PubMed Health⌕ Search

Biomedical subjects

S Chiba

Publications and source records attributed to S Chiba.

At least 55 records · Page 3Linked to original sources

A strong association between HLA-DR9 and gelatin allergy in the Japanese population.

The frequency of HLA class I and II phenotypes was determined among 23 patients with positive gelatin IgE, eight of whom developed anaphylaxis, 18 patients who did not have gelatin IgE but who experienced non-immediate reactions after exposure to gelatin. HLA-DR9, which is unique to Orientals, was present in 56.5% of the gelatin IgE positive patients, as compared to control population frequency of 24% (P < 0.002). In the non-immediate reaction group, who did not generate IgE, phenotype distribution resembled controls. HLA-DR9 positive individuals have a relative risk of 4.1 for developing gelatin allergy with positive IgE.

Anaphylaxis↗

Thyroid function after bone marrow transplantation: possible association between immune-mediated thyrotoxicosis and hypothyroidism.

BACKGROUND: Thyroid dysfunction after bone marrow transplantation (BMT) has been investigated in many studies, and most posttransplant thyroid disorders are now recognized as a late complication of transplantation. However, these studies mainly focused on late thyroid function after BMT, and we have little information on early changes of thyroid function after BMT. METHODS: We prospectively investigated thyroid function in 57 patients receiving BMT. Serum thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels were determined at least monthly in the first 3 months, once between 3 and 12 months and once in the second year after BMT. RESULTS: During the first 6 months after BMT, 24 and 7 patients were diagnosed as having euthyroid sick syndrome (ETS) and thyrotoxicosis, respectively. Of the 52 patients alive 1 year after transplantation, 9 patients were still diagnosed as having ETS, and 8 patients developed hypothyroidism. Patients with thyrotoxicosis showed similar characteristics, and the high incidence of thyrotoxicosis after BMT is a novel finding. The median for the onset of thyrotoxicosis was day 111 after transplantation. Thyrotoxicosis was transient in all of the patients, but in seven patients hypothyroidism followed, the median onset at 12 months after BMT. Serum thyroglobulin levels were elevated in five patients, and antibodies autoreactive to the thyroid gland were detected in seven patients. CONCLUSIONS: Thyrotoxicosis may be a distinct clinical entity of thyroid dysfunction after BMT and may serve to predict the development of hypothyroidism. Immune-mediated thyroid injury may contribute to the development of posttransplant hypothyroidism.

Adolescent↗

Mitogen-activated protein kinase activity regulation role of angiotensin and endothelin systems in vascular smooth muscle cells.

To examine whether angiotensin II and endothelins produced in vascular smooth muscle cells can play roles in the regulation of mitogen-activated protein (MAP) kinase activity in vascular smooth muscle cells, we measured the activity of MAP kinases in cultured vascular smooth muscle cells, and determined effects of renin-angiotensin and endothelin systems activators and inhibitors. Angiotensin II and endothelin-1 produced an activation of MAP kinase activity in vascular smooth muscle cells, whereas the angiotensin receptor antagonist, losartan and the endothelin receptor antagonist, cyclo (D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl, BQ123) inhibited the enzyme activity. MAP kinase activity in vascular smooth muscle cells was also inhibited either by the renin inhibitor pepstatin A or by the angiotensin-converting enzyme inhibitor captopril. The degree of the inhibition of MAP kinase activity by pepstatin A, captopril and losartan was almost the same. Renin produced a considerable increase in MAP kinase activity and the renin-induced MAP kinase activation was inhibited by pepstatin A. The endothelin precursor big endothelin-1 produced an increase of MAP kinase activity in vascular smooth muscle cells, whereas the endothelin-converting enzyme inhibitor phosphoramidon inhibited the enzyme activity. These findings suggest that functional renin-angiotensin system and endothelin system are present in vascular smooth muscle cells and these systems tonically serve to increase MAP kinase activity. It appears that renin or renin-like substances play the determining role in the regulation of renin-angiotensin system in vascular smooth muscle cells.

Angiotensin I↗

Mutations of the Smad4 gene in acute myelogeneous leukemia and their functional implications in leukemogenesis.

The Smad family proteins are critical components of the transforming growth factor (TGF)-beta signaling pathway. TGF-beta is a multipotent cytokine that elicits many biological functions. In particular, TGF-beta exhibits effects on the cell cycle manifested by G1-phase arrest, differentiation, or apoptosis of several target cells, suggesting that disruption of TGF-beta signaling pathway could be involved in cancer formation. Here we show one missense mutation of the Smad4 gene in the MH1 domain (P102L) and one frame shift mutation resulting in termination in the MH2 domain (Delta(483 - 552)) in acute myelogeneous leukemia. Both of the mutated Smad4 proteins lack transcriptional activities. Concomitant expression of the P102L mutant with wild-type Smad4 inactivates wild-type Smad4 through inhibiting its DNA-binding ability. The Delta(483 - 552) mutant blocks nuclear translocation of wild-type Smad4 and thus disrupts TGF-beta signaling. This is the first report showing that mutations in the Smad4 gene are associated with the pathogenesis of acute myelogeneous leukemia and the obtained results should provide useful insights into the mechanism whereby disruption of TGF-beta signaling pathway could lead to acute myelogeneous leukemia. Oncogene (2001) 20, 88 - 96.

Animals↗

Serum levels of fluconazole in patients after cytotoxic chemotherapy for hematological malignancy.

We performed a prospective evaluation of pharmacokinetics of fluconazole administered for prophylactic purposes to 19 patients after cytotoxic chemotherapy for hematological malignancies. On days 7 and 15, we obtained 5 ml of blood from each patient. If fluconazole was administered orally, blood samples were drawn 2, 8, and 24 hr after ingestion of the drug. If it was administered intravenously, blood samples were drawn 1, 8, and 24 hr post-injection. Serum fluconazole levels were analyzed by HPLC with ultraviolet light detection. In patients receiving 200 or 400 mg of fluconazole per day, maximal serum levels were 7.9 and 15.6 mg/l and minimum levels were 5.0 and 10.3 mg/l, respectively. There was no significant difference in serum fluconazole levels comparing the levels after oral and intravenous administration, and pharmacokinetic parameters of fluconazole were comparable at each time point within one dose level. However, considerable variation in serum fluconazole levels was noted in this study, as the maximal serum levels ranged from 4.0 to 13.3 mg/l and from 8.7 to 26.9 mg/l in patients receiving 200 and 400 mg of fluconazole orally, respectively. These variations may be associated with prophylactic failures for patients with insufficient fluconazole concentrations. Multiple regression analysis showed significant correlation between serum fluconazole levels and some variables including dose of fluconazole, age, serum aspartate aminotransferase levels and blood urea nitrogen levels. These variations may be associated with disturbance of body water balance, such as massive hemorrhage and dehydration.

Adult↗

Genetic variability of respiratory syncytial virus subgroup a strain in 15 successive epidemics in one city.

The genetic variability of 125 respiratory syncytial virus (RSV) subgroup A isolates over 15 successive epidemics from 1980 to 1995 in an urban population of Japan was determined. Allocation of isolates into lineages was archived by reverse transcriptase-polymerase chain reaction amplification of selected regions of the nucleoprotein (NP) and attachment (G) protein gene followed by restriction fragment length polymorphism (RFLP) analysis. Three and seven distinct restriction patterns of the NP and G gene were observed, respectively. When the NP and G gene RFLP analyses were combined, ten different genetic lineages were identified in the 125 isolates. The strains with the same genotype were isolated in each epidemic and the dominant lineages were replaced by others after every one to three consecutive epidemics. Nucleotide and amino acid sequencing of the variable region of G gene of these predominant isolates revealed differences of 5--28% between strains. There was, however, no apparent accumulation of diversity with age to indicate progressive changes. The dominant strains were often closely related to those isolated in other parts of the world at a similar time. These observations suggest that dominant RSV strains are replaced frequently by others that have been co-circulating or have recently entered the community from a worldwide reservoir. The change of dominant strains may be influenced by the buildup of immunological resistance in the community to successive epidemics of the same strain.

Amino Acid Sequence↗

Sensitive detection and differentiation of Sapporo virus, a member of the family Caliciviridae, by standard and booster nested polymerase chain reaction.

Norwalk virus and Sapporo virus (SV) were approved as type species of the genus Norwalk-like viruses and the genus Sapporo-like viruses, respectively, in the family Caliciviridae. Nested polymerase chain reaction (PCR), using newly designed primers in the RNA-dependent RNA polymerase region, was developed to detect and differentiate viruses in the three genetic groups of SV based on the relative size of the PCR products obtained. In addition, a booster nested PCR that performs nested PCR in a single tube was introduced to reduce the chance of contamination during the procedure of standard nested PCR. The specificity of the newly developed PCR was confirmed by testing 77 stool specimens and 16 tissue culture fluids derived from growth of unrelated viruses. The sensitivity of the nested PCR was compared with the conventional PCR using Sapp35/Sapp36 primer pair by testing the three cDNA clones obtained from viruses in the SV/SV82, the SV/London92, and the SV/Parkville virus, respectively. This assay can detect SV in a more sensitive way than the conventional PCR and Southern hybridization. Sensitive and suitable methods to detect and differentiate SV are required to obtain accurate epidemiological data on these viruses and the standard and booster nested PCR should be a very useful tool for this purpose.

Caliciviridae↗

Genetic variability of respiratory syncytial virus subgroup B strain isolated during the last 20 years from the same region in Japan: existence of time-dependent linear genetic drifts.

The genetic variability of 32 respiratory syncytial virus (RSV) sub-group B isolates from a single community in Japan during the 20 years from 1980 to 1999 was determined. Two variable regions of the attachment (G) protein gene were amplified by reverse transcriptase-polymerase chain reaction amplification and their products were sequenced directly. Phylogenetic analysis of nucleotide sequences revealed seven distinct branches in which strains isolated during seasons of close proximity were located: however, isolates from the same season were often in plural branches. There was a tendency for recent isolates to lie at the end of each branch and these linear evolutionary changes were typically represented in a branch containing nine strains isolated during 6 seasons from '80 to '86. Three kinds of usages of stop codons were confirmed and isolates located in each branch used the same stop codons. These observations suggest that there are multiple subgroup B lineages co-circulating and that each lineage strain may exhibit linear evolutionary genetic drifts in order to survive over successive epidemics within the same population, although it has a conserved uniform G protein length with the use of the same stop codon.

Amino Acid Sequence↗

Genetic relatedness and variability in inbred and wild populations of the solitary ascidian Ciona intestinalis revealed by arbitrarily primed polymerase chain reaction.

As the first step in the establishment of inbred Ciona intestinalis strains, the genetic backgrounds of several local populations were evaluated on the basis of comparing 313 random amplified polymorphic DNA (RAPD) loci. Cluster analyses of individuals indicated that this species has local genetic characteristics, although various genetic distances among the populations were relatively low. The bulked RAPD analyses revealed that populations from Torihama and from Onagawa were the most distantly related among the 7 populations examined, suggesting that these two populations are the best candidates for outbreeding. Successive inbreeding in the laboratory was achieved using the Onagawa population. Although the genetic similarity of the F(4) progeny became distinctly higher than that of natural populations, F(5) progeny did not survive, presumably owing to homozygous lethal alleles.

Journal Article↗

Expression of peripheral myelin protein zero in sural nerve of patients with Charcot-Marie-Tooth disease 1B.

A Charcot-Marie-Tooth disease 1B (CMT1B) family with a mutation of the Po gene is presented. A to G substitution of nucleotide 389 in exon 3 resulted in Lys 131 Arg substitution. Immunostaining for Po in biopsied sural nerve from one family member with CMT1B was expressed in a small number of myelinated fibers. Immunoblot analysis for Po revealed that it was of normal molecular weight (29 kDa) although significantly reduced in amount. This heterozygous mutation could lead to a reduction in the total amount of normal protein in peripheral nerves through a mechanism of loss of function.

Amino Acid Substitution↗

Fukuyama muscular dystrophy associated with lack of C-terminal domain of dystrophin.

The first reported female patient with the Fukuyama type of congenital muscular dystrophy associated with a lack of C-terminal domain of dystrophin is presented. Clinically, the patient had characteristic features and magnetic resonance imaging findings of Fukuyama muscular dystrophy. Dystrophin analysis revealed a lack of the C-terminal domain but preserved N-terminal and rod domains of dystrophin in biopsied muscle. Moreover, she had reduced expression of merosin, syntrophin, and beta-dystroglycan in the skeletal muscle. Reverse transcriptase-polymerase chain reaction analysis of mRNA in the patient's muscle illustrated a complete lack of exons 71-74 of the dystrophin gene. These deletions, which remove the beta-dystroglycan and syntrophin binding site, may cause changes in the function of both beta-dystroglycan and syntrophin in human muscle.

Alcohol Oxidoreductases↗

A double mutation in a patient with X-linked myotubular myopathy.

In this report a double mutation was identified in a patient with X-linked myotubular myopathy. The mutations present in the patient were a C-->T substitution of nucleotide 163, which led to an Arg 55 stop codon (nonsense mutation), and an "A" insertion at nucleotide 440, which caused a shift of the reading frame and a premature stop at codon 153 (frameshift mutation). The nonsense mutation was heterozygously present in the mother but not identified in the father or in normal controls. The frameshift mutation was not identified in either parent or normal controls (de novo mutation). These mutations are predicted to truncate the myotubularin protein.

Codon, Nonsense↗

Existence of different alpha(1)-adrenoceptor subtypes in junctional and extrajunctional neurovascular regions in canine splenic arteries.

The present study attempted to characterize the alpha(1)-adrenoceptor subtypes mediating vasoconstrictor responses to administered and nerve stimulation-evoked noradrenaline (NA) release in the isolated and perfused canine splenic artery. A previous study demonstrated that periarterial electrical nerve stimulation (30 s trains of pulses at a frequency of 1, 4 or 10 Hz) induced a double peaked vasoconstriction consisting of an initial transient, predominantly P2X-purinoceptor-mediated constriction followed by a prolonged, mainly alpha(1)-adrenoceptor-mediated response in the canine splenic artery. The effects of alpha(1)-adrenoceptor subtype antagonists on neuronally-mediated second peaked vasoconstrictions were analysed. BMY 7378 (10 - 100 nM), a selective alpha(1D)-adrenoceptor antagonist produced a dose-dependent inhibition of the second peak responses at all frequencies used. BMY 7378 (100 nM) reduced these responses by approximately 30%. Exposure of tissues to chloroethylclonidine (CEC, 60 microM), a selective alpha(1B)-adrenoceptor antagonist attenuated the second peak response by approximately 60%, even in the presence of BMY 7378 (100 nM). On the other hand, WB 4101 (100 nM), a selective alpha(1A)-adrenoceptor antagonist potentiated nerve-stimulation-evoked double peaked vasoconstrictions, especially at low frequencies (1 and 4 Hz). Vasoconstrictor responses to administered NA were dose-dependently antagonized by WB 4101 (10 - 100 nM), but were not significantly affected by either BMY 7378 (10 - 100 nM) or by CEC (60 microM). The present results indicate that NA released from sympathetic nerves may junctionally exert its vasoconstrictor effect via activation of postjunctional alpha(1B)- and in part alpha(1D)-adrenoceptors, whereas exogenous NA extrajunctionally activates alpha(1A)-adrenoceptors to produce its vascular action in canine splenic arteries.

Adrenergic alpha-Agonists↗

High within-population mitochondrial DNA variation due to microvicariance and population mixing in the land snail Euhadra quaesita (Pulmonata: Bradybaenidae).

A high level of geographical variation at an exceptionally fine scale was detected in the mitochondrial 16S ribosomal RNA genes of a land snail species Euhadra quaesita from the Kanto region of Japan. In total, 50 haplotypes were detected from 27 populations, with most sample sites possessing private alleles. In some individual populations the different haplotypes do not fall as a monophyletic group, so that some of the haplotypes are phylogenetically distant, differing from each other by > 10%. In contrast, phylogenetically similar haplotypes were found in separate sites at long distances from their main distribution. Together, these findings strongly suggest that contraction and expansion of populations has occurred repeatedly in the past. The subsequent expansion of populations and migration from different areas may have mixed distant populations. This repetition of isolation and mixing has resulted in an exceptionally fine scale of geographical variation, and the accumulation of high genetic diversity within and between populations of this species.

Alleles↗

Vascular responses to beta-adrenoceptor subtype-selective agonists with and without endothelium in rat common carotid arteries.

1. Using the cannula inserting method, vasodilator responses to beta-adrenoceptor agonists (isoprenaline, denopamine and procaterol) were investigated in isolated and perfused rat common carotid arteries. 2. Each beta-adrenoceptor agonist induced a vasodilation in preparations preconstricted by phenylephrine in a dose-related manner. The potencies were in the order of isoprenaline > procaterol >> denopamine. 3. Denopamine-induced dilations were significantly inhibited by 1 nmol betaxolol (a selective beta1-adrenoceptor antagonist), but it was not influenced by 1 nmol ICI 118,551 (a selective beta2-adrenoceptor antagonist). On the other hand, procaterol-induced vasodilations were significantly inhibited by 1 nmol ICI 118,551 but not modified by 10 nmol betaxolol. 4. ACh-induced vasodilations disappeared after intraluminal saponin injection to remove endothelium, but procaterol- and denopamine-induced dilations were not modified by removal of the endothelium. 5. Pretreatment with L-NG-nitroarginine methyl ester (L-NAME) readily inhibited ACh-induced vasodilations. However, neither procaterol- or denopamine-induced vasodilation was modified by L-NAME treatment. 6. From these results, it is concluded that in the rat common carotid arteries (1) there are abundant beta2- and a few beta1-adrenoceptors, and (2) there is no participation of the endothelium-dependent mechanism in beta-adrenoceptor mediated vasodilations.

Adrenergic beta-1 Receptor Agonists↗