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Y Takemoto

Publications and source records attributed to Y Takemoto.

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

Asymmetric alkylation of tert-butyl glycinate Schiff base with chiral quaternary ammonium salt under micellar conditions.

[reaction: see text] The asymmetric alkylation of the tert-butyl glycinate-benzophenone Schiff base 1 with various arylmethyl bromides catalyzed by O-allyl-N-(9-anthracenylmethyl)cinchonidinium bromide (2) proceeded smoothly under micellar conditions (5 equiv of 1 M KOH and 0.4 equiv of Triton X-100) to give the alkylated products in good yields and with good enantioselectivity (72-85% ee), depending on the electrophiles.

Journal Article↗
PubMed2001

Novel sparteine-mediated enantio-dichotomic formal synthesis of R-(-)- and S-(+)-curcuphenol.

High and opposite enantiodiscriminations were observed between tertiary amides and secondary amides in the sparteine-mediated lateral metalation-allylation of 2-ethyl-m-toluamide derivatives (2a, 2e). The results described above have been applied for the formal synthesis of both enantiomers of curcuphenol. The brief mechanistic studies suggested that stereoinformation was introduced after the deprotonation step.

Animals↗
PubMed2001

Asymmetric total synthesis of halicholactone.

The asymmetric total synthesis of the marine metabolite, halicholactone 1, is described. The bisallylic triol 6 with three chiral centers at C8, C12, and C15 was constructed by [2,3]-sigmatropic rearrangement of the sulfoxide 18, which was prepared stereoselectively using the chirality of (diene)Fe(CO)3 complexes. Introduction of the trans-substituted cyclopropane subunit into 21 was successfully achieved using the modified regio- and stereoselective Simmons-Smith reaction. The use of RCM (ring-closing metathesis) methodology (4-->35) was pivotal for the formation of a nine-membered unsaturated lactone fragment of halicholactone 1. As this approach is flexible and stereoselective, other oxylipins could be synthesized by the protocol described herein.

Animals↗
PubMed2001

Urinary trypsin inhibitor concentration can predict the immunological insult of chemotherapy and complications after bone marrow transplantation.

Urinary trypsin inhibitor has attracted attention as an index of the systemic inflammatory response syndrome. In this study, the urine concentration of trypsin inhibitor was measured to compare the immunological insult of conventional chemotherapy and conditioning chemotherapy for bone marrow transplantation. We also investigated whether urinary trypsin inhibitor was a useful index of the complications and outcome of bone marrow transplantation. Urinary trypsin inhibitor concentration was determined before chemotherapy, on the day after finishing chemotherapy (day 0 of transplantation), and during recovery of the white cell count, in 17 patients (seven receiving conventional chemotherapy and 10 receiving conditioning for bone marrow transplantation). Urinary trypsin inhibitor concentrations were significantly higher after conditioning for bone marrow transplantation than after conventional chemotherapy (P < 0.001), indicating that conditioning was more invasive. After bone marrow transplantation, the incidence of severe complications and the mortality rate were higher in patients whose urinary trypsin inhibitor concentrations rose during recovery of the white cell count. Comparison of urinary trypsin inhibitor concentrations suggested that conditioning for bone marrow transplantation was more invasive than conventional chemotherapy. This study also suggested that the urine concentration of trypsin inhibitor could be useful for predicting the risk of complications and outcome of bone marrow transplantation.

Adolescent↗
PubMed2001

Oral eicosapentaenoic acid for complications of bone marrow transplantation.

The 'systemic inflammatory response syndrome' (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B(4), thromboxane A(2), and prostaglandin I(2) were significantly lower in patients receiving EPA than in those not receiving it (all P < 0.01). Cytokines such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-10 were also significantly decreased by EPA (P < 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P < 0.05). The survival rate was significantly higher in the group given EPA (P < 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Renal transplantation with aged donors.

Research indicates that aged heart-beating cadaveric donors cause greater risk factors in kidney transplantation. The influence of age on the outcome of non-heart-beating (NHB) cadaveric renal transplantations has not yet been clarified. From July 1986 to May 1999, 63 patients who received cadaveric renal transplantation at Osaka City University Hospital and Osaka City General Hospital were divided into two groups according to their age. Renal function and graft-survival rates of the two groups were compared. The mean values of nadir donor serum creatinine were significantly worse (P < 0.05) in the aged donor group. In the aged donor group the percentage of immediately functioning grafts was lower and the percentage of non-functioning grafts was higher. During the first 10 years post-transplant, graft survival in the aged donor group was significantly lower than that in the younger donor group. We conclude that cadaveric renal transplantation from NHB aged donors can be to the detriment of renal function and graft survival rates compared to transplantation from younger donors.

Age Factors↗
PubMed2001

Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy.

Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. The hypertrophic process is mediated, in part, by small G proteins of the Rho family. We hypothesized that statins, inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, inhibit cardiac hypertrophy by blocking Rho isoprenylation. We treated neonatal rat cardiac myocytes with angiotensin II (AngII) with and without simvastatin (Sim) and found that Sim decreased AngII-induced protein content, [3H] leucine uptake, and atrial natriuretic factor (ANF) promoter activity. These effects were associated with decreases in cell size, membrane Rho activity, superoxide anion (O2*-) production, and intracellular oxidation, and were reversed with L-mevalonate or geranylgeranylpyrophosphate, but not with farnesylpyrophosphate or cholesterol. Treatments with the Rho inhibitor C3 exotoxin and with cell-permeable superoxide dismutase also decreased AngII-induced O2*- production and myocyte hypertrophy. Overexpression of the dominant-negative Rho mutant N17Rac1 completely inhibited AngII-induced intracellular oxidation and ANF promoter activity, while N19RhoA partially inhibited it, and N17Cdc42 had no effect. Indeed, Sim inhibited cardiac hypertrophy and decreased myocardial Rac1 activity and O2*- production in rats treated with AngII infusion or subjected to transaortic constriction. These findings suggest that statins prevent the development of cardiac hypertrophy through an antioxidant mechanism involving inhibition of Rac1.

Angiotensin II↗
PubMed2001

Significant expression of functional human type 1 mitochondrial ADP/ATP carrier in yeast mitochondria.

As a first step to characterize the unknown functional properties of the human mitochondrial ADP/ATP carrier (AAC), we tried to express human type 1 AAC (hAAC1) in Saccharomyces cerevisiae. Expression of hAAC1 in yeast mitochondrial membrane was very low, although its transcript level was high. Its expression was improved greatly by replacement of its N-terminal region with the corresponding region of yeast type 2 AAC (yAAC2), as observed with the bovine type 1 AAC (bAAC1). This chimeric hAAC1 showed similar ADP transport activity to that of chimeric bAAC1, corresponding to the transport activity of bAAC1 in bovine heart mitochondria. These results suggested that the N-terminal region of yAAC2 is important for expression of the mammalian carriers in yeast mitochondria. Using the present expression system, studies on the functional properties of the human AAC isoforms in relation to their structures are now possible.

Animals↗
PubMed2001

Depressor and bradycardic actions of L-proline injected into the nucleus tractus solitarii of anesthetized rats.

L-Glutamate has been considered to be a neurotransmitter in the nucleus tractus solitarius (NTS) of the afferent baroreflex pathway, though this has not yet been decisively shown. A bolus injection of a neurotransmitter candidate amino acid L-proline into the cisterna magna and that of L-glutamate shows the same pressor action in the freely moving rat, but the actual nuclei responding L-proline remain undetermined. Besides L-glutamate, L-proline might be another candidate amino acid in the NTS. The present study was therefore performed to characterize the circulatory action of L-proline injected into the NTS where responses to glutamate in the anesthetized rat had already been shown. The NTS was first determined as a site on the dorsal surface of the medulla where a microinjection of L-glutamate decreased arterial pressure and heart rate. Microinjected L-proline (1.65 to 13.2 nmol, 33 nl) into the NTS decreased arterial pressure and heart rate in a dose-dependent manner. The injection of a mixed solution (66 nl) of kynurenate, an ionotropic excitatory amino acid receptors antagonist (1.32 nmol), and L-proline (6.6 nmol) into the NTS abolished the depressor and bradycardic actions with L-proline alone (6.6 nmol, 66 nl). However, a mixture of an increased concentration of kynurenate (6.6 nmol) with glutamate augmented the actions seen with glutamate alone (0.66 nmol, 66 nl). D-Proline (13.2 nmol, 66 nl), the optic isomer of L-proline, produced no change in arterial pressure or heart rate, suggesting that the actions of L-proline in the NTS were optically specific. The results indicate that L-proline but not D-proline induces its depressor and bradycardic actions through ionotropic excitatory amino acid receptors in the NTS of the anesthetized rat. L-Proline may become a candidate transmitter of baroreceptor information in the NTS.

Anesthesia↗
PubMed2001

Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women.

OBJECTIVE: To evaluate the contribution of left atrial (LA) volume in predicting atrial fibrillation (AF). PATIENTS AND METHODS: In this retrospective cohort study, a random sample of 2200 adults was identified from all Olmsted County, Minnesota, residents who had undergone transthoracic echocardiographic assessment between 1990 and 1998 and were 65 years of age or older at the time of examination, were in sinus rhythm, and had no history of AF or other atrial arrhythmias, stroke, pacemaker, congenital heart disease, or valve surgery. The LA volume was measured off-line by using a biplane area-length method. Clinical characteristics and the outcome event of incident AF were determined by retrospective review of medical records. Echocardiographic data were retrieved from the laboratory database. From this cohort, 1655 patients in whom LA size data were available were followed from baseline echocardiogram until development of AF or death. The clinical and echocardiographic associations of AF, especially with respect to the role of LA volume in predicting AF, were determined. RESULTS: A total of 666 men and 989 women, mean +/- SD age of 75.2 +/- 7.3 years (range, 65-105 years), were followed for a mean +/- SD of 3.97 +/- 2.75 years (range, < 1.00-10.78 years); 189 (11.4%) developed AF. Cox model 5-year cumulative risks of AF by quartiles of LA volume were 3%, 12%, 15%, and 26%, respectively. With Cox proportional hazards multivariate models, logarithmic LA volume was an independent predictor of AF, incremental to clinical risk factors. After adjusting for age, sex, valvular heart disease, and hypertension, a 30% larger LA volume was associated with a 43% greater risk of AF, incremental to history of congestive heart failure (hazard ratio [HR], 1.887; 95% confidence interval [CI], 1.230-2.895; P = .004), myocardial infarction (HR, 1.751; 95% CI, 1.189-2.577; P = .004), and diabetes (HR, 1.734; 95% CI, 1.066-2.819; P = .03). Left atrial volume remained incremental to combined clinical risk factors and M-mode LA dimension for prediction of AF (P < .001). CONCLUSION: This study showed that a larger LA volume was associated with a higher risk of AF in older patients. The predictive value of LA volume was incremental to that of clinical risk profile and conventional M-mode LA dimension.

Aged↗
PubMed2001

Clinical study on 53 cases of cadaveric kidney transplantation at Osaka City University Hospital.

BACKGROUND: In this study, we examined the effects of nonimmunological factors on cadaver kidney transplant. METHODS: Fifty-three cadaver kidney transplant recipients were studied. They were divided into two groups, Group I ( donor age<60, n=38 ) and Group II ( donor age > or = 60, n=15). These patients were studied to determine whether donor age and recipient Body Mass Index (BMI) affected transplant outcome. RESULTS: The 3 and 5-year overall graft / patient survival was 80.6 / 100% and 72.7 97.3%, respectively. The best S-Cr after transplantation was significantly (p<0.05) lower in Group I compared to Group II. The 1, 5 and 8-year graft survival was significantly (p<0.05) better in Group I. In the low BMI patients of Group II, 5-year graft survival was significantly (p<0.01) better than high BMI patients. DISCUSSION: An aged cadaver donor was a risk factor for decreased posttransplant renal functions and lower graft survival. However, if a recipient with a low BMI can be selected, the outcome of cadaver kidney transplants from aged donors may be improved.

Adult↗
PubMed2000

Synergism between the calmodulin-binding and autoinhibitory domains on calcineurin is essential for the induction of their phosphatase activity.

Elevation of the intracellular calcium concentration is necessary for cell growth and the activation of several lymphokine genes. The immunosuppressive drugs cyclosporin A and FK506 profoundly inhibit the calcium-dependent signaling pathway in T lymphocytes by interfering with the activity of the calcium/calmodulin (CaM)-dependent serine/threonine phosphatase, calcineurin (CN). Little is known, however, about how activation of CN enzyme activity or interaction with its substrate, nuclear factor of activated T cell (NF-AT), is regulated. We show here that the binding of CaM to CN may affect the conformation of CN at both the CaM-binding and the autoinhibitory (AI) domains and that this is critical for activation of CN to dephosphorylate NF-AT. Dissociation of the AI domain from the enzyme active site on CN leads to expose a binding site for NF-AT at the N terminus of CN and allows the CN binding to NF-AT. Since the cytoplasmic form of NF-AT can interact with CN mutants lacking enzyme activity, the interaction of the two molecules is independent of CN enzyme activity and occurs prior to the dephosphorylation of NF-AT. Dephosphorylation converts NF-AT from the cytoplasmic to the nuclear form by exposing the DNA-binding domain on NF-AT, and the nuclear form of NF-AT brings CN together into the nuclei. We therefore propose that the activation of CN by the CaM binding independently regulates the interaction with NF-AT and the dephosphorylation of NF-AT.

3T3 Cells↗
PubMed2000

HS1 interacts with Lyn and is critical for erythropoietin-induced differentiation of erythroid cells.

Erythroid cells terminally differentiate in response to erythropoietin binding its cognate receptor. Previously we have shown that the tyrosine kinase Lyn associates with the erythropoietin receptor and is essential for hemoglobin synthesis in three erythroleukemic cell lines. To understand Lyn signaling events in erythroid cells, the yeast two-hybrid system was used to analyze interactions with other proteins. Here we show that the hemopoietic-specific protein HS1 interacted directly with the SH3 domain of Lyn, via its proline-rich region. A truncated HS1, bearing the Lyn-binding domain, was introduced into J2E erythroleukemic cells to determine the impact upon responsiveness to erythropoietin. Truncated HS1 had a striking effect on the phenotype of the J2E line-the cells were smaller, more basophilic than the parental proerythoblastoid cells and had fewer surface erythropoietin receptors. Moreover, basal and erythropoietin-induced proliferation and differentiation were markedly suppressed. The inability of cells containing the truncated HS1 to differentiate may be a consequence of markedly reduced levels of Lyn and GATA-1. In addition, erythropoietin stimulation of these cells resulted in rapid, endosome-mediated degradation of endogenous HS1. The truncated HS1 also suppressed the development of erythroid colonies from fetal liver cells. These data show that disrupting HS1 has profoundly influenced the ability of erythroid cells to terminally differentiate.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: a case report.

Allogeneic bone marrow transplantation was performed in a 24-year-old woman with acute myelogenous leukemia in the first remission (FAB classification: M4). Graft-versus-host disease occurred from around day 150 after bone marrow transplantation. The levels of tumour necrosis factor-alpha, interleukin 12, and intercellular adhesion molecule-1 were elevated in the early stage of graft-versus-host disease, followed by elevation of interleukin 10 and interleukin 8. Her symptoms subsequently improved and all of these parameters became normal. The levels of thrombomodulin and plasminogen activator inhibitor type 1 showed changes that were in parallel with the clinical course. Interleukin 1beta, interleukin 6, interleukin 2, and interferon-gamma showed no changes throughout the course of her graft-versus-host disease. These findings suggested the possibility that release of inflammatory molecules occurred at the onset of graft-versus-host disease and caused vascular endothelial damage, which led to the exacerbation of her disease.

Adult↗
PubMed2000

Early detection of relapse and evaluation of treatment for mixed chimerism using fluorescence in situ hybridization following allogeneic hematopoietic cell transplant for hematological malignancies.

In order to detect chimerism, fluorescence in situ hybridization (FISH) and cytogenetic analyses were performed on bone marrow cells from 47 patients with hematological malignancies following allogeneic hematopoietic cell transplant (HCT). The dual-color XY, major Bcr-Abl (M-Bcr-Abl), and specific alpha-satellite probes were used for sex-mismatched HCT, chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) cases with karyotypic abnormalities before HCT, respectively. Donor cells were found using FISH analysis in all 32 cases examined within 2 months following HCT, confirming engraftment. In six cases, however, cytogenetic analysis failed to detect donor cells due to lack of metaphases. Relapse occurred in four of the six cases in which mixed chimerism was detected using FISH analysis after 6 months of HCT. In contrast, after 12 months of HCT, no relapse was found in 24 patients without host cells. For two patients with mixed chimerism, gradual reduction of immunosuppressants or donor lymphocyte infusion resulted in the disappearance of host cells as analyzed using FISH analysis. In three extramedullary relapse cases, however, cytogenetic relapse preceded morphological and FISH relapse. These findings suggest that FISH analysis is more useful for detecting residual host cells after HCT, and the combination of FISH and cytogenetic analyses provide a more detailed evaluation for HCT patients. The results also indicate that monitoring of mixed chimerism using FISH analysis after 6 months of HCT is important for allowing the early detection of hematological relapse.

Female↗
PubMed2000

The nucleotide sequence and genome organization of Japanese iris necrotic ring virus, a new species in the genus Carmovirus.

The genome of Japanese iris necrotic ring virus (JINRV) consists of a positive-sense ssRNA of 4014 nucleotides with six major open reading frames (ORFs). A 5'-non-coding region of 31 nucleotides precedes the first initiation codon. Like Carnation mottle virus (CarMV), the 5'-proximal three ORFs encode a 26 kDa protein (p26) and two readthrough proteins, i.e. an 85 kDa putative RNA replicase (p85) and a 99 kDa protein (p99). The central ORF encodes a small 8 kDa protein (p8). The 3'-proximal ORF encodes a 38 kDa capsid protein (p38). Another ORF encoding a 12 kDa protein (p12) overlaps the p99 ORF.JINRV RNA treated with bacterial alkaline phosphatase and tobacco acid pyrophosphatase could not be ligated to an oligoribonucleotide using T4 RNA ligase, indicating that the 5' end of the viral RNA is uncapped. The 3' end is not polyadenylated. Comparison of the genomic organization and the predicted amino acid sequences with those of other viruses confirmed that JINRV should be classified as a member of the genus Carmovirus, family Tombusviridae.

Capsid↗