The Effects of Sex and Estrogen on Radiographic Progression of Ankylosing Spondylitis in Korean Patients

. Ankylosing spondylitis (AS) is a chronic inflammatory disease with obvious male preponderance. Males show more severe radiographic manifestations compared with females. This study aimed to evaluate the effects of sex and estrogen on the radiographic progression of AS. Methods. A total of 101 patients with AS were included in this study. All of the radiographs were scored using the modified Stoke AS Spine Score (mSASSS). Serum levels of 17β-estradiol (E2), dickkopf-1 (Dkk1), and leptin were detected by enzyme-linked immunosorbent assay. The generalized estimating equations model was used to evaluate factors associated with spinal radiographic progression. Results. The mean age at disease onset was 27.3±10.7 years, and 16 patients (15.8%) were female. In the multivariable analysis, body mass index (β-coefficient=0.12; β=0.047) and levels of Dkk1 (β-coefficient=−0.11; β＜0.001), and female (β-coefficient=−1.40; β=0.001) were associated with radiographic progression. Among male patients with AS, baseline C-reactive protein (β=0.11; β=0.005) and mSASSS (β=0.21; p=0.030) were also associated with radiographic progression. E2 and leptin levels were not significantly related to the radiographic progression. Conclusion. Although female patients were associated with less radiographic progression in AS, there was no significant relationship between serum estrogen level and radiographic progression. Results of current study suggests that genetic factors or other environmental factors associated with female may influence radiographic progression in patients with AS.

Neuronal Responses in the Globus Pallidus during Subthalamic Nucleus Electrical Stimulation in Normal and Parkinson's Disease Model Rats

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.

Extracellular High-Mobility Group Box 1 is Increased in Patients with Behcet's Disease with Intestinal Involvement

High-mobility group box 1 (HMGB1) protein has been demonstrated to play an important role in chronic inflammatory diseases including rheumatoid arthritis, and systemic lupus erythematosus. This study investigated the association between extracellular HMGB1 expression and disease activity, and clinical features of Behcet's disease (BD). Extracellular HMGB1 expression in the sera of 42 BD patients was measured and was compared to that of 22 age- and sex-matched healthy controls. HMGB1 expression was significantly increased in BD patients compared to healthy controls (78.70 +/- 20.22 vs 10.79 +/- 1.90 ng/mL, P = 0.002). In addition, HMGB1 expression was significantly elevated in BD patients with intestinal involvement compared to those without (179.61 +/- 67.95 vs 61.89 +/- 19.81 ng/mL, P = 0.04). No significant association was observed between HMGB1 concentration and other clinical manifestations, or disease activity. It is suggested that extracellular HMGB1 may play an important role in the pathogenesis of BD.

Slug suppression induces apoptosis via Puma transactivation in rheumatoid arthritis fibroblast-like synoviocytes treated with hydrogen peroxide

Inadequate apoptosis contributes to synovial hyperplasia in rheumatoid arthritis (RA). Recent study shows that low expression of Puma might be partially responsible for the decreased apoptosis of fibroblast-like synoviocytes (FLS). Slug, a highly conserved zinc finger transcriptional repressor, is known to antagonize apoptosis of hematopoietic progenitor cells by repressing Puma transactivation. In this study, we examined the expression and function of Slug in RA FLS. Slug mRNA expression was measured in the synovial tissue (ST) and FLS obtained from RA and osteoarthritis patients. Slug and Puma mRNA expression in FLS by apoptotic stimuli were measured by real-time PCR analysis. FLS were transfected with control siRNA or Slug siRNA. Apoptosis was quantified by trypan blue exclusion, DNA fragmentation and caspase-3 assay. RA ST expressed higher level of Slug mRNA compared with osteoarthritis ST. Slug was significantly induced by hydrogen peroxide (H2O2) but not by exogenous p53 in RA FLS. Puma induction by H2O2 stimulation was significantly higher in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. After H2O2 stimulation, viable cell number was significantly lower in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. Apoptosis enhancing effect of Slug siRNA was further confirmed by ELISA that detects cytoplasmic histone-associated DNA fragments and caspase-3 assay. These data demonstrate that Slug is overexpressed in RA ST and that suppression of Slug gene facilitates apoptosis of FLS by increasing Puma transactivation. Slug may therefore represent a potential therapeutic target in RA.

Criterion-Related Validity of the Critical Patients' Severity Classification System Developed by the Hospital Nurses' Association / 성인간호학회지

PURPOSE: This study was conducted to test criterion-related validity of the Critical Patients' Severity Classification System (CPSCS) developed by the Hospital Nurses' Association by examining relationships with brain injury severity measured by Glasgow Coma Scale (GCS), recovery state measured by Glasgow Outcome Scale (GOS), and days of stay in ICU of brain injury patients. METHODS: Prospective correlational research design was adopted by including 194 brain injury patients admitted to ICU of one university hospital. RESULTS: The score of CPSCS appeared to significantly discriminate the severity of brain injury. Among nursing activities in CPSCS, Respiratory therapy, IV Infusion and Medication, Monitoring, Activities of Daily Living (ADL), Treatment and Procedure were significant to discriminate the severity of brain injury. Respiratory therapy, Vital Signs, and Monitoring appeared to significantly discriminate the recovery states of 1- and 3-months. Nursing activities significantly contributed to predict the days of ICU stay were Respiratory therapy, ADL, and Teaching and Emotional Support. CONCLUSION: CPSCS developed by the Hospital Nurses Association appeared to be valid to discriminate or predict brain injury severity, recovery states, and days of stay in ICU for brain injury patients.

Abrogation of U266 Multiple Myeloma Cell Proliferation Via Inhibition of NF-kappaB Activation by Curcumin

BACKGROUND: Curcumin is a naturally occurring biologically active compound, and it has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. It is known for its anti-proliferative and proapoptotic effects in several cancer cells. Curcumin's effects on the mechanisms of cell survival and the expression of various cytokines were investigated in U266 cells and the in vivo effects of curcumin were examined using an animal model. METHODS: Cell proliferation assay and flow cytometry were used to examine cell proliferation, along with cell cycle analysis. The protein expressions were analyzed by Western blotting and the expressed levels of cytokines were analyzed by the ELISA method. RESULTS: Curcumin inhibited U266 cell growth in a dose-dependent and time-dependent manner. Cell cycle analysis showed an increased sub-G1 phase, a down regulated cyclinD1 expression and an induced p21 expression. Apoptosis induced a down regulated procaspase 3 expression and it induced cleaved PARP. Curcumin inhibited the IL (interleukin)-6 induced cell signal pathway via decreasing the STAT1 an 3, Erk cyclinD1 and c-myc expressions. Also, administration of 25mg/kg curcumin to a U266 animal model inhibited cancer cell engraftment in the bone marrow and it decreased the IL-6, sIL-6R and IL-8 expression levels. CONCLUSION: Curcumin induced cell cycle arrest and apoptosis and it inhibited the IL-6 mediated signal transduction pathways in U266 cells. Similar to the in vitro results, curcumin inhibited cancer cell proliferation and the expression of cytokine in vivo.

Regulation of aggrecanase-1 and aggrecanase-2 expressions by hypoxia and cytokines in rheumatoid fibroblast-like synoviocytes / 대한내과학회지

BACKGROUND: While aggrecanases (aggrecanase-1 and aggrecanase-2) are substantially responsible for cartilage aggrecan breakdown in rheumatoid arthritis (RA), not much information is available on the regulation or expression of the two key aggrecanases in rheumatoid fibroblast-like synoviocytes (FLS). The aim of this study is to determine the effect of hypoxia and several cytokines on the expression of the aggrecanases in rheumatoid FLS. METHODS: FLS obtained from RA patients were cultured under hypoxic condition for 24 hours. Quantitative polymerase chain reaction assays for mRNA expression of aggrecanase-1 and aggrecanase-2 were performed on FLS cultured under hypoxia. Additionally, to see the effect of various cytokines, same experiments were conducted after treating FLS with IL-1beta, IL-6, EGF, TGF-beta and TNF-alpha, compared with control. RESULTS: Hypoxia significantly increased both aggrecanase-1 and -2 mRNA expression in rheumatoid FLS compared with normoxia. IL-1beta, IL-6, EGF, TGF-beta and TNF-alpha upregulated the mRNA expression of aggrecanase-1. Both EGF and TGF-beta upregulated the mRNA expression of aggrecanase-2, but TNF-alpha significantly downregulated the mRNA expression of aggrecanase-2. CONCLUSIONS: These results showed upregulation of aggrecanase-1 and -2 by hypoxia and differential regulation of aggrecanase-1 and -2 by various cytokines in rheumatoid FLS. It suggests that hypoxia and cytokines enhance the aggrecanase activity of RA FLS and contribute to joint destruction.

Apoptosis Induction by Curcumin in Human Myelogenous Leukemia Cell Lines

BACKGROUND: Curcumin, a naturally occurring biologically active compound extracted from rhizomes of Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. The effects and possible mechanism of this agent were investigated on 2 human myelogenous leukemic cell lines. METHODS: K562 and KG-1 cells were the two cell lines selected. The MTT assay and flow cytometry were used to assess the cytotoxicity and for cell cycle analysis, respectively. The protein expressions were analyzed by Western blotting; the caspase activity was also checked. RESULTS: Both cell lines showed dose-dependent susceptibility to curcumin, and the cell cycle analysis showed an increased sub-G1 phase in the KG-1 cells. In the K562 cell, curcumin down regulated the expressions of PCNA (proliferating cell nuclear antigen) and cyclins D1 and B1. The expression of Akt was also down-regulated, but caspase-3 was activated to induce cleaved PARP (polyadenosine ribose polymerase) and apoptosis. However, the expression of phospho-Erk was unaffected. Co-treatment of cyclosporin A (CsA) with curcumin resulted in an attenuation of apoptosis in the K562 cells, implying curcumin-induced apoptosis is dependent on the release of cytochrome c from the mitochondria. CONCLUSION: Curcumin induced cell cycle arrest and apoptosis in both human myelogenous leukemic cell lines, with the apoptosis appearing to be dependent on the release of cytochrome c from the mitochondria.

Expressions of Leukemia Inhibitory Factor (LIF): Comparison of Normal Pregnancy and Recurrent Abortion / 대한산부인과학회잡지

OBJECTIVE: Successful implantation depends on a complex interaction between the developing blastocyst and the endometrium. Among the steroid hormones, growth factors, and cytokines which participate in preparing the uterus for implantation, leukemia inhibitory factor (LIF) plays an essential role in implantation. We compared the expression of LIF in normal pregnancies to that of recurrent abortions in placenta to elucidate whether spontaneous abortion and expression of LIF has correlation. METHODS: Placental tissues from normal pregnancies and recurrent abortions were fixed and embedded in paraffin. Standard immunohistochemical staining was used to identify LIF. RESULTS: LIF expressions on cytotrophoblast of recurrent abortion were lower than those of normal pregnancy. There were no expressions on syncytiotrophoblast and stroma in the both groups. In the decidua and gland, LIF was expressed in mild degree and there were no differences in LIF expression between normal pregnancy and recurrent abortion. CONCLUSION: LIF expression on cytotrophoblast of recurrent abortion was lower than that of normal pregnancy. LIF may provide paracrine and autocrine signals to both embryonic tissues and uterine epithelium during implantation. The dysfunction of LIF production may be a cause of the unexplained recurrent abortions.

The Effect of Leukemia Inhibitory Factor in Decidualizing Human Endometrial Stromal Cells / 대한산부인과학회잡지

OBJECTIVE: Decidualization of endometrial stromal cells is essential for a successful implantation of the embryo. The process of decidualization can be modulated by sex steroids, growth factors and cytokines. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the interleukin-6 family and has different biological actions in various tissue systems. Recently, LIF has been reported as an important factor for adequate decidualization of endometrium. However, the effect on production of prolactin (PRL), known as the decidualization marker, are not clearly understood. The objective of this study was to determine whether LIF is capable of modulating prolactin production during 8-bromo (Br)-cAMP induced decidualization in vitro. METHODS: Human endometrial stromal cells were cultured and decidualization was induced by 0.5 mM 8-Br-cAMP. Phase contrast microscopy was used to verify morphological changes associated with differentiation in vitro in response to 8-Br-cAMP. Both stromal cells exposed to 8-Br-cAMP and cells not exposed to 8-Br-cAMP were also incubated with LIF (10 ng/mL). PRL levels in each supernatant were measured by a commercial PRL ELISA kit. Immunostaining and reverse transcription-polymerase chain reaction (RT-PCR) for PRL were performed. RESULTS: The concentration of PRL in the supernatant increased significantly in the cells treated with 8-Br-cAMP plus LIF (10 ng/mL) at culture day 6 compared with the others. The results of immunohistochemical staining reflected that of immunoassay. The PRL genes are expressed in the decidualized stromal cells treated with 8-Br-cAMP. No PRL mRNA was detectable in the absence of the 8-Br-cAMP. The intensity of the PCR band measured by densitometry is stronger in the cells treated with 8-Br-cAMP plus LIF than that with the others. CONCLUSION: These results suggested that LIF increased the production of PRL in decidualizing human endometrial stromal cells and may play a role in preparing the human endometrium for implantation through the promotion of PRL production.

The study on the regression time and pattern of the serum beta-hCG in gestational trophoblastic disease / 대한산부인과학회잡지

OBJECTIVES: It is now conventional practice to use human chorionic gonadotropin (hCG) as the marker of tumor activity in gestational trophoblastic disease (GTD). The interpretation of serial serum beta-hCG regression patterns is important in monitoring the course of the disease. The purpose of this study was to establish a regression time and pattern of the serum beta-hCG in which GTD is divided into hydatidiform mole and malignant trophoblastic disease. MATERIALS & METHODS: During the period from January 1990 through December 2000, 46 patients with GTD were histopathologically diagnosed and treated at the department of Obstetrics and Gynecology in Hanyang University Hospital. For the purpose of analysis and comparison, patients were divided into 19 cases of hydatidiform mole and 27 cases of malignant trophoblastic disease which was subdivided into nonmetastatic (17) and metastatic (10). Patients were followed clinically and by weekly estimations of quantitative serum beta-hCG until negative (<3 mIU/ml). After three consecutive negative beta-hCG, serum beta-hCG were drawn monthly in all patients for one year. The level of serum beta-hCG was detected by two-site sandwich immunoassay (Chiron Diagnostics Automated Chemiluminescence System 180). The obtained data were analyzed using t test and ANOVA test by SPSS. RESULTS: The incidence of the GTD compared with delivery was one per 182.7 deliveries. The mean value of serum beta-hCG regression time in hydatidiform mole was 12.8+/-1.1 (SEM) weeks (7.0-26.0 weeks) and 17.9+/-1.4 (SEM) weeks (8.0-34.0 weeks) in malignant trophoblastic disease. The regression time was significantly shorter in hydatidiform mole than that of malignant trophoblastic disease (P<0.01). The differences of mean value of serum beta-hCG regression time between the groups with nonmetastatic (18.0 weeks) and metastatic (17.8 weeks) were not statistically significant(P =0.946). The mean values of serum beta-hCG in both hydatidiform mole and malignant trophoblastic disease declined following a log-normal distribution. CONCLUSIONS: The regression pattern of serum beta-hCG in present study was similar to that of which in Western and also similar to that of which in Korea in 1980s. The present study supports the continued use of individual patients serum beta-hCG regression curve to make treatment decision and to recognize malignant trophoblastic disease promptly.

Induction of Prostate Apoptosis by Low Dose Terazosin in Benign Prostatic Hyperplasia / 대한비뇨기과학회지

No abstract available.

Increased Expression of Caveolin-1 in Renal Cell Carcinoma / 대한비뇨기과학회지

No abstract available.

Quantitative Measurement of Hepatitis B Virus DNA by Competitive Nested Polymerase Chain Reaction / 대한임상병리학회지

BACKGROUND: We performed competitive nested polymerase chain reaction (PCR) to evaluate the clinical utility of quantitative measurement of HBV DNA by PCR and it's correlation with other serologic hepatits B markers. Because hepatitis markers such as HBsAg, HBeAg, anti-HBe can not accurately reflect the replication of hepatitis B virus (HBV). METHODS: The internal standard was generated from the HBV core gene by point mutation, which would result in restriction site for the restriction enzyme Eco RI and performed competitive nested PCR followed by densitometric scanning of the amplified products of agarose gel. RESULTS: The sensitivity of nested PCR was 5 molecules in direct observation of agarose gel, but because of the background effect as taking polaroid photo graph it was 50 molecules by using densitometer. When DNA pellets for original 250 microL serum were diluted with 40 microL distilled water the low detection limit was 5.0 x10(3) molecules/microL, however it could be lowered when less diluted. Lower detection limit of densitometer was 6.25 pg by twofold serial dilution of 100 pg of purified HBV DNA PCR products, and regression showed y=0.93x-0.33 (y : density, x : concentration, 6.25 pg considered as 6.25 density). The reproducibility of the densitometer from high concentration was 4.3 +/-0.6 x10(6) molecules/microL(mean +/-SD, CV 14%), and low concentration was 3.7 +/-0.7 x10(4) molecules/microL(mean +/-SD, CV : 20%) Higher concentration of HBV DNA in HBeAg positive cases comparing with HBeAg negative cases was statistically significant (p<0.01). There was no correlation between HBV DNA concentration and serum value of alanine aminotransferase. CONCLUSION: Quantification of HBV DNA should be very useful in clinical follow-up of Post-therapy Patients and in anticipating Prognosis and infectivity of the disease, especially in cases of atypical hepatitis B and hepatitis B without seroconversion of routine hepatitis B markers. The shortcoming of the method seemed to be a rough estimate of HBV concentration as measuring the ratio of specimen/internal standard of two consecutive concentration among 10 folds serially diluted internal standard.

Serum Angiotensin-Coverting Enzyme Levels in Coal Worker's Pneumoconiosis / 영남의대학술지

We measured fasting Serum Angiotensin-Converting Enzyme (SACE) in 100 healthy controls and 75 coal worker's pneumoconiosis (CWP) patients by a commercial kits (ACEcolor®, Fujirio Inc., Japan) and evaluated this manual method. The linear range extends to an activity of 80U/L. Precision on a commercial control serum (ACE control-N®, Sigma Co.) with a mean value of 9.47U/L yielded a within-run and between-run CVs are 5.6% (N=15) and 6.9% (N=14) respectively. Save in 75 CWP was 20.3±5.7U/L (mean±s.d.); higher than in healthy controls (13.4±3.9U/L, P<0.01). No correlation was found between SACE, sex, and age. The results suggest that the measurement for SACE and follow-up SACE in coal workers may be a useful diagnostic tools for CWP.

Medium Supplementation and Atmospheric Condition for Growth of Campylobacter pylori isolated from gastric biopsy tissue / 영남의대학술지

Experiments were conducted to define the optimal constituents of culture medium and atmospheric condition for growth of Campylobacter pylori. Two clinical isolates were streaked onto various media, incubated in two different atmospheric conditions (microaerophilic condition and carbon dioxide incubator), and growth was assessed semiquantitatively according to relative colony size and extent of growth through the streak. The growth obtained on Campy media, composed of GC agar base plus 1% hemoglobin, 0.2% activated charcoal, 1% IsoVitaleX, vancomycin 6mg /L nalidixic acid 20mg/L and amphotercin 2 mg/L, was used as reference. Our conclusions were as follows: Tryptic soy agar base was not acceptable for the growth of C. pylori. The organism grew in both atmospheric conditions, but generally showed a scantier growth in the carbon dioxide incubator than under the microaerophilic condition, however GC agar containing 1% hemoglobin and 0.2% activated charcoal supported well the growth of C. pylori in the carbon dioxide incubator. The authors have found that the GC agar base supplemented with 1% hemoglobin and 0.2% charcoal was the most satisfactory medium and a microaerophilic condition was optimal atmospheric condition for the growth of Campylobacter pylori in this study.

Diagnostic Significance of Cold Agglutinin and Antimycoplasma Antibody for Mycoplasma pneumoniae Infection / 영남의대학술지

A study to evaluate the diagnostic significance of M. pneumoniae Infection by measurements of cold agglutinin and antimycoplasma antibody titers is performed with 191 pediatric patients who have visited Yeungnam University Hospital during the period through January to July, 1987. Forty eight of 191 cases made follow up tests feasible. The results obtained are as follows: 1. It is necessary to perform routine combined measurements of cold agglutinin and antimycoplasma antibody titers for the all pediatric pneumonia caser since a large proportion of pneumonia in children is caused by M. pneumonia. 2. For the diagnosis of M. pneumoniae Infection, measurements of cold agglutinin titer alone seems to be less significant than to check both cold agglutinin and antimycoplasma antibody titers. 3. The measurement of antimycoplasma antibody titer appeared to be more specific than cold agglutinin test in the diagnosis of M. pneumoniae Infection. 4. The present study urges the necessity of follow up study of cold agglutinin and antimycoplasma antibody titer for those who initially presented with normal titers in both tests, but are clinically suspected for M. pneumoniae Infection.

Statistical Analysis of Antimicrobial Susceptibility Tested on Various Clinical Isolates of Bacteria / 영남의대학술지

Antimicrobial susceptibility of the bacterial strains isolated from clinical specimens during the period from June, 1983 to June, 1986 in Yeungnam Medical Center was studied and the following results were obtained. 1. Staphylococcus aureus was highly susceptible to cephalothin and its susceptibility to methicillin was gradually reduced. 2. Streptococcus strains except enterococcus were generally susceptible to penicillin, while most enterococci were susceptible to only ampicillin. 3. Gram-negative rods including Escherichia coli were highly susceptible to amikacin and tobramycin. 4. Serratia were generally less susceptible to the amtimicrobials tested than other Enterobacteriaceae. Among them, Serratia marcescens showed the highest susceptibility to amikacin and chloramphenicol. 5. Pseudomonas aeruginosa revealed the highest susceptibility to amikacin and tobramycin and moderate susceptibility to carbenicillin and gentamycin. 6. Acinetobacter calcoaceticus revealed low susceptibility to most antimicrobials tested, showing only 30% susceptibility to amikacin, tobramycin and gentamycin in 1986.

Diagnostic Significance of Total Lactate Dehydrogenase(LD) and LD Isoenzyme Measurement in the Body Fluids / 영남의대학술지

Body fluid Lactate dehydrogenase and its isoenzyme Measurement was performed in 132 patients: 8 cases with peritonitis, 21 cases with malignant ascites, 43 cases with liver cirrhosis, 48 cases with tuberculous pleuritis, 12 cases with malignant pleural effusion respectively. Body fluid protein and glucose contents, red blood cell counts, white blood cell counts, cytologic examination were also performed as a comparative study. The results were as follows: 1. Measurement of total LD and protein amount could differentiate between transudate and exudates in the ascitic fluids. 2. In the malignant exudate of ascites and pleural fluid, the activity of LD2 isoenzyme was statistically increased compared with that of inflammatory exudates and the activity of LD4 isoenzyme was also incereased compared with that of serum (P<0.05). 3. The inflammatory exudates of pleural fluid and ascites demonstrated the increase of LD5 isoenzyme activity statistically compared with that of serum and malignant exudates (P<0.05). 4. A difference of total LD activity between malignant ascites and inflammatory ascites was significant statistically, while this was not observed in the pleural exudate. 5. Total LD and LD5 isoenzyme activity didn't correlated with the number of white blood cells in the exudate.