosuppression, 3 patients had grade 3 nausea & vomiting. 2 patients had empyema, and 2 patients had wound infection. CONCLUSIONS: The outcome of this trial indicated that the intrapleural chemotherapy with cisplatin and cytarabine with little treatment related mortality and morbidity.

A study of condylar positional changes before & after stabilization splint therapy / 대한치과교정학회지

Stabilization splint therapy precedes orthodontic intervention to enable the operator to find a "true" centric(which is stable and comfortable); to test the patient's response to a change in the occlusion, prior to embarking upon a complex course of occlusal therapy ; and finally, to see if the centric relation position can be stabilized. For this study, 47 malocclusion patients enrolled for orthodontic treatment at the Department of Orthodontics, College of Dentistry, Chosun University, comprised the malocclusion group, little variation of growth factor by the second molar eruption. They had Cr-Co discrepancy beyond normal range. For each patients the stabilization splint with mutually protected type of occlusal scheme was applied for 3 months. Condylar positions in CR and CO were measured using Panadent articulators, Panadent condylar position indicator(CPI), and transcranial projection before & after stabilization splint therapy. On the basis of this study, the results of this study were as follows: 1. In all samples using CPI, there were statistical significances in CR-CO discrepancy(P0.05) before & after stabilization splint therapy. To sum up, CPI might be more effective than transcranial projection to reveal the changes between CR-CO discrepancies and stabilization splint might be more useful appliance for displaying the vertical changes, than the antero-posterior changes, of condylar position.