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Biomedical subjects

H Yanagi

Publications and source records attributed to H Yanagi.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Translocation of the aortic valve for aortic stenosis in a patient with severe calcification in the aortic root: report of a case].

A 65-year-old woman was admitted to the hospital because of anterior chest pain. Computed tomography and transthoracic 2-D echocardiogram demonstrated aortic valvular stenosis with calcification of whole aortic root. Cardiac catheterization study showed a transaortic pressure gradient of 73 mmHg and coronary angiography showed 75% stenosis at the right coronary ostia. Aortic valve replacement and coronary artery bypass grafting were planned. At operation, sinotubular junction and bilateral coronary ostia severely calcified with stenosis, prompted us to translocate the aortic valve with the composite graft, a 19 mm Bicarbon prosthesis and 25 mm woven Dacron graft. The postoperative course was uneventful. On cardiac catheterization done 27 days after operation, satisfactory valve motion and patent coronary bypass grafts were confirmed.

Aged↗
PubMed2000

Effect of physical activity during teenage years, based on type of sport and duration of exercise, on bone mineral density of young, premenopausal Japanese women.

In this cross-sectional study, 91 healthy premenopausal women aged 20-39 years were investigated to determine the effect of physical activities during their teenage years on their current bone mineral densities (BMD). We measured whole-body BMD (WBMD), lumbar BMD (LBMD), and radial BMD (RBMD) with dual energy X-ray absorptiometry (DXA). Using a questionnaire, we asked the women about their physical activities during junior and senior high school and at present. We also asked about their current nutritional status and past and current milk intake. After adjusting for age, body mass index (BMI), current total calorie and calcium (Ca) intake, and milk intake when they were teenagers and at present, we determined that subjects who exercised during extracurricular activities at each of the three periods (during junior and senior high school and at present) had significantly higher WBMD and LBMD (P <0.01, respectively) than did those who did not exercise at those times. Subjects who played high-impact sports at each period had significantly higher WBMD and LBMD than did subjects who played low-impact sports (P <0.05, respectively). Subjects who had exercised regularly from their teenage years to the present had significantly higher BMD at all sites than BMD in other subjects after adjusting for the potential confounders described above (P <0.05, respectively). Our data suggest that continuous exercise beginning in junior high school, especially high-impact sports, may be associated with greater current bone mass. It is important to incorporate adequate exercise beginning in the teenage years to lower one's future risk for osteoporosis.

Adolescent↗
PubMed2000

Proteasome-dependent degradation of cytosolic chaperonin CCT.

The chaperonin containing t-complex polypeptide 1 (CCT) is a heterooligomeric molecular chaperone that assists in the folding of actin, tubulin, and other cytosolic proteins. We show here that degradation of CCT in mammalian cells is inhibited by a proteasome-specific inhibitor, lactacystin. When CCT synthesis was inhibited by growth arrest of cells, the decrease in CCT levels was much slower in the presence of lactacystin than in its absence. Pulse-chase experiments indicated that degradation of CCT is inhibited 2- to 2.5-fold by addition of lactacystin. In addition, CCT degradation rate in ts85 cells that produce thermolabile ubiquitin-activating enzyme E1 was reduced 3-fold at the nonpermissive temperature compared to the degradation at the permissive temperature. These results indicate that the ubiquitin-proteasome system is involved in CCT degradation.

Acetylcysteine↗
PubMed2000

Results of pharmacokinetic modulating chemotherapy in combination with hepatic arterial 5-fluorouracil infusion and oral UFT after resection of hepatic colorectal metastases.

BACKGROUND: Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic concept in combination with continuous 5-fluorouracil (5-FU) infusion and UFT. UFT enhanced plasma 5-FU concentration and antitumor effects during 5-FU infusion. The authors report on their experiences with arterial 5-FU infusion and UFT after resection of hepatic colorectal secondaries. METHODS: Fifty-eight patients were divided into two groups after hepatectomy. Group A, 30 patients, underwent hepatic arterial infusion (HAI) via implantable port system with perfusion 5-FU for 2 consecutive days per week at 600 mg/m(2)/day, and oral administration of UFT at 400 mg/day for 5-7 days per week, repeated 10 times, and Group B, 28 patients, underwent oral administration of UFT at 400 mg/day for 6 months. All the patients were managed at the outpatient clinic at Hyogo College of Medicine, and recurrence, survival, and toxicity were documented. Plasma 5-FU concentrations during chemotherapy were detected using high performance liquid chromatography. RESULTS: Maximum plasma concentrations of 5-FU in Group A reached 144.0 ng/mL and in Group B 58.7 ng/mL. Cumulative 5-year survival rate after hepatectomy in Group A was 59% and in Group B was 27%. (P = 0.00001) HAI-PMC drastically decreased hepatic recurrence (median hepatic recurrence free times were 34.2 months in Group A vs. 18.4 months in Group B; P = 0.00002). Grade 3 toxicity in Group A was found in 3 patients CONCLUSIONS: Pharmacokinetic modulating chemotherapy was designed as a uracil-related biochemical modulation. HAI-PMC significantly decreased hepatic recurrence after curative resection. This new chemotherapy concept significantly improved prognosis in patients with hepatic colorectal metastases.

Administration, Oral↗
PubMed2000

Transcriptional regulation of the mouse cytosolic chaperonin subunit gene Ccta/t-complex polypeptide 1 by selenocysteine tRNA gene transcription activating factor family zinc finger proteins.

The chaperonin containing t-complex polypeptide 1 (CCT) is a molecular chaperone assisting in the folding of proteins in eukaryotic cytosol, and the Ccta (encoding the alpha subunit of CCT)/t-complex polypeptide 1 gene encodes the alpha subunit of CCT. We show here that transcription of the mouse Ccta gene is regulated by selenocysteine tRNA gene transcription activating factor (Staf) family zinc-finger transcription factors ZNF143 and ZNF76. Reporter gene assay using HeLa cells indicated that the Ccta gene promoter contains two 18-base pair-long cis-acting elements with similar sequences at -70 and -20 base pairs (designated CCT alpha subunit gene transcription activating element 1 (CAE1) and CAE2, respectively). By yeast one-hybrid screening of CAE1-binding factors, we isolated human ZNF143, which is known to activate transcription of selenocysteine tRNA and small nuclear RNA genes. DNA binding domains of ZNF143 and ZNF76 produced in E. coli recognized CAE1 and CAE2 elements in electrophoretic mobility shift assay. HeLa cell nuclear extract contained a protein that specifically binds to CAE1 and CAE2 and recognized by anti-ZNF143 antibody. Transcription from a minimal Ccta promoter containing CAE2 element in HeLa cells was enhanced by overexpression of full-length ZNF143 and ZNF76 but inhibited by that of their DNA binding domains alone. These results demonstrate that the Staf family proteins control transcription of at least one of the chaperone-encoding genes besides that of tRNA and small nuclear RNA genes. These RNA and chaperone genes are suggested to be coregulated to facilitate synthesis of mature proteins during active cell growth.

Animals↗
PubMed2000

Dynamic interplay between antagonistic pathways controlling the sigma 32 level in Escherichia coli.

The heat-shock response in Escherichia coli depends primarily on the transient increase in the cellular level of heat-shock sigma factor final sigma(32) encoded by the rpoH gene, which results from both enhanced synthesis and transient stabilization of normally unstable final sigma(32). Heat-induced synthesis of final sigma(32) was previously shown to occur at the translation level by melting the mRNA secondary structure formed within the 5' coding sequence of rpoH including the translation initiation region. The subsequent decrease in the final sigma(32) level during the adaptation phase has been thought to involve both shutoff of synthesis (translation) and destabilization of final sigma(32)-mediated by the DnaK-DnaJ chaperones, although direct evidence for translational repression was lacking. We now show that the heat-induced synthesis of final sigma(32) does not shut off at the translation level by using a reporter system involving translational coupling. Furthermore, the apparent shutoff was not observed when the synthesis rate was determined by a very short pulse labeling (15 s). Examination of final sigma(32) stability at 10 min after shift from 30 to 42 degrees C revealed more extreme instability (t(1/2)=20 s) than had previously been thought. Thus, the dynamic change in final sigma(32) stability during the heat-shock response largely accounts for the apparent shutoff of final sigma(32) synthesis observed with a longer pulse. These results suggest a mechanism for maintaining the intricate balance between the antagonistic pathways: the rpoH translation as determined primarily by ambient temperature and the turnover of final sigma(32) as modulated by the chaperone (and presumably protease)-mediated autogenous control.

Amino Acid Sequence↗
PubMed2000

mRNA splicing-mediated C-terminal replacement of transcription factor Hac1p is required for efficient activation of the unfolded protein response.

Eukaryotic cells control the levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) by a transcriptional induction process termed the unfolded protein response (UPR) according to the needs within the ER. In Saccharomyces cerevisiae, expression of the UPR-specific transcription factor Hac1p is tightly regulated at the level of mRNA splicing that depends on an unconventional system. Thus, HAC1 precursor mRNA is constitutively expressed but not translated. A sensor molecule Ire1p/Ern1p-mediated signaling from the ER specifically removes an intron of 252 nucleotides from the precursor mRNA, and the resulting mature mRNA is translated to produce Hac1p. Because the 5' splice site is located near the C-terminal end of the Hac1p-coding region, this splicing replaces the last 10 codons of the ORF with an exon encoding 18 aa without affecting the N-terminal 220-aa region which contains the DNA-binding domain. Here, we found that this C-terminal 18-aa segment functions as a potent activation domain. Therefore, the splicing event joins the HAC1 DNA-binding domain to its activation domain, allowing rapid posttranscriptional generation of a potent transcriptional activator (238-aa Hac1p) that activates the UPR efficiently. This suggests that the UPR is hardly activated by Hac1p produced without splicing (230-aa Hac1p) which may occur in the absence of Ire1p/Ern1p-mediated signaling from the ER. Based on these and other results, we propose that the control of expression and activity of Hac1p meets the requirements of the ER.

Basic-Leucine Zipper Transcription Factors↗
PubMed2000

Abundant expression of 150-kDa oxygen-regulated protein in mouse pancreatic beta cells is correlated with insulin secretion.

The 150-kDa oxygen-regulated protein (ORP150) is a member of glucose-regulated proteins (GRPs), which are induced by stressful conditions such as oxygen or glucose deprivation. Here we investigated the highly abundant expression of ORP150 in mouse pancreas and its relationship with insulin secretion. Immunohistochemical analysis revealed that ORP150 expression was restricted to islets, especially to beta cells. The beta cell-specific expression was also observed in a mouse insulinoma cell line, MIN6, which secretes insulin in response to increased glucose concentration. Furthermore, ORP150 in islets dramatically diminished by fasting, concomitant with reduction of the serum insulin level. These results strongly suggest the role for ORP150 in insulin secretion.

Animals↗
PubMed2000

The effectiveness of preoperative intraluminal brachytherapy in preventing wall penetration and nodal involvement of rectal carcinomas.

A retrospective review was conducted of 115 patients with middle or lower rectal carcinoma, without distant metastasis, who were consecutively treated with preoperative intraluminal brachytherapy and radical surgery (IBT group). Another 115 rectal carcinoma patients treated with surgery alone were reviewed as a control (NIBT group). We investigated whether conventional pathologic stagings were correlated with prognosis. All tumors were diagnosed by the TNM classification. According to the distribution of pathologic staging in the resected specimens, the prevalence of totally ablated tumors (stage T0) in the IBT group was significantly higher than that in the NIBT group, but there were no significant differences in the distribution of other T stages between the two groups. Good local control was achieved for the stage-T3 tumors in the IBT group, similarly to the T < or = 2 tumors in both groups. In the IBT group, the survival period of the patients with stage-T4 tumors even after radiotherapy was significantly shorter than that of those with T3 tumors (P = 0.042), while those with N < or = 2-stage tumors had significantly longer survival periods than those with N3-stage tumors (P = 0.047). These findings demonstrate the usefulness of analyzing clinicopathologic parameters to predict local control and the prolongation of survival. Determining these factors will also help to identify high-risk patients likely to require more effective adjuvant chemotherapy.

Adult↗
PubMed2000

Association of Trp64Arg polymorphism of the beta3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity.

OBJECTIVE: To investigate whether Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) gene and Gln223Arg polymorphism of the leptin receptor (Ob-R) gene are associated with obesity in Japanese schoolchildren. DESIGN: Population study of participants from a rural town located within 50 km northeast of Tokyo based on school medical examinations. SUBJECTS: 553 Japanese schoolchildren (291 boys and 262 girls) who were 9-15 y old with a mean age of 11.9 +/- 1.8 y. MEASUREMENTS: DNA was extracted from whole blood and genotyped by PCR-RFLP. Height, weight and blood pressure were measured in school medical examinations. Total cholesterol, triglyceride and HDL-cholesterol concentrations were measured by an autoanalyzer. Obesity index, body mass index (BMI) and LDL-cholesterol concentration were calculated by the respective formulae. RESULTS: In Trp64Arg polymorphism of the beta3-AR gene, the number of obese subjects with Trp/Arg or Arg/Arg genotypes was significantly higher than that of the non-obese subjects (chi2=5.79, P=0.02). The obesity index of subjects with the Arg/Arg or Arg/Trp genotype was significantly higher than that of those with the Trp/Trp genotype (8.2 +/- 18.7% vs 4.5 +/- 15.8%, P=0.04). Moreover, after adjustments for age and gender, BMI of subjects with the Trp/Arg or Arg/Arg genotype was significantly higher than that of those with the Trp/Trp genotype (19.4 +/- 3.6 kg/m2 vs 18.9 +/- 3.2 kg/m2, P= 0.02). However, no significant differences were observed in the clinical characteristics among the genotype groups of the Ob-R gene. CONCLUSIONS: Trp64Arg polymorphism of the beta3-AR gene appears to be a genetic risk factor for obesity in Japanese children, but Gln223Arg polymorphism of the Ob-R gene does not appear to be associated with obesity.

Adolescent↗
PubMed2000

Upregulation of cytosolic chaperonin CCT subunits during recovery from chemical stress that causes accumulation of unfolded proteins.

The chaperonin containing TCP-1 (CCT) is a molecular chaperone consisting of eight subunit species and assists in the folding of actin, tubulin and some other cytosolic proteins. We examined the stress response of CCT subunit proteins in mammalian cultured cells using chemical stressors that cause accumulation of unfolded proteins. Levels of CCT subunit proteins in HeLa cells were coordinately and transiently upregulated under continuous chemical stress with sodium arsenite. CCT subunit levels in several mammalian cell lines were also upregulated during recovery from chemical stress caused by sodium arsenite or a proline analogue, L-azetidine-2-carboxylic acid. Several unidentified proteins that were newly synthesized and associated with CCT were found to increase concomitantly with CCT subunits themselves and known substrates during recovery from the stress. These results suggest that CCT plays important roles in the recovery of cells from protein damage by assisting in the folding of proteins that are actively synthesized and/or renatured during this period.

Animals↗
PubMed2000

Cerebral blood volume and oxygenation among poststroke hemiplegic patients: effects of 13 rehabilitation tasks measured by near-infrared spectroscopy.

OBJECTIVE: To measure with near-infrared spectroscopy (NIRS) the changes in cerebral hemodynamics and oxygenation in the prefrontal cortex of poststroke patients with hemiplegia performing several rehabilitation tasks and to analyze the different effects of the tasks. DESIGN: Case series pilot study. SETTING: Hospitals and facilities near Tsukuba, Japan. PARTICIPANTS: Twenty-four healthy volunteers and 44 patients with hemiplegia. INTERVENTIONS: For healthy volunteers, conventional rehabilitation tasks of head-up tilt (HUT), calculation, and ergometer. For patients with hemiplegia, these 3 tasks plus reading aloud, listening to music, reciprocal extension, nonparalyzed extension, passive range of motion, pulley, bridge, facilitation, stand-up, and gait. MAIN OUTCOME MEASURES: Changes in cerebral blood volume (CBV) and cerebral oxygen volume (COV) in the prefrontal region sensed by a noninvasive NIRS device placed midforehead in healthy volunteers or on the impaired side in patients with hemiplegia. Computer analysis of the quality and quantity of the CBV and COV change patterns. RESULTS: In healthy subjects, the change patterns of the 3 tasks were clearly different: decrease in COV with HUT, limited increase in CBV and COV with calculation tasks, and gradual increase in CBV and COV with ergometer tasks. In patients with hemiplegia, significant (positive) CBV changes were observed in ergometer, facilitation, stand-up, and gait and significant (negative) changes with Romover. Significant (positive) COV changes were observed in ergometer and facilitation and (negative) in HUT. CONCLUSIONS: NIRS is useful for monitoring the change in regional hemodynamics and oxygenation in rehabilitation; some tasks commonly used in rehabilitation, such as ergometer and facilitation, increase both CBV and COV in the affected prefrontal cortex of patients with hemiplegia.

Adult↗
PubMed2000

Production of three distinct mRNAs of 150 kDa oxygen-regulated protein (ORP150) by alternative promoters: preferential induction of one species under stress conditions.

150 kDa oxygen-regulated protein (ORP150) is one of the endoplasmic reticulum (ER)-resident stress proteins. We have cloned and sequenced the entire human ORP150 gene covering over 15-kb. Analyses of transcription initiation sites and transcriptional regulatory sequences revealed that at least three distinct mRNA species were produced by alternative promoters: two of them starting from alternative exon 1 (1A or 1B), and the third one starting from exon 2, six nucleotides upstream of the first AUG initiation codon. Among them, the transcript that begins with exon 1B was preferentially induced by hypoxia or tunicamycin treatment. A cis-acting segment involved in the stress-dependent induction was found at the 5'-end of exon 1A, which could account for the selective induction of the transcription from exon 1B. Furthermore, in vitro analyses of translation of the third mRNA suggested the constitutive expression of the cytosolic ORP150 due to the lack of the signal peptide resulting from differential translation initiation.

Base Sequence↗
PubMed2000

Overexpression of trigger factor prevents aggregation of recombinant proteins in Escherichia coli.

To examine the effects of overexpression of trigger factor (TF) on recombinant proteins produced in Escherichia coli, we constructed plasmids that permitted controlled expression of TF alone or together with the GroEL-GroES chaperones. The following three proteins that are prone to aggregation were tested as targets: mouse endostatin, human oxygen-regulated protein ORP150, and human lysozyme. The results revealed that TF overexpression had marked effects on the production of these proteins in soluble forms, presumably through facilitating correct folding. Whereas overexpression of TF alone was sufficient to prevent aggregation of endostatin, overexpression of TF together with GroEL-GroES was more effective for ORP150 and lysozyme, suggesting that TF and GroEL-GroES play synergistic roles in vivo. Although coexpression of the DnaK-DnaJ-GrpE chaperones was also effective for endostatin and ORP150, coexpression of TF and GroEL-GroES was more effective for lysozyme. These results attest to the usefulness of the present expression plasmids for improving protein production in E. coli.

Chaperonin 10↗
PubMed2000

Overexpression of protein disulfide isomerase DsbC stabilizes multiple-disulfide-bonded recombinant protein produced and transported to the periplasm in Escherichia coli.

Dsb proteins (DsbA, DsbB, DsbC, and DsbD) catalyze formation and isomerization of protein disulfide bonds in the periplasm of Escherichia coli. By using a set of Dsb coexpression plasmids constructed recently, we analyzed the effects of Dsb overexpression on production of horseradish peroxidase (HRP) isozyme C that contains complex disulfide bonds and tends to aggregate when produced in E. coli. When transported to the periplasm, HRP was unstable but was markedly stabilized upon simultaneous overexpression of the set of Dsb proteins (DsbABCD). Whereas total HRP production increased severalfold upon overexpression of at least disulfide-bonded isomerase DsbC, maximum transport of HRP to the periplasm seemed to require overexpression of all DsbABCD proteins, suggesting that excess Dsb proteins exert synergistic effects in assisting folding and transport of HRP. Periplasmic production of HRP also increased when calcium, thought to play an essential role in folding of nascent HRP polypeptide, was added to the medium with or without Dsb overexpression. These results suggest that Dsb proteins and calcium play distinct roles in periplasmic production of HRP, presumably through facilitating correct folding. The present Dsb expression plasmids should be useful in assessing and dissecting periplasmic production of proteins that contain multiple disulfide bonds in E. coli.

Calcium Chloride↗
PubMed2000

ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response.

Transcription of genes encoding molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) is induced by accumulation of unfolded proteins in the ER. This intracellular signaling, known as the unfolded protein response (UPR), is mediated by the cis-acting ER stress response element (ERSE) in mammals. In addition to ER chaperones, the mammalian transcription factor CHOP (also called GADD153) is induced by ER stress. We report here that the transcription factor XBP-1 (also called TREB5) is also induced by ER stress and that induction of CHOP and XBP-1 is mediated by ERSE. The ERSE consensus sequence is CCAAT-N(9)-CCACG. As the general transcription factor NF-Y (also known as CBF) binds to CCAAT, CCACG is considered to provide specificity in the mammalian UPR. We recently found that the basic leucine zipper protein ATF6 isolated as a CCACG-binding protein is synthesized as a transmembrane protein in the ER, and ER stress-induced proteolysis produces a soluble form of ATF6 that translocates into the nucleus. We report here that overexpression of soluble ATF6 activates transcription of the CHOP and XBP-1 genes as well as of ER chaperone genes constitutively, whereas overexpression of a dominant negative mutant of ATF6 blocks the induction by ER stress. Furthermore, we demonstrated that soluble ATF6 binds directly to CCACG only when CCAAT exactly 9 bp upstream of CCACG is bound to NF-Y. Based on these and other findings, we concluded that specific and direct interactions between ATF6 and ERSE are critical for transcriptional induction not only of ER chaperones but also of CHOP and XBP-1.

Activating Transcription Factor 6↗
PubMed2000

150-kDa oxygen-regulated protein (ORP150) functions as a novel molecular chaperone in MDCK cells.

To assess the participation of the 150-kDa oxygen-regulated protein (ORP150) in protein transport, its function in Madin-Darby canine kidney (MDCK) cells was studied. Exposure of MDCK cells to hypoxia resulted in an increase of ORP150 antigen and increased binding of ORP150 to GP80/clusterin (80-kDa glycoprotein), a natural secretory protein in this cell line. In ORP150 antisense transformant MDCK cells, GP80 was retained within the endoplasmic reticulum after exposure to hypoxia. Metabolic labeling showed the delay of GP80 maturation in antisense transformants in hypoxia, whereas its matured form was detected in wild-type cells, indicating a role of ORP150 in protein transport, especially in hypoxia. The affinity chromatographic analysis of ORP150 suggested its ability to bind to ATP-agarose. Furthermore, the ATP hydrolysis analysis showed that ORP150 can release GP80 at a lower ATP concentration. These data indicate that ORP150 may function as a unique molecular chaperone in renal epithelial cells by facilitating protein transport/maturation in an environment where less ATP is accessible.

Adenosine Triphosphate↗