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1.
Psychiatry Investigation ; : 197-206, 2022.
Article in English | WPRIM | ID: wpr-926916

ABSTRACT

Objective@#Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). @*Methods@#We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the “population proportion” (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). @*Results@#We first constructed the “K-PERS-I,” comprising five factors based on the PPS, and then the “K-PERS-II” comprising six factors based on the ERS. The instruments accurately predicted participants’ status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. @*Conclusion@#The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.

2.
Psychiatry Investigation ; : 187-195, 2021.
Article in English | WPRIM | ID: wpr-903220

ABSTRACT

Objective@#To investigate the association between genetic polymorphisms of brain-derived neurotrophic factor (BDNF) or serotonin transporter gene-linked polymorphic region (5-HTTLPR) and tinnitus, and the mediating effects of psychological distress on this association. @*Methods@#Eighty-six patients experiencing tinnitus and 252 controls were recruited. The Tinnitus Handicap Inventory was used to assess the severity of tinnitus and the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory-II (BAI-II), and the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K) were used to assess psychological distress. We compared the association of BDNF rs6265 (Val66Met) and 5-HTTLPR variants in the two groups. The mediating effects of BDI-II, BAI-II, and BEPSI-K were examined using multiple regression analysis and validated by the Sobel test and bootstrapping. @*Results@#No significant differences were found between the groups regarding BDNF Val66Met and 5-HTTLPR, but the 5-HTTLPR variants trended toward association. Depressive symptoms appeared to act as a mediator on the relationship within the 5-HTTLPR s/s genotype and the severity of tinnitus. @*Conclusion@#Our findings provide a speculative idea on the association between the serotonergic system and tinnitus and suggest that depressive symptoms act as a mediator in tinnitus. Therefore, screening for depressive symptoms in patients with tinnitus is essential and intervention for depressive symptoms may help alleviate the severity of tinnitus.

3.
Psychiatry Investigation ; : 187-195, 2021.
Article in English | WPRIM | ID: wpr-895516

ABSTRACT

Objective@#To investigate the association between genetic polymorphisms of brain-derived neurotrophic factor (BDNF) or serotonin transporter gene-linked polymorphic region (5-HTTLPR) and tinnitus, and the mediating effects of psychological distress on this association. @*Methods@#Eighty-six patients experiencing tinnitus and 252 controls were recruited. The Tinnitus Handicap Inventory was used to assess the severity of tinnitus and the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory-II (BAI-II), and the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K) were used to assess psychological distress. We compared the association of BDNF rs6265 (Val66Met) and 5-HTTLPR variants in the two groups. The mediating effects of BDI-II, BAI-II, and BEPSI-K were examined using multiple regression analysis and validated by the Sobel test and bootstrapping. @*Results@#No significant differences were found between the groups regarding BDNF Val66Met and 5-HTTLPR, but the 5-HTTLPR variants trended toward association. Depressive symptoms appeared to act as a mediator on the relationship within the 5-HTTLPR s/s genotype and the severity of tinnitus. @*Conclusion@#Our findings provide a speculative idea on the association between the serotonergic system and tinnitus and suggest that depressive symptoms act as a mediator in tinnitus. Therefore, screening for depressive symptoms in patients with tinnitus is essential and intervention for depressive symptoms may help alleviate the severity of tinnitus.

4.
Article in English | WPRIM | ID: wpr-914082

ABSTRACT

The mainstay of schizophrenia treatment is pharmacological therapy using various antipsychotics including first- and second-generation antipsychotics which have different pharmacokinetic and pharmacodynamic property leading to differential presentation of adverse events (AEs) and treatment effects such as negative symptoms, cognitive symptoms and cormorbid symptoms. Major treatment guidelines suggest the use of antipsychotic monotherapy (APM) as a gold standard in the treatment of schizophrenia. However, the effects of APM is inadequate and less potent to achieve symptom remission as well as functional recovery in real practice which has been consistently reported in numerous controlled clinical trials, large practical trials, independent small studies and systematic reviews till today. Therefore antipsychotic polypharmacy (APP) regardless of the class of antipsychotics has been also commonly utilized for many reasons in real world practice. However, APP has also crucial pitfalls including increase of total psychotics including antipsychotics, high-doses of antipsychotics used, poor compliance, drug-drug interaction and risks for developing AEs, all of which are paradoxically related to poor clinical outcomes, whereas APP has also substantial advantages in reduction of re-hospitalization, severe psychopathology and targeted control of concurrent symptoms. Given currently limited therapeutic options, it is also important to properly utilize APP in order to maximize its clinical utility and minimize its risk for better treatment outcomes for patients with schizophrenia, based on risk/benefit with full understanding of pharmacological and clinical issues on APP. The present paper intends to address intriguing and important issues in the use of APP in real world practice.

5.
Article | WPRIM | ID: wpr-836019

ABSTRACT

Methods@#The study involved 226 people who participated in the Korean Early Psychosis Cohort Study, and we divided the participants into two groups according to the degree of trauma.Positive and Negative Syndrome Scale (PANSS) and Social and Occupational Functioning Assessment Scale (SOFAS) were compared at the start of the study and at 12 months after the treatment using paired t-test and repeated measures analysis of variance. @*Results@#At the beginning of the study, there was no significant difference between the two groups. But after 12 months of treatment, the high trauma group showed less improvement in PANSS negative score, general psychopathological score, total score, and SOFAS than the low trauma group. @*Conclusion@#In patients with early psychosis and at least moderate severity of premorbid trauma, negative symptoms, general psychopathological, and social and occupational functional improvements after treatment are less.

6.
Psychiatry Investigation ; : 163-174, 2020.
Article | WPRIM | ID: wpr-832502

ABSTRACT

Objective@#For the proper treatment of first-episode psychosis, assessment of treatment response, remission, relapse, and recovery is important. Therefore, the present study aimed to develop operational definitions of clinical outcomes in first-episode psychosis. @*Methods@#A questionnaire was developed by a panel of experts and underwent three revisions. The final survey was presented to 150 psychiatrists who were members of the Korean Society for Schizophrenia Research. Respondents selected factors that they believed were important to consider while defining treatment response, remission, relapse, and recovery using a 6-point Likert scale. Selected factors that constituted each definition were statistically extracted, and operational definitions were developed. @*Results@#A total of 91 experts responded to the survey. The extent of reduction in psychopathology, socio-occupational functioning, and duration of each state were the core factors of each definition. Outcomes obtained from discussions and consultations by experts have been summarized and proposed. @*Conclusion@#The criteria developed in this survey tended to be somewhat stricter than those used by other studies. The fundamental reason for this is that this survey focused on first-episode psychosis. A better understanding of each definition in first-episode psychosis is necessary to improve effective treatment outcomes.

7.
Article in English | WPRIM | ID: wpr-739466

ABSTRACT

OBJECTIVE: This study evaluated gender differences in the relationship between psychiatric distress and subjective tinnitus severity. METHODS: This cross-sectional study included 134 female and 114 male patients who visited the otology outpatient clinic at Seoul St. Mary’s Hospital for tinnitus from February to July 2015. Patients completed a series of instruments, including the Tinnitus Handicap Inventory, Beck Depression Inventory, Korean version of Brief Encounter Psychosocial Instrument (BEPSI-K), and visual analogue scales assessing various tinnitus characteristics (loudness, awareness, annoyance, and effect on life). RESULTS: Tinnitus severity did not significantly differ between the gender groups (p=0.632), and it correlated significantly with tinnitus characteristics and psychiatric distress. Partial correlations between tinnitus severity and depressive symptoms were stronger in males (r=0.411, p<0.01) than in females (r=0.304, p<0.01) while controlling for duration of tinnitus and tinnitus characteristics. However, stress (BEPSI-K) was positively correlated with tinnitus severity in only males (r=0.463, p<0.01). A multiple regression analysis revealed that effect of tinnitus on life, depressive symptoms, and stress were significantly associated with tinnitus severity in males, whereas only tinnitus annoyance and depressive symptoms were associated with tinnitus severity in females. CONCLUSION: Tinnitus severity was significantly correlated with depressive symptoms and stress, and there were gender differences in the relationship between tinnitus severity and psychiatric components. It is necessary to be vigilant of psychiatric symptoms among patients with tinnitus who visit the otology outpatient clinic, especially for male patients.


Subject(s)
Ambulatory Care Facilities , Cross-Sectional Studies , Depression , Female , Humans , Male , Otolaryngology , Seoul , Stress, Psychological , Tinnitus , Weights and Measures
8.
Article in English | WPRIM | ID: wpr-739463

ABSTRACT

Phentermine is a sympathomimetic amine, like amphetamine, which is one of the most often prescribed drugs for weight loss. Although exact mechanism of phentermine causing psychosis is still not clear, numerous reports already showed that phentermine can induce psychosis. Psychotic symptoms are generally resolved once the medications are stopped. In contrast, we present a case of a 25-years-old Asian female patient who developed psychotic symptoms repeatedly after phentermine administrations. This case suggests that phentermine can cause psychotic episodes repeatedly, resulting in chronic occupational and social impairment. Therefore, a precautious measure such as government regulations for physicians prescribing and an education for patients taking phentermine are urgently needed.


Subject(s)
Amphetamine , Asians , Education , Female , Government Regulation , Humans , Phentermine , Psychotic Disorders , Recurrence , Weight Loss
9.
Article in English | WPRIM | ID: wpr-71424

ABSTRACT

The present study details the rationale and methodology of the Korean Early Psychosis Cohort Study (KEPS), which is a clinical cohort investigation of first episode psychosis patients from a Korean population. The KEPS is a prospective naturalistic observational cohort study that follows the participants for at least 2 years. This study includes patients between 18 and 45 years of age who fulfill the criteria for one of schizophrenia spectrum and other psychotic disorders according to the diagnostic criteria of DSM-5. Early psychosis is defined as first episode patients who received antipsychotic treatment for fewer than 4 consecutive weeks after the onset of illness or stabilized patients in the early stages of the disorder whose duration of illness was less than 2 years from the initiation of antipsychotic treatment. The primary outcome measures are treatment response, remission, recovery, and relapse. Additionally, several laboratory tests are conducted and a variety of objective and subjective psychiatric measures assessing early life trauma, lifestyle pattern, and social and cognitive functioning are administered. This long-term prospective cohort study may contribute to the development of early intervention strategies and the improvement of long-term outcomes in patients with schizophrenia.


Subject(s)
Cohort Studies , Early Intervention, Educational , Humans , Life Style , Outcome Assessment, Health Care , Prospective Studies , Psychotic Disorders , Recurrence , Schizophrenia , Schizophrenia Spectrum and Other Psychotic Disorders
10.
Article in English | WPRIM | ID: wpr-108190

ABSTRACT

Tuberous sclerosis is not as rare as once thought and has high psychiatric comorbidities. However, bipolar or psychotic features associated with tuberous sclerosis have been rarely reported. This report first presents a tuberous sclerosis patient, resembling a schizoaffective disorder of bipolar type. A patient with known tuberous sclerosis displayed mood fluctuation and psychotic features. Her symptoms did not remit along with several psychiatric medications. After hospitalization, the patient responded well with lamotrigine and aripiprazole without exacerbation. As demonstrated in this case, tuberous sclerosis may also encompass bipolar affective or psychotic features. We would like to point out the necessity to consider bipolarity in evaluating and treating tuberous sclerosis.


Subject(s)
Aripiprazole , Comorbidity , Hospitalization , Humans , Psychotic Disorders , Tuberous Sclerosis
11.
Article in English | WPRIM | ID: wpr-210154

ABSTRACT

OBJECTIVE: Despite numerous atypical antipsychotics (AAP) available, many patients with schizophrenia still experience lack of efficacy and persistent side-effects. Switching from one AAP to another with a different side-effect profile has become a common clinical strategy. We aimed to investigate effect of switching to amisulpride in patients who showed suboptimal effect and/or tolerability to current antipsychotics treatment. METHODS: This was a 6-week, prospective, multicenter, open-label, flexible-dose study in patients with schizophrenia. Switching to amisulpride was achieved using cross-titration within 7 days (day 1: 300 mg on day 1 then flexibly dosed 400–800 mg/day). The primary end-point measure was proportion of patients achieving improvement in clinical benefit at week 6 based on Clinical Global Impressions-Clinical Benefit (CGI-CB). Secondary endpoints included change in scores in CGI-CB, CGI-Severity (CGI-S), Subjective Satisfaction Scores (SSS), Brief Psychiatric Rating Scale (BPRS), and Simpson and Angus Rating Scale. RESULTS: Among 37 patients switched to amisulpride, 76% completed study and 56.8% had clinical benefit measure by CGI-CB. CGI-CB and CGI-S scores showed significant improvement at week 6 compared to baseline (mean changes of CGI-CB and CGI-S scores: −1.7+1.0, p<0.0001 and −0.6±0.0, p=0.001, respectively). SSS scores also improved significantly (mean change: 2.1±2.6, p<0.0001). Mean weight of patients significantly lowered compared to baseline (mean change: −1.2±2.0, p<0.0001). CONCLUSION: Patients with schizophrenia who showed suboptimal efficacy or tolerability with their current antipsychotics and thereby switched to amisulpride resulted in clinical benefit in terms of both improved efficacy and tolerability. The small sample size limits generalizability of the study results.


Subject(s)
Antipsychotic Agents , Brief Psychiatric Rating Scale , Humans , Prospective Studies , Sample Size , Schizophrenia
12.
Psychiatry Investigation ; : 173-178, 2014.
Article in English | WPRIM | ID: wpr-225630

ABSTRACT

OBJECTIVE: Cigarette smoking is associated with a variety of health problems including cardiovascular, pulmonary, neoplasms, endocrinopathies including diabetes, the metabolic syndrome, and chronic inflammation. Adiponectin is an adipocyte-derived plasma protein that is closely associated with insulin sensitivity and the metabolic syndrome. The aim of this study was to evaluate the changes of plasma adiponectin levels after smoking cessation. METHODS: Thirty seven smokers that wanted to stop smoking without any nicotine replacement therapy or medication were recruited for this study. Fifteen smokers succeeded in stopping smoking (validated by urine cotinine levels < or =50 ng/mL) and 22 smokers failed. Therefore, only the 15 that succeeded were included in the analysis. The plasma adiponectin levels were determined using a commercially available enzyme-linked immunosorbent assay. RESULTS: The mean age of the successful 15 was 35+/-9.3 years old. They were all males. The daily smoking habit was a mean of 13.5+/-5.4 cigarettes per day. The mean Nicotine Dependence Syndrome Scale (NDSS) and Fagerstrom Test for Nicotine Dependence (FTND) scores were 55.6+/-9.6 and 2.9+/-1.9. During the study period of three months, the mean body mass index (BMI), body fat mass (BFM), waist-hip ratio (WHR) and body weight increased by 1.1 kg/m2, 3.0%, 0.02%, and 2.9 kg, respectively. The baseline mean adiponectin level in the subjects was 11.9+/-5.2 mg/L. The mean adiponectin levels measured at one and three months were 16.0+/-5.1 mg/L and 14.7+/-4.5 mg/L respectively. The mean plasma adiponectin levels of the successful group was significantly increased after four weeks when compared to the baseline (z=-2.401, p=0.016). However, the decrease in plasma adiponectin levels at one and three months was not statistically significant. CONCLUSION: Even though the decrease over the next two months was not significant, these findings, the increase of plasma level of adiponectin after smoking cessation, provide preliminary data for future research on the possible mechanisms associated with smoking cessation and changes in body metabolism.


Subject(s)
Adiponectin , Adipose Tissue , Body Mass Index , Body Weight , Cotinine , Enzyme-Linked Immunosorbent Assay , Ghrelin , Humans , Inflammation , Insulin Resistance , Leptin , Male , Metabolism , Nicotine , Plasma , Smoke , Smoking Cessation , Smoking , Tobacco , Tobacco Products , Tobacco Use Disorder , Waist-Hip Ratio
13.
Article in Korean | WPRIM | ID: wpr-59313

ABSTRACT

Neuroacanthocytosis is a rare hereditary disorder characterized by various neurological symptoms and the presence of abnormal red blood cell called acanthocytosis. Degeneration of striatum, which accounts for characteristic motor and psychiatric symptoms, mainly attributes to the pathology of neuroacanthocytosis. We experienced a case of chorea-acanthocytosis. He was a 50 year-old-man who presented with orofacial dyskinesia, dysarthria, uncontrolled lip biting, generalized choreic movements and sensorymotor polyneuropathy. He was also suffered from obsessive eating behavior, disinhibition, impulsivity and sleep disturbance. After antipsychotic medication, his psychiatric problems were improved. Clinicians must consider psychiatric managements of progressive neurological disorder for patients' quality of life and reducing their caregiver's burden.


Subject(s)
Abetalipoproteinemia , Antipsychotic Agents , Bites and Stings , Chorea , Dysarthria , Erythrocytes , Feeding Behavior , Humans , Lip , Movement Disorders , Nervous System Diseases , Neuroacanthocytosis , Polyneuropathies , Quality of Life
14.
Article in Korean | WPRIM | ID: wpr-156500

ABSTRACT

OBJECTIVE: Haloperidol, a typical antipsychotic, has been the preferred agent for the pharmacological treatment of delirium. Recent studies have shown that atypical antipsychotics can be as effective as haloperidol in managing delirium. However, there are few comparative studies between atypical antipsychotics in the treatment of delirium. We investigated the efficacy and side effects of aripiprazole and quetiapine for the treatment of patients with delirium. METHODS: Forty two inpatients with delirium according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Text Revision and Korean version of Delirium Rating Scale-Revised-98 (K-DRS-98) criteria were included. They were assigned to either aripiprazole or quetiapine groups, with a flexible dosing schedule. K-DRS-98 and Clinical Global Impression-Severity (CGI-S) were used for evaluating the severity of delirium. The degree of sedation was assessed by using the Richmond Agitation-Sedation Scale (RASS) six times per day. The severity of side effect was evaluated with the Drug-Induced ExtraPyramidal Symptoms Scale and the Barnes Akathisia Rating Scale. K-DRS-98 and RASS were conducted daily until the remission of delirium while other measurements were conducted twice at the point of baseline and remission. For statistical analysis, t-test, Fisher's exact test, Mann-Whitney test, analysis of covariance were conducted. RESULTS: The scores of K-DRS-98 in both groups significantly decreased after treatment (p or =-3 (p=0.034). The scores on sleep cycle of K-DRS-98-severity more significantly decreased in the quetiapine group than aripiprazole group (F=4.291, p=0.045). There were no significant side effects both groups including extrapyramidal symptoms. CONCLUSION: These results suggest that both aripiprazole and quetiapine appear to be effective and tolerable in the treatment of delirium. Aripiprazole may be less sedative than quetiapine and it may be more useful than aripiprazole in sleep problem of delirium. To validate our results, further studies with double-blind, placebo-controlled with a large sample will be required.


Subject(s)
Antipsychotic Agents , Appointments and Schedules , Delirium , Diagnostic and Statistical Manual of Mental Disorders , Dibenzothiazepines , Haloperidol , Humans , Inpatients , Piperazines , Psychomotor Agitation , Quinolones
15.
Article in Korean | WPRIM | ID: wpr-105360

ABSTRACT

No abstract available.

16.
Psychiatry Investigation ; : 224-227, 2010.
Article in English | WPRIM | ID: wpr-148395

ABSTRACT

Post-menopausal women experience variable biological and psychological changes. The effect of reduced levels of estrogen can effect on post-menopausal depression. Estrogen triggers physiological responses by binding to the estrogen receptor (ER). Two subtypes of ER, ERa and ERb are now known. We investigated the significance of ERa and ERb polymorphisms and post-menopasal depression in this study. Forty three women with post-menopausal depression and 63 post-menopausal women without depression as normal controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate genotypes of ERa and ERb polymorphisms. Genotypes of PvuII and XbaI polymorphism of ERa receptor were significantly different in patients with post-menopausal depression comparing with controls. Genotypes of ERb did not show association with post-menopausal depression. Our study showed that ERa receptor polymorphism had an association with depression in post-menopausal women. It suggests that investigation of ER genes and their functions might be important for understanding pathophysilogical mechanism of post-menopausal depression.


Subject(s)
Depression , Estrogens , Female , Genotype , Humans , Menopause
17.
Article in English | WPRIM | ID: wpr-196693

ABSTRACT

When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2alpha phosphorylation. Transcription of two downstream targets of eIF2alpha, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuronal differentiation of mouse embryonic stem (mES) cells. Finally, chemical endoplasmic reticulum (ER) stress inducers, thapsigargin, tunicamycin, and brefeldin A, dose-dependently increased both mRNA and protein expressions of NF-L, and, its expression was specific to BIP-positive rBMSCs. Our results showing the induction of UPR during neuronal differentiations of rBMSCs and mES cells as well as NF-L expression by ER stress inducers strongly suggest the potential role of UPR in neuronal differentiation.


Subject(s)
Activating Transcription Factor 4/genetics , Animals , Apoptosis/drug effects , Bone Marrow Cells/cytology , Cell Differentiation , Culture Media/pharmacology , Embryonic Stem Cells/cytology , Endoplasmic Reticulum/genetics , Gene Expression/drug effects , Heat-Shock Proteins/genetics , Mice , Microtubule-Associated Proteins/genetics , Molecular Chaperones/genetics , Nerve Tissue Proteins/genetics , Neurofilament Proteins/genetics , Neurons/cytology , Nuclear Proteins/genetics , Protein Folding , Rats , Stromal Cells
18.
Psychiatry Investigation ; : 102-105, 2008.
Article in English | WPRIM | ID: wpr-33386

ABSTRACT

OBJECTIVE: We previously reported an association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). This paper expands upon previous findings suggesting that DTNBP1 variants may play a role in the response to acute mood stabilizer treatment. METHODS: A total of 45 BID patients were treated with antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52 (+/-19.87) days. After treatment, the patients were evaluated using the Clinical Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C). RESULTS: There was no association between the variants investigated and response to mood stabilizer treatment, even after considering possible stratification factors. CONCLUSION: Although the small number of subjects is an important limitation in our study, DTNBP1 does not seem to be involved in acute antimanic efficacy.


Subject(s)
Antimanic Agents , Bipolar Disorder , Humans , Pharmacogenetics , Valproic Acid
19.
Article in Korean | WPRIM | ID: wpr-41840

ABSTRACT

OBJECTIVE: Human papillomaviruses are associated with the majority of cervical cancers. There is a wide effort focused on searching for the target of the involvement of p53-independent HPV-16E6 interacting proteins. We identified Cdc7 (cell division cycle 7-related protein kinases) as a binding partner of E6 and investigated its biological function in cervical cancer cells. METHODS: The baits, E6, fused to the LexA-BD subunit using pBTM116 vector were used to screen an oligoneucleotide primed human HeLa cDNA library cloned in pGAD10 vector. Yeast two-hybrid screens were performed. Immunoprecipitation assay was performed to determine whether E6-Cdc7 interaction occurred. Cells treated with siRNA were analysed by flow cytometry. RESULTS: We have delinated the interactions of E6 with five proteins, namely the IRF-3 (interferon regulatory factor-3), PRKCL?1 (protein kinase C-like 1), PIST (PDZ/coiled-coil domain binding gene), BARD1 (BRCA1 assocated ring domain 1), and Cdc7. The in vitro result of the interaction between E6 and Cdc7 was confirmed by immunoprecipitation experiments. Down-regulation of Cdc7 by small interfering RNA in HeLa cell lines causes an abortive S phase, leading to cell death. CONCLUSION: We have identified the new protein of interaction with HPV E6, Cdc7 kinase. It has been implicated in S phase signaling of cell cycle and the inhibition of Cdc7 induced cell death. But, further investigation is needed to know the biologic function of Cdc7 kinase in cervical carcinogenesis.


Subject(s)
Carcinogenesis , Cell Cycle , Cell Death , Clone Cells , Down-Regulation , Flow Cytometry , Gene Library , HeLa Cells , Humans , Immunoprecipitation , Phosphotransferases , RNA, Small Interfering , S Phase , Uterine Cervical Neoplasms , Yeasts
20.
Article in Korean | WPRIM | ID: wpr-720991

ABSTRACT

BACKGROUND: Blood transfusion is important for life saving treatment in many patients with tolerable adverse effects. Some data suggest that transfusions might cause an increased risk for post-operative infections and a higher relapse or mortality rate in cancer patients. We investigated whether immune dysfunction might result after transfusions from the cellular components. METHODS: We studied 5-week-old mice BALB/c (H-2d, donor), C3H/He (H-2k, recipient), and C57/BL (H-2b, third party). We obtained irradiated spleen cells (SP) from the BALB/c or C57/BL, and injected them into the C3H/He with intraperitoneal IL-2 administration. After 24 hours, we obtained bone marrow (BM), thymus and SP. We identified mixed lymphocyte proliferation (MLR) by the BrdU method and we used irradiated BALB/c SP, as a stimulator for that trial. For the analysis of immune cells, we analyzed the cell surface markers from each organ. For cytokines, we identified TNF-alpha, IFN-gamma, TGF-beta, and IL-10 by ELISA from the supernatant of the MLR. RESULTS: The cell proliferation decreased according to specific H-2 complexes. There were increased CD4+CD25+ cells in the thymus. For the paracrine effects, the B-C3H SP showed ratio-dependent inhibitory effects, although the C-C3H SP inhibited some cell proliferation. There was no difference in the IFN-gamma, TNF-alpha and TGF-beta between the control and experimental groups. However, IL-10 was higher in the 1:10 ratio mixture in the control and transfused SP compared to the other groups. CONCLUSION: The results of this study suggested that the cellular components in transfusions might contribute to the immune regulatory effects by CD4+CD25+ cells after 24 hours.


Subject(s)
Animals , Blood Transfusion , Bone Marrow , Bromodeoxyuridine , Cell Proliferation , Cytokines , Enzyme-Linked Immunosorbent Assay , Humans , Immunomodulation , Interleukin-10 , Interleukin-2 , Lymphocytes , Mice , Mortality , Recurrence , Spleen , Thymus Gland , Transforming Growth Factor beta , Tumor Necrosis Factor-alpha
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