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M Yoshida

Publications and source records attributed to M Yoshida.

At least 181 records · Page 10Linked to original sources
PubMed2001

Backward spreading of memory-retrieval signal in the primate temporal cortex.

Bidirectional signaling between neocortex and limbic cortex has been hypothesized to contribute to the retrieval of long-term memory. We tested this hypothesis by comparing the time courses of perceptual and memory-retrieval signals in two neighboring areas in temporal cortex, area TE (TE) and perirhinal cortex (PRh), while monkeys were performing a visual pair-association task. Perceptual signal reached TE before PRh, confirming its forward propagation. In contrast, memory-retrieval signal appeared earlier in PRh, and TE neurons were then gradually recruited to represent the sought target. A reasonable interpretation of this finding is that the rich backward fiber projections from PRh to TE may underlie the activation of TE neurons that represent a visual object retrieved from long-term memory.

Action Potentials↗
PubMed2001

Rotation of the c subunit oligomer in fully functional F1Fo ATP synthase.

The F(1)F(o)-type ATP synthase is the smallest motor enzyme known. Previous studies had established that the central gamma and epsilon subunits of the F(1) part rotate relative to a stator of alpha(3)beta(3) and delta subunits during catalysis. We now show that the ring of c subunits in the F(o) part moves along with the gamma and epsilon subunits. This was demonstrated by linking the three rotor subunits with disulfide bridges between cysteine residues introduced genetically at the interfaces between the gamma, epsilon, and c subunits. Essentially complete cross-linking of the gamma, epsilon, and c subunits was achieved by using CuCl(2) to induce oxidation. This fixing of the three subunits together had no significant effect on ATP hydrolysis, proton translocation, or ATP synthesis, and each of these functions retained inhibitor sensitivity. These results unequivocally place the c subunit oligomer in the rotor part of this molecular machine.

Dicyclohexylcarbodiimide↗
PubMed2001

PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines.

Extensive allelotyping studies have implicated several tumor-suppressor loci on chromosomes 3p, 5q, 6q, 8p, 9pq, 10q, 11q, 14q, 17p, 18q and 19p in human kidney tumorigenesis. The PTEN (also called MMAC1 and TEP1) gene, a candidate tumor suppressor located at chromosome 10q23.3, is mutated in a variety of sporadic malignancies as well as in patients with Cowden disease. To investigate the potential role of the PTEN gene in renal tumorigenesis, we searched for abnormalities of the gene in 68 primary renal-cell carcinomas (RCCs) as well as in 17 renal carcinoma-derived cell lines, using DNA-SSCP, sequencing and microsatellite analysis. Five of 68 (7.5%) primary RCCs exhibited intragenic mutations (3 missense, 1 deletion and 1 splice-site), and 1 of 17 (5.9%) cell lines had an insertion mutation. Loss of heterozygosity of the PTEN gene occurred in 25% of primary RCCs, including the 3 cases with intragenic mutation and the 1 PTEN-mutated cell line. Clinical and histopathological examinations revealed that 4 of the 5 primary tumors with PTEN mutation were high-grade, advanced clear-cell RCCs with distant metastases or renal vein tumor invasions, resulting in poor prognostic courses. The other was a low-stage papillary/chromophilic RCC. Our data suggest that PTEN mutation is observed in a subset of RCCs and that, especially in clear-cell RCCs, it occurs as a late-stage event and may contribute to the invasive and/or metastatic tumor phenotype.

Carcinoma, Renal Cell↗
PubMed2001

Synchronized domain-opening motion of GroEL is essential for communication between the two rings.

Escherichia coli chaperonin GroEL consists of two stacked rings of seven identical subunits each. Accompanying binding of ATP and GroES to one ring of GroEL, that ring undergoes a large en bloc domain movement, in which the apical domain twists upward and outward. A mutant GroEL(AEX) (C138S,C458S,C519S,D83C,K327C) in the oxidized form is locked in a closed conformation by an interdomain disulfide cross-link and cannot hydrolyze ATP (Murai, N., Makino, Y., and Yoshida, M. (1996) J. Biol. Chem. 271, 28229-28234). By reconstitution of GroEL complex from subunits of both wild-type GroEL and oxidized GroEL(AEX), hybrid GroEL complexes containing various numbers of oxidized GroEL(AEX) subunits were prepared. ATPase activity of the hybrid GroEL containing one or two oxidized GroEL(AEX) subunits per ring was about 70% higher than that of wild-type GroEL. Based on the detailed analysis of the ATPase activity, we concluded that inter-ring negative cooperativity was lost in the hybrid GroEL, indicating that synchronized opening of the subunits in one ring is necessary for the negative cooperativity. Indeed, hybrid GroEL complex reconstituted from subunits of wild-type and GroEL mutant (D398A), which is ATPase-deficient but can undergo domain opening motion, retained the negative cooperativity of ATPase. In contrast, the ability of GroEL to assist protein folding was impaired by the presence of a single oxidized GroEL(AEX) subunit in a ring. Taken together, cooperative conformational transitions in GroEL rings ensure the functional communication between the two rings of GroEL.

Bacterial Proteins↗
PubMed2001

Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin.

Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of histone deacetylases (HDACs). TSA is proposed to block the catalytic reaction by chelating a zinc ion in the active-site pocket through its hydroxamic acid group. On the other hand, the epoxyketone is suggested to be the functional group of TPX capable of alkylating the enzyme. We synthesized a novel TPX analogue containing a hydroxamic acid instead of the epoxyketone. The hybrid compound cyclic hydroxamic acid-containing peptide (CHAP) 1 inhibited HDAC1 at low nanomolar concentrations. The HDAC1 inhibition by CHAP1 was reversible as it was by TSA, in contrast to the irreversible inhibition by TPX. CHAP with an aliphatic chain length of five, which corresponded to that of acetylated lysine, was stronger than those with other lengths. These results suggest that TPX is a substrate mimic and that the replacement of the epoxyketone with the hydroxamic acid converted TPX to an inhibitor chelating the zinc like TSA. Interestingly, HDAC6, but not HDAC1 or HDAC4, was resistant to TPX and CHAP1, whereas TSA inhibited these HDACs to a similar extent. HDAC6 inhibition by TPX at a high concentration was reversible, probably because HDAC6 is not alkylated by TPX. We further synthesized the counterparts of all known naturally occurring cyclic tetrapeptides containing the epoxyketone. HDAC1 was highly sensitive to all these CHAPs much more than HDAC6, indicating that the structure of the cyclic tetrapeptide framework affects the target enzyme specificity. These results suggest that CHAP is a unique lead to develop isoform-specific HDAC inhibitors.

3T3 Cells↗
PubMed2001

Crystal structure of a depsipeptide, Boc-(Leu-Leu-Lac)3-Leu-Leu-OEt.

A sequential polydepsipeptide, Boc-(Leu-Leu-Lac)3-Leu-Leu-OEt (1) (Lac = L-lactic acid residue) has been synthesized by the segment condensation method. The sequential unit of 1, -Leu-Leu-Lac-, is consisted of two amino acid residues and one hydroxy acid residue. X-ray diffraction measurement with an imaging plate detector and a direct-methods procedure of Shake-and-Bake successfully revealed the crystal structure of 1. In the solid state, the 11-mer depsipeptide, 1, have clear alpha-helical conformation even with the three ester linkages.

Crystallization↗
PubMed2001

Preferential recognition of a fragment species of osteoarthritic synovial fluid fibronectin by antibodies to the alternatively spliced EIIIA segment.

OBJECTIVE: To characterize the species of synovial fluid (SF) fibronectin (FN) bearing the alternatively spliced EIIIA segment. METHODS: SF from patients with osteoarthritis (OA) and rheumatoid arthritis (RA), as well as corresponding affinity isolation products, were subjected to 1-dimensional and 2-dimensional electrophoresis followed by Western blot analysis. RESULTS: Regardless of the clinical type of arthritis, a polyclonal antibody that recognizes antigenic determinants throughout the FN molecule produced staining of predominantly approximately 200+ and approximately 170-kd species in reduced 1-dimensional electrophoresis. Despite the overall prevalence of the larger species, 4 monoclonal antibodies (mAb) reactive with sequences lying near the center of the EIIIA segment exhibited a relative failure to recognize the larger of these 2 species in OA, but not RA, SF. The absence of recognition of EIIIA sequences within the approximately 200+ kd forms of OA SF FN was unrelated to their derivation from dimers, since anti-EIIIA mAb recognized the smaller fragment species in preference to both monomeric and dimeric forms. The approximately 170-kd EIIIA+ fragments were observed to have minimal gelatin-binding capacity and appeared on 2-dimensional electrophoresis to extend from the N-terminus of FN through at least the center of the EIIIA segment. Similar results were obtained for samples obtained by needle aspiration or arthroscopic lavage, suggesting a widespread applicability of these findings. CONCLUSION: The approximately 170-kd EIIIA+ species of FN could potentially constitute a soluble "vehicle" by which chondrocyte-regulating EIIIA sequences, liberated from inhibitory flanking C-terminal sequences, could reach cells in the arthritic joint. Additionally, "FN species-specific" recognition of this segment within OA SF could constitute a marker by which to gauge the activity of the OA disease process.

Alternative Splicing↗
PubMed2001

Is skeletal muscle damaged by the oxidative stress following anaerobic exercise?

We investigated whether the injury of skeletal muscle owing to the action of free radicals and the subsequent oxidative damage to tissues occurred during anaerobic exercise. To estimate injury to skeletal muscle, we determined certain indices of oxidative damage to skeletal muscle; i.e., leukocyte counts, concentrations of hypoxanthine, xanthine, urate, tissue- and serum-type CK-M isoforms, myoglobin, and total antioxidant capacity (TAC) of serum. Blood for these tests was collected at 3 min post-exercise. Post-anaerobic exercise concentrations of lactate were significantly increased from pre-exercise. The neutrophil and lymphocyte counts and alanine concentration were significantly increased by anaerobic exercise, even when the results were corrected for plasma volume changes; the plasma concentrations of hypoxanthine, urate, and TAC of serum were also significantly increased. The plasma concentration of xanthine was negatively correlated with TAC of serum. The activities of tissue- and serum-type CK-M were significantly increased post-exercise. When the hypoxanthine, urate, TAC of serum, myoglobin, and tissue- and serum-type CK-M were corrected for plasma volume changes, the post-exercise increases were no longer significantly different from the pre-exercise results. We suggest that these latter test results following anaerobic exercise exclude the presence of oxidative damage to skeletal muscle.

Adult↗
PubMed2001

Incomplete atrioventricular septal defect with hypoplastic left ventricle and left atrioventricular valve stenosis.

A 2-month-old male infant with incomplete atrioventricular septal defect associated with a hypoplastic left ventricle and left atrioventricular valve stenosis successfully underwent biventricular repair. Echocardiography showed marked dilatation in the right ventricle and a diminutive left ventricle. However, the left ventricular chamber occupied the apex. Left atrioventricular valve stenosis was due to a solitary papillary muscle. Cardiac catheterization showed pulmonary/systemic flow ratio of 3.61, left ventricular end-diastolic volume of 63% of normal, and right ventricular end-diastolic volume of 324% of normal. During surgical repair, the solitary papillary muscle was divided longitudinally and the ostium primum was closed with a bovine pericardium. Postoperative left ventricular function was appropriate. Even when the preoperative end-diastolic left ventricular volume is small, if the left ventricle chamber is at the apex, then the left ventricular performance can be expected to be appropriate to tolerate the volume load after ostium primum closure.

Heart Septal Defects, Atrial↗
PubMed2001

Prolonged bone marrow failure with monosomy 7 after engraftment failure following bone marrow transplantation.

A patient with acute myelogenous leukemia developed prolonged bone marrow failure along with the monosomy 7 chromosome abnormality. The patient had undergone bone marrow transplantation with CD34+ selection following induction failure. However, she then suffered engraftment failure and long-term pancytopenia. Her white blood cell count gradually increased with supportive therapy including granulocyte colony-stimulating factor (G-CSF), and chromosomal analysis of bone marrow cells revealed an abnormal karyotype. Thirty months after the bone marrow transplantation we observed monosomy 7 together with the existing chromosomal abnormality in the patient's bone marrow cells. It has been reported that some patients with idiopathic and posthepatitis aplastic anemia develop clonal disorders such as myelodysplastic syndrome/acute myelogenous leukemia with monosomy 7. The findings in our case suggest that the appearance of monosomy 7 in patients with aplastic anemia may be caused by prolonged low-level hematopoiesis, with or without G-CSF stimulation.

Adolescent↗
PubMed2001

Acute effects of stereotactic radiosurgery on the kinetics of glucose metabolism in metastatic brain tumors: FDG PET study.

UNLABELLED: Hyperacute changes in the expression of glycolysis-associate gene products as well as FDG uptake in tumor cells after high-dose irradiation reflect response of the cells to noxious intervention and may be a potential indicator of the outcome of treatment. To understand acute effects on the kinetics of glucose metabolism of tumors in vivo after high-dose irradiation, we analyzed dynamic FDG PET data in patients with metastatic brain tumors receiving stereotactic radiosurgery. MATERIALS AND METHODS: We studied 5 patients with metastatic brain tumors by means of dynamic FDG PET before and 4 hours after stereotactic radiosurgery. Rate constants of glucose metabolism (K1*- k3*) were determined in a total of 13 tumors by a non-linear least squares fitting method for dynamic PET and arterial blood sampling data. Rate constants after radiosurgery were compared with those before radiosurgery. Changes in the rate constants induced by the therapy were also correlated with changes in tumor size evaluated by CT and/or MRI 6 months later. RESULTS: Four hours after radiosurgery, the phosphorylation rate indicated by k3* was significantly higher (0.080 +/- 0.058) than that before radiosurgery (0.049 +/- 0.023) (p < 0.05, paired t test), but there was no significant change in the membrane transport rates indicated by K1* and k2*. Although increases in the net influx rate constant K* (= K1*k3*/(k2* + k3*)) were correlated with increases in k3*, K* after radiosurgery (0.027 +/- 0.011) was not significantly different from that before the therapy (0.024 +/- 0.012). The reduction in the tumor size was correlated with k3* after radiosurgery. CONCLUSION: Acceleration of the phosphorylation process was demonstrated in vivo in metastatic brain tumors as early as 4 hours after stereotactic radiosurgery, as shown experimentally in vitro in a previous report. The phenomenon may be a sensitive indicator of cell damage.

Aged↗
PubMed2001

Left ventricular contractility is reduced by hypercapnic acidosis and thoracolumbar epidural anesthesia in rabbits.

PURPOSE: We have previously observed that sympathetic blockade by epidural anesthesia (EA) modifies the cardiovascular response to marked hypercapnic acidosis in dogs. Our objective was to determine whether the combination of marked hypercapnic acidosis and EA reduce left ventricular contractility. METHODS: We randomly assigned 22 Japanese white rabbits anesthetized with isoflurane (1.0%) to two groups according to the absence (control group, n= 11) or presence (EA group, n= 11) of thoracolumbar EA. After epidural injection (0.5 mL.kg(-1) of 0.9% saline in the control group or 1% mepivacaine in the EA group) and during subsequent hypercapnia (mean arterial CO2 tension 85 mmHg), we measured left ventricular pressure, left ventricular volume by using conductance catheter and plasma catecholamine concentrations. Left ventricular contractility was assessed by the slope of the linear approximation of the left ventricular end-systolic pressure-volume relationship, [i.e., end-systolic elastance (Ees)]. RESULTS: The combination of hypercapnic acidosis and thoracolumbar EA caused a 65% decrease in Ees (P <0.05). Hypercapnic acidosis alone caused a 16% decrease (P <0.05) and thoracolumbar EA alone caused a 49% decrease in Ees (P <0.05). In the EA group, epidural injection caused an 85% decrease in the epinephrine concentration (P <0.05) and a 39% decrease in the norepinephrine concentration (P <0.05), even during hypercapnic acidosis. However, in the control group, hypercapnic acidosis caused no change in the circulating epinephrine concentration but a 74% increase in the circulating norepinephrine concentration (P <0.05). CONCLUSION: Combined hypercapnic acidosis and EA markedly reduce left ventricular contractility in an additive fashion in rabbits receiving general anesthesia.

Acidosis↗
PubMed2001

Combination chemotherapy of irinotecan plus cisplatin for advanced gastric cancer: efficacy and feasibility in clinical practice.

BACKGROUND: A previous phase II study showed that a combination of irinotecan (CPT-11) with cisplatin (CDDP) was effective for advanced gastric cancers, but was associated with substantial neutropenia and diarrhea. The aim of this retrospective study was to evaluate the efficacy and feasibility of the combination in clinical practice. METHODS: The subjects comprised 65 patients with advanced gastric cancer treated with CPT-11 (70mg/m2, day 1, day 15) and CDDP (80mg/m2, day 1) as first-line chemotherapy between April 1993 and March 1999. Patient backgrounds, response rates, response durations, times to progression, and survival rates were investigated retrospectively. RESULTS: The overall response rate and the response rates for measurable metastatic lesions and primary sites were 43% (28/65), 48% (31/64), and 24% (10/42). Leucopenia of grade 4 and diarrhea of grade 3 or 4 were observed in 6 (9%) and 5 (8%) patients, respectively. Among the 19 patients with peritoneal metastasis, leucopenia of grade 4 and diarrhea of grade 3 or 4 were observed in only 1 of the 18 patients who received sufficient oral intake (6%). There were no treatment-related or early deaths within 30 days from the last treatment day. The median survival times of all patients, patients with an intestinal type of adenocarcinoma, and patients with a diffuse type were 365, 472, and 291 days, respectively. Multivariate analysis showed that the histological type of cancer was a significant independent prognostic factor (P = 0.0169). CONCLUSION: This retrospective study confirmed the efficacy and feasibility of this combination therapy in clinical practice.

Adenocarcinoma↗
PubMed2001

Histone deacetylase as a new target for cancer chemotherapy.

Trichostatin A (TSA) and trapoxin (TPX), inhibitors of the eukaryotic cell cycle and inducers of morphological reversion of transformed cells, inhibit histone deacetylase (HDAC) at nanomolar concentrations. Recently, FK228 (also known as FR901228 and depsipeptide) and MS-275. antitumor agents structurally unrelated to TSA, have been shown to be potent HDAC inhibitors. These inhibitors activate the expression of p21Waf1 in a p53-independent manner. Changes in the expression of regulators of the cell cycle, differentiation, and apoptosis with increased histone acetylation may be responsible for the cell cycle arrest and antitumor activity of HDAC inhibitors. TSA has been suggested to block the catalytic reaction by chelating a zinc ion in the active site pocket through its hydroxamic acid group. On the other hand, an epoxyketone has been suggested to be the functional group of TPX capable of alkylating the enzyme. We synthesized a novel TPX analogue containing a hydroxamic acid instead of the epoxyketone. The hybrid compound, called cyclic hydroxamic-acid-containing peptide 1 (CHAP1) inhibited HDAC at low nanomolar concentrations. The HDAC1 inhibition by CHAPI was reversible, as is that by TSA, in contrast to irreversible inhibition by TPX. Interestingly, HDAC6, but not HDAC1 or HDAC4, was resistant to TPX and CHAP1, while TSA inhibited these HDACs to a similar degree. CHAP31, the strongest HDAC inhibitor obtained from a variety of CHAP derivatives, exhibited antitumor activity in BDF1 mice bearing B16/BL6 tumor cells. These results suggest that CHAP31 is promising as a novel therapeutic agent for cancer treatment, and that CHAP may serve as a basis for new HDAC inhibitors and be useful for combinatorial synthesis and high-throughput screening.

Animals↗
PubMed2001

Visual function after removal of subretinal neovascular membranes in patients with age-related macular degeneration.

BACKGROUND: Retinal pigment epithelial (RPE) cells have been transplanted to replace the RPE cells lost after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration. The purpose of this study was to analyze the visual function of eyes with altered RPE after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration, and to determine the effect of proliferated or migrated RPE cells on visual function. METHODS: Forty-seven patients with age-related macular degeneration underwent excision of CNVs following vitrectomy and tamponade with sulfur hexafluoride (SF6) or silicone oil. The appearance of pre- or subretinal fibrosis and pigmentation of the lesion was considered to indicate proliferation and migration of RPE cells. Microperimetry was also performed. RESULTS: A significant correlation was found between the size of CNVs removed by surgery and the size estimated by indocyanine green angiography (P=0.0126). The mean number of RPE cells lost was estimated at 1.52 x 10(4). Pre- or subretinal fibrosis or pigmentation was observed in 37 patients (75.5%). The number of eyes with fibrosis was significantly higher in eyes with silicone oil tamponade than with SF6 tamponade (P=0.0016). A statistically significant correlation was not found between the presence of fibrosis or pigmentation and the postoperative visual acuity. Not all patients used the area of pigmentation for fixation, and microperimetry showed that some of the patients had scotomas in well-pigmented areas. CONCLUSIONS: Fibrosis and pigmentation after excision of CNVs may not always indicate normal function in these areas. These observations are especially relevant for transplantation of pigment epithelial cells in the future.

Aged↗
PubMed2001

Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy.

We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children. We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32 +/- 1.42 versus 0.75 +/- 0.78 g/day; P = 0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45 +/- 1.50 versus 0.63 +/- 0.56 g/day; P = 0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy in Japanese children.

Adolescent↗
PubMed2001

History of pancreaticojejunostomy in pancreaticoduodenectomy: development of a more reliable anastomosis technique.

The history of pancreaticojejunostomy in pancreaticoduodenectomy is described. Many types of operations have been devised in search of a more reliable method of anastomosis. To perform a safe and reliable pancreaticoenteric anastomosis it is necessary to understand the organ characteristics of the pancreas. We investigated factors required for a reliable pancreaticojejunostomy and devised a new surgical technique that meets those requirements. We introduce the theoretical substantiation and clinical usefulness of our new surgical technique while reviewing the history of pancreaticojejunostomy after pancreaticoduodenectomy. The unique aspect of our method is approximation of the pancreas stump and jejunal wall by six to eight interrupted sutures. It is speculated that too many sutures and tying too tight in the anastomosis may cause ischemia and necrosis of the pancreatic stump by restricting the tissue blood flow. Our method allows us not only to reduce the number of sutures, but also to avoid some of the complicated manipulations done in any other existing methods. The newly devised pancreaticojejunostomy is an excellent surgical technique with anastomotic failure seen in only two patients and no deaths out of 162 consecutive patients.

Adenocarcinoma↗