Biomedical subjects

T Takeda

Publications and source records attributed to T Takeda.

At least 325 records · Page 18Linked to original sources

PubMed1998

[Prospective matched control study concerning the treatment and quality of life of hemophiliacs with inhibitors].

Factor VIII (IX) inhibitors represent one of the most serious problems for the treatment of patients with hemophilia. The Blood Products Research Organization (Japan) has supported a study group for treatment of hemophiliacs with inhibitors. In 1995 the study group started a prospective matched control study of hemophiliacs with and without inhibitors and compared such factors as quality of life and economic cost. Each inhibitor patient was matched with a control patient in terms of age, type of hemophilia, and severity of hemophilia. A total of 136 patient-pairs were enrolled. Bleeding episodes were more frequent in the control group than in the inhibitor group. Days of hospitalization, days in wheelchairs, and the number of impaired joints were significantly higher for the inhibitor group. Number of blood-product infusions, days of bed rest at home, and days of brace use were the same for both groups. Blood-product expenditures were significantly higher for the inhibitor group than for the control group (yen 10,872,283/patient/year vs. yen 4,327,542/patient/year). Our study highlighted the higher cost of treatment and lower quality of life for hemophiliaes with Factor VII inhibitors.

Adult↗

PubMed1998

[A case of lymphocytic interstitial pneumonia].

A 56-year-old female was admitted on November 1995 to our hospital because of the abnormal shadow on her chest X-ray. Although the chest X ray film revealed diffuse reticulonodular shadows in the bilateral lung fields and right hilar lymphadenopathy, she had not any complaints. Furthermore, mediastinal lymphadenopathy and polyclonal hypergammaglobulinemia were noted. For a further examination, transcutaneous thoracoscopic lung biopsy was performed on August 1996. The lung specimens showed a interstitial infiltration of small lymphocytes exclusively around bronchioles. And the diagnosis of lymphocytic interstitial pneumonia (LIP) was made. She had been suffered from bronchial asthma for 27 years. This is the first report of LIP accompanied with bronchial asthma. Its relationship between LIP and bronchial asthma remains unclear. In the 2 years of follow-up, she remained asymptomatic with unchanged chest radiogram. And her pulmonary function was preserved for the 2 years. But lymphocytic interstitial pneumonia may induce malignant lymphoproliferative disease potentially, we should carefully follow up.

Asthma↗

PubMed1998

[An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis].

A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.

Aged↗

PubMed1997

Alternative mRNA splicing of 3'-terminal exons generates ascorbate peroxidase isoenzymes in spinach (Spinacia oleracea) chloroplasts.

We have isolated two cDNA clones encoding spinach (Spinacia oleracea) stromal and thylakoid-bound ascorbate peroxidase isoenzymes [Ishikawa, Sakai, Yoshimura, Takeda and Shigeoka (1996) FEBS Lett. 384, 289-293]. The gene (ApxII) encoding both chloroplastic ascorbate peroxidase isoenzymes was isolated and the organization of the gene was determined. Alignment between the cDNAs and the gene for chloroplastic ascorbate peroxidase isoenzymes indicates that both enzymes arise from a common pre-mRNA by alternative splicing of two 3'-terminal exons. Genomic Southern-blot analysis supported this finding. The gene spanned nearly 8.5 kbp and contained 13 exons split by 12 introns. The penultimate exon 12 (residues 7376-7530) for the stromal ascorbate peroxidase mRNA consisted of one codon for Asp365 before the TAA termination codon, and the entire 3'-untranslated region, including a potential polyadenylation signal (AATAAA). The final exon 13 (residues 7545-7756) for the thylakoid-bound ascorbate peroxidase mRNA consisted of the corresponding coding sequence of the hydrophobic C-terminal region, the TGA termination codon and the entire 3'-untranslated region, including a potential polyadenylation signal (AATATA). Both exons were interrupted by a 14 bp non-coding sequence. Northern-blot and reverse transcription-PCR analysis showed that the transcripts for stromal and thylakoid-bound ascorbate peroxidase are present in spinach leaves.

Alternative Splicing↗

PubMed1997

Sensory feedback contributes to early movement-evoked fields during voluntary finger movements in humans.

Neuromagnetic field changes accompanying voluntary movement in humans ('movement-evoked fields' or MEFs) were recorded over the scalp using a whole-head MEG system during the performance of self-paced finger movements in order to determine the contribution of sensory feedback to the generation of these brain responses. It was found that cooling the subject's arm resulted in delays of 8 ms or more in the latency of the early movement-evoked field component (MEFI). These delays were attributed to increases in conduction times in the afferent pathways as confirmed by electrically evoked somatosensory responses and suggest a peripheral origin of the MEFI. In a second experiment, we demonstrated the effects of sensory input to the contralateral hand during a simple button pressing task in 4 subjects. The results indicated that responses over the hemisphere ipsilateral to the side of movement which resembled previously reported ipsilateral MEFs can be elicited by the spread of mechanical stimulation to opposite side of the body when a mechanical trigger is used. These experiments provide further evidence that early movement-evoked fields produced by unilateral finger movements are observed primarily over the contralateral somatosensory cortex and represent sensory feedback to the somatosensory cortex from the periphery.

Arm↗

PubMed1997

Direct demonstration of the bifunctional property of Tetrahymena 14-nm filament protein/citrate synthase following expression of the gene in Escherichia coli.

Tetrahymena 14-nm filament protein/citrate synthase (49K protein) is a bifunctional protein with roles in the cytoskeleton and as a citrate synthase. Though previous studies have shown that the 49K protein is derived from a single transcript of a single gene, direct demonstration of the 49K protein's bifunctional property remained to be elucidated. In this study, a recombinant 49K protein was expressed in Escherichia coli, purified and characterized. The citrate synthase activity of the recombinant 49K protein was comparable to that of the 49K protein purified from Tetrahymena. The recombinant 49K protein formed 14-nm filaments, but only of short length. The filaments were elongated in the presence of a soluble fraction of Tetrahymena. These results suggest that the 49K protein itself is bifunctional, but some co-factor(s) is necessary for elongation of filaments.

Amino Acid Sequence↗

PubMed1997

Purification, characterization and cloning of a novel variant of the superantigen Yersinia pseudotuberculosis-derived mitogen.

The novel superantigen designated as Yersinia pseudotuberculosis-derived mitogen typeB (YPMb) was purified from the cell lysate of Y. pseudotuberculosis O:6 strain (R-104). Proliferative response of human peripheral blood mononuclear cells to the purified YPMb was detectable at a concentration of as low as 1 pg/ml, that is comparable to the previously documented YPM (YPMa). The Vbeta repertoire specificity (3, 9, 13.1 and 13.2) of YPMb was also the same as that of YPMa. A gene (ypmB) encoding YPMb was cloned and its nucleotide sequence was determined. The open reading frame (ORF 453 bp) of the ypmB encodes a protein with 150 amino acid residues, though the precursor protein of YPMa consists of 151 amino acid residues. There is a nucleotide sequence homology of 88.9% between ypmB and ypmA. The low homology in the downstream of the structural gene between ypmB and ypmA and the difference in the GC content in the ORF of ypmB and ypmA from that of the base usage of Y. pseudotuberculosis suggest that the ypm gene originates from another organism. The alignment of the amino acid sequences of mature proteins of YPMb and YPMa revealed that there is 83% homology (108 amino acid residues are identical). Between YPMa and YPMb, the central region is less homologous than the N- and C-terminal regions. Based on the functional similarity of two superantigen molecules, the less homology suggested that the central region is less important for the function of both YPM molecules.

Amino Acid Sequence↗

PubMed1997

Vasopressin and oxytocin receptor mRNAs are expressed in the rat inner ear.

The cause of endolymphatic hydrops, a characteristic finding in Menière's disease, is not known. To study the possible involvement of the neurohormones vasopressin and oxytocin in this condition, we investigated whether transcripts of the genes encoding the arginine vasopressin (AVP) and oxytocin receptors are expressed in the rat inner ear. Utilizing the reverse transcription-polymerase chain reaction (RT-PCR) method, primers specific for each receptor showed a single message band of the expected size in the rat inner ear. When the PCR products were cloned, the sequences were identical to those of the real-type (V2) AVP receptor and oxytocin receptor transcripts. The finding of vasopressin and oxytocin receptor mRNAs in the inner ear suggests that these neurohypophyseal hormones may have roles in the regulation of inner ear fluid. In particular, the presence of vasopressin receptor mRNA in the inner ear supports the hypothesis of a relationship between high plasma vasopressin levels and endolymphatic hydrops.

Animals↗

PubMed1997

Oct-1, silencer sequence, and GC box regulate thyroid hormone receptor beta1 promoter.

Thyroid hormone, acting through thyroid hormone receptors (TRs), plays a crucial role in brain development and its insufficiency results in irreversible brain damage. TR alpha mRNA is expressed continuously from early embryonic stages, but the level of TR beta1 mRNA in brain is more abundant in adult than in fetus. To identify important factors which regulate TR beta1 expression, we compared mouse fetal and adult brain nuclear extracts by DNase I footprinting and electrophoretic gel mobility shift assays (EMSA) of the TR beta1 promoter. We carried out transient transfection studies in COS 1 cells using the TR beta1 promoter fused to Luciferase gene, and used mutated promoter vectors and various expression vectors. In DNase I footprinting using the fragment -950 to -717, fetal brain nuclear extracts protected the areas -910 to -884 and -815 to -800 more than did adult extracts. In EMSA, proteins in fetal nuclear extracts bound to a silencer sequence (-924 to -916), GC box (-901 to -887), and E box (-810 to -805), more strongly than did proteins in adult brain extracts. The bands formed on GC box were not supershifted by Sp-1, Sp-2, Sp-3, Sp-4, EGR-1, or EGR-2 antibodies. Three bands were detected on the octamer binding site probe (-913 to -906) and one protein was supershifted by Oct-1 antibody. Adult brain extracts appear to contain more Oct-1 protein than do fetal extracts. The other two bands were more intense in fetal extracts than in adult extracts, but were not supershifted by either Oct-1 or Oct-2 antibodies. Mutation of the silencer response element, mutation of the GC box, and Oct-1 over expression in COS 1 cells increased TR beta1 promoter function as assayed by Luciferase reporter. Mutation of the octamer binding site, to which only Oct-1 bound in COS 1 cells, decreased Luciferase reporter activity. Thus the TR beta1 promoter was regulated negatively by the proteins bound to the silencer sequence and the GC box, and positively by Oct-1. Silencer and GC box binding proteins are more abundant in fetal brain, and Oct-1 is more abundant in adult brain. The results may be responsible for increased amounts of TR beta1 present in late fetal and adult brain.

Animals↗

PubMed1997

Beta-trace gene expression is regulated by a core promoter and a distal thyroid hormone response element.

We isolated and characterized the human beta-Trace protein (betaTP) gene promoter. betaTP, also known as prostaglandin D2 synthase, is a lipocalin secreted from the choroid plexus and meninges into cerebrospinal fluid. Basal transcription of the betaTP gene is directed from a core promoter found within the first 325 bases of the 5'-flanking sequence. The betaTP gene promoter is responsive to thyroid hormone (3,3',5-triiodothyronine, T3) and efficiently repressed by unliganded human thyroid hormone receptor beta (TRbeta). Functional analysis of the betaTP promoter in TE671 cells revealed that responsiveness to T3 occurs in sequences 2.5 kilobase pairs 5' of the start site. Within the hormone-responsive region we identified a thyroid hormone response element (TRE) located from -2576 to -2562 base pairs relative to the transcription start site. The betaTP TRE is composed of two directly repeated consensus half-sites separated by a 3-base pair space (DR3). The betaTP TRE forms specific complexes with TRbeta. We have shown that a gene active in the choroid plexus and meninges is responsive to T3. T3 may play a role in the regulated transport of substances into the cerebrospinal fluid and ultimately the brain.

Base Sequence↗

PubMed1997

Mass screening for neuroblastoma and mortality in birth cohorts.

Mortality resulting from neuroblastoma in birth cohorts in both Sapporo City and the whole of Japan was investigated to evaluate the effects of a high-performance liquid chromatography (HPLC) mass screening program, targeting on 6 month-old infants. In Sapporo City, the non-HPLC screened cohort showed no reduction in mortality at 4 years of age compared with the pre-screening cohort. However, the HPLC screened cohort showed a reduction of 69% in mortality compared with the pre-screening cohort. On a nation-wide scale, there was a significant decline in mortality for the non-HPLC screened cohort compared with the pre-screening cohort; for the HPLC screened cohort for 1989-1991, there was also a reduction in mortality for children younger than 2 years of age. The incidence of neuroblastoma at 1-4 years of age in the HPLC cohort in Sapporo City was about half that in the pre-screening cohort, along with and probably because of an increasing incidence among infants in the same cohort. Our findings suggest that HPLC screening may detect some poor-prognosis neuroblastoma cases at early stages, thus providing for more favorable therapy.

Adolescent↗

PubMed1997

Human cortico-hippocampal activity related to auditory discrimination revealed by neuromagnetic field.

We carried out multi-dipole estimation and pursued spatio-temporal brain activity on a time scale of several milliseconds during an auditory discrimination task using a whole-cortex type SQUID system. Neuronal activities were estimated in the medial (hippocampus, parahippocampal gyrus, etc.) and lateral temporal cortices (superior and middle temporal gyri, etc.), the dorsolateral prefrontal cortex (middle and inferior frontal gyri, etc.) and the parietal cortex (supramarginal gyrus, etc.) in the 280-400 ms latency range. The activity in the posterior hippocampal region was the most prominent and long-lasting in parallel with the activities in the other regions. Therefore, the posterior hippocampal region is a central structure engaged in auditory discrimination. The whole-cortex neuromagnetic measurements provided the possibility of imaging the time-varying activities of the human cortico-hippocampal neural networks.

Adult↗

PubMed1997

Clinical role for a superantigen in Yersinia pseudotuberculosis infection.

Yersinia pseudotuberculosis is an enteric pathogen that causes a variety of clinical symptoms in the human. Recently, we reported the production of a superantigen (Y. pseudotuberculosis-derived mitogen, YPM) by this organism and characterized the gene structure of ypm. To further study the potential pathogenic role of YPM in Y. pseudotuberculosis infection, we assayed IgG anti-YPM antibodies and T cell antigen receptor-Vbeta expression of the T cells in peripheral blood and in mesenteric lymph node in patients acutely infected with Y. pseudotuberculosis. 20 out of 33 patients (61%) had an elevated antibody titer compared with healthy controls (P = 0.0001). Patients with systemic symptoms such as lymphadenopathy, transient renal dysfunction, and arthritis had significantly higher titers of anti-YPM than patients with gastrointestinal tract symptoms alone. T cells bearing the Vbeta3 gene segment were significantly increased (P = 0.009) among acute phase patients compared with healthy children. During the convalescence phase of the illness, there was a reduction in the abnormal level of Vbeta3 T cells. Moreover, in the mesenteric lymph node, an elevated level of Vbeta3 T cells compared with peripheral blood and a sequence diversity in the junctional region of the T cell antigen receptor beta-chain containing Vbeta3 element was observed in one patient. Together, these findings suggest that YPM was produced in vivo and played an important role in the pathogenesis of Y. pseudotuberculosis infection.

Adolescent↗

PubMed1997

The function of retinoid X receptors on negative thyroid hormone response elements.

Retinoid X receptors (RXRs) form heterodimers with thyroid hormone receptors (TRs). RXRs increase DNA binding affinity of TRs and T3-mediated transactivation on positive T3 response elements (TREs). However, the role of RXRs on negative TREs, and the relation of RXRs to the dominant negative effect of mutant TRs, are not defined. To clarify the function of RXRs on negative TREs, we performed transient cotransfection studies using the rat glycoprotein hormone alpha promoter fused to luciferase gene (alphaLuc), and human TRH promoter fused to luciferase gene (TRH-Luc) as reporters. We found that the JEG-3 cell-alphaLuc system was very sensitive to TR regulation. Using TRbeta1 wild-type (WT) expression vector, 6.2 ng/well (170 ng/10 cm dish), and 0.2 ng/well (11 ng/10 cm dish) caused maximal, and half maximal, inhibition of Luc activities in the presence of 1 nM T3. A T3 dose dependent inhibition study was also performed. From these studies, we determined that the appropriate conditions in which to study alphaLuc transactivation, in a linear portion of the dose response curve, was using 0.8 ng/well TRbeta1 expression vector and 0.1 nM T3. Under these conditions, TRbeta1 mutant R316H (GH), but not G345R (Mf), showed a weak dominant negative effect at a 1:1 ratio in the presence of 0.1 nM T3 although neither mutant had detectable T3 binding affinity. Moreover this dominant negative effect of R316H on the alphaLuc reporter was enhanced in the presence of RXRgamma. Mutant G345R showed a stronger dominant negative effect than did R316H when using a double palindromic TRE fused to herpes simplex thymidine kinase-Luc reporter as a positive TRE. These results conform to the clinical features of R316H which is associated with apparent pituitary resistance of thyroid hormone (PRTH). Mutant R316H also showed a weak dominant negative effect with TRH-Luc at a 1:1 ratio in the absence or presence of RXRgamma. However RXRgamma did not enhance the dominant negative effect as it did using alphaLuc reporter gene. Electrophoretic gel mobility shift assay (EMSA) showed that RXR alpha augmented the DNA binding affinity of wild type and R316H TRs as heterodimers on the previously reported negative TREs of glycoprotein hormone alpha promoter, suggesting that RXR does not produce its response by removing TRs from these TREs. RXR alpha augmented DNA binding affinity of TRbeta1WT, and R316H showed a weaker heterodimer band than did the wild type in EMSA. Using the TRH-Luc reporter, basal activity was increased by wild type TRbeta1. However a TRbeta1 DNA binding domain mutant, (C127S) which can not bind to DNA, did not increase the basal activity. This indicates that DNA binding of the TR is required for increasing basal activity of TRH promoter. These results indicate that (1) RXR-TR heterodimers play a role in basal transactivation and T3 suppression of negatively regulated genes, and (2) RXRs increase the dominant negative effect of some mutant TRs on specific negative TREs. (3) This effect occurs without removing TRs from the TRE. (4) The differential dominant negative effect of mutant R316H (negative TRE > positive TRE) may explain, at least in part, the presentation of R316H as PRTH. (5) Augmentation of basal activity by wild type TRs on a negative TRE requires DNA binding.

Animals↗

PubMed1997

Functional characterization of the fission yeast Start-specific transcription factor Res2.

In the fission yeast Schizosaccharomyces pombe, transcriptional activation at Start is mediated by complexes that bind the MCB. Two such complexes have been identified; both contain the Cdc10 protein in partnership with either the Res1 or Res2 protein. Characterization of null mutants suggests that the Res1-Cdc10 complex predominantly functions in mitotic cells whereas the Res2-Cdc10 complex is required for meiosis and spore formation. Here we have characterized the functional domains of the Res2 protein. The N-terminus is both necessary and sufficient for DNA binding, whereas the C-terminus is the region involved in the interaction with the Cdc10 protein. The centrally located ankyrin repeats are dispensable for both functions. Res2 binds to DNA as a dimer. In addition, complexes containing both Res1 and Res2 can form and bind to DNA in vitro. Furthermore, the major MCB-specific complex detected in extracts from wild-type cells contains Res1 and Res2; the complex is lost when either gene is deleted and can be recognized by antibodies specific to both proteins. In order to understand the basis for the specific function of Res2 in meiosis, hybrids between Res1 and Res2 were constructed and their functions analysed. The results indicate an absolute requirement for the Res2 C-terminus for normal meiosis to occur whereas the origin of the DNA-binding region is irrelevant. The implications of these results for the regulation of the MCB-binding complexes will be discussed.

Cell Cycle Proteins↗

PubMed1997

Detection of C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP-B) receptor mRNAs in rat inner ear.

C-Type natriuretic peptide (CNP) is the third member of the natriuretic peptide family which plays an important role in body fluid homeostasis. To determine a possible role of CNP in regulation of an inner ear fluid, we investigated the expression of CNP and atrial natriuretic peptide B receptor (ANP-B receptor) mRNAs in rat inner ear using a reverse transcription polymerase chain reaction (RT-PCR) method. Amplification products with sizes expected for CNP and ANP-B were detected in the inner ear. After cloning and analysis, the sequences for PCR products were identical to those of CNP or ANP-B receptor in the brain. These results indicate that both CNP and ANP-B receptor are expressed in the inner ear of the rat and suggest that CNP may play a role in inner ear function (such as regulation of inner ear fluid) in an autocrine and/or paracrine manner.

Animals↗

PubMed1997

Nucleotide sequence of a gene encoding the novel Yersinia enterocolitica heat-stable enterotoxin that includes a pro-region-like sequence in its mature toxin molecule.

A novel ST (Y-STc) produced by a pathogenic strain of Yersinia enterocolitica was recently purified and the mature toxin was found to include the pro-region-like sequence (Yoshino et al., FEBS Lett 362: 319-322, 1995). In the present study, we report the nucleotide sequence of the ystC gene. We also present the amino acid sequence of a ystC gene product secreted by a recombinant strain of Escherichia coli. From the nucleotide sequence of ystC gene, the Y-STc precursor protein was deduced to consist of 72 amino acid residues and to be comprised of two regions (pre- and mature toxin regions), while the known ST precursor proteins are comprised of three regions (pre-, pro-, and mature toxin regions). Therefore, we concluded that a long polypeptide corresponding to a pro-toxin of other Sts is secreted as the Y-STc mature toxin. This implies that the proteolytic processing of a pro-form appearing in the periplasm is not essential for the secretion of Yersinia-ST to the extracellular through the outer membrane. The recombinant Y-STc released by E. coli was found to be shorter and composed of C-terminal 24 amino acid residues of the native Y-STc. On the basis of these results, we propose that the cleavage site between the pro- and mature toxin regions of ST depends on both the amino acid sequence of the pro-toxin and on the bacterial protease system responsible for the maturation.

Amino Acid Sequence↗

PubMed1997

The novel heat-stable enterotoxin subtype gene (ystB) of Yersinia enterocolitica: nucleotide sequence and distribution of the yst genes.

The gene (ystB) encoding the novel subtype of the heat-stable enterotoxin (Y-STb) was cloned from the chromosome of a clinical isolate of Yersinia enterocolitica 84-50 (serotype O:5, biotype 1A) and the nucleotide sequence was determined. The ystB contained 216 base pairs that encoded a protein of 71 amino acid residues. The C-terminal 30 residues of the precursor protein exactly corresponded to the amino acid sequence of the Y-STb toxin, purified from the culture supernatant of the wild strain. Homology search revealed that there are 76.9% nucleotide sequence similarity between ystB and the Yersinia kristensenii ST gene, and 73.5% with the Y. enterocolitica prototype sequence of yst (ystA). When tested with the PCR generated ystB specific probe, 36 of 304 Y. enterocolitica strains from 18 countries hybridized with the probe. All the ystB probe positive strains belonged to biotype 1A and mostly to the so-called non-pathogenic serotype O:5, O:6, O:7,8 O:7,13 and O:10, while ystA was predominantly found among the pathogenic serotypes (78.5%). Out of 36 ystB gene positive strains, 18 were clinical origin from six countries, which were also positive in the suckling mice assay suggesting that ystB may play an important role in the pathogenesis, and the so-called non-pathogenic serotypes could be virulent for human.

Amino Acid Sequence↗