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Biomedical subjects

I Iwata

Publications and source records attributed to I Iwata.

At least 19 recordsLinked to original sources

High ambient ammonia promotes growth in a ureogenic goby, Mugilogobius abei.

Mugilogobius abei has the ability to produce large amounts of urea when exposed to high ambient ammonia. Despite this metabolically costly approach, and reports of growth inhibition effects of ammonia on fish, M. abei exposed to ammonia shows no adverse effects on growth. To investigate this observation the growth of M. abei was measured at room temperatures for 8 weeks at a constant ration level under solitary and grouped conditions, in 20% SW with or without (control) 2 mM NH(4)Cl. Furthermore, pituitary mRNA levels of growth hormone, oxygen consumption, incorporation of external (15)N-ammonia into amino acid and protein fractions as well as behavioral activities were also examined. The specific growth rates of ammonia-exposed fish under grouped condition over the 8 weeks were significantly higher than those of control, while those rates under solitary condition were not significantly different between the treatments. The pituitary of ammonia-exposed fish had higher growth hormone mRNA than in control fish. The use of (15)N isotope revealed that M. abei can actively use external ammonia as a supplementary nitrogen source. Oxygen consumption of ammonia-exposed fish was significantly lower than that of control fish. Locomotor activity and aggressive behavior under grouped condition were significantly reduced in ammonia-exposed fish as compared to those of control. These combined alterations in the ammonia-exposed fish may result in the higher growth rates.

Amino Acids↗

Association study between CD30 and CD30 ligand genes and type 1 diabetes in the Japanese population.

CD30-CD30 ligand (CD30L) signal transduction appears to protect against autoimmune diabetes by preventing expansion of autoreactive T cells and suppressing Th1-cytokine response. The purpose of this study was to determine whether CD30 or CD30L genes serve as a novel susceptibility gene for type 1 diabetes in humans. We screened CD30 and CD30L genes for polymorphisms in Japanese patients with type 1 diabetes and control subjects. Then, association studies were performed between each of the identified polymorphisms and type 1 diabetes. Direct-sequencing analysis of the CD30 and CD30L genes revealed four polymorphisms: one in the CD30 gene (-201G/A from the transcription start site), and three in the CD30L gene [CA repeat in the promoter, 276G/A in the exon 3, -73T/C in the intron 3 (IVS3 -73T/C)]. Association studies revealed no association between the CD30 and CD30L genes and type 1 diabetes in the whole population. In the female and male subpopulations, however, the frequency of (CA)(9) allele of the CD30L gene promoter or T allele of IVS3 -73T/C polymorphism in the CD30L gene was slightly higher in female patients with type 1 diabetes than that in control females. In conclusion, we could not find significant association between CD30 or CD30L genes and type 1 diabetes, but (CA)(9) allele in the promotor or T allele of -73T/C in intron 3 in CD30L gene might play a minor role in the pathogenesis of type 1 diabetes, only in the Japanese female population.

Adolescent↗

Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population.

Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes because they co-localize to Chromosome 2q33 with the IDDM12 locus. After determining the genomic structure and screening for polymorphisms of the ICOS gene, we performed association studies between newly identified polymorphisms of the ICOS gene, together with known polymorphisms of CD28 and CTLA-4 genes, and type 1 diabetes. The 49A/G dimorphism in exon 1 and the (AT)n in the 3' untranslated region of the CTLA-4 gene were significantly associated with type 1 diabetes. Evaluation of the CTLA-4 49A-3'(AT)n 86-bp haplotype frequency in patients and controls confirmed the results from the analysis of each polymorphic site. Dimorphism in intron 3 of the CD28 gene was associated with type 1 diabetes only in the early-onset group. In contrast, there was no association with the microsatellite polymorphisms in the ICOS gene or dimorphisms in the promotor region of CTLA-4. Of the three genes encoding co-stimulatory molecules, the CTLA-4 gene appears to confer risks for the development of type 1 diabetes.

Abatacept↗

Structure of the mouse NDRF gene and its regulation during neuronal differentiation of P19 cells.

We have isolated and characterized the mouse gene for NDRF (neuroD-related factor), a basic helix-loop-helix transcription factor implicated in neural development and function. The gene consists of two exons and the entire protein-coding sequence is encoded by a single downstream exon. RNA blot hybridization analysis revealed that NDRF mRNA was detectable at day 4 and increased to a maximal level at day 6 during neuronal differentiation of P19 cells. To elucidate the regulatory mechanisms of the NDRF gene expression during this process, a construct containing the genomic DNA fragment of about 3 kbp upstream of the NDRF coding region fused to a luciferase reporter gene was transfected into P19 cells, and stable transformants were pooled for assay of luciferase activities. When the stable transformants were treated with RA and aggregated to induce neuronal differentiation, the luciferase activities were induced in a temporal expression pattern similar to that of the endogenous NDRF mRNA. Further experiments using a series of deletion and mutation constructs indicated that the 376-bp sequence in the 5'-flanking region of the NDRF gene is important, and that one of the E boxes in the sequence plays a critical role in the regulated expression. Transient transfection experiments also showed that the same E box is required for the transactivation of the NDRF promoter activity by neurogenin 1. These results suggest that the NDRF gene expression is regulated by an E box-binding factor during neuronal differentiation of P19 cells.

Animals↗

Suppression of insulitis and diabetes in B cell-deficient mice treated with streptozocin: B cells are essential for the TCR clonotype spreading of islet-infiltrating T cells.

In order to clarify the role of B cells in the development of insulitis and diabetes, B cell-deficient (B(-)) mice treated with streptozocin (STZ) were studied. The extent of insulitis and the cumulative incidence of diabetes were significantly suppressed in B(-) mice (P < 0.0001), indicating that B cells are crucial for the progression of insulitis and diabetes. Accumulation of both CD4(+) T cells and B cells was observed in islets of B(+) mice, while CD4(+) T cells but not B cells were found in B(-) mice. A few CD8(+) T cells and macrophages were detectable in both types of mice. The immunohistochemical study did not reveal any change in the subpopulations of infiltrating lymphocytes except for the absence of B cells in the B(-) mice. TCR V(beta) gene repertoire usage of islet-infiltrating T cells was restricted to some extent in the B(+) or B(-) mice, but there was no significant difference between the B(+) and B(-) mice, suggesting that the initial islet-reactive T cell response can occur in the absence of B cells. In contrast, TCR clonotype spreading of islet-infiltrating T cells was significantly suppressed in B(-) mice compared with B(+) mice (P < 0.0001). These data suggest that initial priming of T cells is not impaired and TCR V(beta) repertoire usage is not limited by the lack of B cells, while B cells are important essentially for the spreading of islet-infiltrating clonal T cells in autoimmune diabetic mice induced with STZ.

Animals↗

[The frequency of Streptococcus pneumoniae strains and sensitivity surveillance for several antibiotics in Gifu Prefecture].

The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics. A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S. pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the resistant bacteria being relatively prominent. In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference. PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).

Amoxicillin↗

Dermatomyositis associated with invasive thymoma.

We report a case of dermatomyositis (DM) associated with invasive thymoma in a 22-year-old woman who was admitted to our hospital complaining of dyspnea which required ventilation support. The reddened elevated scaly eruptions were prominent over the extensor surfaces. Chest X-ray and computed tomography showed mediastinal masses, which were diagnosed as mixed type thymoma. Muscle and skin biopsy specimens were compatible with DM. She was treated with methylprednisolone pulse therapy followed by extended removal of the anterior mediastinal tumor and subsequent radiotherapy. She has had a good clinical course without recurrence of thymoma or DM for more than 3 years. The role of thymoma in the development of DM is discussed.

Adult↗

Association of polymorphism in the NeuroD/BETA2 gene with type 1 diabetes in the Japanese.

NeuroD/BETA2, a transcription factor of the insulin gene, also plays an important role in the development of pancreatic beta-cells. Recently, the NeuroD/BETA2 gene has been mapped to the long arm of human chromosome 2 (2q32) where the IDDM7 gene has previously been mapped, implying its involvement in diabetes. To identify mutations in the NeuroD/BETA2 gene that may predispose patients to develop diabetes, we studied the gene in 50 Japanese subjects with diabetes (4 with type 1 and 46 with type 2) by the polymerase chain reaction (PCR) followed by single-strand conformation polymorphism and sequencing analyses. Further analysis was performed in 392 Japanese subjects (60 with type 1 and 158 with type 2 diabetes and 174 healthy control subjects) by mismatch PCR restriction fragment length polymorphism. We found a DNA polymorphism of the NeuroD/BETA2 gene. A nucleotide G-to-A transition results in the substitution of alanine to threonine at codon 45 (Ala45Thr). The frequencies of heterozygotes for the Ala45Thr variant were 9.8% in the control subjects, 9.5% in the patients with type 2 diabetes, and 25.0% in the patients with type 1 diabetes, a significant difference (P = 0.006). Because the variant of the NeuroD/BETA2 gene (Ala45Thr) is associated with type 1 but not type 2 diabetes, it may be implicated in the loss of pancreatic beta-cells in type 1 diabetes.

Adult↗

[A case of idiopathic aneurysm of the inferior vena cava].

Congenital aneurysms of the inferior vena cava (IVC) are very rare, and to our knowledge, only 4 cases have been previously reported. We describe the fifth case of fusiform aneurysm and briefly review the literature. A 62-year-old woman was admitted to our hospital for investigation of a mass shadow on the right hemidiaphragm on a chest roentgenogram. CT, MRI, and DSA examinations revealed an aneurysmal dilatation of the IVC measuring 51x50x38 mm inferior to the right atrium, and the diagnosis of fusiform aneurysm of the IVC was made. The newer imaging techniques of CT, MRI, and DSA have facilitated the diagnosis of this abnormality.

Aneurysm↗

Increase in the concentration of immunoreactive endothelin in human pregnancy.

Maternal plasma concentrations of immunoreactive endothelin (ir-ET) during pregnancy, labour and after birth were measured by radioimmunoassay. Concentrations of ir-ET in the umbilical artery, umbilical vein, amniotic fluid and neonatal urine were also examined. The mean (+/- S.E.M.) plasma ir-ET concentration in early pregnancy (4-7 weeks) was 13.7 +/- 0.5 pmol/l, which was significantly higher than that in non-pregnant women (5.9 +/- 0.3 pmol/l). During pregnancy, plasma ir-ET concentrations gradually decreased to a minimum of 11.5 +/- 0.4 pmol/l in weeks 20-23, and then increased again towards term (12.5 +/- 0.4 pmol/l after 36 weeks of pregnancy). In women undergoing vaginal delivery, the mean plasma ir-ET concentration (17.1 +/- 0.7 pmol/l) increased significantly, compared with that in late pregnancy. After delivery, the plasma ir-ET concentration decreased abruptly to 4.0 +/- 0.2 pmol/l on the first day. Plasma ir-ET concentrations in umbilical vessels were significantly higher than those in maternal plasma. In addition, concentrations in the umbilical artery were significantly higher than those in the umbilical vein in cases of vaginal delivery. Concentrations of ir-ET in amniotic fluid were much higher than those in maternal or fetal plasma. ir-ET concentrations in neonatal urine on day 1 after birth were below the detection limit (less than 0.1 pmol/l) by radioimmunoassay in 70% of the cases examined but on day 5 after birth ir-ET was present at measurable concentrations in all cases. It is suggested that endothelin may act as a circulating hormone during pregnancy and labour in both maternal and fetal circulations.

Amniotic Fluid↗

[A case of Swyer-James syndrome diagnosed by selective alveolobronchography].

A 33-year-old male was admitted to our hospital for further investigation of unilateral hyperlucency of the left upper and middle lung fields on chest X-ray. A pulmonary scan showed decreased perfusion of the left upper and middle lung fields. Pulmonary arteriography demonstrated small left pulmonary arteries with diminished peripheral vascular branches. Left bronchogram showed almost normal distribution of main and subsegmental bronchi, but poor filling by contrast in the peripheral bronchi. From these findings, the patient was diagnosed as having Swyer-James syndrome. In order to demonstrate the alveoli in this syndrome, selective alveolobronchography (SAB) was performed. SAB revealed coarse ring shadows of B1+2.

Adult↗

[Immunohistochemical and electromicroscopic study of a case of primary nodular pulmonary amyloidosis].

A 41-year-old man was hospitalized for further evaluation of an abnormal chest films which revealed a nodular shadow in the right middle lung field, which remarkably enlarged during one year. As no diagnostic procedures ruled out lung carcinoma of right S6, a right lower lobectomy was performed. Pathologically the nodules were composed of amorphous and eosionphilic materials which were diagnosed as amyloid by Congo-red stain and electron microscopic examination. Since there were no deposits in other organs and there was no abnormality of serologic and urinary protein analysis, a diagnosis of primary nodular pulmonary amyloidosis was established.

Adult↗

[Prenatal evaluation of the platelet counts in the fetuses and the neonates of the mothers complicated with idiopathic thrombocytopenic purpura].

We investigated 25 pregnancies with ITP. The results were as follows. 1. The platelet counts of the maternal blood just before delivery were not correlated with those of the cord blood. 2. It was suggested that the maternal PAIgG value just before delivery could foretell the onset of neonatal thrombocytopenic purpura. 3. The platelet counts in fetal scalp blood were correlated with those of the cord blood, but falsely lower platelet counts were found in the fetal scalp samples. 4. We saw 5 cases of percutaneous umbilical blood sampling (PUBS) in pregnancies with ITP. PUBS was found to be a useful and safe method. The indications for PUBS and fetal platelet transfusion in pregnancy with ITP are discussed.

Cesarean Section↗

Clinical evaluation of a direct colorimetic method for determination of amniotic phospholipids.

Evaluation of amniotic phospholipids, which are a parameter of fetal lung maturation, is important in the management of premature infants. The method available for measuring the lecithin/sphingomyelin (L/S) ratio, which appears to provide an index to fetal lung maturity, is laborious, involving determinations of phospholipids, and so is unsuitable for rapid quantitative measurement of phospholipids in the amniotic fluid in the perinatal period. We developed a simple, sensitive colorimetric assay for phospholipids without their extraction. This assay is based on the fact that phospholipids form stable hydrophobic complexes with Co(SCN)4, Fe(SCN)2- and Fe(SCN)3 within about 1 hr. Amniotic fluid samples (n = 115) were collected from women with normal and abnormal pregnancies in week 16-41 of pregnancy, and these samples were examined both by thin layer chromatography (TLC) and by our method of phospholipid determination. Good correlations were observed between the L/S ratio determined by TLC and the values obtained by this method. Moreover the distributions of the dipalmitoylphosphatidylcholine (DPPC) content and DPPC/sphingomyelin (SM) ratio were similar to those of the PC content and L/S ratio. This method was proved to be more accurate than other methods such as TLC and the shake test for predicting neonatal RDS.

Amniotic Fluid↗

[Effect of low-dose aspirin therapy on utero-placental blood flow and malondialdehyde (MDA) as an indicator of its therapeutic effect].

Pregnancy-induced hypertension (PIH) and preeclampsia develop when an imbalance occurs between prostacyclin (PGI2) and thromboxane A2 (TXA2) production. PGI2 promotes vasodilation and decreases platelet adhesiveness, while TXA2 acts as a vasoconstrictor and enhances platelet aggregation and adhesion to vascular walls. The PGI2/TXA2 ratio appears to be important in pregnancy and the development of the functioning uteroplacental unit. Recently, antiplatelet treatment such as low-dose aspirin therapy has been effective in preventing the development of PIH and preeclampsia. TXA2 breaks down spontaneously into a stable substance, TXB2, which is inactive. Another stable, inactive metabolite, malondialdehyde (MDA), is formed via the same pathway. TXB2 and MDA are produced in approximately equimolar quantities. We studied the effects of a low-dose aspirin prescription. Production of MDA was remarkably suppressed during the low-dose aspirin therapy. Furthermore, pulsed doppler ultrasound assessment of blood flow was performed in the fetal descending aorta, umbilical artery and uterine artery of the low-dose aspirin therapy patients. Doppler abnormalities were improved during the therapy. It is concluded that low-dose aspirin improves the uteroplacental blood flow assessed by pulse doppler waveform and that determination of MDA is useful as an indicator of platelet thromboxane synthesis.

Adult↗

Immunoreactive corticotropin-releasing hormone, adrenocorticotropin and cortisol in human plasma during pregnancy and delivery and postpartum.

The activity of the hypothalamo-pituitary adrenal axis was examined, by measuring the levels of immunoreactive (IR) corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and cortisol (F) in human plasma during normal pregnancy and after delivery with or without complications and during normal postpartum using a specific RIA. The level of IR-CRH in maternal plasma increased progressively during pregnancy, increased further at delivery and declined rapidly to the non-pregnant level on the 1st day postpartum. The level of IR-F in maternal plasma also increased progressively during pregnancy, increased further at delivery, but decreased slowly postpartum, not returning to the non-pregnant level within 5 days. Significant correlations were found between the level of IR-CRH and IR-ACTH, IR-CRH and IR-F, and IR-ACTH and IRF in maternal plasma both during pregnancy and after delivery. It is noteworthy that the concentration of IR-CRH in the maternal plasma at delivery was higher in multiple pregnancy than in normal pregnancy, and that the level of IR-CRH in the umbilical cord in uncomplicated cases was much lower than that in the maternal plasma, and was significantly lower than those in the umbilical cord plasma in cases of asphyxia, IUGR or premature delivery. The level of IR-F, not IR-CRH and IR-ACTH, at normal vaginal delivery was significantly higher than that at elective cesarean section. On these results, we investigated the feto-maternal-hypothalamo-pituitary adrenal axis during pregnancy and delivery, in which CRH plays an important role.

Adrenocorticotropic Hormone↗