Early growth response (Egr)-1 is a Cys2-His2-type zincfinger transcription factor. It has been shown to induce survival and proliferation of immature and mature B cells, respectively, but its role in the differentiation of B cells into plasma cells remains unclear. To examine the effects of Egr-1 deficiency on the activation of B cells, naive B cells from Egr1-/- mice and their wild-type (WT) littermates were activated to proliferate and differentiate, and then assayed by FACS. Proportions of cells undergoing proliferation and apoptosis did not differ between Egr1-/- and WT mice. However, Egr1-/- B cells gave rise to fewer plasma cells than WT B cells. Consistently, Egr1-/- mice produced significantly lower titer of antigen-specific IgG than their WT littermates upon immunization. Our results demonstrate that Egr-1 participates in the differentiation program of B cells into plasma cells, while it is dispensable for the proliferation and survival of mature B cells.
Animals ; Apoptosis ; B-Lymphocytes* ; Immunization ; Immunoglobulin G ; Mice ; Plasma Cells* ; Transcription Factors

BACKGROUND: Bevantolol HCl was developed as the first antihypertensive agent that has selective beta1 and alpha1 blocking effects with an additional calcium antagonistic activity. It's expected that antihypertensive effect is comparable to other beta-blockers without any significant adverse effect on lipid and glucose metabolism observed in other drugs, and It has less negative inotropic effect due to peripheral vasodilatation mediated through alpha1 and calcium channel blocking effects. To evaluate the antihypertensive effect and safety of bevantolol HCl, we investigated 73 patients with mild to moderately severe essential hypertension. METHODS: Patients who showed either systolic blood pressure 150-209 mmHg or diastolic pressure 95-119 mmHg, were enrolled in this study. Following placebo period of 2weeks, bevantolol HCl was administered in daily dose of 100-200 mg for 12 weeks. RESULTS: Of the 73 patients, 55 patients who were able to receive bevantolol HCl were observed for the safety and 45 patients who completed this study were evaluated for the antihypertensive effect of the drug. 1) Antihypertensive effect: The mean systolic and diastolic blood pressure significantly decreased from 156.7+/-11.7 mmHg to 144.0+/-16.7 mmHg and from 101.6+/-6.4 mmHg to 93.2+/-9.7 mmHg in two weeks of observation in 37/45 patients (82.2%) and was consistently effective for 12 weeks (p<0.01). Blood pressure under 139/89 mmHg was achieved in 20 out of 45 patients (44.4%). The heart rate also declined from 74.9+/-10.5/min to 69.1+/-14.2/min and the effect lasted for 12 weeks (p<0.01). 2) Safety: Mild adverse effects were observed in 27 out of 55 patients. Only one patient developed a significant bradycardia with heart rate of 40/min, which required withdrawal of the drug. No significant changes in the lipid profiles were observed. CONCLUSION: Bevantolol HCl is highly effective and generally well tolerated with an acceptable safety profile in patients with mild to moderately severe essential hypertension.
Blood Pressure ; Bradycardia ; Calcium ; Calcium Channels ; Glucose ; Heart Rate ; Humans ; Hypertension* ; Metabolism ; Vasodilation

BACKGROUND: The purpose of this study was to survey the nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) among the patients admitted in a medical intensive care unit (MICU) and analyze risk factors associated with the colonization. METHODS: The study was carried out on patients admitted into the MICU in a 1,250-bed tertiary care university hospital from January through December 2006. Nasal surveillance cultures were obtained from patients within 24 hours of admission to the unit. Data were analyzed retrospectively by the review of medical records. RESULTS: A total of 312 patients were screened with active nasal cultures; 36 patients (11.6%) were positive for MRSA. Of these, 22 (7.1%) were positive in the nasal cultures only and 14 (4.5%) were positive in the cultures of other specimens (13, sputum; 1, joint fluid) in addition to the nasal swabs. Among the risk factors for MRSA nasal colonization were sex (man), route of admission (from other ICUs or wards), a history of ICU admission during the recent 12 months, and prolonged hospital days in ICU. CONCLUSION: MRSA nasal carrier rate was found higher in this study than in those reported in the literature. Most of the patients colonized with MRSA in the nostril were not colonized with the organism elsewhere in the body. Whether or not active surveillance for MRSA should be performed would depend on the nasal colonization rate of the patients at the time of admission to the ICU.
Colon* ; Humans ; Intensive Care Units* ; Critical Care* ; Joints ; Medical Records ; Methicillin Resistance* ; Methicillin-Resistant Staphylococcus aureus* ; Retrospective Studies ; Risk Factors ; Sputum ; Tertiary Healthcare

BACKGROUND: Keratinocyte-derived interleukin-1(IL-1)alpha is one of the key cytokines in initiation of cutaneous inflammation. Release of IL-1alpha from human keratinocytes may be induced by proinflammatory stimuli including ultraviolet B(UVB) irradiation, and subsequently, keratinocyte-derived IL-1alpha may exert numerous paracrine and autocrine effects. 1,25-dihydroxyvitamin D3(1,25(OH)2D3) is involved in the regulation of keratinocyte proliferation and differentiation and is also recognized to have immunoregulatory properties such as an antiinflammatory effect. OBJECTIVE: The purpose of this study was to investigate the in vitro effects of 1,25-(OH)2D3 on the production of IL-1alpha by UVB irradiation in cultured human keratinocyte cell line HaCaT cells. RESULTS: are summerized as follows; 1. The vialility of cultured HaCaT cells measured by MTS assay at 24 hours after UVB irradiation was significantly reduced at the doses of above 100 mJ/cm2 of UVB(p<0.05). 2. The secretion of IL-1alpha by HaCaT cells was significantly increased at the doses of above 30 mJ/cm2 of UVB(p<0.05). UVB irradiation could not influence on the secretion of IL-1beta by HaCaT cells. 3. At the concentrations of 10-8M and 10-6M of 1,25(OH)2D3, the production of IL-1alpha by HaCaT cells(48 hours after 100 mJ/cm2 UVB irradiation) was significantly inhibited in both culture supernatants and cell lysates(p<0.05). CONCLUSION: UVB irradiation increased the production of IL-1alpha by HaCaT cells and this stimulatory effect on the production of IL-1alpha induced by UVB irradiation was suppressed by 1,25-(OH)2D3. Calcipotriol(MC-903) had similar suppressive effect on the production of IL-1alpha induced by UVB irradiation in HaCaT cells to that of 1,25(OH)2D3.
Calcitriol* ; Cell Line* ; Cytokines ; Humans* ; Inflammation ; Interleukin-1alpha* ; Keratinocytes*

BACKGROUND: Mycoplasma pneumoniae is the most frequent cause of respiratory tract infections in schoolaged children and adolescents. For appropriate use of antibiotics, diagnosis of M. pneumoniae infection in routine clinical practice has been based on serology using a single serum sample. We evaluated the seroprevalence of anti-M. pneumoniae-specific antibodies in 500 asymptomatic, healthy persons in Jeonnam Province. METHODS: Sera were collected from 500 healthy persons in Jeonnam Province. Anti-M. pneumoniae antibody titer was measured using a microparticle agglutination assay Serodia Myco II (Fujirebio, Japan) and VIRCELL IgM Mycoplasma ELISA kits (Vircell, Granada, Spain). RESULTS: Anti-M. pneumoniae antibody titers in 500 healthy individuals were 1:20 in 344 (68.8%), 1:40 in 16 (3.2%), 1:80 in 71 (14.2%), 1:160 in 45 (9.0%), 1:320 in 14 (2.8%), and <1:320 in 10 (2.0%). The positive rate of M. pneumoniae IgM antibodies was 3.2% (15/473). The prevalence of IgM was 10.0% in the 7~9 years, 9.1% in the 10~19 years, and 5.0% in the 20~29 years old group, which was significantly higher than that in elderly people. CONCLUSION: Some of healthy people showed a high anti-M. pneumoniae antibody titer (>1:160) and positive IgM, and an assessment of current infection with single serum serology has its limitation for the diagnosis of M. pneumoniae infections.
Adolescent ; Aged ; Agglutination ; Anti-Bacterial Agents ; Antibodies* ; Child ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin M ; Jeollanam-do* ; Mycoplasma pneumoniae* ; Mycoplasma* ; Pneumonia ; Pneumonia, Mycoplasma* ; Prevalence* ; Respiratory Tract Infections ; Seroepidemiologic Studies

BACKGROUND: Postprimary pulmonary tuberculosis is located mainly in upper lobes. The tuberculous lesion involving the lower lobes usually arises from the upper lobe cavity through endobronchial spread. When tuberculosis is confined to the lower lung field, it often masquerades as pneumonia, lung cancer, bronchiectasis, or lung ahscess. Thus the correct diagnosis may be sometimes delayed for a long time. METHODS: We carried out, retrospectively, a clinical study on 50 patients confirmed with lower lung field tuberculosis who visited the Department of Pulmonary Medicine at Hanyang University Hospital from January 1992 to December 1994. The following results were obtained. RESULTS: Lower lung field tuberculosis without concomitant upper lobe disease occurred in fifty patients representing 6.9% of the total admission with active pulmonary tuberculosis over a period of 3 years. It occurred most frequently in the third decade but age distribution was relatively even. The mean age was 43 years old. Female was more frequently affected than male (male to female ratio 1:1.9). The most common symptom was cough(68%), followed by sputum(52%), fever(38%), and chest discomfort(30%). On chest X-ray of the S0patients, consolidation was the most common finding in 52%, followed by solitary nodule(22%), collapse(16%), cavitary lesion(l0%), in decreasing order. The disease confined to the right side in 25 cases, left side 20 cases, and both sides 5 cases. Endobronchial tuberculosis (1) Endobronchial involvement was proved by bronchoscopic examination in 20 of S0patients. (2) Mean age was 44years old and female was more affected than man (male to female ratio 1 : 3). Sputum AFB stain and Mycobacterium tuberculosis culture were positive only in 50% of cases unlikely upper lobe tuberculosis, additional diagnostic methods were needed. In our study, bronchoscopic examination and percutaneous fine needle aspiration biopsy increased diagnostic yield by 18% and 32%, respectively. The most common associated condition was diabetes mellitus(18%) and others were anemia, anorexia nervosa, stomach cancer, and systemic steroid usage. CONCLUSION: When we find a lower lung field lesion, we should suspect tuberculosis if the patient has diabetes mellitus, anemia, systemic steroid usage, malignancy or other immune suppressed states. Because diagnostic yield of sputum AFB smear & Mycobacterium tuberculosis culture was low, additional diagnostic methods such as bronchoscopy and fine needle aspiration biopsy were needed.
Adult ; Age Distribution ; Anemia ; Anorexia Nervosa ; Biopsy ; Biopsy, Fine-Needle ; Bronchiectasis ; Bronchoscopy ; Diabetes Mellitus ; Diagnosis ; Female ; Humans ; Lung Neoplasms ; Lung* ; Male ; Mycobacterium tuberculosis ; Pneumonia ; Pulmonary Medicine ; Retrospective Studies ; Sputum ; Stomach Neoplasms ; Thorax ; Tuberculosis* ; Tuberculosis, Pulmonary

BACKGROUND: This cross-sectional study assessed the sleep quality using the ActiGraph and investigated the relationship between the parameters of sleep assessment and the type of shift work in Korean firefighters. METHODS: The participants were 359 firefighters: 65 day workers (control group) and 294 shift workers (shift work group: 77 firefighters with 3-day shift, 72 firefighters with 6-day shift, 65 firefighters with 9-day shift, and 80 firefighters with 21-day shift). Sleep assessments were performed using the ActiGraph (wGT3X-BT) for 24 hours during day shift (control and shift work group) and night shift and rest day (shift work group). The participants recorded bed time and sleep hours during the measurement period. RESULTS: Sleep efficiency, total sleep time, and percentage of wake after sleep onset during night work were lower in the shift work group than control group (p < 0.05). Sleep efficiency decreased in night shift and increased in rest day, whereas wake after sleep onset increased in night shift and decreased in rest day (p < 0.05). Among shift work groups, sleep efficiency of 6-day shift was higher in day shift, and sleep efficiency of 21-day shift was lower in night shift than other shift groups (p < 0.05). CONCLUSION: We found that the sleep quality in night shift of the shift work group was poorer than the control group. As to the type of shift work, sleep quality was good in 6-day shift and poor in 21-day shift. Thus, fast rotating shift such as 6-day shift may be recommended to improve the sleep quality of the firefighters.
Cross-Sectional Studies ; Firefighters ; Humans

PURPOSE: To evaluate the pathological and clinical effects of preoperative chemoradiation (CCRT) in cases of locally advanced rectal cancer and to determine the predictive factors for tumor downstaging. MATERIALS AND METHODS: From March 2004 to August 2008, 33 patients with locally advanced rectal cancer were treated with preoperative CCRT. Twenty-eight patients (84.8%) were treated using a concomitant boost technique while five (15.2%) patients were treated using a cone down boost technique. All patients received 50.4 Gy of irradiation and concurrent chemotherapy with 5-fluorouracil. The median follow-up duration was 24.2 months (range, 9.8 to 64.7 months). RESULTS: Thirty-one (93.9%) patients underwent surgery. Twenty-four patients (72.7%) underwent anal sphincter-preserving surgery. The 3-year disease free survival (DFS) and overall survival rates were 63.4% and 78.8%, respectively. Post-operative factors were more important for DFS. Pathologic N stage, margin status, and pathologic differentiation were significant prognostic factors (p=0.001, 0.029, 0.030). Tumor size and lymphovascular invasion were also associated with marginal significance (p=0.081, 0.073). However, only pre-treatment T stage was a significant pre-operative factor (p=0.018). The complete pathological response rate was 9.1%. T-downstaging was observed in ten (30.3%) patients, whereas N-downstaging was found in 24 (72.7%) patients. Pre-treatment T stage and the interval between CCRT and operation were the predictive factors for downstaging in a univariate analysis (p=0.029, 0.027). Pre-treatment carcinoembryogenic antigen was also associated with marginal significance (p=0.068). CONCLUSION: The survival of rectal cancer patients can be better determined based on post-operative findings. Therefore, pre-operative CCRT for downstaging of the tumor seems to be important. Pre-treatment T stage and the interval between CCRT and operation can be used to predict downstaging.
Disease-Free Survival ; Fluorouracil ; Follow-Up Studies ; Humans ; Rectal Neoplasms ; Survival Rate

BACKGROUND: So far, there have been numerous reports on organ damage due to cryptococcosis, however, cases of lung localization have been infrequently reported. Recently pulmonary cryptococcosis has been reported more frequently than before due to enhanced diagnostic techniques and increased underlying diseases. METHODS: The author, therefore, analyzed the clinical manifestations of 5 cryptococcosis cases that we experienced at Hanyang University Hospital from 1985 to 1996 and 9 cases reported in Korea from 1984 and 1996 retrospectively. The following results were obtained. RESULTS: Cryptococcosis occured frequently over sixth decade and the male to female ratio was 3.6:1. Underlying diseases included acute rejection after kidney transplantation, rheumatoid arthritis, autoimmune hepatitis, diabetes mellitus and state of bilateral adrenalectomy. Remaining 8 cases had no evidence of an underlying disease. Because the symptoms were subacute & nonspecific, and not improved by conventional antibiotics, 6 patients of 14 pulmonary cryptococcosis patients were treated as pulmonary tuberculosis before correct diagnosis was made. There were three asymptomatic cases. According to the results of CXR, solitary alveolar consolidation was the most common finding(8 cases) followed by diffuse infiltration(5 cases). It also showed pleural effusion, hilar lymphadenopathy and cavity formation that was rarely reported in world literature. The diagnosis was made through fine needle aspiration biopsy in 10 cases, open thoracotomy in 2 cases, transbronchial lung biopsy in 1 case and thoracentesis with pleural biopsy in 1 case. Only one case showed positive result in sputum stain and culture ,serum latex agglutination test for cryptococcus neoformans. Treatment modalities were various such as fluconazole, amphotericin B, flucytosine, ketoconazole, surgery and it's combination. After 1990 year, there was a trend that fluconazole or ketoconazole are more used than other therapeutic modalities. CONCLUSION: Because the symptoms are subacute & nonspecific and not improved by conventional antibiotics, pulmonary cryptococcosis is likely to misdiagnosis as pulmonary tuberculosis in Korea. Because the diagnostic yield of sputum stain, culture and serologic test for pulmonary cryptococcosis is low, histologic diagnosis is need in most pulmonary cryptococcosis.
Adrenalectomy ; Amphotericin B ; Anti-Bacterial Agents ; Arthritis, Rheumatoid ; Biopsy ; Biopsy, Fine-Needle ; Cryptococcosis* ; Cryptococcus neoformans ; Diabetes Mellitus ; Diagnosis ; Diagnostic Errors ; Female ; Fluconazole ; Flucytosine ; Hepatitis, Autoimmune ; Humans ; Ketoconazole ; Kidney Transplantation ; Korea ; Latex Fixation Tests ; Lung ; Lymphatic Diseases ; Male ; Pleural Effusion ; Retrospective Studies ; Serologic Tests ; Sputum ; Thoracotomy ; Tuberculosis, Pulmonary

This study was to clarify population pharmacokinetics (PK) of sildenafil and its metabolite, N-desmethyl sildenafil (NDS) in Korean healthy male population using a pooled data from multiple clinical trials in consideration of inter-institution and inter-laboratory difference. A population PK analysis was performed with data of 243 healthy volunteers from five single-center (4 centers) comparative PK trials. The dataset included 7,376 sildenafil and NDS concentration (3,688 for each analyte) observed during 24 hours after the single dose of original sildenafil (either 50 mg or 100 mg of Viagra®). The plasma concentration was assayed in two laboratories. Various model structure was tested and the final model was evaluated using visual predictive checks. Demographic and clinical variables were assessed as potential covariates for PK parameters. A one-compartment first-order elimination model with proportional error was selected for the dispositional characteristics of sildenafil, and two-compartment model was chosen for NDS. Three transit compartments with Erlang-type absorption for fast absorption pathway and one compartment for slow absorption pathway constructed overall absorption model. The first-pass effect was rejected since it does not improve the model. The difference of NDS level by the bioanalysis laboratory was selected as the only covariate. Even though a direct comparison was difficult, the general trend in PK of sildenafil and NDS for Korean healthy male was considered similar to that of the other populations reported previously. It is recommended that the laboratory effect should be explored and evaluated when dataset is built using results from several laboratories.
Absorption ; Administration, Oral* ; Asian Continental Ancestry Group ; Dataset ; Healthy Volunteers ; Humans ; Male* ; Pharmacokinetics* ; Plasma ; Sildenafil Citrate* ; Volunteers*