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Biomedical subjects

A Itakura

Publications and source records attributed to A Itakura.

At least 19 recordsLinked to original sources

IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis.

IgE hyperproduction frequently observed in patients with atopic dermatitis (AD) may greatly contribute to the pathogenesis of AD, but its mechanisms are still unclear. NC/Nga mice raised in nonsterile circumstances spontaneously suffered from AD-like skin lesions with elevation of plasma IgE levels. We investigated mechanisms of the IgE hyperproduction in NC/Nga mice. Splenic T cells from SPF NC/Nga mice had a level of CD40 ligand (CD40L) expression comparable to that of BALB/c mice. Although there was no difference in the expression of CD40 on B cells between NC/Nga and BALB/c mice, B cells of NC/Nga mice produced much more IgE in the presence of soluble CD40L and IL-4. The stimulation with CD40L and/or IL-4 resulted in tyrosine phosphorylation of Janus kinase 3 (JAK3) in B cells, which was more strongly inducible in NC/Nga mice than in BALB/c mice. In B cells isolated from PBMC of AD patients with high serum IgE levels, JAK3 was constitutively phosphorylated at the tyrosine residue, and its phosphorylation was enhanced by the treatment with CD40L and/or IL-4 as was that in splenic B cells of NC/Nga mice with dermatitis and high IgE levels. Thus, it is suggested that constitutive and enhanced JAK3 phosphorylation in B cells highly sensitive to CD40L and IL-4 may be attributable to IgE hyperproduction in NC/Nga mice and patients with AD.

Aluminum Hydroxide

Role of nerve growth factor in cutaneous wound healing: accelerating effects in normal and healing-impaired diabetic mice.

Four full-thickness skin wounds made in normal mice led to the significant increase in levels of nerve growth factor (NGF) in sera and in wounded skin tissues. Since sialoadenectomy before the wounds inhibited the rise in serum levels of NGF, the NGF may be released from the salivary gland into the blood stream after the wounds. In contrast, the fact that messenger RNA and protein of NGF were detected in newly formed epithelial cells at the edge of the wound and fibroblasts consistent with the granulation tissue produced in the wound space, suggests that NGF was also produced at the wounded skin site. Topical application of NGF into the wounds accelerated the rate of wound healing in normal mice and in healing-impaired diabetic KK/Ta mice. This clinical effect of NGF was evaluated by histological examination; the increases in the degree of reepithelialization, the thickness of the granulation tissue, and the density of extracellular matrix were observed. NGF also increased the breaking strength of healing linear wounds in normal and diabetic mice. These findings suggested that NGF immediately and constitutively released in response to cutaneous injury may contribute to wound healing through broader biological activities, and NGF improved the diabetic impaired response of wound healing.

Animals

Preeclampsia with fetal death in a patient with schistosomiasis japonica.

A case of preeclampsia with fetal death at 32 weeks' gestation is reported. Liver examination of the patient revealed network patterns on ultrasonography and linear calcifications on unenhanced CT scans in the liver. These findings are typical of those of chronic schistosomal infection. Indeed, liver biopsy specimens showed eggs of schistosoma japonicum. We diagnosed her case as preeclampsia with liver cirrhosis due to chronic schistosomiasis japonica. Schistosomal placentitis may have been present and may have contributed to preeclampsia and fetal death.

Adult

Hepatocyte growth factor in human amniotic fluid promotes the migration of fetal small intestinal epithelial cells.

OBJECTIVE: Previously we reported on the abundant existence of hepatocyte growth factor in amniotic fluid. This study was conducted to clarify the effects of hepatocyte growth factor in amniotic fluid on fetal intestinal epithelial cells. STUDY DESIGN: Amniotic fluid samples were obtained from 22 cases at various gestational ages. The effects of amniotic fluid and recombinant human hepatocyte growth factor on proliferation, migration, and morphogenesis of intestine 407 cells (a cell line derived from fetal intestinal epithelial cells) were investigated. RESULTS: The mobility of intestine 407 cells was stimulated by amniotic fluid in proportion to the concentration of hepatocyte growth factor in amniotic fluid with the same effect observed with recombinant human hepatocyte growth factor. This activity was neutralized by addition of antihuman hepatocyte growth factor antibody. Neither increased deoxyribonucleic acid synthesis nor morphogenesis in response to amniotic fluid was identified under the conditions used. CONCLUSION: Amniotic fluid stimulates intestinal epithelial cell migration by way of hepatocyte growth factor in amniotic fluid during development of the fetal intestine.

Amniotic Fluid

Involvement of hepatocyte growth factor in formation of bronchoalveolar structures in embryonic rat lung in primary culture.

To clarify the role of hepatocyte growth factor (HGF) in embryonic lung development, organoids from fetal rat lung were cultured in collagen gels with or without HGF antisense oligonucleotides. Cyst-like structures formed within 24 h in organoids isolated from fetuses after 14 days' gestation, but this was abolished by the oligonucleotide addition, apparently by interference with the endogenous expression of HGF. Electron microscopy revealed two types of structure: an alveolar type characterized by osmiophilic lamellar bodies in the cytoplasm and lumen, and a bronchial type consisting of epithelial cells bearing microvilli on their apical surfaces. HGF mRNA was detectable from day 14 in fetal lung by RT-PCR. Our results suggest that HGF plays, coordinately with its expression, a crucial role in the morphogenesis of both alveolar and bronchial epithelia in the rat fetal lung.

Animals

Fetal heart rate patterns associated with periventricular leukomalacia.

OBJECTIVE: Our purpose was to assess the applicability of fetal heart rate (FHR) monitoring to detect fetuses at risk of developing periventricular leukomalacia (PVL). METHODS: FHR tracings obtained for babies delivered under 33 weeks' gestation and with a birth weight under 2000 g were assessed for baseline heart rate, variability, deceleration and "flip flap' (an oscillatory tracing pattern). RESULTS: PVL developed in 19 of the 103 infants studied. All of these infants were among the fetuses who exhibited average and increased variability. In addition, PVL was detected in 10 (47.6%) of the 21 flip flap positive fetuses, and in 9 (11.0%) of the 82 flip flap negative fetuses. The incidence of PVL was significantly higher in the flip flap positive fetuses (P < 0.005). CONCLUSION: The possibility that an unstable intrauterine environment, reflected by a flip flap pattern, is related to the subsequent development of PVL is indicated.

Female

Timing of insults causing abnormal outcome in preterm infants 1989-1992.

OBJECTIVE: The purpose of this study was to clarify the influence of timing of brain insults causing abnormal outcome in preterm infants. METHODS: One hundred and thirty-one preterm infants were examined. The timing of brain insult was estimated from EEG or clinical findings. Development was assessed until a corrected age of 48 months. RESULTS: 39% and 4% of infants, respectively, born before and after the 28-week time point subsequently died (P < 0.05). Abnormal development was observed in 16% of the first group and 13% of the second (N.S.). None of those born before 28 weeks showed intrauterine injuries while nine of the infants which were born after this time showed intrauterine injuries (P < 0.05). Fetal distress was noted in all infants suffering neonatal death born after 28 weeks. CONCLUSION: Intrauterine brain insult was concluded to be the cause of neonatal death or abnormal development in many infants born after 28 weeks.

Brain Injuries

Human amniotic fluid motogenic activity for fetal alveolar type II cells by way of hepatocyte growth factor.

OBJECTIVE: To find out if hepatocyte growth factor (HGF) in amniotic fluid (HGF-AF) has a direct effect on fetal lung development, we investigated the effects of AF as well as recombinant human HGF (rhHGF) on proliferation, migration, and morphogenesis of fetal alveolar type II cells in vitro. METHODS: Amniotic fluid samples were obtained from 37 women at various gestational ages. Mitogenic, motogenic, and morphogenic activity was investigated by 5-bromo-2'-deoxyuridine incorporation, Boyden chamber assay, and culture in collagen-gels, respectively. RESULTS: The motility of AK-D cells was stimulated by AF from 14 to 31 weeks' gestation in proportion to the concentration of HGF-AF, and this effect was comparable to that observed with rhHGF. Furthermore, this activity was neutralized by anti-human HGF antibody. However, AF samples subsequent to 32 weeks had no motogenic influence despite the continued presence of immunoreactive HGF-AF. Neither increased DNA synthesis nor morphogenesis in response to AF was identified under the conditions used. CONCLUSION: The present study suggests that AF stimulates alveolar type II cell migration by way of HGF-AF in vitro.

Amniotic Fluid

Possible involvement of placental proteases in bradykinin (BK) degradation.

The hydrolysis of bradykinin (BK) by human placental subcellular fractions and pregnancy sera was studied in the presence of inhibitors by measuring amino acids liberated from BK by high-performance liquid chromatography. The effects of the inhibitors DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (MGTA, for kininase I), phosphoramidon (for endopeptidase 24.11) and captopril and rentiapril (for angiotensin-converting enzyme [ACE, kininase II]) suggested the essential roles of the above three proteases in BK degradation: among the three proteases, kininase I and endopeptidase 24.11 appeared to be the most important in kininase action in the placenta microsomes, whereas kininase I and ACE appeared to be the most important in kininase action in the placental cytosol, lysosome and pregnancy serum. Measurements of BK concentrations in the umbilical arterial blood, umbilical venous blood and maternal plasma revealed higher concentrations in the mother than in the fetus. The present data suggest that degradation of BK in the placenta and pregnancy serum might contribute to the gradient of BK between mother and fetus.

3-Mercaptopropionic Acid

Increased mitochondrial damage by lipid peroxidation in trophoblast cells of preeclamptic placentas.

Lipid peroxides and their related free radicals have been implicated in the pathogenesis of placental dysfunction in preeclampsia. Recent studies suggest that the placenta is a source of the increased lipid peroxides in the maternal circulation of women with preeclampsia. We examined intracellular localization of 4-hydroxy-2-nonenal (HNE: a major aldehydic product of lipid peroxidation)-modified proteins in human placentas by immunohistochemistry, and immunoblotting. The trophoblast layer of the chorionic villi showed intense immunoreactivity for HNE-modified proteins in 4 of 12 preeclamptic placentas, whereas no staining was observed in 12 normal placentas. Immunoblotting revealed that three immunoreactive proteins with apparent molecular mass of 110 kDa, 75 kDa, and 70 kDa were localized in the mitochondrial fraction. The present results indicate that the damage to mitochondrial proteins by lipid peroxidation by products and subsequent dysfunction of trophoblasts contribute to the pathophysiology of preeclampsia.

Aldehydes

Levels of hepatocyte growth factor and its messenger ribonucleic acid in uncomplicated pregnancies and those complicated by preeclampsia.

The purpose of this study was to elucidate the possible relationship between hepatocyte growth factor (HGF) expression and the pathogenesis of preeclampsia. The concentration of immunoreactive HGF was measured and the expression of HGF messenger ribonucleic acid (mRNA) assessed in human placentas obtained from two groups: uncomplicated and preeclamptic pregnancies at various gestational weeks. In addition, the localization of HGF mRNA and c-met protein was analyzed using in situ hybridization and immunohistochemical staining, respectively. The expression of HGF mRNA and the concentration of immunoreactive HGF were highest in second trimester and were significantly decreased in preeclamptic placentas compared with the uncomplicated cases in third trimester. HGF mRNA was localized to placental mesenchymal cells, whereas c-met protein was demonstrated on cytotrophoblast. These results provide evidence of an abnormality of HGF expression in the preeclamptic placentas. Such placentas exhibit the abnormally shallow trophoblast invasion of the uterus, and reduced expression of HGF could well account for this morphometric change.

Blotting, Northern

A live birth from intracytoplasmic injection of a testicular spermatozoon.

Testicular sperm was retrieved from a man with complete epididymal obstruction, and intracytoplasmic sperm injection was performed on his wife's oocytes. In four mature treated, two fertilized eggs were obtained, and a clinical pregnancy was established with embryo transfers. One healthy girl (2715 g) was delivered by cesarean section at 38 weeks' gestation. Our case shows that the use of testicular sperm can result in a normal live birth.

Adult

Conservative handling of the uterus in a 10-week cervical pregnancy case.

A patient with a living 10-week old cervical pregnancy who desired to preserve fertility was successfully treated with methotrexate, intraamniotic KCI injection and endocervical curettage. In the case of living cervical pregnancy even after 10 weeks, conservative treatment remains an option, although intensive management and care should be given.

Adult

Oxytocin is hydrolyzed by an enzyme in human placenta that is identical to the oxytocinase of pregnancy serum.

The hydrolysis of oxytocin (OT) by human placental subcellular fractions and pregnant sera was studied in the presence of bestatin, a potent inhibitor of aminopeptidases, and the antibody against pregnant serum oxyotocinase (P-LAP)(EC 3.4 11.3) by measuring liberated amino acids by high performance liquid chromatography (HPLC). Our immunotitration study and the effect of bastatin on the oxytocin-degrading protease showed that the initiating and responsible protease in oxyotocin degradation in human placenta and pregnant serum is P-LAP.

Amino Acid Sequence

Timing of periventricular leukomalacia using neonatal electroencephalography.

OBJECTIVE: To estimate the timing of brain damage involved in the onset of periventricular leukomalacia in the perinatal period we recorded and analyzed neonatal electroencephalograms (EEGs). METHODS: Twenty-four preterm birth infants proved by real time ultrasonic examination or MRI to be suffering from periventricular leukomalacia underwent serial electroencephalography from soon after birth. RESULTS: Thirteen (54%) demonstrated intrauterine injury patterns, 2 infants (8%) showed postnatal injury, and in the remaining 9 cases (38%) the time of injury could not be determined by electroencephalography. Antepartum maternal hemorrhage (6), premature rupture of membranes (3), twining (3), chorioamnionitis (2), and perinatal asphyxia (2) were complications encountered in the group with intrauterine injury patterns. CONCLUSIONS: Our observations suggest that more than half of periventricular leukomalacia cases are associated with premature birth infants showing intrauterine injury patterns on electroencephalography, indicating the existence of intrauterine insult.

Brain Injuries

Relationship between the changes in maternal serum placental leucine aminopeptidase (P-LAP) activity and umbilical artery waveforms in normal pregnancy.

The relation between placental leucine aminopeptidase (P-LAP) activity in maternal sera and umbilical artery waveforms (systolic/diastolic ratio, S/D) obtained by pulsed Doppler has been examined by cross-sectional study in 26 normal pregnancies during weeks 26-38. A negative correlation was seen to exist suggesting that P-LAP may have a role in the regulation of uteroplacental blood flow.

Adult

A prospective study on the relationship between intrapartum maternal group-B streptococcal concentration and signs of infection in neonates.

OBJECTIVE: Our purpose was to examine the effects of intrapartum vaginal Group-B streptococcal (GBS) colonization on neonatal signs of infection. STUDY DESIGN: We performed a quantitative GBS culture of vaginal specimens in 1,280 pregnancies within 24 hours before delivery and examined signs of neonatal infection within 48 hours after birth. Among them, 287 pregnant women had premature ruptures of membranes. RESULTS: The rate of vaginal GBS colonization in groups with and without ruptured membranes was 22.0% and 11.3%, respectively. The incidence of neonates with signs of infection born to GBS-carrier women in each group was 28.6% and 8.8%, respectively. There were significant differences between the groups with regard to both the rate of colonization and the incidence of infection. Signs of neonatal infection increased in proportion to the maternal GBS concentration only in women with ruptured membranes. CONCLUSION: This study suggests that there is an important association between maternal GBS concentration and mild neonatal infections after birth, especially in women with premature ruptures of membranes.

Female