No abstract available.
Child ; Health Promotion ; Humans ; Immunization* ; Child Health

Phosphodiesterase (PDE) 4 inhibitors have been shown to induce the cAMP-mediated signaling pathway by inhibiting cAMP hydrolysis. This study investigated the effect of a PDE4 inhibitor on the expression of the inducible cAMP early repressor (ICER), which is an endogenous inhibitor of CRE- mediated transcription, in osteoblastic cells. RT-PCR analysis revealed that rolipram, a PDE4 inhibitor, stimulates the ICER mRNA in a dose dependent manner. The induction of ICER mRNA expression by rolipram was suppressed by the inhibitors of protein kinase A (PKA) and p38 MAPK, suggesting the involvement of PKA and p38 MAPK activation in ICER expression by rolipram. It was previously shown that rolipram induced the expression of TNF-related activation-induced cytokine (TRANCE, also known as RANKL, ODF, or OPGL) in osteoblasts. This paper provides evidences that a transcriptional repressor like ICER might modulate TRANCE mRNA expression by rolipram in osteoblasts.
3', 5'-Cyclic-Nucleotide Phosphodiesterase/*antagonists & inhibitors ; Animals ; Animals, Outbred Strains ; Cyclic AMP-Dependent Protein Kinases/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression/drug effects ; Mice ; Osteoblasts/*drug effects/metabolism ; Phosphodiesterase Inhibitors/*pharmacology ; Research Support, Non-U.S. Gov't ; Rolipram/*pharmacology ; Transcription Factors/genetics/*metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Previous reports showed that homocysteine damages mitochondrial gene expression, function and structure. In recent years, homocysteine and mitochondrial DNA (mtDNA) content are reported to relate with insulin resistance. The aim of this study is to investigate the correlation of plasma homocysteine level and mitochondrial DNA content in peripheral blood. METHODS: The mtDNA content, homocysteine and insulin resistance parameters were measured in healthy women (n=60). Plasma homocysteine level was measured by ion-exchange chromatography method and the mtDNA content in peripheral blood was measured by real time PCR method using ABI Prism 7700 machine. RESULTS: Significant correlation was found between homocysteine and mtDNA content (r=-0.507, p<0.05). Homocysteine was correlated with age (r=0.397), cholesterol (r=0.327), LDL-cholesterol (r=0.318), apolipoprotein B (r=0.387), HbA1c (r=0.274) positively and folate (r=-0.262), apolipoprotein A1 (r=-0.293), VO2max (r=-0.332) negatively. Mitochondrial DNA content was correlated with age (r=-0.535), BMI (r=-0.397), cholesterol (r=-0.340), LDL-cholesterol (r=-0.319), apolipoprotein B (r=-0.367) negatively and apolipoprotein A1 (r=0.346), lactate (r=0.307), VO2max (r=0.308) positively. All correlations were statistically significant(p<0.05). CONCLUSION: In this study, plasma homocysteine level was related with mitochondrial DNA content negatively and these two factors are estimated to be concerned with insulin resistance.
Apolipoprotein A-I ; Apolipoproteins ; Cardiovascular Diseases ; Cholesterol ; Chromatography, Ion Exchange ; DNA, Mitochondrial* ; Female ; Folic Acid ; Genes, Mitochondrial ; Homocysteine* ; Humans ; Hyperhomocysteinemia ; Insulin Resistance ; Lactic Acid ; Plasma* ; Real-Time Polymerase Chain Reaction ; Risk Factors

PURPOSE: Neoadjuvant chemotherapy is the standard treatment for patients with locally advanced breast cancer and is increasingly considered for patients with operable disease. Recently, as many clinical trials have demonstrated favorable outcomes of anthracycline-taxane based regimen, this approach has been widely used in the neoadjuvant setting. METHODS: We compared women who received adriamycine and docetaxel (AD) with adriamycin, cyclophosphamide followed by paclitaxel (AC-T) as neoadjuvant chemotherapy. The AD group was scheduled for six cycles of AD (50 mg/m2 and 75 mg/m2, respectively) at a 3-week interval. The AC-T group was scheduled for four cycles of adriamycin and cyclophosphamide (50 mg/m2 and 500 mg/m2, respectively) followed by four cycles of paclitaxel (175 mg/m2) at a 3-week interval. RESULTS: The responses of chemotherapy were equivalent (overall response rate [AD, 75.7% vs. AC-T, 80.9%; P = 0.566], pathologic complete response [pCR] rate [breast and axilla: AD, 10.8% vs. AC-T, 12.8%; P = 1.000; breast only: AD, 18.9% vs. AC-T, 14.9%, P = 0.623], breast conserving surgery rate [P = 0.487], and breast conserving surgery conversion rate [P = 0.562]). The pCR rate in the breast was higher in the human epidermal growth factor receptor 2 (HER2) positive cases (HER2 positive 33.3% vs. negative 10%, P = 0.002). Although nonhematologic toxicities were comparable, hematologic toxicities were more severe in the AD group. Most women in the AD group suffered from grade 3/4 neutropenia (P < 0.001) and neutropenic fever (P < 0.001). CONCLUSION: Tumor responses were not different in various variables between the two groups. However, AC-T was a more tolerable regimen than AD in patients with breast cancer receiving neoadjuvant chemotherapy.
Breast ; Breast Neoplasms ; Cyclophosphamide ; Doxorubicin ; Female ; Fever ; Humans ; Mastectomy, Segmental ; Neoadjuvant Therapy ; Neutropenia ; Paclitaxel ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Taxoids

Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, is primarily expressed in serotonergic neurons of the raphe nuclei. Simple tandem repeat polymorphisms, typically one to four nucleotides long, are tandemly repeated several times and often characterized by many alleles. To identify the presence of polymorphic repeats, we sequenced the 5'-upstream region of the mouse TPH gene. For the detection of any allelic variants, polymerase chain reaction, nonisotopic single-strand conformation polymophism, and DNA sequencing analyses of the tandem repeat sequences were performed using genomic DNA extracted from 60 ICR mice. Two dinucleotide repeats, 5'-(AC/TG)22-3' and 5'-(GT/CA)17-3', were identified at approximately -5.7 kb and -3.4 kb upstream from the transcriptional initiation site of the mouse TPH gene, respectively. Minor allelic variants, 5'-(AC/TG)21-3' and 5'-(GT/CA)18-3', were observed in heterozygous pairs from 3 of 60 and 1 of 60 ICR mice, respectively. The identification of these microsatellites in the mouse TPH promoter raises the possibility that identical and/or other polymorphic sequences might exist in the upstream region of the human TPH gene.
Alleles ; Animals ; Dinucleotide Repeats* ; DNA ; Humans ; Mice* ; Mice, Inbred ICR ; Microsatellite Repeats ; Nucleotides ; Polymerase Chain Reaction ; Raphe Nuclei ; Sequence Analysis, DNA ; Serotonergic Neurons ; Serotonin ; Tandem Repeat Sequences ; Tryptophan Hydroxylase* ; Tryptophan*

Recently, nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to be useful in the chemoprevention of colon cancer. To investigate whether indomethacin, an NSAIDs, induces apoptosis and thus assess the possibility of its application in the chemoprevention of human lung cancer, we have performed MTT assay, TUNEL assay, DAPI staining, and flow cytometric analysis using human lung carcinoma cell line NCI-H1299. Through morphological and biochemical analyses, it was demonstrated that NCI-H1299 cells treated with indomethacin (0.5 mM) exhibit classical apoptotic features. These results suggest that indomethacin induces apoptosis in NCI-H1299 cells and that NSAIDs, including indomethacin, may be a useful tool for the chemoprevention of human lung cancer.
Anti-Inflammatory Agents, Non-Steroidal ; Apoptosis* ; Cell Line ; Chemoprevention ; Colonic Neoplasms ; Humans* ; In Situ Nick-End Labeling ; Indomethacin* ; Lung Neoplasms ; Lung*

BACKGROUND/AIMS: The meaning of specialized intestinal metaplasia (SIM) in the diagnosis of Barrett's esophagus (BE) is not clear. This study was designed to determine the clinical significance of SIM in the diagnosis of Barrett's esophagus. MATERIALS AND METHODS: Biopsies were taken from 601 subjects with endoscopically suspected columnar-lined esophagus. Under light microscopy with Alcian-blue stain, SIM was identified. Demographic characteristics, gastroesophageal (GE) reflux symptoms and endoscopic findings were compared between the SIM-present group and the SIM-absent group. RESULTS: Among 601 subjects, 184 (30.6%) were confirmed by pathology to have SIM. Age over 40 years (P<0.001) and a medication history of proton pump inhibitor or H2 blocker were found more frequently in the SIM-present group (P=0.01) than in the SIM-absent group. Any of 7 GE reflux symptoms (heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough and epigastric soreness) were more frequent in the SIM-present group than SIM-absent group (P<0.001). Specifically, heartburn, chest pain and cough were significantly more common in the SIM-present group. There was no clinically significant difference associated with endoscopic findings or other clinical characteristics. CONCLUSIONS: When subjects with endoscopically suspected BE are analyzed based on the presence or absence of SIM, the SIM-present group was significantly associated with GE reflux symptoms suggestive of frequent GE reflux. However, the presence of SIM did not correlate with endoscopic findings.
Barrett Esophagus ; Biopsy ; Chest Pain ; Cough ; Esophagus ; Gastroesophageal Reflux ; Heartburn ; Hoarseness ; Light ; Metaplasia ; Microscopy ; Prospective Studies ; Proton Pumps ; Sensation

BACKGROUND/AIMS: Chronic gastritis is a common finding during endoscopy and it is very important to describe it correctly. This study was designed to evaluate the distribution of endoscopic gastritis and the differences according to age, sex or area. MATERIALS AND METHODS: A clinical analysis was conducted on 25,536 subjects who had undergone an upper endoscopy for routine health check-up. Endoscopic gastritis was classified into four types, superficial gastritis, erosive gastritis, atrophic gastritis and intestinal metaplasia. The distribution of the four types of gastritis was evaluated according to sex, age and area. RESULTS: 51.6% of the patients had experienced at least one of the symptoms (epigastric pain or discomfort, soarness, dyspepsia, abdominal pain) on at least a few occasions during the previous year. The incidence of normal gastric finding was 3,593 (14.1%). 21,943 (85.9%) subjects have at least more than one of endoscopic gastritis. The number of cases with superficial gastritis was 7,983 (31.3%), erosive gastritis 6,054 (23.7%), atrophic gastritis 6,918 (27.1%), and intestinal metaplasia 1,181 (7.1%). Erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men than women (P<0.001) and in the older age group (> or =60 years) than younger age group (P<0.001). CONCLUSIONS: The prevalence of endoscopic gastritis was very common, 85.9%. In addition, erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men and in the older age group, which is similar to gastric cancer or peptic ulcer. Cautious regular endoscopic follow-up might be necessary regardless of gastrointestinal symptoms in Korea.
Dyspepsia ; Endoscopy ; Female ; Gastritis ; Gastritis, Atrophic ; Helicobacter pylori ; Humans ; Incidence ; Korea ; Male ; Metaplasia ; Peptic Ulcer ; Prevalence ; Stomach Neoplasms

BACKGROUND/AIMS: Chronic gastritis is a common finding during endoscopy and it is very important to describe it correctly. This study was designed to evaluate the distribution of endoscopic gastritis and the differences according to age, sex or area. MATERIALS AND METHODS: A clinical analysis was conducted on 25,536 subjects who had undergone an upper endoscopy for routine health check-up. Endoscopic gastritis was classified into four types, superficial gastritis, erosive gastritis, atrophic gastritis and intestinal metaplasia. The distribution of the four types of gastritis was evaluated according to sex, age and area. RESULTS: 51.6% of the patients had experienced at least one of the symptoms (epigastric pain or discomfort, soarness, dyspepsia, abdominal pain) on at least a few occasions during the previous year. The incidence of normal gastric finding was 3,593 (14.1%). 21,943 (85.9%) subjects have at least more than one of endoscopic gastritis. The number of cases with superficial gastritis was 7,983 (31.3%), erosive gastritis 6,054 (23.7%), atrophic gastritis 6,918 (27.1%), and intestinal metaplasia 1,181 (7.1%). Erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men than women (P<0.001) and in the older age group (> or =60 years) than younger age group (P<0.001). CONCLUSIONS: The prevalence of endoscopic gastritis was very common, 85.9%. In addition, erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men and in the older age group, which is similar to gastric cancer or peptic ulcer. Cautious regular endoscopic follow-up might be necessary regardless of gastrointestinal symptoms in Korea.
Dyspepsia ; Endoscopy ; Female ; Gastritis ; Gastritis, Atrophic ; Helicobacter pylori ; Humans ; Incidence ; Korea ; Male ; Metaplasia ; Peptic Ulcer ; Prevalence ; Stomach Neoplasms