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N Sasaki

Publications and source records attributed to N Sasaki.

At least 91 records · Page 5Linked to original sources
PubMed2001

[A case of 'hallucination of soliloquy' with hypothyroidism induced Hashimoto disease. Meaning of psychopathological research about symptomatic psychosis].

We describe the first reported case of symptomatic psychosis with the 'hallucination of soliloquy.' A 48[correction of 40]-year-old woman with Hashimoto disease exhibited of compulsive checking, mysophobia, and excessive hand washing. When these obsessive-compulsive symptoms diminished, she began to suffer from the 'hallucination of soliloquy', the automatic flow of meaningless words inside her mind. As the 'soliloquy' increased, her mood became unstable and she attempted suicide by analgesic ingestion. After this, she was admitted to the psychiatric ward of a general hospital. The administration of clomipramine (150 mg daily) decreased the 'soliloquy' symptoms, but they did not resolve. When hypothyroidism became available, thyroid hormone treatment (levothyroxine at 50 mg daily) was started. Four weeks later, her 'soliloquy' symptoms had almost resolved and after three months in a stable state, thyroid hormone treatment was stopped and her 'soliloquy' symptoms soon reappeared. After thyroid hormone treatment was resumed, her 'soliloquy' symptoms disappeared immediately. Typical auditory hallucinations and delusions of reference were not observed throughout the clinical course. We speculate that the symptoms were symptomatic psychosis induced by hypothyroidism secondary to Hashimoto disease, because the changes of her hallucinations were related to free T3 values and the symptoms disappeared soon after starting thyroid hormone treatment. The main features of this case were 'soliloquy' alternating with obsessive-compulsive symptoms, but her 'soliloquy' symptoms were thought to be autochthonous ideas rather than obsessive thoughts. Furthermore, the symptoms in this case were different from schizophrenia, since there was no disturbance of communication, and she had the sensation of both speaking and hearing her own voice. The psychopathology of this 'hallucination of soliloquy' may be related to the theory of 'vocalization of background thinking' (N. Nakayasu). Detailed observation of patients with symptomatic psychosis and a psychopathological description of their symptoms may help to contribute to the etiologic elucidation and treatment of psychosis.

Female↗
PubMed2001

[Pure red cell aplasia developing during the course of primary macroglobulinemia associated with pseudochylothorax and IgA nephropathy].

A 74-year-old man who had undergone artificial pneumothorax therapy for pulmonary tuberculosis 40 years earlier was admitted because of blurred vision, headache, and numbness of the lower limbs in October 1997. He presented with anemia and leukocytopenia with monoclonal gammopathy of IgM (kappa). His bone marrow was diffusely infiltrated with small lymphocytes, plasmacytoid lymphocytes, and plasma cells expressing IgM, kappa surface immunoglobulin. On the basis of these findings, primary macroglobulinemia (PMG) was diagnosed. CT scan of the chest demonstrated pleural effusion of the right lung encapsulated in a thickened pleura, and pseudochylothorax was diagnosed from a specimen of chyliform fluid which contained numerous cholesterol crystals and was positive for Mycobacterium tuberculosis (MT) on PCR assay. The patient's condition was also complicated by chronic renal failure due to IgA nephropathy, which may have been a consequence of the tuberculosis, possibly due to an abnormal IgA-mediated immune response to MT. The patient gradually developed pure red cell aplasia during the course, probably due to an autoimmune mechanism. Later in the course, immunoglobulin gene analysis of the malignant cells of PMG showed that they were derived from antigenically selected cells. In the context of antigenic stimulation, the role of MT antigen in the pathogenesis of PMG was of interest in this patient.

Aged↗
PubMed2001

Effect of the extracellular matrix on pancreatic endocrine cell function and its biocompatibility in dogs.

The effect of the synthetic extracellular matrix (ECM) in a diffusion chamber for a bioartificial endocrine pancreas (Bio-AEP) on pancreatic endocrine cells in vitro and its biocompatibility in dogs were investigated. Two different types of ECM were used: type I collagen treated with low antigen (type I LA), and reconstituted basement membrane matrix (Matrigel) derived from Englbreth-Holm-Swarm (EHS) mouse sarcoma. Matrigel contains growth and differentiation factors and cell adhesion molecules such as laminin, heparan sulfate proteoglycan, and entactin. Purified porcine pancreatic endocrine (PE) cells were suspended in type I LA or Matrigel and then placed into a 12-well culture plate (4 x 10(7) cells/ml gel/well). The insulin accumulation from PE cells in Matrigel was significantly greater than that in type I LA (9.3 +/- 3.6 mU/well vs. 2.3 +/- 1.3 mU/well). When Bio-AEP with Matrigel and PE cells was implanted into the abdominal cavity of a pancreatectomized diabetic dog, the exogenous insulin requirement for maintaining normoglycemia was reduced for the first 4 weeks. However, after 6 weeks of implantation, fasting blood glucose levels suddenly increased. Laparotomy revealed encapsulated Bio-AEP with thick fibrous tissue. Following removal of the Bio-AEP from the abdominal cavity, another Bio-AEP containing type I LA and PE cells was implanted into the same dog. The exogenous insulin requirement was gradually decreased to almost half that of preimplantation levels. Bio-AEPs containing type I LA or Matrigel, but not PE cells, were implanted into the abdominal cavities of four healthy dogs. After 4 weeks of implantation, the Bio-AEP with Matrigel was encapsulated with fibrous tissue similar to that in the diabetic dog, but the Bio-AEP with type I LA was not. These results indicate that Matrigel may be incompatible with dogs and that the type I LA is more suitable for Bio-AEP.

Animals↗
PubMed2001

Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue.

PURPOSE: Activation of transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-kappaB is constitutively activated in human gastric carcinoma tissues and, if so, to determine any correlation between NF-kappaB activity and clinicopathological features of gastric carcinoma. EXPERIMENTAL DESIGN: NF-kappaB activation was determined by immunohistochemical analysis of formalin-fixed, paraffin-embedded specimens from 64 gastric carcinoma patients. We quantified nuclear staining of RelA as a marker of NF-kappaB activation. RESULTS: Nuclear translocation of RelA was significantly high in tumor cells in comparison to that in adjacent normal epithelial cells (22.5 +/- 2.4% versus 8.6 +/- 1.5%, P < 0.0001). There was a significant correlation between NF-kappaB activation (nuclear translocation of RelA) and expression of urokinase-type plasminogen activator, an invasion-related factor and target of NF-kappaB in tumor cells (rho = 0.393; P = 0.0013). NF-kappaB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion of tumor cells (P = 0.0126), depth of invasion (P = 0.0539), peritoneal metastases (P = 0.0538), and tumor size (P = 0.0164). CONCLUSIONS: Collectively, the data show that NF-kappaB is constitutively activated in human gastric carcinoma tissues and suggest that NF-kappaB activity is related to tumor progression due to its transcriptional regulation of invasion-related factors such as urokinase-type plasminogen activator.

Active Transport, Cell Nucleus↗
PubMed2001

[Embolization of the bilateral internal pudendal arteries for intractable priapism in a child with chronic myelogenous leukemia].

Priapism is an uncommon clinical symptom in children with chronic myelogenous leukemia (CML). Here we report a 14-year-old boy with this symptom, which had appeared 4 days prior to hospitalization. Peripheral blood examination revealed a leukocyte count of 510,000/microliter, (87% neutrophils, 3% eosinophils, 6% basophils, and 1.6% lymphocytes), a hemoglobin level of 6.5 g/dl and a platelet count of 640,000/microliter. Karyotype analysis revealed the Ph1 chromosome and myeloid hyperplasia in the bone marrow. The patient was diagnosed as having chronic myelogenous leukemia (CML) complicated by priapism. In an unsuccessful attempt to alleviate and improve the priapism, urokinase was injected and hydroxyurea was administered for the CML. Angiography confirmed the presence of venous return from the scrotum, and embolization of the bilateral internal pudendal arteries was performed to reduce the amount of inflow. Although this relieved the patient of his pain and prevented penile necrosis, the patient's future sexual potency was sacrificed. Selective embolization of the pudendal arteries can be one of the most effective ways of treating intractable priapism, if angiography confirms the presence of venous return from the penis.

Adolescent↗
PubMed2000

Insertion or deletion of a single residue in the strut sequence of Dictyostelium myosin II abolishes strong binding to actin.

The strut loop, one of the three loops that connects the upper and lower 50K subdomains of myosin, plays a role as a "strut" to keep the relative disposition of the two subdomains. A single residue was either inserted into or deleted from this loop. The insertion or deletion mutation abolished the in vivo motor functions of myosin, as revealed by the fact that the mutant myosins did not complement the phenotypic defects of the myosin-null cells. In vitro studies of purified full-length myosins and their subfragment-1s (S1s) revealed that the insertion mutants virtually lost the strong binding to actin although their motor functions in the absence of actin remained almost normal, showing that only the hydrophobic actin-myosin association was selectively affected by the insertion mutations. Unlike the insertion mutants, the deletion mutant showed defects both in the strong-binding state and the rate-limiting step of ATPase cycle. These results indicate the functional importance of the strut loop in establishing the strong-binding state of myosin and thereby achieving successful power strokes.

Actins↗
PubMed2000

Suppression of intestinal polyposis in Apc(delta 716) knockout mice by an additional mutation in the cytosolic phospholipase A(2) gene.

Arachidonic acid is a precursor for biosynthesis of eicosanoids, including prostaglandins, thromboxanes, leukotrienes, and lipoxins. Cytosolic phospholipase A(2) (cPLA(2)) plays a key role in the release of arachidonic acid as the substrate of cyclooxygenase-1 (COX-1) or COX-2. We found that the level of cPLA(2) mRNA was markedly elevated in the polyps and correlated with the polyp size in the small intestine of the Apc(delta)(716) knockout mouse, a model for human familial adenomatous polyposis. To determine the role of cPLA(2) in intestinal tumorigenesis, we then introduced a cPLA(2) gene mutation into Apc(delta)(716) mice. In the compound mutant mice, the size of the small intestinal polyps was reduced significantly, although the numbers remained unchanged. These results provide direct genetic evidence that cPLA(2) plays a key role in the expansion of polyps in the small intestine rather than in the initiation process. In contrast, colonic polyps were not affected in either size or number. Interestingly, group X sPLA(2) was constitutively expressed in the colon at much higher levels than in the small intestine. These results suggest that in the colon, group X sPLA(2) supplies arachidonic acid in both the normal epithelium and the polyps even in the absence of cPLA(2).

Animals↗
PubMed2000

Adenosine primes the opening of mitochondrial ATP-sensitive potassium channels: a key step in ischemic preconditioning?

BACKGROUND: Adenosine can initiate ischemic preconditioning, and mitochondrial ATP-sensitive potassium (K(ATP)) channels have emerged as the likely effectors. We sought to determine the mechanistic interactions between these 2 observations. METHODS AND RESULTS: The mitochondrial flavoprotein oxidation induced by diazoxide (100 micromol/L) was used to quantify mitochondrial K(ATP) channel activity in intact rabbit ventricular myocytes. Adenosine (100 micromol/L) increased mitochondrial K(ATP) channel activity and abbreviated the latency to mitochondrial K(ATP) channel opening. These potentiating effects were entirely prevented by the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline (100 micromol/L) or by the protein kinase C inhibitor polymyxin B (50 micromol/L). The effects of adenosine and diazoxide reflected mitochondrial K(ATP) channel activation, because they could be blocked by the mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (500 micromol/L). In a cellular model of simulated ischemia, adenosine mitigated cell injury; this cardioprotective effect was blocked by 5-hydroxydecanoate but not by the surface-selective K(ATP) channel blocker HMR1098. Moreover, adenosine augmented the cardioprotective effect of diazoxide. A quantitative model of mitochondrial K(ATP) channel gating reproduced the major experimental findings. CONCLUSIONS: Our results support the hypothesis that adenosine receptor activation primes the opening of mitochondrial K(ATP) channels in a protein kinase C-dependent manner. The findings provide tangible links among various key elements in the preconditioning cascade.

Adenosine↗
PubMed2000

Evidence against functional heteromultimerization of the KATP channel subunits Kir6.1 and Kir6.2.

K(ATP) channels consist of pore-forming potassium inward rectifier (Kir6.x) subunits and sulfonylurea receptors (SURs). Although Kir6.1 or Kir6.2 coassemble with different SUR isoforms to form heteromultimeric functional K(ATP) channels, it is not known whether Kir6.1 and Kir6.2 coassemble with each other. To define the molecular identity of K(ATP) channels, we used adenoviral gene transfer to express wild-type and dominant-negative constructs of Kir6.1 and Kir6.2 in a heterologous expression system (A549 cells) and in native cells (rabbit ventricular myocytes). Dominant-negative (DN) Kir6.2 gene transfer suppressed current through heterologously expressed SUR2A + Kir6.2 channels. Conversely, DN Kir6.1 suppressed SUR2B + Kir6.1 current but had no effect on coexpressed SUR2A + Kir6. 2. We next probed the ability of Kir6.1 and Kir6.2 to affect endogenous K(ATP) channels in adult rabbit ventricular myocytes, using adenoviral vectors to achieve efficient gene transfer. Infection with the DN Kir6.2 virus for 72 h suppressed pinacidil-inducible K(ATP) current density measured by whole-cell patch clamp. However, there was no effect of infection with the DN Kir6.1 on the K(ATP) current. Based on these functional assays, we conclude that Kir6.1 and Kir6.2 do not heteromultimerize with each other and that Kir6.2 is the sole K(ATP) pore-forming subunit in the surface membrane of heart cells.

Adenoviridae↗
PubMed2000

Arp2/3 complex-independent actin regulatory function of WAVE.

We report that WAVE1/Scar1, a WASP-family protein that functions downstream of Rac in membrane ruffling, can induce part of the reorganization of the actin cytoskeleton without Arp2/3 complex. WAVE1 has been reported to associate and activate Arp2/3 complex at its C-terminal region that is rich in acidic residues. The deletion of the acidic residues abolished the interaction with and the activation ability of Arp2/3 complex. The expression of the mutant WAVE1 lacking the acidic residues (DeltaA), however, induced actin-clustering in cells as the wild-type WAVE1 did. In addition, this actin-clustering could not be suppressed by the coexpression of the Arp2/3 complex-sequestering fragment (CA-region) derived from N-WASP, which clearly inhibits Rac-induced membrane ruffling. This study therefore demonstrates that WAVE1 reorganizes the actin cytoskeleton not only through Arp2/3 complex but also through another unidentified mechanism that may be important but has been neglected thus far.

3T3 Cells↗
PubMed2000

Selective pharmacological agents implicate mitochondrial but not sarcolemmal K(ATP) channels in ischemic cardioprotection.

BACKGROUND: Pharmacological evidence has implicated ATP-sensitive K(+) (K(ATP)) channels as the effectors of cardioprotection, but the relative roles of mitochondrial (mitoK(ATP)) and sarcolemmal (surfaceK(ATP)) channels remain controversial. METHODS AND RESULTS: We examined the effects of the K(ATP) channel blocker HMR1098 and the K(ATP) channel opener P-1075 on surfaceK(ATP) and mitoK(ATP) channels in rabbit ventricular myocytes. HMR1098 (30 micromol/L) inhibited the surfaceK(ATP) current activated by metabolic inhibition, whereas the drug did not blunt diazoxide (100 micromol/L)-induced flavoprotein oxidation, an index of mitoK(ATP) channel activity. P-1075 (30 micromol/L) did not increase flavoprotein oxidation but did elicit a robust surfaceK(ATP) current that was completely inhibited by HMR1098. These results indicate that HMR1098 selectively inhibits surfaceK(ATP) channels, whereas P-1075 selectively activates surface K(ATP) channels. In a cellular model of simulated ischemia, the mitoK(ATP) channel opener diazoxide (100 micromol/L), but not P-1075, blunted cellular injury. The cardioprotection afforded by diazoxide or by preconditioning was prevented by the mitoK(ATP) channel blocker 5-hydroxydecanoate (500 micromol/L) but not by the surfaceK(ATP) channel blocker HMR1098 (30 micromol/L). CONCLUSIONS: The cellular effects of mitochondria- or surface-selective agents provide further support for the emerging consensus that mitoK(ATP) channels rather than surfaceK(ATP) channels are the likely effectors of cardioprotection.

Adenosine Triphosphate↗
PubMed2000

In vivo conformation of mitochondrial DNA revealed by pulsed-field gel electrophoresis in the true slime mold, Physarum polycephalum.

Pulsed-field gel electrophoresis (PFGE) was used to examine the in vivo and in vitro conformations of Physarum polycephalum mitochondrial DNA (mtDNA). We used plugs containing isolated mitochondria, isolated mitochondrial nucleoids (mt-nuclei), and isolated mtDNA, in addition to whole cells. The mtDNA contained in the myxamoebae, plasmodia, isolated mitochondria, and isolated mt-nuclei was circular, but most of the isolated mtDNA had been site-specifically fragmented and linearized during DNA preparation and storage under low ionic strength conditions. Restriction mapping of Physarum mtDNA by the direct digestion of the isolated mt-nuclei from two different strains, DP89 x AI16 and KM88 x AI16, resulted in the circular form. A linear mitochondrial plasmid, mF, is known to promote mitochondrial fusion and integration of itself into the mtDNA in Physarum. Linearization of mtDNA by the integration of the mF plasmid was demonstrated when we used PFGE to analyze isolated mitochondria from the plasmodial strain DP89 x NG7 carrying the mF plasmid (mF+). The PFGE system can be used not only to determine whether the form of mtDNA is linear or circular but also to analyze the dynamic conformational changes of mtDNA.

Animals↗
PubMed2000

Activation of mitochondrial ATP-dependent potassium channels by nitric oxide.

BACKGROUND: Nitric oxide (NO) has been implicated as a mediator of "second-window" ischemic preconditioning, and mitochondrial ATP-dependent K(+) (mitoK(ATP)) channels are the likely effectors. The links between NO and mitoK(ATP) channels are unknown. METHODS AND RESULTS: We measured mitochondrial redox potential as an index of mitoK(ATP) channel opening in rabbit ventricular myocytes. The NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP, 0.1 to 1 mmol/L) oxidized the mitochondrial matrix dose-dependently without activating sarcolemmal K(ATP) channels. SNAP-induced oxidation was blocked by the selective mitoK(ATP) channel blocker 5-hydroxydecanoate and by the NO scavenger 2-(4-carboxyphenyl)-4,4', 5,5'-tetramethylimidazole-1-oxyl-3-oxide. SNAP-induced mitochondrial oxidation was detectable either by photomultiplier tube recordings of flavoprotein fluorescence or by confocal imaging. SNAP also enhanced the oxidative effects of diazoxide when both agents were applied together. Exposure to 1 mmol/L 8Br-cGMP failed to mimic the effects of SNAP. CONCLUSIONS: NO directly activates mitoK(ATP) channels and potentiates the ability of diazoxide to open these channels. These results provide novel mechanistic links between NO-induced cardioprotection and mitoK(ATP) channels.

Animals↗
PubMed2000

Visceral mast cell tumors in dogs: 10 cases (1982-1997).

OBJECTIVE: To characterize the clinical features of visceral mast cell tumors (MCT) without associated cutaneous involvement in dogs. DESIGN: Retrospective study. ANIMALS: 10 dogs with histologically confirmed MCT without associated cutaneous lesions. PROCEDURE: Information on signalment, clinical signs, laboratory examinations, and time from first admission to death was obtained from the medical record of each dog. RESULTS: Purebred male dogs of miniature breeds appeared to have a higher prevalence of visceral MCT. Clinical signs included anorexia, lethargy, vomiting, and diarrhea. Anemia (n = 7), hypoproteinemia (5), and mastocythemia (5) were detected. Treatments, including glucocorticoids, were not successful. Primary sites of tumors were the gastrointestinal tract (n = 6) and the spleen or liver (1); the primary site was not confirmed in the remaining 3 dogs. In 7 dogs, tumors were categorized as grade II or III, on the basis of histologic findings. The prognoses were poor, and all dogs died within 2 months after first admission. CONCLUSIONS AND CLINICAL RELEVANCE: Visceral MCT is uncommon in dogs, and the prognosis is extremely poor. Biological behavior and drug susceptibility of visceral MCT may be different from cutaneous MCT. The lack of specific clinical signs may result in delay of a definitive diagnosis. The rapid progression of clinical signs and difficulty in diagnosis contributes to a short survival time.

Animals↗
PubMed2000

Molecular composition of mitochondrial ATP-sensitive potassium channels probed by viral Kir gene transfer.

Heart cells contain ATP-sensitive potassium (KATP) channels in both the sarcolemma and the inner mitochondrial membrane. The sarcolemmal channels are believed to be heteromultimeric complexes of sulfonylurea receptors (SUR) and potassium inward rectifier (Kir) gene products, but the molecular identity of mitochondrial KATP (mitoKATP) channels remains unclear. To probe the molecular composition of KATP channels, we used adenoviral gene transfer to express wild-type (WT) and dominant-negative (AFA) constructs of Kir6.1 and 6.2 in rabbit ventricular myocytes. None of the Kir6.1 or 6.2 constructs affected mitoKATPchannel activity as assayed by confocal imaging of flavoprotein fluorescence, contradicting the proposal, based on subcellular antibody localization, that Kir6.1 forms part of mitoKATP channels. As previously reported, dominant-negative Kir6.2 gene transfer suppressed sarcolemmal KATP current, while Kir6.1 constructs had no effect on sarcolemmal activity. Immunohistochemistry with an anti-Kir6.1 antibody revealed expression of this protein in heart but no apparent co-localization with mitochondria. Thus, the available evidence indicates that both Kir6.1 and 6.2 are expressed in ventricular myocytes, but neither plays a discernible functional role in the mitoKATP channel.

Adenosine Triphosphate↗