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N Fujita

Publications and source records attributed to N Fujita.

At least 55 records · Page 3Linked to original sources
PubMed2001

Multiple variants of receptor-type protein tyrosine phosphatase beta are expressed in the central nervous system of Xenopus.

We have isolated cDNA clones encoding the Xenopus homologue of receptor-type protein tyrosine phosphatase beta (RPTPbeta), and identified 13 forms of the mRNA provably generated by alternative splicing. All the conceptual translates have a carbonic anhydrase-like domain, a fibronectin type III-like repeat and a spacer in the extracellular segment. Eleven of them (designated XRPTPbeta.1-XRPTPbeta.11) also have highly conserved two intracellular PTP domains, whereas the other two variants (sXRPTPbeta.1 and sXRPTPbeta.2) have neither transmembrane nor cytoplasmic segment. There are five peptides that can be inserted in various combinations into the spacer region. Northern and Western blot analyses show central nervous system-specific expression of the XRPTPbeta mRNAs and proteins. Chondroitinase ABC treatment of the brain and spinal cord extracts results in separation of six protein bands on the Western blot, in association with a decrease in the size of major bands, indicating that the major XRPTPbeta variants are chondroitin sulfate proteoglycans. The results of these as well as reverse-transcribed polymerase chain reaction analyses suggest that the amounts of different XRPTPbeta variants are regulated in tissue- and developmental stage-specific manners.

Amino Acid Sequence↗
PubMed2001

Extravascular contribution of blood oxygenation level-dependent signal changes: a numerical analysis based on a vascular network model.

In this study, the extravascular (EV) contribution to blood oxygenation level-dependent (BOLD) signal changes was evaluated, based on a numerical analysis of the nondimensional Bloch-Torrey equation for a vascular network model of randomly oriented paramagnetic vessels. From a statistical point of view, the susceptibility-induced EV BOLD signal changes for both gradient- and spin-echoes are shown to be proportional to cerebral blood volume (CBV). These changes can be expressed by a function of two nondimensional parameters: one represents the characteristic phase change of the signal induced by the deoxyhemoglobin-containing vessels, and the other represents a diffusion effect relative to the vessel radius. The numerical results showed excellent agreement with the analytical solutions obtained previously for the regimes of small and large diffusion effects. Based on the numerical results for gradient- and spin-echoes, it is possible to show the dependence of the EV BOLD contribution on the echo time, the static magnetic field strength, and the stimulation-induced CBV change. This dependence can be demonstrated for vessels of small, intermediate, and large radii, which correspond respectively to the slow, intermediate, and fast diffusion regimes. A more realistic functional MRI (fMRI) simulation which includes an intravascular (IV) contribution is presented, with emphasis on the field strength dependence of the BOLD signal changes.

Electromagnetic Fields↗
PubMed2001

Association between IA-2 autoantibody epitope specificities and age of onset in Japanese patients with autoimmune diabetes.

The IA-2 is a major autoantigen of type 1 diabetes belonging to the protein tyrosine phosphatase family. We report on the humoral autoimmunity to an alternatively-spliced variant of IA-2 (IA-2 variant) and autoimmune-mediated diabetes age of onset association with IA-2 autoantibody epitope specificities, in 144 recent-onset patients with type 1 diabetes and 54 GAD autoantibody-positive patients with type 2 diabetes. The cytoplasmic domain of IA-2 (IA-2ic) detected a somewhat greater proportion of patients expressing autoantibodies than IA-2 variant (56%vs. 52% of patients with type 1 diabetes and 17%vs. 9% of GAD autoantibody-positive patients with type 2 diabetes). Conversely, only 1% of IA-2 variant autoantibody-positive patients failed to react to IA-2ic construct. Among 80 patients with type 1 diabetes who were positive for autoantibodies to IA-2ic, 8% recognized the juxtamembrane region (JM, representing amino acids 601-629) only, 64% bound the protein tyrosine phosphatase (PTP)-like domain of IA-2 only, and 29% bound both JM and PTP epitopes. Autoantibodies to the PTP-like domain were prevalent in children and adolescents with type 1 diabetes. The age of disease onset in patients with IA-2JM autoantibodies only, was significantly higher than those in patients reacted with the PTP-like domain of IA-2 (P< 0.02). Among GAD autoantibody-positive patients with type 2 diabetes reacted with IA-2ic, 44% bound the JM region only, and 33% bound epitopes in the PTP-like domain only; 22% had autoantibodies to both regions. The frequency of GAD autoantibody-positive patients with type 2 diabetes positive for autoantibodies to the JM region only, was significantly higher than that in patients with type 1 diabetes (P< 0.01). IA-2PTP autoantibodies were significantly associated with HLA-DR4, while the additional reactivity to IA-2JM was associated with HLA-DR9 allele. These results suggest that autoantibody recognition of IA-2 epitopes in autoimmune diabetes is associated with age of disease onset, which may reflect the intensity of the beta-cell destruction process.

Adolescent↗
PubMed2001

Hepatosplanchnic oxygenation is better preserved during mild hypothermic than during normothermic cardiopulmonary bypass.

PURPOSE: To assess and compare the effects of normothermic and mild hypothermic cardiopulmonary bypass (CPB) on hepatosplanchnic oxygenation. METHODS: We studied 14 patients scheduled for elective coronary artery bypass graft surgery who underwent normothermic (>35 degrees C; group I, n=7) or mild hypothermic (32 degrees C; group II, n=7) CPB. After induction of anesthesia, a hepatic venous catheter was inserted into the right hepatic vein to monitor hepatic venous oxygen saturation (ShvO(2)) and hepatosplanchnic blood flow by a constant infusion technique that uses indocyanine green. RESULTS: The ShvO(2) decreased from a baseline value in both groups during CPB and was significantly lower at ten minutes and 60 min after the onset of CPB in group I (39.5 +/- 16.2% and 40.1 +/- 9.8%, respectively) than in group II (61.1 +/- 16.2% and 61.0 +/- 17.9%, respectively; P <0.05). During CPB, the hepatosplanchnic oxygen extraction ratio was significantly higher in group I than in group II (44.0 +/- 7.2% vs 28.7 +/- 13.1%; P <0.05). CONCLUSION: Hepatosplanchnic oxygenation was better preserved during mild hypothermic CPB than during normothermic CPB.

Cardiopulmonary Bypass↗
PubMed2001

Decrease in N-acetylaspartate/creatine ratio in the motor area and the frontal lobe in amyotrophic lateral sclerosis.

We studied whether N-acetylaspartate (NAA), a neuronal marker, is reduced in the brain of 14 patients with clinically definite amyotrophic lateral sclerosis (ALS) and whether NAA levels in the motor area and frontal lobe correlate with the clinical features, including frontal lobe function. We also studied 14 normal controls were evaluated. We obtained peak integrals in 1H magnetic resonance spectroscopy (MRS) for NAA, creatine (Cr), and choline-containing compounds (Cho). Severity of the disease was determined using the manual muscle strength test, and the Norris limb and bulbar scales. In the patients, the NAA/Cr ratio was reduced in the motor area and frontal lobe, while the Cho/Cr ratio was normal throughout the brain. There were significant correlations between the NAA/Cr ratio in the motor area and the Norris limb scale (r = 0.50; P < 0.01) and between the NAA/Cr ratio in the frontal lobe and the number of categories achieved in the Wisconsin Card Sorting test (r = 0.71; P < 0.05), implying frontal lobe dysfunction. These correlations suggest that a reduced NAA/Cr ratio is a marker of cortical neuronal loss and dysfunction in ALS.

Adult↗
PubMed2001

Correlation between plasma endotoxin, plasma cytokines, and plasminogen activator inhibitor-1 activities in septic patients.

The objective of this study was to evaluate the relation between the clinical and plasma parameters and the changes in plasma endotoxin activity with 2 hours of endotoxin-adsorbing therapy using polymyxin B (PMX). A total of 88 consecutive patients were admitted for PMX treatment of severe sepsis or septic organ failure. Standard supportive care was continued without alteration during PMX treatment. Endotoxin, tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-10, and plasminogen activator inhibitor-1 (PAI-1) activities and clinical parameters were measured before, immediately after, and the day after PMX treatment. The mean APACHE II and III scores were 24.2 +/- 1.0 and 85.8 +/- 3.0, respectively. The 2-week survival rate was 51.1%. In survivors, TNFalpha, IL-6, IL-10, and PAI-1 activities were significantly decreased during the 2-hour PMX treatment, the following day, or both times. There was no significant change in the parameters, except for TNFalpha, after PMX in nonsurvivors. In the subgroup whose plasma endotoxin decreased more than 30%, IL-6, TNFalpha, and PAI-1 significantly decreased after 2 hours of PMX or the following day (or both), but all four parameters in nonsurvivors showed no significant change. Hence PMX adsorbed plasma endotoxins and contributed to reductions in plasma proinflammatory cytokine levels and to improved clinical parameters during the 2-hour treatment. Changes in these parameters correlated with changes in plasma endotoxin activity in survivors whose plasma endotoxin levels were adequately reduced.

APACHE↗
PubMed2001

Differential diagnosis of large-sized pedunculated polypoid lesions of the gallbladder by endoscopic ultrasonography: a prospective study.

PURPOSE: We have previously reported the effectiveness of endoscopic ultrasonography (EUS) for the differential diagnosis of pedunculated polypoid lesions of the gallbladder, based on retrospective studies using resected specimens. We proposed the following diagnostic criteria for EUS findings: when the contour of a lesion is nodular or smooth, the lesion is diagnosed as a neoplasm, and when a lesion has a granular contour, it is diagnosed as a nonneoplasm. The present study was designed to verify the clinical utility of our EUS ctiteria prospectively. METHODS: Forty-six consecutive patients with pedunculated polypoid lesions of the gallbladder 10mm or greater in size diagnosed as nonneoplasms at the initial EUS, all of whom underwent follow-up examinations, were enrolled in this study. The occurrence of changes in these lesions during the observation period was examined. RESULTS: No evident changes in lesions were observed in 43 of the 46 patients. Spontaneous self-detachment of lesions was recognized during the observation period in the other 3 patients. CONCLUSIONS: EUS is useful for determining treatment indications for pedunculated polypoid lesions of the gallbladder, even when the lesions are large, and contributes to avoiding unnecessary surgery.

Adenomatous Polyps↗
PubMed2001

Surgically treated primary lung cancer associated with Brugada syndrome: report of a case.

A 71-year-old man with primary lung cancer associated with Brugada syndrome was safely operated on following the placement of an implantable cardioverter defibrillator (ICD). During examinations for Brugada syndrome, a tumor in the apicoposterior segment of the left lung was incidentally detected by chest computed tomography. Following the implantation of an ICD, surgical treatment of the left lung tumor was scheduled. A lung biopsy was thoracoscopically performed and adenocarcinoma was diagnosed based on a frozen section analysis. A left upper lobectomy with lymph node dissection was performed through a standard posterolateral thoracotomy. Ventricular fibrillation, which occurred during the night of the first day following surgery, was successfully managed by the ICD.

Adenocarcinoma↗
PubMed2001

Clinicopathological features of myeloid/natural killer (NK) cell precursor acute leukemia.

Four patients (three males and one female) were diagnosed as myeloid/natural killer (NK) cell precursor acute leukemia in our department. Two patients showed the extramedullary involvement at initial presentation. Leukemic cells expressed CD7, CD33, CD45 and CD56 in all patients. Additionally, CD13, CD34, HLA-DR, cytoplasmic CD3 and myeloperoxidase were expressed in some patients. Trisomy 10 was found in two patients, which has not been reported in this disease. Therefore, myeloid/NK cell precursor acute leukemia might be rather heterogeneous especially in chromosomal abnormality though it seemed to constitute the distinct clinical entity among acute myeloid leukemia of M0 subtype.

Acute Disease↗
PubMed2001

The isolation and characterization of a waxy mutant of diploid wheat (Triticum monococcum L.).

A waxy mutant of diploid wheat (Triticum monococcum L.) was isolated by screening M(3) seeds derived from 1% ethyl methanesulfonate (EMS) mutagenized materials with KI-I(2) staining of endosperm starch. This mutant was controlled by a single waxy gene that completely lacked amylose, the 59-kDa waxy protein and the granule-bound starch synthase I (GBSS I) activity in the endosperm. Moreover, the T. monococcum exhibited the gene dosage effects in terms of amylose content, the amount of waxy protein and the GBSS activity. The chain length distribution of amylopectin of the waxy mutant endosperm starch slightly differed from that of the wild type; the long chains of DP>==19 were more enriched in the waxy amylopectin than those in the wild type. The mutant can be an important material for studies on starch metabolism and breeding in Triticum species.

Journal Article↗
PubMed2001

Functional analyses of MeCP2 mutations associated with Rett syndrome using transient expression systems.

Rett syndrome, an X-linked neurodevelopmental disorder, is a major cause of mental retardation in females. Recent genetic analyses have revealed that mutations in the methyl-CpG-binding protein gene encoding MeCP2 are associated with Rett syndrome. In this study, we used transient expression systems to investigate the functional significance of mutations seen in patients with Rett syndrome. Missense mutations in the methyl-CpG-binding domain were analyzed by the transfection in mouse L929 cells and Drosophila SL2 cells. The L929 cells were utilized to investigate the effects of mutations on the affinity for heterochromatin, where methylated CpG dinucleotides are extremely enriched. The SL2 cells were utilized to analyze their effects on transcriptional repression activities. R106W and F155S mutations led to the substantial impairment of MeCP2 functions, showing the loss of accumulation of the mutated protein to mouse heterochromatin and the reduction of the transcriptional repressive activity in Drosophila SL2 cells. Intriguingly, the R133C mutant retained the functionality equivalent to MeCP2 in these analyses. On the other hand, the T158M mutation exhibited the intermediate level of the impairment of functions in both analyses. Thus, these functional assays are useful to evaluate the consequences of mutation in the methyl-CpG-binding domain of MeCP2 and provide an insight into the relationship between the genotype and the severity of Rett syndrome.

Animals↗
PubMed2001

Regulation of transcription and chromatin by methyl-CpG binding protein MBD1.

DNA methylation is important for epigenetic regulation of genome, and it is interpreted by specific protein factors that contain a highly conserved methyl-CpG binding domain (MBD). There are at present five mammalian MBD family proteins: MBD1, MBD2, MBD3, MBD4 and MeCP2. In the family of methyl-CpG binding proteins, MBD1 is characterized by the presence of MBD, two or three cysteine-rich CXXC motifs, and the C-terminal transcriptional repression domain (TRD). In addition, MBD1 has at least five isoforms due to alternative splicing events, resulting in the existence of CXXC1, CXXC2, and CXXC3 in MBD1 isoform v1 (MBD1v1) and MBD1v2, and CXXC1 and CXXC2 in MBD1v3 and MBD1v4. MBD1v1 represses transcription preferentially from both unmethylated and hypomethylated promoters, while MBD1v3 inhibits hypermethylated but not unmethylated promoter activities. The MBD and CXXC3 sequences are responsible for the ability to bind methylated and unmethylated DNAs, respectively. MBD1 is also found to be a chromosomal protein that forms many foci within the nucleus. These findings suggest that MBD1 is a unique transcriptional regulator depending on the density of methyl-CpG pairs.

Animals↗
PubMed2001

Effects of small doses of prostaglandin E(1) on systemic hemodynamics and jugular venous oxygen saturation during cardiopulmonary bypass.

STUDY OBJECTIVE: To examine the effects of small doses of prostaglandin E(1) (PGE(1)) on systemic hemodynamics and cerebral oxygenation during cardiopulmonary bypass(CPB). DESIGN: Randomized, prospective study. SETTING: Cardiac surgery at Saitama Cardiovascular and Pulmonary Center. PATIENTS: Forty patients who underwent elective coronary artery bypass surgery. INTERVENTIONS: The study was performed at the stable CPB period. Patients were randomly divided into four groups: control group (n = 10) received an infusion of saline, PGE(1) 10 group (n = 10) received an infusion of PGE(1) 10 ng/kg/min, PGE(1) 25 group (n = 10) received an infusion of PGE(1) 25 ng/kg/min, and the PGE(1) 50 group (n = 10) received an infusion of PGE(1) 50 ng/kg/min. MEASUREMENTS: After measuring the baseline partial pressure of the arterial oxygen saturation (SpO(2)), mixed venous oxygen saturation (SvO(2)), and jugular venous oxygen saturation (SjvO(2)), blood gases, and cardiovascular hemodynamic values, PGE(1) was infused intravenously at rate of between 10 and 50 ng/kg/min. PGE(1) infusion continued 30 minutes after the start of drug infusion, and the blood gas analysis and cardiovascular hemodynamic values were simultaneously determined together with the hemodynamic values at 2, 5, 10, 20, and 30 minutes during drug infusion. At 30 minutes after discontinuation of the drug infusion, the blood gas analyses were simultaneously determined together with the hemodynamic values. MAIN RESULTS: Mean arterial pressure (MAP) in PGE(1) 25 and 50 groups was decreased 20 and 30 minutes after the start of PGE(1) infusion compared with the baseline value (p < 0.05). In contrast, SvOm(2) in PGE(1) 25 and 50 groups was increased 20 and 30 minutes after the start of PGE(1) infusion compared with the baseline value (p < 0.05). There was no change in SjO(2) value despite a decrease in MAP during the study. CONCLUSIONS: Cerebral oxygenation estimated by SjvO(2) was maintained despite a decrease in MAP during the administration rate of PGE(1) between 10 and 50 ng/kg/min.

Aged↗
PubMed2001

Hepatitis C virus core particle detected by immunoelectron microscopy and optical rotation technique.

Hepatitis C Virus (HCV) are 55-65 nm spherical particles, but the internal structure of the virion remains to be clarified. To clarify the morphology of HCV core particles, we performed an immune electron microscopy (IEM) using plasma samples from two blood donors with high HCV RNA titers and a detergent-treated anti-HCV core antibody-free plasma sample with high HCV RNA titer (1.5x10(8) copies/ml). Spherical particles, with 33-40 nm in diameter (an average diameter of 37 nm) were found in 1.22-1.25 g/ml fractions after sucrose density gradient centrifugation by conventional electron microscopy (EM). IEM using rabbit polyclonal antibody (RR8) specific to the putative HCV core protein and goat anti-rabbit IgG colloidal gold particles revealed that these spherical particles specifically reacted with RR8. This finding indicates that the spherical particles are naked HCV core particles. Some of the HCV core particles had an icosahedron-like structure. Optical rotation technique showed that the HCV core particle exhibits six-fold symmetry and that the length of regular hexagon side is approximately 20 nm. These findings showed that HCV core particles are spherical particles of 33-40 nm in diameter and that HCV core particles may possess an icosahedron-like structure and a buoyant density of 1.22-1.25 g/ml.

Journal Article↗
PubMed2001

DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain.

Astrocyte differentiation, which occurs late in brain development, is largely dependent on the activation of a transcription factor, STAT3. We show that astrocytes, as judged by glial fibrillary acidic protein (GFAP) expression, never emerge from neuroepithelial cells on embryonic day (E) 11.5 even when STAT3 is activated, in contrast to E14.5 neuroepithelial cells. A CpG dinucleotide within a STAT3 binding element in the GFAP promoter is highly methylated in E11.5 neuroepithelial cells, but is demethylated in cells responsive to the STAT3 activation signal to express GFAP. This CpG methylation leads to inaccessibility of STAT3 to the binding element. We suggest that methylation of a cell type-specific gene promoter is a pivotal event in regulating lineage specification in the developing brain.

Animals↗
PubMed2001

Molecular mechanism in activation of glutathione system by ropinirole, a selective dopamine D2 agonist.

We have previously reported that ropinirole, a non-ergot dopamine agonist, has neuroprotective effects against 6-hydroxydopamine in mice based on in vivo antioxidant properties such as the glutathione (GSH)-activating effect. In the present study, we determined that the effects of ropinirole on the level of expression of GSH-related enzyme mRNA, these enzymes were shown to regulate GSH contents in the brain. This study focused on the mechanism of GSH enhancement by ropinirole. Striatal GSH contents were significantly increased by 7-day daily administration of ropinirole. Furthermore, the expression levels of gamma-glutamylcysteine synthetase (gamma-GCS), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) mRNA increased following daily injections of ropinirole for 7 days. In addition, ropinirole treatment for 7 days suppressed auto-oxidation in mouse striatal homogenates, in contrast to the vehicle treatment. In conclusion, ropinirole was able to suppress auto-oxidation, most probably by increasing GSH levels due to an increase of GSH synthesis. In addition, it is likely that auto-oxidation was also suppressed by the activation of GSH-regulating enzymes such as GPx, GR, and GST in the mouse striatum. Thus, our results indicate that the GSH-activating effect of ropinirole may render this dopamine agonist beneficial as a neuroprotective drug.

Animals↗
PubMed2001

Time course of changes in jugular venous oxygen saturation during hypothermic or normothermic cardiopulmonary bypass in patients with diabetes mellitus.

BACKGROUND: Preexisting diabetic mellitus is a risk factor determining postoperative neurological disorders. The present study assesses the effects of normothermic and hypothermic cardiopulmonary bypass (CPB) on jugular venous oxygen saturation (SjvO2)in patients with preexisting diabetic mellitus. METHODS: Sixteen diabetic patients who underwent elective coronary artery bypass grafting surgery were randomly divided into two groups: Group DN (n=8, diabetic patients) underwent normothermic CPB (>35 degrees C), and group DH (n=8, diabetic patients) underwent hypothermic CPB (32 degrees C). Controls were 16 age-matched non-diabetic patients (normothemic group, CN: n=8; hypothemic group, CH: n=8). A 4.0 F fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor SjvO2 values. Hemodynamic parameters and arterial and jugular venous blood gases were measured seven times. RESULTS: Cerebral desaturation, which was defined as SjvO2 values below 50%, was observed during normothermic CPB in diabetic patients (at the onset of CPB: 46+/-3%, at 20 min after onset of CPB: 49+/-3%, means+/-SD, respectively). No cerebral desaturation occurred in diabetic and control patients during hypothermic CPB. CONCLUSIONS: Patients with preexisting diabetes mellitus experienced cerebral desaturation during normothermic CPB.

Aged↗