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Biomedical subjects

T Tamura

Publications and source records attributed to T Tamura.

At least 451 records · Page 25Linked to original sources
PubMed1997

[Sézary syndrome with two lymphocyte subpopulations expressing either CD4+/CD8- or CD4-/CD8+].

A 61-year-old man was admitted in March 1996 complaining of erythroderma, and Sézary syndrome was diagnosed. The leukocyte count was 33,590/microliter with 70.9% abnormal lymphocytes expressing two different types of antigenicity, either CD4+/CD8- (44.5%) or CD4-/CD8+ (48.9%). Clonal T-cell receptor beta rearrangement was not found on Southern blot analysis. He suffered repeated sepsis dueto methicillin-resistant Staphylococcus aureus. Combination chemotherapy was not effective for erythroderma and organomegaly, and deoxycoformycin revealed a transient effect. He died of MRSA enterocolitis in July 1996.

CD4 Antigens↗
PubMed1997

Classification of acceleration waveforms during walking by wavelet transform.

In this study we have attempted to classify the acceleration signal, while walking both at horizontal level, and upstairs and downstairs, using wavelet analysis. The acceleration signal close to the body's center of gravity was measured while the subjects walked in a corridor and up and down a stairway. The data for four steps were analyzed and the Daubecies 3 wavelet transform was applied to the sequential data. The variables to be discriminated were the waveforms related to levels -4 and -5. The sum of the square values at each step was compared at levels -4 and -5. Downstairs walking could be discriminated from other types of walking, showing the largest value for level -5. Walking at horizontal level was compared with upstairs walking for level -4. It was possible to discriminate the continuous dynamic responses to walking by the wavelet transform.

Acceleration↗
PubMed1997

[A 13-week subchronic oral toxicity study of carob germ colour in F344 rats].

A13-week subchronic oral toxicity study of carob germ colour, one of natural colour additives was carried out in F344 rats at dose levels of 5.0, 1.7, 0.6, 0.2 and 0% in the powdered diet. Rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No animals died during the experiment and no changes in body weights and food intakes were observed in any dosed groups. Changes indicating obvious toxicity of carob germ colour were not observed in the organ weights, hematological, serum biochemical and histopathological examinations. These findings indicate that the treatment of 5% carob germ colour in diet for 13 weeks did not cause any significant toxicity in rat.

Administration, Oral↗
PubMed1997

Serum levels of pro-gastrin-releasing peptide for follow-up of patients with small cell lung cancer.

To assess the clinical usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for small cell lung carcinoma (SCLC), we measured serum levels of Pro-GRP with a newly developed ELISA and measured serum levels of neuron-specific enolase (NSE) in 44 patients with untreated SCLC and 77 patients with untreated non-SCLC. We prospectively measured serum levels of Pro-GRP and NSE in SCLC patients after initial treatment until relapse. The sensitivity (70%) and specificity (91%) of Pro-GRP were similar to those of NSE (70 and 86%). Thirty-nine % of patients who had a partial response still had elevated serum levels of Pro-GRP at the time of restaging after initial treatment. In follow-up study, 94% of patients had elevated serum levels of Pro-GRP again at the time of relapse, whereas 37% of patients showed elevated levels of NSE. Levels of Pro-GRP increased a median of 35 (-95 to 151) days before clinical evidence of relapse was detected with successive physical examinations and imaging studies, whereas levels of NSE increased 20 (-85 to 124) days after relapse was detected (P < 0.05). Pro-GRP was helpful as a diagnostic aid and a marker for therapeutic effect and relapse in patients with SCLC, supplemented to serum NSE.

Adult↗
PubMed1997

Limited sampling model for the area under the concentration versus time curve of irinotecan and its application to a multicentric phase II trial.

We previously established a limited sampling model (LSM) for the area under the concentration versus time curve (AUC) of irinotecan (CPT-11). Using this LSM, we performed a pharmacokinetic-pharmacodynamic analysis of CPT-11 in a multicentric Phase II study for non-small cell lung cancer. Ten institutes participated in this study, 36 patients were registered, and 30 patients were evaluable for the pharmacokinetic-pharmacodynamic analysis. CPT-11 and etoposide were administered daily for three consecutive days, both at a dose of 60 mg/m2. Blood samples were obtained 4 and 8 h after infusion on days 1 and 3. When using the LSM, there is a significant possible source of error in the timing of these selected points. In this study, however, the sample timing error was small. Mean timing errors were 1.0-4.0 min at each point. The estimated CPT-11 AUCs were: Day 1 Day 2 Day 1 + 3 Mean +/- SD (mg.h/liter) 3.76+/-0.68 4.10+/-0.86 7.86+/-1.43 Range 2.01-5.03 2. 29-5.72 4.30-10.68 Max/min 2.50 2.45 2.48 High interpatient variability was observed in the AUC. The CPT-11 AUC correlated positively with the grade of emesis (P = 0.003) and the percent decreases in WBC count (P = 0.001) and absolute neutrophil count (P =0.0006), but it did not correlate with the grade of diarrhea or response. We concluded that the LSM was useful in estimating individual pharmacokinetic parameters in multicentric trials.

Aged↗
PubMed1996

Molecular cloning of a novel 120-kDa TBP-interacting protein.

TATA-binding protein (TBP) is a central component for transcriptional regulation and is a target for various transcription regulators. Using histidine-tagged TBP as a ligand for affinity-purification of proteins bound to TBP, we purified a 120-kD protein, termed TBP-interacting protein 120 (TIP120), from rat liver nuclear extracts. The entire cDNA sequence of TIP120 contained an open reading frame encoding a novel polypeptide of 1230 amino acids. The recombinant TIP120 interacted directly with TBP under a physiological condition in vitro. Immunoprecipitation analysis indicated that TIP120 was associated with TBP in nuclear extracts. Interestingly, the N-terminal region of TIP120 exhibited sequence similarity to that of Drosophila TAF80, which was shown to bind directly to TBP. This novel TBP-binding protein is considered to participate in transcription regulation through the interaction with TBP.

Amino Acid Sequence↗
PubMed1996

Interferon-gamma induces Ice gene expression and enhances cellular susceptibility to apoptosis in the U937 leukemia cell line.

The roles of interferons (IFNs) in apoptosis are not fully understood. In this study we show that in the U937 monoblastic leukemia cell line, pretreatment with IFN-gamma enhanced sensitivity to apoptosis triggered by gamma-irradiation or antitumor agents (etoposide or adriamycin), as well as by anti-Fas antibody. In addition, IFN-gamma caused an increased expression of the interleukin-1 beta-converting enzyme (Ice) gene, following strong induction of the interferon regulatory factor-1 (IRF-1) gene, the product of which is a transcriptional activator of the Ice gene. An inhibitor of ICE/Ced-3 family proteases, Z-Asp-CH2-DCB, blocked apoptosis in control cells as well as in IFN-gamma-pretreated cells. These results suggest that enhanced susceptibility of IFN-gamma-pretreated cells to apoptosis is mediated through the induction of Ice by IRF-1. This pathway is not affected by interleukin-1 beta (IL-1 beta) since neutralizing antibody against IL-1 beta failed to suppress the IFN-gamma-mediated enhancement of cell death, and IL-1 beta itself did not mimic the effect of IFN-gamma.

Antibiotics, Antineoplastic↗
PubMed1996

Tricorn protease (TRI) interacting factor 1 from Thermoplasma acidophilum is a proline iminopeptidase.

Tricorn protease (TRI), a high molecular mass complex from the archaeon T. acidophilum, forms the core of a modular proteolytic system; upon interacting with low molecular mass factors intrinsic activities are enhanced and novel activities are generated. Here we characterize the first factor, F1, which turns out to be homologous with several bacterial proline iminopeptidases (PIPs). Surprisingly, it cleaves not only typical PIP substrates such as H-Pro-AMC, but a wide spectrum of amino acid substrates and several peptide substrates without a proline at the N-terminus. The pip gene encodes a 293 amino acid residue protein with a molecular mass of 33,487 Da. By means of site-directed mutagenesis we identified Ser105 and His271 as the active site nucleophile and proton donor, respectively. Experiments with inactive mutant PIPs indicate that the activities elicited by interacting with TRI are contributed by PIP.

Amino Acid Sequence↗
PubMed1996

Tricorn protease--the core of a modular proteolytic system.

Large macromolecular assemblies have evolved as a means of compartmentalizing reactions in organisms lacking membrane-bounded compartments. A tricorn-shaped protease was isolated from the archaeon Thermoplasma and was shown to form a multisubunit proteolytic complex. The 120-kilodalton monomer assembled to form a hexameric toroid that could assemble further into a capsid structure. Tricorn protease appeared to act as the core of a proteolytic system; when it interacted with several smaller proteins, it displayed multicatalytic activities.

Amino Acid Sequence↗
PubMed1996

Overexpression of cysteine sulfinic acid decarboxylase stimulated by hepatocarcinogenesis results in autoantibody production in rats.

We developed a novel and efficient cDNA subtraction method to isolate rat hepatocellular carcinoma (HCC)-related genes. cDNAs from Solt-Farber procedure-driven HCCs were synthesized on Latex beads. The subtraction was accomplished by a simple centrifugation, PCR amplification, and dot blot screening. Among 2000 clones from the subtracted cDNA library, one clone with a full-length HCC-related cDNA was eventually obtained. Sequence analysis of this clone showed it to exhibit 90 and 60% similarity with the rat cysteine sulfinic acid decarboxylase (CSAD) and mammalian glutamic acid decarboxylases (GAD), respectively. Differences between our sequence data on CSAD and those reported previously were observed at two positions, which arose from a single amino acid substitution and frame shift mutation. The CSAD expression was restricted to the liver and kidney of rats. During hepatocarcinogenesis, expression of the CSAD mRNA and its protein was stimulated in the precancerous liver and maintained its high expression afterward. Interestingly, a high level of anti-CSAD autoantibody was detected in the HCC-bearing rats. The titer of anti-CSAD autoantibodies in these rats was 30-200 times higher than that in normal rats. The anti-CSAD autoantibody appeared in the precancerous state and was maintained afterward, and its pattern of appearance was similar to that of CSAD mRNAs and proteins. Thus, we propose that the high-titer CSAD autoantibody resulted from increased CSAD gene expression in the liver due to stimulation by the HCC. These results remind us of human autoimmune diseases including insulin-dependent diabetes mellitus and stiff-man syndrome, which are caused by autoantibodies against GAD.

Amino Acid Sequence↗
PubMed1996

Serial angiographic follow-up after successful direct angioplasty for acute myocardial infarction.

This serial follow-up study was designed to identify the time course of reocclusion and/or restenosis after direct angioplasty for acute myocardial infarction. Direct angioplasty for acute myocardial infarction was attempted in 160 patients. Of the 141 patients who underwent successful reperfusion and were discharged, 137 (97%) were enrolled in this study. At the 3-week follow-up study (100% eligible), angiographic restenosis of the infarct-related artery was documented in 21 patients (16%), 9 (43%) of which were reocclusions. At 4 months in 100 patients (92% of those eligible), restenosis was newly documented in 28 infarct-related arteries (28%), 3 of which were reocclusions (11%). At 1 year in 64 patient (89% of those eligible), restenosis was newly documented in 5 infarct-related arteries (7.8%), with no reocclusions. The cumulative restenosis rate was 20% at 3 weeks, 43% at 4 months, and 47% at 1 year; when divided into occlusive and nonocclusive types, restenosis rates were 12% and 8.8% at 3 weeks and 14% and 29% at 4 months, respectively. Restenosis was most prevalent within the first 4 months and rarely occurred after that. When restenosis is manifested as reocclusion, it occurs earlier than in nonocclusive restenosis, often within 3 weeks.

Aged↗
PubMed1996

Tyrosine phosphorylation of the juxtamembrane domain of the v-Fms oncogene product is required for its association with a 55-kDa protein.

Tyrosine autophosphorylation of the v-Fms oncogene product results in the formation of high affinity binding sites for cellular proteins with Src homology 2 (SH2) domains that are involved in various signal cascades. Tryptic digestion of the autophosphorylated v-Fms and of its cellular counterpart, the feline c-Fms polypeptide, gave rise to at least six common major phosphopeptides, four of which have been characterized previously. Employing site-directed mutagenesis and phosphopeptide mapping of in vitro phosphorylated glutathione S-transferase v-Fms fusion proteins as well as full-length v-Fms molecules expressed in various cells, we show here that Tyr543 of the juxtamembrane domain and Tyr696 of the kinase insert domain constitute major autophosphorylation sites. Recombinant fusion proteins containing the tyrosine-phosphorylated kinase insert domain bind the growth factor receptor bound protein 2 and the p85 and p110 subunits of phosphatidylinositol 3'-kinase. In contrast, fusion proteins containing the juxtamembrane domain phosphorylated on Tyr543 fail to bind any of the known SH2 domain-containing cellular proteins but associate specifically with an as yet undefined 55-kDa cellular protein that by itself is phosphorylated on tyrosine.

3T3 Cells↗
PubMed1996

Promoter structure of the mouse TATA-binding protein (TBP) gene.

5'-RACE and genomic cloning were used to determine that the mouse TBP (mTBP) gene consists of one 5'-terminal non-coding exon followed by seven protein-coding exons. The region upstream of the first exon lacks a TATA-box. Hence, as with the case of other genes carrying TATA-less promoter, transcription starts from a cluster of sites which are located at the restricted region of mTBP gene. Interestingly, sequences of this region are well conserved between human and mouse TBP genes, suggesting that both mouse and human TBP genes drive mRNA synthesis in a similar way, and the sequence homology between two genes was used to assign a putative start point for the human TBP gene. Mouse, human, and Trimersurus gramineus (green habu snake) TBP genes share two GC-rich regions in their promoter regions. Thus, it is probable that diverse species of vertebrates commonly use TATA-less promoter bearing GC-rich regions to direct ubiquitous TBP expression.

Amino Acid Sequence↗
PubMed1996

Pharmacological characterization of 5-hydroxytryptamine-induced motor activity (in vitro) in the guinea pig gastric antrum and corpus.

In order to characterize the receptor subtypes involved in 5-hydroxytryptamine (5-HT)-induced circular muscle motor responses of the guinea pig gastric antrum and corpus, we examined the effects of several antagonists in vitro. 5-HT evoked concentration-dependent contractions of the gastric antrum and relaxations of the corpus. 5-HT induced antral contractions were abolished by pretreatment with atropine and tetrodotoxin. Methysergide, ketanserin, granisetron and [1-[2-(methylsulphonylamino)ethyl]-4-piperidinyl]methyl 1-methyl-1 H-indole-3-carboxylate maleate salt (GRl13808A), but neither 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190) nor N2-[(4R)-4-hydroxy-1-(1-methyl-1 H-indol-3-yl)carbonyl-L-prolyl]-N- methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide (FK888), inhibited 5-HT (3 x 10(-6) M: submaximal concentration)-induced antral contractions concentration dependently and shifted the 5-HT concentration-response curve to the right. 5-HT (3 x 10(-6) M)-induced corporal relaxation was not affected by tetrodotoxin, ketanserin, granisetron or GR113808A. At 10(-7) M, neither methysergide nor NAN-190 affected corporal relaxation, but at a high concentration (10(-6) M) they both inhibited it and shifted the 5-HT concentration-response curve to the right. We conclude that 5-HT-induced antral contraction is mediated by cholinergic neurons via 5-HT2A, 5-HT3 and 5-HT4 receptors, whereas corporal relaxation is mediated via 5-HT1-like receptors on smooth muscle that are sensitive to methysergide and NAN-190.

Animals↗
PubMed1996

HTF: A b-ZIP transcription factor that is closely related to the human XBP/TREB5 and is activated by hepatocellular carcinoma in rats.

We screened for rat hepatocellular carcinoma (HCC)-related genes by a novel cDNA subtraction method and obtained one gene. This gene was transcribed as 2.0- and 2.5-kb mRNAs, and its transcription was specifically enhanced in HCC. These cDNAs had the same open reading frame, but the 2.5 kb transcript had an extra 495 bases of 5'-UTR at the 5'-terminus. The deduced aa sequence revealed a basic-leucine zipper (b-ZIP) and proline/glutamine-rich structures, both of which are characteristic motifs for transcription factors. We designated the translation product of this gene HTF (Hepatocarcinogenesis-related Transcription Factor). Electrophoretic mobility shift assay demonstrated the DNA-binding ability of the recombinant HTF. It is most interesting that HTF had a considerable homology with human XBP/TREB5, which has been reported to be a binding factor for the X-box of the MHC class II gene and for the 21-bp enhancer of the HTLV-1 LTR. Genomic Southern analysis suggested that the 2.0- and 2.5-kb mRNAs are transcribed by a dual promoter of a single gene. Our results may suggest that HTF is a b-ZIP-type transcription factor involved in rat hepatocellular carcinoma.

Amino Acid Sequence↗
PubMed1996

The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures.

Interleukin (IL)-11 is a multifunctional cytokine whose role in osteoclast development has not been fully elucidated. We examined IL-11 production by primary osteoblasts and the effects of rat monoclonal anti-mouse glycoprotein 130 (gp130) antibody on osteoclast formation, using a coculture of mouse osteoblasts and bone marrow cells. IL-1, TNF alpha, PGE2, parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) similarly induced production of IL-11 by osteoblasts, but IL-6, IL-4, and TGF beta did not. Primary osteoblasts constitutively expressed mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Osteotropic factors did not modulate IL-11R alpha mRNA at 24 h, but steady-state gp130 mRNA expression in osteoblasts was upregulated by 1 alpha,25(OH)2D3, PTH, or IL-1. In cocultures, the formation of multinucleated osteoclast-like cells (OCLs) in response to IL-11, or IL-6 together with its soluble IL-6 receptor was dose-dependently inhibited by rat monoclonal anti-mouse gp130 antibody. Furthermore, adding anti-gp130 antibody abolished OCL formation induced by IL-1, and partially inhibited OCL formation induced by PGE2, PTH, or 1 alpha,25(OH)2D3. During osteoclast formation in marrow cultures, a sequential relationship existed between the expression of calcitonin receptor mRNA and IL-11R alpha mRNA. Osteoblasts as well as OCLs expressed transcripts for IL-11R alpha, as indicated by RT-PCR analysis and in situ hybridization. These results suggest a central role of gp130-coupled cytokines, especially IL-11, in osteoclast development. Since osteoblasts and mature osteoclasts expressed IL-11R alpha mRNA, both bone-forming and bone-resorbing cells are potential targets of IL-11.

Animals↗
PubMed1996

Mitochondrial targeting of glutathione reductase requires a leader sequence.

Glutathione reductase (GR), which catalyzes the conversion of glutathione disulfide to glutathione, is encoded in nuclear DNA, but is active in cytoplasm and mitochondria. However, analyses of known protein and DNA sequences for human GR have not revealed a potential mitochondrial targeting signal (MTS). We generated two 5'-truncated GR clones, which resulted in omission of the N-terminal 5 or 10 amino acids, to disable a potential targeting signal, and generated two GR clones containing synthetic MTS cDNAs. Transfection of Chinese hamster ovary cells with the full length human GR cDNA or with the 5'-truncated clones increased cytosolic GR activities 6- to 14-fold, but increased mitochondrial activities less than 2-fold. In contrast, transfection with either of the GR clones containing MTS cDNAs increased GR activities in mitochondria more than 24-fold. We conclude that the existing protein and DNA sequences for human GR do not contain a MTS and that such a signal is needed for effective mitochondrial targeting.

Animals↗