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Biomedical subjects

T Yuasa

Publications and source records attributed to T Yuasa.

At least 55 records · Page 3Linked to original sources

[Therapeutic strategies for Parkinson's disease and guidelines for the 21st century].

Parkinson's disease(PD) is one of the most common neurodegenerative disorders, characterized clinically by resting tremor, rigidity and akinesia. The pathological hallmarks of PD is the loss of neurons of the substantia nigra and the existence of Lewy bodies. Among multifactorial theories of gene-environment interaction supporting the pathogenesis of this disease, recent topics focus on the findings of single gene mutations found in several forms of familial PDs. The mutations of the gene encode the protein alpha-synuclein, UCH-L1 and Parkin located on the chromosomes 4q21-23, 4p and 6p25.2-27 respectively. Molecular pathology and histochemical studies reveal that one of these proteins is closely associated with parts of Lewy bodies, or has the function of the ubiqitin system of protein metabolism. Although the typical PD shows good response to levodopa therapy, its side effects, which arise after 5 to 10 years of treatment, rather narrow the therapeutic window of PD. As a result we must make available various new therapeutic tools in order to prevent disability and get a favourable QOL in the PD patient's life span. The various tools adopted here include surgical treatments, transcraial magnetic stimulation methods, nonconvulsive electric stimulation therapy, and the design of new drugs. In this issue the frontier of PD therapy and research will be reviewed and new promising insights and guidelines for the current century will be discussed.

Forecasting↗

[Clinical criteria for the diagnosis for PSP].

In attempts to improve the accuracy of its clinical identification, investigators have proposed numerous diagnostic criteria for progressive supranuclear palsy(PSP). We compared with six different sets of previously published criteria for the clinical diagnosis of PSP. Among of them, the NINDS-SPSP criteria are a most prominent diagnostic standard. But in the clinical area, the NINDS-SPSP criteria have some weak point. We plan to make up this point for using the neuroimaging techniques.

Humans↗

[Parkinson's disease and depression].

Up to 40% of cases of Parkinson's disease are associated with the occurrence of depression. The symptoms of the patients' depressive state may be factors such as significant weight change, insomnia or hypersomnia, psychomotor retardation, fatigue or loss of energy, feelings of worthlessness or inappropriate guilt, decreased concentration and indecisiveness, and recurrent thoughts of death or suicidal ideation. Given these conditions, drugs prove ineffective in many cases. Electroconvulsive therapy (ECT) has been reported to be beneficial in cases of drug-resistant depression. ECT has also been applied to Parkinsonian patients with depression and found to be effective with both depression and the Parkinsonian symptom. Transcranial magnetic stimulation(TMS) has recently been investigated for application in cases of depression and has become known as a valuable tool for depression therapy. TMS is easily implemented even in outpatient therapy. TMS will make a great contribution to the therapy of depression with Parkinson's disease.

Depression↗

Stimulatory function of paired immunoglobulin-like receptor-A in mast cell line by associating with subunits common to Fc receptors.

Paired Ig-like receptors (PIR) are polymorphic type I transmembrane proteins belonging to an Ig superfamily encoded by multiple isotypic genes. They are expressed on immune cells such as mast cells, macrophages, and B lymphocytes. Two subtypes of PIR have been classified according to the difference in the primary structure of the PIR transmembrane and cytoplasmic regions. These subtypes are designated as PIR-A and PIR-B. In this study, the transmembrane and cytoplasmic regions of the PIR-A subtype were shown to mediate activation signal events such as cytoplasmic calcium mobilization, protein tyrosine phosphorylations, and degranulation in rat mast cell line RBL-2H3. The association of the Fc receptor gamma and beta subunits with PIR-A was shown to be responsible for PIR-A function but not required for membrane expression of PIR-A on COS-7 cells. We further revealed the role of two charged amino acid residues in the transmembrane region, namely arginine and glutamic acid, in PIR-A function and its association with the above subunits. In contrast to the inhibitory nature of the PIR-B subtype, present findings reveal that PIR-A potentially acts as a stimulatory receptor in mast cells, suggesting a mechanism for regulation of mast cell functions by the PIR family.

Amino Acid Sequence↗

Fission yeast condensin complex: essential roles of non-SMC subunits for condensation and Cdc2 phosphorylation of Cut3/SMC4.

The condensin complex in frog extracts, containing two SMC (structural maintenance of chromosomes) and three non-SMC subunits, promotes mitotic chromosome condensation, and its supercoiling activity increases during mitosis by Cdc2 phosphorylation. Here, we report that fission yeast has the same five-member condensin complex, each of which is essential for mitotic condensation. The condensin complex was purified and the subunits were identified by microsequencing. Cnd1, Cnd2, and Cnd3, three non-SMC subunits showing a high degree of sequence conservation to frog subunits, are essential for viability, and their gene disruption leads to a phenotype indistinguishable from that observed in cut3-477 and cut14-208, known mutations in SMC4 and SMC2-like subunits. Condensin subunits tagged with GFP were observed to alter dramatically their localization during the cell cycle, enriched in the nucleus during mitosis, but cytoplasmic during other stages. This stage-specific alteration in localization requires mitosis-specific phosphorylation of the T19 Cdc2 site in Cut3. The T19 site is phosphorylated in vitro by Cdc2 kinase and shows the maximal phosphorylation in metaphase in vivo. Its alanine substitution mutant fails to suppress the temperature-sensitive phenotype of cut3-477, and shows deficiency in condensation, probably because Cut3 T19A remains cytoplasmic. Therefore, direct Cdc2 phosphorylation of fission yeast condensin may facilitate its nuclear accumulation during mitosis.

Amino Acid Sequence↗

Detection of circulating testicular cancer cells in peripheral blood.

Patients who receive peripheral blood stem cell transplants are at risk of developing cancer recurrence due to the presence of malignant cells in the transplants. We investigated a sensitive method to detect malignant cells in the peripheral blood and peripheral blood stem cells of patients with testicular cancer using nested, reverse transcription-polymerase chain reaction (RT-PCR) to measure alpha-fetoprotein gene expression. Using this technique, a single cancer cell could be detected in 10(6) peripheral blood mononuclear cells. This is the first report of an attempt to detect circulating malignant cells in the peripheral blood of patients with testicular cancer by nested RT-PCR.

Actins↗

Modulation of immunoglobulin (Ig)E-mediated systemic anaphylaxis by low-affinity Fc receptors for IgG.

It is widely accepted that immunoglobulin (Ig)E triggers immediate hypersensitivity responses by activating a cognate high-affinity receptor, FcepsilonRI, leading to mast cell degranulation with release of vasoactive and proinflammatory mediators. This apparent specificity, however, is complicated by the ability of IgE to bind with low affinity to Fc receptors for IgG, FcgammaRII and III. We have addressed the in vivo significance of this interaction by studying IgE-mediated passive systemic anaphylaxis in FcgammaR-deficient mice. Mice deficient in the inhibitory receptor for IgG, FcgammaRIIB, display enhanced IgE-mediated anaphylactic responses, whereas mice deficient in an IgG activation receptor, FcgammaRIII, display a corresponding attenuation of IgE-mediated responses. Thus, in addition to modulating IgG-triggered hypersensitivity responses, FcgammaRII and III on mast cells are potent regulators of IgE-mediated responses and reveal the existence of a regulatory pathway for IgE triggering of effector cells through IgG Fc receptors that could contribute to the etiology of the atopic response.

Anaphylaxis↗

Induction of neuronal nitric oxide synthase by methylmercury in the cerebellum.

A free radical, nitric oxide (NO), besides being a messenger molecule in the brain, becomes a neurotoxin if overproduced. We recently reported that methylmercury (MeHg) induces neuronal NO synthase (nNOS) in Purkinje cells. In the present study, we examined the distribution and the mechanism of nNOS induction by MeHg. Subcutaneous administration of MeHg chloride to mice, 10 mg/kg/day for 9 days, increased calcium-dependent NOS activity to 60% more than the controls only in the cerebellum but not in other brain regions. The Western blots showed a comparable increase in nNOS protein in the cerebellum. A N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, did not block, but rather enhanced, the increase in the nNOS activity. Another NMDA antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), did not affect the nNOS activity. The Western blots of protein kinase C (PKC), which is an important cofactor regulating nNOS, did not change after the administration of MeHg. These results show that MeHg induces biologically active nNOS selectively in the cerebellum. The induction is independent of PKC and is not reduced by the blockade of the NMDA receptor.

Animals↗

Deletion of fcgamma receptor IIB renders H-2(b) mice susceptible to collagen-induced arthritis.

Autoimmune diseases, like rheumatoid arthritis, result from a dysregulation of the immune response culminating in hyperactivation of effector cells leading to immune-mediated injury. To maintain an appropriate immune response and prevent the emergence of autoimmune disease, activation signals must be regulated by inhibitory pathways. Biochemical and genetic studies indicate that the type IIB low-affinity receptor for immunoglobulin (Ig)G (FcgammaRIIB) inhibits cellular activation triggered through antibody or immune complexes and may be an important component in preventing the emergence of autoimmunity. To investigate the role of FcgammaRIIB in the development of type II collagen (CII)-induced arthritis (CIA), a model for rheumatoid arthritis in humans, we have examined its contribution in determining the susceptibility to CIA in the nonpermissive H-2(b) haplotype. H-2(b) mice immunized with bovine CII do not develop appreciable disease. In contrast, immunization of the FcgammaRIIB-deficient, H-2(b) mice with bovine CII induced CIA at an incidence of 42.2%. The maximal arthritis index of the FcgammaRIIB-deficient mice developing CIA (6.9 +/- 3.6) was comparable to that of DBA/1 mice (8.6 +/- 1.9), an H-2(q) strain susceptible for CIA induction. IgG1, IgG2a, and IgG2b antibody responses against CII were elevated in the FcgammaRIIB-deficient animals, especially in those mice showing arthritis, but less pronounced than DBA/1 mice. Histological examinations of the arthritic paws from FcgammaRIIB-deficient mice revealed that cartilage was destroyed and bone was focally eroded in association with marked lymphocyte and monocyte/macrophage infiltration, very similar to the pathologic findings observed in DBA/1 mice. These results indicate that a nonpermissive H-2(b) haplotype can be rendered permissive to CIA induction through deletion of FcgammaRIIB, suggesting that FcgammaRIIB plays a critical role in suppressing the induction of CIA.

Animals↗

Histological and compositional evaluations of three types of calcium phosphate cements when implanted in subcutaneous tissue immediately after mixing.

To evaluate the soft tissue response of calcium phosphate cement (CPC), consisting of an equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) under conditions close to those encountered in actual surgical procedures, we implanted three types of CPC [conventional CPC (c-CPC), fast-setting CPC (FSCPC), and antiwashout type FSCPC (aw-FSCPC; formerly called nondecay type FSCPC or nd-FSCPC)] subcutaneously in the abdomens of rats immediately (1 min) after mixing. At 1 week after surgery, histological examination and compositional analysis were performed using light microscopy and powder X-ray diffraction (XRD), respectively. The implanted c-CPC was crumbled completely, whereas FSCPC and aw-FSCPC retained their shape. Large vesicles containing copious inflammatory effusion were subcutaneously formed around the c-CPC. Histologically, many foreign-body giant cells were collected around the c-CPC, and moderate inflammatory cell infiltration was observed at 1 week after surgery. In contrast, the FSCPC and aw-FSCPC were covered with a thin layer of granulation tissue that included few giant cells and presented slight inflammatory cell infiltration, and no effusion was observed. The XRD analysis of the c-CPC revealed the presence of some unreacted DCPA even 1 week after implantation, whereas almost no DCPA was found in the FSCPC or aw-FSCPC. In conclusion, it was found that CPC does not always show excellent tissue response. When c-CPC is implanted subcutaneously in rats immediately after mixing, it fails to set and causes a severe inflammatory response. Therefore, the type of CPC should be chosen according to the clinical particulars. CPC should be used in a manner that assures its setting reaction. We recommend the use of FSCPC and aw-FSCPC for surgical applications, such as orthopedics, plastic and reconstructive surgery, and oral and maxillofacial surgery, where the cement might otherwise crumble due to the pressure before setting.

Animals↗

Elevated DNase activity and caspase expression in association with apoptosis in failing ischemic sheep left ventricles.

We examined the DNase activity as well as the expression of the caspases in left ventricles of failing sheep hearts and compared it with samples from normal controls. The sheep model of chronic ischemic heart failure was developed by intracoronary microembolisation. Moderate heart failure was defined as a decrease of left ventricular (LV) ejection fraction (EF) to 35% or less and was stable for four weeks after the last embolisation. The failing hearts were harvested from these animals six months later. Bovine pancreas DNase I was used as a standard for the DNase zymograms. In normal sheep left ventricles, a low level of the DNase I-like activity was detected (1.16 +/- 0.17 pg/100 microg protein, n = 20), whereas it was elevated (3.64 +/- 0.49 pg/100 microg, n = 32, p < 0.001) in the ischemic failing LV samples. The identity of the DNase in sheep is yet to be fully characterised. However, we also detected the expression of caspase-2 and caspase-3 by Western blotting. There was a 2.2-fold increased expression of caspase-2 p < 0.001 = and a 2.6-fold increased expression of caspase-3 p < 0.001) in failing left ventricles compared to normal samples.

Animals↗

Two-dimensional guided M-mode color tissue Doppler echocardiography in artificial preexcitation models.

The purpose of this study was to analyze the left ventricular contraction patterns in artificial preexcitation models by using 2-dimensional guided M-mode color tissue Doppler echocardiography. Three types of preexcitation models were produced in 12 patients by right atrio-mitral annular sequential pacing, carried out at the left ventricular lateral, posterior, and posteroseptal walls. Tissue Doppler M-mode was recorded at anteroseptal, posterior, lateral, and posteroseptal sites in the parasternal short-axis view. The time interval from the onset of the QRS complex during sinus rhythm or from the annular pacing spike during fusion beats to the beginning of systolic motion was measured. During sinus rhythm, the time interval at the anteroseptal wall was shortest. During fusion beats, the time intervals at the mitral annular pacing sites were shortest. In preexcitation models, tissue Doppler M-mode could clearly distinguish the difference of left ventricular contraction patterns and detect the earliest contraction site of the left ventricle.

Cardiac Pacing, Artificial↗

Expression of transitional cell-specific genes, uroplakin Ia and II, in bladder cancer: detection of circulating cancer cells in the peripheral blood of metastatic patients.

BACKGROUND: Uroplakins (UP), urothelium-specific transmembrane proteins, are present only in urothelia and may be good candidates as tumor markers specific for transitional cell carcinomas (TCC). We investigated the expression of UP-Ia and UP-II genes in the tissues and peripheral blood of patients with TCC. METHODS: We investigated UP-Ia and UP-II gene expression in tissues from 12 patients with TCC by reverse transcription-polymerase chain reaction (RT-PCR). HT1197, a TCC cell line, was used as an indicated cell line to assess a detection system for the UP-II gene-expressing cancer cells by nested RT-PCR. We also investigated UP-II gene expression in the peripheral blood of 12 other patients with TCC by nested RT-PCR. RESULTS: Prior to the investigation of UP-Ia and UP-II gene expression, a partial nucleotide sequence of human UP-II gene cDNA was determined to prepare the primers for RT-PCR. Uroplakin genes were expressed in both cancerous and non-cancerous urothelia taken from all patients examined by RT-PCR. The detection sensitivity of our assay showed that one cancer cell could be detected in 5 mL peripheral blood. UP-II gene-expression was detected in the peripheral blood from all three patients with metastatic TCC but not from the nine patients with non-metastatic TCC nor the three healthy volunteers. CONCLUSIONS: Uroplakins may be employed as tumor markers for transitional cell cancer, because they are highly conserved and well expressed, not only in non-cancerous cells but also in cancer cells. Furthermore, detection of UP-II gene expression in blood by nested RT-PCR may provide helpful information in the diagnosis and management of TCC.

Adult↗

Crystallographic studies on a family B DNA polymerase from hyperthermophilic archaeon Pyrococcus kodakaraensis strain KOD1.

A hyperthermostable family B DNA polymerase from the hyperthermophilic archaeon, Pyrococcus kodakaraensis strain KOD1, has been crystallized by the hanging-drop vapor diffusion method at 293 K with 2-methyl-2,4-pentanediol as the precipitant. The diffraction pattern of a crystal extends to 3.0 A resolution, and two full sets of 3.0 A resolution diffraction data for native crystals were successfully collected at 290 K and 100 K upon exposure to synchrotron radiation at KEK-PF, Japan. The crystals belong to the space group, P212121, with unit-cell dimensions of a = 112.8, b = 115.4, and c = 75.4 A at 290 K, and a = 111.9, b = 112.4, and c = 73.9 at 100 K. Structural analysis by means of the multiple isomorphous replacement method is now in progress.

Crystallography, X-Ray↗

Overproduction of gamma interferon in B/Jas inbred rabbits with herpes simplex virus encephalitis.

Inbred rabbits of the B/Jas strain are highly susceptible to herpes simplex virus type-1 (HSV-1) encephalitis, developing seizures of encephalitis after intravenous injection of the KOS strain of the virus. Anti-viral interferon activity became detectable in the serum just prior to or at the onset of seizures, its level being lower in the serum than in the cerebrospinal fluid. The activity was of gamma interferon, as suggested by the acid instability and the inability of Mx protein induction. An immunohistochemical analysis of the brain tissues of encephalitic rabbits showed that MHC class I antigen was expressed on the microglia cells of inflamed lesions but not on these cells in uninflamed areas. These findings were discussed in correlation with the pathogenesis of herpetic encephalitis in the inbred rabbits.

Animals↗

Detection of the earliest ventricular contraction site in patients with Wolff-Parkinson-White syndrome using two-dimensional guided M-mode tissue Doppler echocardiography.

OBJECTIVE: The purpose of this study was to examine the feasibility of M-mode tissue Doppler imaging for localizing the accessory pathway in patients with Wolff-Parkinson-White (WPW) syndrome. METHODS: Two-dimensional guided tissue Doppler M-mode was recorded at the mitral and tricuspid annular levels in 13 WPW patients. Time intervals were measured from the onset of the delta wave or the R wave to the beginning of the ventricular systolic motion. The earliest contraction site was defined as the site demonstrating the shortest time interval, and compared with the earliest activated site determined by body surface mapping and the successful ablation site. RESULTS: In 6 patients with a left-sided pathway, tissue Doppler localization was identical to the ablation site. In 3 with a left-sided pathway and 3 with a right-sided pathway, localization was judged as an adjacent region of the ablation site. In 1 patient with a right lateral pathway, the pathway location was misdiagnosed. The tissue Doppler diagnosis for the left-sided pathways correlated well with the ablation site, in contrast to the right-sided pathways (p = 0.05). Prediction of the accessory pathway localization by tissue Doppler M-mode was equivalent to localization based on body surface mapping. CONCLUSIONS: In WPW syndrome, tissue Doppler M-mode can detect the earliest contraction sites and seems helpful in localizing the left-sided accessory pathways, but is of limited use for right-sided pathways.

Adolescent↗