BACKGROUND AND OBJECTIVES : Anti-endothelial cell antibodies (AECA) are found in the sera of many patients with Kawasaki disease (KD). In this study, the pathogenic role of AECA in the development of coronary arterial lesions of KD was investigated. SUBJECTS AND METHODS : Serum IgM-AECA concentrations were measured in 22 KD patients. Cultured human coronary artery endothelial cells (HCAEC) were incubated with either acute or convalescent phase sera, and their expressions of intercellular adhesion molecule-1 (ICAM-1) assessed. IgM fractions of the sera were purified, and their ability to induce ICAM-1 mRNA and protein expressions evaluated. To address the signal transduction pathways involved in IgM-AECA-induced ICAM-1 expression, the blocking effect of four protein kinase inhibitors, PD98059, SB203580, dimethylaminopurine (DMAP) and parthenolide were measured. RESULTS : IgM-AECA was present in 14 out of 22 (64%) acute KD sera. ICAM-1 expression of HCAEC incubated with acute KD sera (117.1+/-46.7) and AECA-positive acute KD sera (143.3+/-37.5) were significantly higher than those of the convalescent KD sera (88.9+/-14.4, p<0.05) or AECA-negative acute KD sera (71.2+/-11.8, p<0.05), respectively. IgM-AECA from KD patients significantly induced ICAM-1 protein and mRNA expression. The upregulation of ICAM-1 expression was significantly inhibited by SB203580, DMAP and parthenolide, but not by PD98059. CONCLUSION : IgM-AECA was detected in the sera of about 2/3 of acute KD patients, which activated endothelial cells by upregulation of ICAM-1 expression, possibly via p38, JNK MAPK and NF-kappaB signal transduction pathways. Thus, IgM-AECA may play a pathogenic role in the development of coronary arterial lesions in KD patients.
Antibodies ; Coronary Vessel Anomalies ; Coronary Vessels ; Endothelial Cells ; Humans ; Immunoglobulin M ; Intercellular Adhesion Molecule-1 ; Mucocutaneous Lymph Node Syndrome* ; NF-kappa B ; Protein Kinase Inhibitors ; RNA, Messenger ; Signal Transduction ; Up-Regulation

Objective : The breast-feeding rate has decreased in Korea despite of the active encouraging effort of breast-feeding for the last 10 years. So we investigated the factors that are related to breast-feeding failure. METHOD: 1807 specific questionares of mothers who visited the six university hospitals in Seoul from October 1993 to December 1995 were analysed by ANOVA and multiple logistic regression using SAS program. RESULTS: 1) Exclusive breast-feeding rate for the first 6 months was 20.0%. The factors of breast feeding success were antenatal plan for breast-feeding, the first successful breast-feeding and breast-feeding in the hospital after delivery (P<0.01). 2) The duration of breast-feeding was 5.2+/-4.4 months. It was significantly longer in the first successful breast-feeding (P<0.01). The earlier the first breast-feeding, the longer the breast-feeding duration (P<0.01). 3) The breast feeding rate for the first feeding after delivery was significantly higher in normal delivery (46.5%) and the rooming-in (57.4%) than in Cesarean section (37.1%) and the nursery (39.1%) (P<0.01). 4) The first time of breast-feeding was 64.8+/-62.8 hours after delivery and was significantly earlier in the local clinic, normal delivery and rooming-in than in the hospital, Cesarian section and the nursery (P<0.01). The first breast-feeding was successful in 46.9% and was significantly higher in antenatal education (P<0.01). 5) The reasons for the breast-feeding failure within postnatal one month were the insufficient milk (37.1%), the physician' s recommendation (18.8%), the inverted nipple (12.1%), the baby's poor suckling power (10.5%) and thin breast-milk (7.0%). The reasons to switch the successful breast-feeding to formula-feeding before 6 months of age were the return to work (25.1%), the convenience of formula-feeding (17.4%), the excellency of formula (10.0%) and maternal conveniency (6.2%). 6) The reasons to consider the breast milk insufficient were too frequent feeding with crying (38.7%) and poor sleeping with irritability (19.0%). The reasons to consider the breast milk thin were the loose stool (51.1%) and watery nature of breast milk (48.9%). The effort to increase the breask milk was present in 68.2%. The most frequent effort was to increase the maternal intake (67.6%) instead of the frequent baby' s suckling (25.6%). 7) Persons who recommended to stop breast feeding were family members 62.7%, pediatricians 25.5%, obstetricians 10.7%, nurses 1.1%. The maternal diseases to stop breast feeding by physician such as mastitis (11.1%), hepatitis B (4.9%) and tuberculosis (2.5%) were relatively appropriate. But the baby' s diseases such as jaundice (29.9%), loose stool (22.2%) and vomiting (2.8%) were inappropriate. CONCLUSIONS: To increase the breast-feeding rate, we recommend the antenatal plan for breast-feeding, the early breast-feeding as soon as possible and the exclusive breast-feeding in the hospital after delivery. The mothers should make an effort to increase the breast milk by frequent suckling. The physicians should be better prepared to assist the breast-feeding mothers and monitor continuously to resume even after the temporary hold of breast-feeding.
Breast Feeding ; Cesarean Section ; Crying ; Female ; Hepatitis B ; Hospitals, University ; Humans ; Jaundice ; Korea ; Logistic Models ; Mastitis ; Milk ; Milk, Human ; Mothers ; Nipples ; Nurseries ; Pregnancy ; Prenatal Education ; Return to Work ; Seoul ; Tuberculosis ; Vomiting

Fetal alcohol syndrome (FAS) is a developmental neuropathology resulting from in utero exposure to ethanol; many of ethanol's effects are likely to be mediated by the neurotransmitter gamma-aminobutyric acid (GABA). We studied modulation of the neurotransmitter receptor GABABR and its capacity for intracellular signal transduction under conditions of ethanol treatment (ET) and RNA interference to investigate a potential role for GABA signaling in FAS. ET increased GABAB1R protein levels, but decreased protein kinase A-alpha (PKA-alpha), calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of cAMP-response element binding protein (p-CREB), in cultured hippocampal neurons harvested at gestation day 17.5. To elucidate GABAB1R response to ethanol, we observed the effects of a GABABR agonist and antagonist in pharmacotherapy for ethanol abuse. Baclofen increased GABABR, CaMKII and p-CREB levels, whereas phaclofen decreased GABABR, CaMKII and p-CREB levels except PKA-alpha. Furthermore, when GABAB1R was knocked down by siRNA treatment, CaMKII and p-CREB levels were reduced upon ET. We speculate that stimulation of GABAB1R activity by ET can modulate CaMKII and p-CREB signaling to detrimental effect on fetal brain development.
Animals ; Baclofen ; Brain ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Carrier Proteins ; Ethanol ; Fetal Alcohol Syndrome ; gamma-Aminobutyric Acid ; Hippocampus ; Neurons ; Neurotransmitter Agents ; Phosphorylation ; Pregnancy ; Protein Kinases ; Rats ; Receptors, Neurotransmitter ; RNA Interference ; RNA, Small Interfering ; Signal Transduction