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Biomedical subjects

Y Ono

Publications and source records attributed to Y Ono.

At least 127 records · Page 7Linked to original sources

[Development and assessment of real cardiac motion simulation phantom].

To evaluate cardiac images obtained by multi-slice CT, assessments of the temporal resolution and reconstruction algorithm are essential. For these purposes, we have designed and developed a cardiac motion phantom. Using suitable driver sequences, the phantom allowed for modeling of real left ventricular motion, which was characterized by fast pumping, slow pumping, fast filling and slow filling. Our phantom seems to be useful for use in the fundamental assessments and researches of cardiac CT.

Humans↗

[Early replacement of intravenous aminophylline administration with oral theophylline in treating acute exacerbation of asthma].

Intravenous (i.v.) administration of aminophylline has been used to relieve acute exacerbation of bronchial asthma for almost a century. Despite confidence in its effectiveness, controversy has arisen about its efficacy. We currently use aminophylline in the routine treatment of asthma since the drug is essentially useful. Continuous aminophylline infusion tends to be used rather haphazardly in hospital wards, and the criteria for termination of an infusion have not been clarified. We therefore attempted to determine: 1) whether continuous aminophylline infusion is actually beneficial, 2) whether the TDM (treatment drug monitoring) system can be used to establish a protocol for prescribed dosing after an early switch from i.v. to oral administration, and 3) whether adherence to the protocol would contribute to decreases in the duration of hospitalization and in medical expenses. Seventeen patients with acutely exacerbated asthma were enrolled in this study. Nine patients were prescribed oral theophylline on the second hospital day (p.o. group), while eight received continuous i.v. aminophylline (i.v. group). The serum theophylline concentrations were maintained in the therapeutic range in both groups. Peak flow, symptom scores, and QOL scores showed significant improvements in the p.o. group on the third hospital day. It might therefore be possible, by using the TDM system, to set the dosage of theophylline so that hospitalization is shortened.

Administration, Oral↗

[Adenocarcinoma of the renal pelvis and transitional cell carcinoma of the ureter occurring 11 years after radical cystectomy for bladder cancer: a case report].

We report a case of upper urinary tract carcinoma which recurred 11 years after total cystectomy. A 52-year-old man presented with complaints of a sense of residual urine and terminal miction pain. Urinary cytology, cystoscopic examination and intravenous pyelography revealed normal findings. Twenty months later, because class V urinary cytologic findings were detected, transurethral biopsy was performed. Carcinoma in situ was diagnosed pathologically. Therefore, total cystectomy and ileal conduit urinary diversion were performed. The pathological diagnosis was transitional cell carcinoma, grade 3, pTis. At 127 months postoperatively, laboratory examination revealed an extremely high serum level of LDH (3,084 U/l). The right kidney was not visualized on IVP and computed tomography revealed a right renal irregular mass. On the suspicion of a renal pelvic tumor, right total nephroureterectomy was done. The pathologic diagnosis was renal pelvic adenocarcinoma and ureteral transitional cell carcinoma. The patient was treated postoperatively with 3 cycles of systemic chemotherapy and radiotherapy. The serum level of LDH returned to normal. However, one year later, the serum level of LDH elevated to 1,118 U/l. He died of retroperitoneal lymph node, left adrenal gland and pulmonary metastases.

Adenocarcinoma↗

[Dissecting aneurysm of the middle cerebral artery (M1-2 portion) with subarachnoid hemorrhage: a case report].

We report a SAH case of a ruptured dissecting aneurysm of the middle cerebral artery following parietooccipital subcortical hemorrhage. A 68-year-old woman was admitted to our hospital, complaining of headache. On admission she was alert with left homonymous hemianopsia. A CT scan disclosed subcortical hemorrhage in the right parieto-occipital lobe. An angiogram revealed no abnormal vessels. Seven days after admission, she suddenly lapsed into unconsciousness with left hemiparesis. A CT scan demonstrated subarachnoid hemorrhage with a right sylvian hematoma. A second angiogram revealed fusiform dilatation of the M2 branches and aneurysmal dilatation at the M1-M2 bifurcation. Following conservative therapy, she died 21 days after admission. The relationship between subcortical hemorrhage and the subsequent subarachnoid hemorrhage was not certain. We discuss and review the treatment of a dissecting aneurysm of the middle cerebral artery.

Aged↗

Consensus statement on transcultural issues in depression and anxiety from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care physicians with a better understanding of transcultural issues in depression and anxiety. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Five faculty invited by the chair also participated: Laurence J. Kirmayer, Jean-Pierre Lepine, Keh-Ming Lin, Osamu Tajima, and Yutaka Ono. EVIDENCE: The consensus statement is based on the 5 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles, and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSION: The consensus statement underlines the prevalence of depression and anxiety disorders across all cultures and nations while recognizing that cultural differences exist in symptom presentation and prevalence estimates. In all countries, the recognition of depression by clinicians in the primary care setting is low (generally less than 50%), and the consensus group recommends a 2-step process to aid the recognition and diagnosis of depression. In line with the low recognition of depression and anxiety disorders is the finding that only a small proportion of patients with depression or anxiety are receiving appropriate treatments for their condition. Biological diversity across ethnic groups may account for the differential sensitivity of some groups to psychotropic medication, but this area requires further investigation.

Anxiety Disorders↗

[Peripheral blood stem cell harvest for patients with germ cell tumors].

From January 1996 to December 1999, fifteen patients with germ cell tumors underwent peripheral blood stem cell harvest during 15 courses of bleomycin, etoposide, cisplatin (BEP), 4 courses of etoposide, ifosfamide, cisplatin (VIP) and 3 courses of high-dose etoposide mobilization at Nagoya University Hospital. We performed 29 aphereses during BEP, eight during VIP, and six during high-dose etoposide. Although we were able to harvest 4.4 x 10(6)/kg of median CD34 positive cells per apheresis during BEP, the number of stem cells (more than 4 x 10(6)/kg of CD34 positive cells), which are needed for tandem high-dose chemotherapy, could not be obtained during four courses of BEP. For three patients in whom white blood cell counts at nadir were 2,000/microL or more, however, the required number of CD34 positive cells were harvested. VIP provided only 1.7 x 10(6)/kg of median CD34 positive cells per apheresis, while, 7.3 x 10(6)/kg of CD34 positive cells were harvested during high-dose etoposide mobilization. The dose of G-CSF was a significant factor for the number of CD34 positive cells harvested during BEP (p = 0.02); however, there might be some relationship between the harvest and the number of the peripheral white blood cells on the day of apheresis (p = 0.08), the day to start G-CSF (p = 0.13), or the day to initiate apheresis (p = 0.27). Based on our experience, it is recommended that 5 micrograms/kg of G-CSF should be started from the 14th or 15th day of BEP until the last apheresis and that aphereses should be performed between the 19th and 21st day, especially at the days when the peripheral white blood cell count increases beyond 10,000/microL.

Adolescent↗

[Surgical treatment of infectious endocarditis complicated by discrete subaortic stenosis: report of a case].

A 39-year-old male with a history of cardiac murmur from early childhood was diagnosed as having infectious endocarditis (IE) complicated by discrete subaortic stenosis (DSS). Echocardiography revealed severe aortic regurgitation, subaortic membranous structure and mild mitral regurgitation. The pressure gradient across the subaortic stenosis was 105 mmHg according to continuous Doppler wave ultrasonography. Aortic valve replacement and resection of subaortic membranous tissue and mitral annuloplasty were performed. Postoperative cardiac catheterization demonstrated that the hemodynamic data were remarkably improved, and the patient was free of symptoms. He is currently well at 6 months after the operation.

Adult↗

Loss of calpain 3 proteolytic activity leads to muscular dystrophy and to apoptosis-associated IkappaBalpha/nuclear factor kappaB pathway perturbation in mice.

Calpain 3 is known as the skeletal muscle-specific member of the calpains, a family of intracellular nonlysosomal cysteine proteases. It was previously shown that defects in the human calpain 3 gene are responsible for limb girdle muscular dystrophy type 2A (LGMD2A), an inherited disease affecting predominantly the proximal limb muscles. To better understand the function of calpain 3 and the pathophysiological mechanisms of LGMD2A and also to develop an adequate model for therapy research, we generated capn3-deficient mice by gene targeting. capn3-deficient mice are fully fertile and viable. Allele transmission in intercross progeny demonstrated a statistically significant departure from Mendel's law. capn3-deficient mice show a mild progressive muscular dystrophy that affects a specific group of muscles. The age of appearance of myopathic features varies with the genetic background, suggesting the involvement of modifier genes. Affected muscles manifest a similar apoptosis-associated perturbation of the IkappaBalpha/nuclear factor kappaB pathway as seen in LGMD2A patients. In addition, Evans blue staining of muscle fibers reveals that the pathological process due to calpain 3 deficiency is associated with membrane alterations.

Animals↗

Sol-gel polycondensation in a cyclohexane-based organogel system in helical silica: creation of both right- and left-handed silica structures by helical organogel fibers.

Chiral amide- and urea-type organic gelators (1-6), based on cyclohexanediamine, have been prepared, and the superstructures of the organogels were evaluated by circular dichroism (CD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The CD spectrum of the amide-based organogel system 1+2 exhibited a negative sign for the first Cotton effect, indicating that the dipole moments in the gelator aggregate orient into an anticlockwise direction. In contrast, the system 3+4 has a positive sign for the first Cotton effect, indicating that they orient into a clockwise direction. In the mixture of urea- and amide-based organogels, CD spectra of 5+2 and 6+4 revealed negative and positive signs, respectively. The helical structure of the amide-based organogels 1+2 and 3+4 clearly showed left- and right-handed structures, respectively, by SEM. To transcribe the chiral, helical structures of the organogels into silica gel, the sol-gel polycondensation of tetraethoxysilane (TEOS) was carried out in acetonitrile or ethanol. Very surprisingly, the left- and right-handed structures of the silica can be created by transcription of left- and right-handed structures of the organogels 1+2 (R enantiomer) and 3+4 (S enantiomer), respectively. In addition, in the mixture systems of urea- and amide-based organogels, the right- and left-handed structures of the organogels 5+2 (R enantiomer) and 6+4 (S enantiomer) were precisely transcribed into the silica structure. The findings suggest that the sol-gel polycondensation proceeds along the surface of the helical structure of the organogels. We therefore believe that the sol-gel polycondensation by means of molecular assembly templates abundantly built in the organogel phase is a new strategy to create superstructured silica materials.

Journal Article↗

Phosphorylation of tau is regulated by PKN.

For the phosphorylation state of microtubule-associated protein, tau plays a pivotal role in regulating microtubule networks in neurons. Tau promotes the assembly and stabilization of microtubules. The potential for tau to bind to microtubules is down-regulated after local phosphorylation. When we investigated the effects of PKN activation on tau phosphorylation, we found that PKN triggers disruption of the microtubule array both in vitro and in vivo and predominantly phosphorylates tau in microtubule binding domains (MBDs). PKN has a catalytic domain highly homologous to protein kinase C (PKC), a kinase that phosphorylates Ser-313 (= Ser-324, the number used in this study) in MBDs. Thus, we identified the phosphorylation sites of PKN and PKC subtypes (PKC-alpha, -betaI, -betaII, -gamma, -delta, -epsilon, -zeta, and -lambda) in MBDs. PKN phosphorylates Ser-258, Ser-320, and Ser-352, although all PKC subtypes phosphorylate Ser-258, Ser-293, Ser-324, and Ser-352. There is a PKN-specific phosphorylation site, Ser-320, in MBDs. HIA3, a novel phosphorylation-dependent antibody recognizing phosphorylated tau at Ser-320, showed immunoreactivity in Chinese hamster ovary cells expressing tau and the active form of PKN, but not in Chinese hamster ovary cells expressing tau and the inactive form of PKN. The immunoreactivity for phosphorylated tau at Ser-320 increased in the presence of a phosphatase inhibitor, FK506 treatment, which means that calcineurin (protein phosphatase 2B) may be involved in dephosphorylating tau at Ser-320 site. We also noted that PKN reduces the phosphorylation recognized by the phosphorylation-dependent antibodies AT8, AT180, and AT270 in vivo. Thus PKN serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly.

Amino Acid Sequence↗

Abnormal cardiac autonomic nervous activity after right ventricular outflow tract reconstruction.

BACKGROUND: There are few studies of cardiac autonomic nervous activity (CANA) in patients with congenital heart disease. Methods and Results-We evaluated CANA in 54 patients after closure of an atrial/ventricular septal defect (group A), 54 patients after successful right ventricular outflow tract reconstruction (RVOTR) (group B1), 35 RVOTR patients with residual stenosis (group B2), and 47 controls. Cardiac parasympathetic nervous activity (PSNA) was estimated by heart rate (HR) change after cholinergic blockade, HR variability, and arterial baroreflex sensitivity (BRS). Cardiac sympathetic nervous activity was estimated by the heart-to-mediastinum (123)I-metaiodobenzylguanidine activity ratio (H/M) and HR increase after isoproterenol infusion (ss). HR response (DeltaHR) and peak oxygen uptake (VO(2)) were measured by exercise test. There was no difference in ss among study groups. Group A exhibited mildly impaired PSNA, which recovered 1 year after surgery, and no change in H/M. Impaired PSNA and low H/M were found in groups B1 and B2 compared with controls (P<0.001), although the PSNA tended to recover 1 year after re-RVOTR. In group B1, PSNA and ss were related to DeltaHR, and BRS correlated inversely with the number of surgical procedures and age at RVOTR and positively correlated with the follow-up period, whereas DeltaHR correlated with peak VO(2) (P<0.01 to 0.001). CONCLUSIONS: After RVOTR, postsynaptic ss-sensitivity is maintained and is important in DeltaHR during exercise, as is PSNA, although ventricular sympathetic denervation is common. Impaired PSNA immediately after RVOTR improves with improved DeltaHR and results in future amelioration of aerobic capacity, whereas ventricular sympathetic reinnervation is uncertain.

Adolescent↗

Association of immature hypophosphorylated protein kinase cepsilon with an anchoring protein CG-NAP.

Protein kinase C (PKC) family requires phosphorylation of itself to become competent for responding to second messengers. Much attention has been focused on elucidating the role of phosphorylation in PKC activity; however, it remains unknown where this modification takes place in the cells. This study examines whether anchoring protein is involved in the regulation of PKC phosphorylation. A certain population of PKC epsilon in rat brain extracts as well as that expressed in COS7 cells was associated with an endogenous anchoring protein CG-NAP (centrosome and Golgi localized PKN- associated protein). Pulse chase experiments revealed that the associated PKC epsilon was an immature species at the hypophosphorylated state. In vitro binding studies confirmed that non- or hypophosphorylated PKC epsilon directly bound to CG-NAP via its catalytic domain, whereas sufficiently phosphorylated PKC epsilon did not. PKC epsilon mutant at a potential phosphorylation site of Thr-566 or Ser-729 to Ala, possessing almost no catalytic activity, was associated and co-localized with CG-NAP at Golgi/centrosome area. On the other hand, wild type and a phosphorylation-mimicking mutant at Thr-566 were mainly distributed in cytosol and represented second messenger-dependent catalytic activation. These results suggest that CG-NAP anchors hypophosphorylated PKCepsilon at the Golgi/centrosome area during maturation and serves as a scaffold for the phosphorylation reaction.

A Kinase Anchor Proteins↗

Evolution of aortic regurgitation following simple patch closure of doubly committed subarterial ventricular septal defect.

We reviewed the Doppler echocardiographic findings of the aortic valve and associated aortic regurgitation (AR) in 55 patients who underwent patch closure of doubly committed subarterial ventricular septal defect (VSD). The maximal diameter of the VSD measured > or = 5 mm, whereas the postoperative follow-up interval was > or = 5 years. Twenty-three patients underwent closure before they developed aortic cusp prolapse or AR (group A). In 15 patients the VSD was closed when aortic cusp prolapse was recognized, but AR was absent (group B). Aortic cusp prolapse with AR was detected before closure in a further 15 patients (group C). Of 8 patients with no AR before closure, AR was detected during follow-up in 6 group A and in 2 group B patients. In group C, AR resolved after surgery in 4 patients, whereas AR grade improved in a further 8 patients and remained unchanged in 3. Although residual AR was more frequent in patients with aortic cusp prolapse and AR before closure, it was silent and asymptomatic.

Adolescent↗

H(2)O(2)-induced tyrosine phosphorylation of protein kinase cdelta by a mechanism independent of inhibition of protein-tyrosine phosphatase in CHO and COS-7 cells.

It has been proposed that H(2)O(2) increases tyrosine phosphorylation of cellular proteins by inhibiting protein-tyrosine phosphatase through oxidation of the cysteine residue of the enzyme essential for its catalytic activity. Tyrosine phosphorylation of the delta isoform of protein kinase C (PKC) was induced by H(2)O(2) in CHO and COS-7 cells. H(2)O(2) also induced activation of mitogen-activated protein kinase. Vanadate and molybdate, which inhibit protein-tyrosine phosphatase by binding to its active site, did not induce tyrosine phosphorylation of PKCdelta, but enhanced H(2)O(2)-induced tyrosine phosphorylation of PKCdelta in the cell. The oxoanions, however, generated the active form of mitogen-activated protein kinase. Another protein-tyrosine phosphatase inhibitor, phenylarsine oxide, which bridges the thiol residues of the enzyme, induced tyrosine phosphorylation of PKCdelta, and the reaction was enhanced by vanadate. These results suggest that inhibition of protein-tyrosine phosphatase is insufficient for induction of tyrosine phosphorylation of PKCdelta in the cells, and that presumably activation of protein-tyrosine kinase may be essential for tyrosine phosphorylation of the PKC isoform.

3T3 Cells↗

Dual effects of PKNalpha and protein kinase C on phosphorylation of tau protein by glycogen synthase kinase-3beta.

We analyzed the effects of PKNalpha and protein kinase C (PKC) on phosphorylation of tau protein by glycogen synthase kinase (GSK)-3beta using monoclonal antibodies (AT8, AT180, and AT270). These antibodies are highly specific for phosphorylated tau in Alzheimer paired helical filaments, and recognize phosphorylated Ser202/Thr205, Thr231, and Thr181 of tau protein, respectively. Immunoblot analysis demonstrated that PKNalpha and PKC did not directly phosphorylate their sites, whereas GSK-3beta efficiently did so. Incubating GSK-3beta with PKNalpha or PKC subtypes inhibited subsequent GSK-3beta-induced AT8 and AT270 immunoreactivity. However, the constitutive active form of the GSK-3beta(S9A) mutant was almost totally inert to each enzyme. Incubating tau with PKNalpha increased the GSK-3beta-induced AT180 immunoreactivity, which was further enhanced when the S9A mutant was used instead of the wild type GSK-3beta. These results suggest that PKNalpha and PKC directly inhibit GSK-3beta activity at least in part by phosphorylating Ser9 of GSK-3beta, and that they indirectly suppress GSK-3beta-stimulated phosphorylation of tau at amino acids Ser202/Thr205 and Thr181, but enhanced phosphorylation at Thr231 through phosphorylation at other sites of tau.

Amino Acid Sequence↗

Two actions of frabin: direct activation of Cdc42 and indirect activation of Rac.

Frabin is an actin filament-binding protein which shows GDP/GTP exchange activity specific for Cdc42 small G protein and induces filopodium-like microspike formation and c-Jun N-terminal kinase (JNK) activation presumably through the activation of Cdc42. Frabin has one actin filament-binding (FAB) domain, one Dbl homology (DH) domain, first pleckstrin homology (PH) domain adjacent to the DH domain, one cysteine-rich FYVE domain, and second PH domain from the N-terminus to the C-terminus in this order. Different domains of frabin are involved in the microspike formation and the JNK activation, and the association of frabin with the actin cytoskeleton through the FAB domain is necessary for the microspike formation, but not for the JNK activation. We have found here that frabin induces the formation of not only filopodium-like microspikes but also lamellipodium-like structures in NIH3T3 and L fibroblasts. We have analysed the mechanism of frabin in these two actions and found that frabin induces filopodium-like microspike formation through the direct activation of Cdc42 and lamellipodium-like structure formation through the Cdc42-independent indirect activation of Rac small G protein. The FAB domain of frabin in addition to the DH domain and the first PH domain is necessary for the filopodium-like microspike formation, but not for the lamellipodium-like structure formation. The FYVE domain and the second PH domain in addition to the DH domain and the first PH domain are necessary for the lamellipodium-like structure formation. We show here these two actions of frabin in the regulation of cell morphology.

3T3 Cells↗

Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A.

A defect of the gene for p94 (calpain 3), a skeletal muscle-specific calpain, is responsible for limb girdle muscular dystrophy type 2A (LGMD2A), or 'calpainopathy', which is an autosomal recessive and progressive neuromuscular disorder. To study the relationships between the physiological functions of p94 and the etiology of LGMD2A, we created transgenic mice that express an inactive mutant of p94, in which the active site Cys129 is replaced by Ser (p94:C129S). Three lines of transgenic mice expressing p94:C129S mRNA at various levels showed significantly decreased grip strength. Sections of soleus and extensor digitorum longus (EDL) muscles of the aged transgenic mice showed increased numbers of lobulated and split fibers, respectively, which are often observed in limb girdle muscular dystrophy muscles. Centrally placed nuclei were also frequently found in the EDL muscle of the transgenic mice, whereas wild-type mice of the same age had almost none. There was more p94 protein produced in aged transgenic mice muscles and it showed significantly less autolytic degradation activity than that of wild-type mice. Although no necrotic-regenerative fibers were observed, the age and p94:C129S expression dependence of the phenotypes strongly suggest that accumulation of p94:C129S protein causes these myopathy phenotypes. The p94:C129S transgenic mice could provide us with crucial information on the molecular mech-anism of LGMD2A.

Animals↗