Dual-specificity tyrosine (Y)-phosphorylation-regulated protein kinase 1A (Dyrk1A) is the mammalian homologue of Drosophila melanogaster minibrain and its human gene is mapped to the Down syndrome critical region of chromosome 21. Dyrk1A phosphorylates several transcription factors, including NFAT and CREB and a number of cytosolic proteins such as APP, tau, and alpha-synuclein. Although Dyrk1A is involved in the control of cell growth and postembryonic neurogenesis, its potential role during cell death and signaling pathway is not clearly understood. In the present study, we show that Dyrk1A is activated under the condition of apoptotic cell death. In addition, Dyrk1A is coupled to JNK1 activation, and directly interacts with apoptosis signal-regulating kinase 1 (ASK1). Moreover, Dyrk1A positively regulates ASK1-mediated JNK1-signaling, and appears to directly phosphorylate ASK1. These data indicate that Dyrk1A regulates cell death through facilitating ASK1-mediated signaling events.
alpha-Synuclein ; Cell Death ; Chromosomes, Human, Pair 21 ; Cytosol ; Down Syndrome ; Drosophila melanogaster ; Humans ; MAP Kinase Kinase Kinase 5 ; Neurogenesis ; Protein Kinases ; Proteins ; Signal Transduction ; Transcription Factors ; Tyrosine

OBJECTIVE: To investigate the association between endometriosis and polymorphisms of N-acetyl transferase 2 (NAT2), glutathione S-transferase M1 (GSTM1), and cytochrome P450 (CYP) 1A1 genes in Korean infertile patients. MATERIALS AND METHODS: A total of 303 infertile patients who had undertaken diagnostic laparoscopy during January, 2001 through December, 2003 at Samsung Cheil Hospital enrolled in this study. The patients were grouped according to laparoscopic findings: minimal to mild endometriosis (group I: n=147), moderate to severe endometriosis (group II: n=57), normal pelvic cavity (n=99). Peripheral blood was obtained and genomic DNA was extracted. The genotypes of each genes were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). For NAT2, RFLP was used to detect the wild type (wt) and mutant (mt) alleles, enabling classification into slow (mt/mt) or fast (wt/wt or wt/mt) acetylation genotypes. For GSTM1, PCR was used to distinguish active (+/- or +/+) from null (-/-) genotypes. For CYP1A1, MspI digestion was used to detect the wild type (A1A1), heterozygote (A1A2) or mutant (A2A2) genotypes. RESULTS: The genotype frequencies of NAT2 slow acetylator was 12.8%, 10.9%, 12.8% in group I, group II and control, respectively. The genotype frequencies of GSTM1 null mutation was 55.3%, 41.8%, 53.2% in group I, group II and control, respectively. The genotype frequencies of CYP1A1 MspI polymorphism was 16.3%, 9.1%, 18.1% in group I, group II and control, respectively. No significant difference was observed between endometriosis and normal controls in the genotype frequencies of the NAT2, GSTM1, CYP1A1 MspI polymorphism. CONCLUSION: The NAT2, GSTM1, CYP1A1 gene polymorphism may not be associated with the susceptibility of endometriosis in Korean women.
Acetylation ; Alleles ; Classification ; Cytochrome P-450 CYP1A1 ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Digestion ; DNA ; Endometriosis* ; Female ; Genotype ; Glutathione Transferase* ; Glutathione* ; Heterozygote ; Humans ; Laparoscopy ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Transferases*

OBJECTIVE: To evaluate the effects of recombinant FSH (rFSH) and urinary FSH (uFSH) on the gene expressions of human endometrial stromal cells in vitro. METHODS: Endometrial tissue was obtained from a pre-menopausal women undergoing hysterectomy. Primary endometrial stromal cells were isolated and in vitro cultured with FBS-free DMEM/F-12 containing 0, 10, 100, and 1,000 mIU/ml of rFSH and uFSH for 48 hours, respectively. Total RNA was extracted from the cultured cells and subjected to real time RT-PCR for the quantitative analysis of progesterone receptor (PR), estrogen receptor alpha/beta (ER-alpha/beta), cyclooxygenase 2 (Cox-2), leukemia inhibitory factor (LIF), homeobox A10-1 and -2 (HoxA10-1/-2). RESULTS: Both hormone treatments slightly increased (< 3 folds) the expressions of PR, ER-beta and HoxA10-1/-2 gene. However, ER-alpha expression was increased up to five folds by treatments of both FSH for 48 hours. The LIF expression by the 10 mIU/ml of uFSH for 12 hours was significantly higher than that of rFSH (p<0.01). After 24 hours treatment of two kinds of hormones, the expression patterns of LIF were similar. The 100 and 1,000 mIU/ml of rFSH induced significantly higher amount of Cox-2 expression than those of uFSH, respectively (p<0.05). CONCLUSION: This study represents no adversely effect of exogeneous gonadotropins, rFSH and uFSH, on the expression of implantation related genes. We suggest that rFSH is applicable for the assisted reproductive technology without any concern on the endometrial receptivity.
Cells, Cultured ; Cyclooxygenase 2 ; Estrogens ; Female ; Gene Expression* ; Genes, Homeobox ; Gonadotropins ; Humans* ; Hysterectomy ; Leukemia Inhibitory Factor ; Receptors, Progesterone ; Reproductive Techniques, Assisted ; RNA ; Stromal Cells*

No abstract available.
Epidermolysis Bullosa ; Muscular Dystrophy, Duchenne ; Ornithine Carbamoyltransferase ; Polymerase Chain Reaction* ; Preimplantation Diagnosis*

Kimura's disease is an uncommon, chronic inflammatory disease of unknown etiology. It is an important category of reactive lymphadenopathy in the oriental population. The most common sites are the subcutis of the head and neck, and parotid gland. It's clinical course is benign nature. The treatment modalities for this disease are steroid therapy, radiation therapy and surgical excision. We experienced a case of soft tissue mass in the left arm. It was slightly tender and relatively movable. We excised the mass, which was turned out to be Kimura's disease on microscopic examination.
Arm ; Head ; Lymphatic Diseases ; Neck ; Parotid Gland

Objective: This study aimed to evaluate the following null hypothesis: there are no differences in the morphology of the temporomandibular joint (TMJ) structures in relation to vertical and sagittal cephalometric patterns. Methods: This retrospective study was performed with 131 participants showing no TMJ symptoms. The participants were divided into Class I, II, and III groups on the basis of their sagittal cephalometric relationships and into hyperdivergent, normodivergent, and hypodivergent groups on the basis of their vertical cephalometric relationships. The following measurements were performed using cone-beam computed tomography images and compared among the groups: condylar volume, condylar size (width, length, and height), fossa size (length and height), and condyle-to-fossa joint spaces at the anterior, superior, and posterior condylar poles. Results: The null hypothesis was rejected. The Class III group showed larger values for condylar width, condylar height, and fossa height than the Class II group (p < 0.05). Condylar volume and superior joint space in the hyperdivergent group were significantly smaller than those in the other two vertical groups (p < 0.001), whereas fossa length and height were significantly larger in the hyperdivergent group than in the other groups (p < 0.01). The hypodivergent group showed a greater condylar width than the hyperdivergent group (p < 0.01). The sagittal and vertical cephalometric patterns showed statistically significant interactions for fossa length and height. Conclusions TMJ morphology differed across diverse skeletal cephalometric patterns. The fossa length and height were affected by the interactions of the vertical and sagittal skeletal patterns.

Objective: This study aimed to evaluate the following null hypothesis: there are no differences in the morphology of the temporomandibular joint (TMJ) structures in relation to vertical and sagittal cephalometric patterns. Methods: This retrospective study was performed with 131 participants showing no TMJ symptoms. The participants were divided into Class I, II, and III groups on the basis of their sagittal cephalometric relationships and into hyperdivergent, normodivergent, and hypodivergent groups on the basis of their vertical cephalometric relationships. The following measurements were performed using cone-beam computed tomography images and compared among the groups: condylar volume, condylar size (width, length, and height), fossa size (length and height), and condyle-to-fossa joint spaces at the anterior, superior, and posterior condylar poles. Results: The null hypothesis was rejected. The Class III group showed larger values for condylar width, condylar height, and fossa height than the Class II group (p < 0.05). Condylar volume and superior joint space in the hyperdivergent group were significantly smaller than those in the other two vertical groups (p < 0.001), whereas fossa length and height were significantly larger in the hyperdivergent group than in the other groups (p < 0.01). The hypodivergent group showed a greater condylar width than the hyperdivergent group (p < 0.01). The sagittal and vertical cephalometric patterns showed statistically significant interactions for fossa length and height. Conclusions TMJ morphology differed across diverse skeletal cephalometric patterns. The fossa length and height were affected by the interactions of the vertical and sagittal skeletal patterns.

OBJECTIVE: Embryonic stem (ES) cells could be differentiated into the specific cell types by alternation of culture condition and modification of gene expression. This study was performed to evaluate the differentiation protocol for mouse and human ES cells to insulin secreting cells. METHODS: Undifferentiated mouse (JH-1) and human (Miz-hES1) ES cells were cultured on STO feeder layer, and embryoid bodies (EBs) were formed by suspension culture. For the differentiation, EBs were cultured by sequential system with three stage protocol. The differentiating ES cells were collected and marker gene expressions were analyzed by semi-quantitative RT-PCR in each stage. Amount of secreted insulin levels in culture media of human ES cells were measured by human insulin specific RIA kit. RESULTS: During the differentiation process of human ES cells, GATA-4, alpha-fetoprotein, glucose transporter-2 and Ngn-3 expression were increased whereas Oct-4 was decreased progressively. Insulin and albumin mRNAs were expressed from stage II in mouse ES cells and from stage III in human ES cells. We detected 3.0~7.9 microU/ml secretion of insulin from differentiated human ES cells by in vitro culture for 36 days. CONCLUSION: The sequential culture system could induce the differentiation of mouse and human ES cells into insulin secreting cells. This is the first report of differentiation of human ES cells into insulin secreting cells by in vitro culture with serum and insulin free medium.
alpha-Fetoproteins ; Animals ; Culture Media ; Embryoid Bodies ; Embryonic Stem Cells* ; Feeder Cells ; Gene Expression ; Glucose ; Humans ; Insulin* ; Insulin-Secreting Cells* ; Mice ; RNA, Messenger

A hyperglycemic hyperosmolar state is usually associated with type 2 diabetes. It has significant mortality and morbidity and is rare in the pediatric population. We describe a rare case of a 15-year-old boy with type 2 diabetes who presented to the emergency department with a mixed hyperglycemic hyperosmolar state and diabetic ketoacidosis. Excessive consumption of high-sugar carbonated drinks may have worsening the initial presentation. The patient recovered without any complications. We highlight the fact that gradual correction of osmolarity and sodium is important to avoid cerebral edema despite severe dehydration.
Adolescent* ; Brain Edema ; Carbonated Beverages ; Dehydration ; Diabetes Mellitus, Type 2* ; Diabetic Ketoacidosis* ; Emergency Service, Hospital ; Humans ; Hyperglycemic Hyperosmolar Nonketotic Coma ; Male* ; Mortality ; Osmolar Concentration ; Sodium

The optimal and alternative antimicrobial regimens to treat neurosyphilis in human immunodeficiency virus (HIV) infected patients remain controversial. Little is known concerning the efficacy of ceftriaxone. A 75-year-old heterosexual man visited an outpatient clinic due to incidentally detected positive serum Venereal disease research laboratory (VDRL) and Fluorescent treponemal antibody absorbed tests in routine preoperative checkup. Because of benzathine penicillin was unavailable to use, 4-week regimen with doxycycline was started. After 2 weeks doxycycline treatment, a severe headache suddenly occurred. Cerebrospinal fluid (CSF) analysis showed mild lymphocyte-dominant pleocytosis, increased protein, and weakly reactive VDRL test. ELISA for HIV antibody and Western blot assay revealed he is infected with HIV. Initial CD4+ T cell count was 220/mm3 and the load of HIV RNA was 5,200 copies/mL. The most probable diagnosis was deemed to be neurosyphilis, considering the possibilities of Jarisch-Herxheimer reaction or doxycycline-induced pseudotumor cerebri. In the absence of procaine penicillin G in our hospital, intravenous ceftriaxone was administered and highly active antiretroviral therapy was started. After 14days of treatment, the patient no longer had a headache and the CSF profile was improved. Additional follow-up CSF analysis was done 3months after treatment. CSF pleocytosis and protein level were decreased and the CSF VDRL was converted to negative. Ceftriaxone may be a good alternative in the treatment of neurosyphilis in HIV infected patient.
Aged ; Ambulatory Care Facilities ; Antiretroviral Therapy, Highly Active ; Blotting, Western ; Ceftriaxone ; Cell Count ; Doxycycline ; Enzyme-Linked Immunosorbent Assay ; Ethylenediamines ; Follow-Up Studies ; Headache ; Heterosexuality ; HIV ; Humans ; Leukocytosis ; Neurosyphilis ; Penicillin G Benzathine ; Penicillin G Procaine ; Pseudotumor Cerebri ; RNA ; Sexually Transmitted Diseases