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Y Wada

Publications and source records attributed to Y Wada.

At least 361 records · Page 20Linked to original sources
PubMed1998

Microtubule-stimulated phosphorylation of tau at Ser202 and Thr205 by cdk5 decreases its microtubule nucleation activity.

Phosphorylation of tau, a heat-stable neuron-specific microtubule-associated protein, by cdk5 was stimulated in the presence of microtubules (MTs). This stimulation was due to an increased phosphorylation rate and there was no increase in total amount of phosphorylation. Two-dimensional phosphopeptide map analysis showed that MTs stimulated phosphorylation of a specific peptide. Using Western blotting with antibodies that the recognized phosphorylation-dependent epitopes within tau, the phosphorylation sites stimulated by the presence of MTs were found to be Ser202 and Thr205 (numbered according to the human tau isoform containing 441 residues). MT-dependent phosphorylation at Thr205 was observed in situ in rat cerebrum primary cultured neurons. Stimulated phosphorylation at Ser202 and Thr205 decreased the MT-nucleation activity of tau, which is in contrast to MT-independent phosphorylation at Ser235 and Ser404.

Animals↗
PubMed1998

Site-directed mutagenesis in hemoglobin: attempts to control the oxygen affinity with cooperativity preserved.

We synthesized three artificial human hemoglobin mutants in which Lys-66(E10)beta was replaced by Ser, Arg or Thr by site-directed mutagenic protein engineering. These engineered hemoglobins were designated as eHb K66betaS, eHb K66betaR and eHb K66betaT, respectively. By synthesizing these mutants we attempted to control the oxygen affinity of hemoglobin with cooperativity preserved and to clarify the functional role of Lys-66(E10)beta, as well. Such attempts may be useful for creating an oxygen carrier suitable as a blood substitute. The oxygen affinities of eHbs K66betaS, K66betaR and K66betaT were 1.3-, 1.5- and 2.3-fold, respectively, lower than that of reconstituted Hb A. Their allosteric properties such as the Bohr effect and the effect of inositol hexaphosphate were well preserved. Since the oxygen affinity of eHb K66betaT is comparable with that of red cells, it may be a potential candidate for a blood substitute. X-Ray crystallographic data for Hb Chico [Lys-66beta-->Thr], which is identical with eHb K66betaT, together with our computer simulation indicate that an interaction between the introduced Thr and the distal His via a water molecule lowers the oxygen affinity for the T state eHb K66betaT.

Amino Acid Substitution↗
PubMed1998

Reduced interhemispheric EEG coherence in Alzheimer disease: analysis during rest and photic stimulation.

The present study was conducted to examine interhemispheric electroencephalogram (EEG) coherence at rest and during photic stimulation (5, 10, and 15 Hz) in 10 patients with presenile dementia of the Alzheimer type (AD; mean age at onset, 56 years) and 10 sex- and age-matched control subjects. Compared with the control subjects, the AD patients had significantly lower interhemispheric coherence in the resting EEG for the delta, theta-2, alpha, and beta-1 frequency bands. EEG analysis during photic stimulation also showed that the patients had significantly lower coherence, irrespective of the stimulus frequency. In addition, when we examined the changes in coherence from the resting state to the stimulus condition (i.e., coherence reactivity), significant group differences were found at the brain region primarily involved in visual functioning; the patients had significantly smaller coherence reactivity to photic stimulation at 5 and 15 Hz over the posterior regions. These findings suggest that AD patients have an impairment of interhemispheric functional connectivity in both nonstimulus and stimulus conditions. The findings also suggest a failure of normal stimulation-related brain activation in AD.

Aged↗
PubMed1998

Evidence on N-acetyltransferase allele-associated metabolism of hydrazine in Japanese workers.

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Adult↗
PubMed1998

Schwannoma of the liver: report of two surgical cases.

Two surgical cases of benign schwannoma of the liver were examined: A 64-year-old female who was admitted to hospital for the treatment of early gastric cancer (case 1) and a 69-year-old female who had pitting edema in the legs (case 2). Diagnostic imaging revealed large solid masses located in the caudate lobe through to the left lobe of the liver in case 1 and in the left lobe in case 2. Both patients showed no signs of von Recklinghausen's disease. Partial hepatectomies were performed and the maximum diameter of their resected hepatic tumors was 4 cm and 15 cm, respectively. Histologically, the well-demarcated tumors were yellowish in color, elastic-hard in consistency and consisted predominantly of short spindle-shaped cells proliferating in an interlacing fashion. The tumor lesions were separated by fibrous bands and surrounded by a lymphoid cuff. Immunohistochemically, the tumor cells were positive for S-100 protein. The tumors were diagnosed as benign hepatic schwannoma.

Aged↗
PubMed1998

Prevalence of GBV-C/HGV infection in pregnant Japanese women.

Recently, a novel viral agent, hepatitis G virus, was identified by independent researchers from the serum of patients with liver disease, and termed GBV-C or HGV. At present, GBV-C and HGV are considered to be separate isolates of the same virus; however, the role of this virus in acute and chronic liver disease remains uncertain. Although vertical transmission is known to be one of the routes of transmission, the prevalence of GBV-C/HGV viremia in pregnant Japanese women is unknown. Thus, we determined this prevalence using the reverse transcription polymerase chain reaction (RT-PCR).

Female↗
PubMed1998

Assessment of proliferating cell nuclear antigen expression and prognosis in patients with renal cell carcinoma with pulmonary metastases.

BACKGROUND: The presence of proliferating cell nuclear antigen (PCNA) has been suggested as a more important prognostic marker than either grade or mitotic index in the prognosis of patients with renal cell carcinoma. We assessed the immunoreactivity of PCNA in primary lesions and pulmonary metastases from patients with renal cell carcinoma and correlated the results with various histopathologic features and prognostic factors. METHODS: We studied the relationship between PCNA expression and clinical prognostic factors from resected primary lesions and pulmonary metastases from 10 patients and primary lesions from 32 patients with renal cell carcinoma without metastases. The cells were immunohistochemically stained with PCNA monoclonal antibody (PC-10) and 1000 nuclei were counted. The results were expressed as a ratio of stained to total cells (PCNA labeling index, LI %). RESULTS: The PCNA LI of pulmonary metastatic nuclei was significantly higher than the PCNA LI of renal lesions either from patients with (P < 0.05) or without (P < 0.01) metastases. Also, the mean PCNA LI of the pulmonary lesions in patients dying within 3 years of diagnosis was higher than the mean PCNA LI of patients surviving greater than 3 years. CONCLUSION: Our findings suggest that the PCNA LI, which was determined by immunohistochemical analysis, is an important marker reflecting the biologic behavior of renal cell carcinomas. The degree of PCNA expression in this study was of prognostic significance.

Aged↗
PubMed1998

Pharmacologic actions of temiverine (p-INN) and its active metabolite, RCC-36, on isolated human urinary bladder muscle.

BACKGROUND: Temiverine (p-INN) is a newly synthesized drug that is expected to have anticholinergic action. We investigated the pharmacologic actions of temiverine and its active metabolite, RCC-36, on isolated human bladder. METHODS: Effects of temiverine and RCC-36 on the detrusor contractions induced by acetylcholine, potassium chloride (KCl), calcium chloride (CaCl2), and electric field stimulation were evaluated using the muscle-bath technique, and compared with the effects of atropine and oxybutynin. RESULTS: Atropine (10(-9) to 10(-6) mol/L), oxybutynin (10(-8) to 10(-5) mol/L), temiverine (10(-8) to 10(-5) mol/L), and RCC-36 (10(-8) to 3 x 10(-6) mol/L) caused a parallel shift to the right of the concentration-response curves to acetylcholine stimulation. The rank order of pA2 value was atropine > oxybutynin = RCC-36 > temiverine. Atropine did not suppress the maximum contractile response to acetylcholine, but the other drugs significantly suppressed this at the higher concentrations. Each drug caused a concentration-dependent inhibition of KCl (80 mmol/L)-, and CaCl2 (5 mmol/L)-induced contractile responses. Rank order of maximum inhibition was RCC-36 = temiverine > oxybutynin > atropine. Each drug caused a concentration-dependent inhibition of electric field-induced contraction with or without 10(-6) mol/L atropine pretreatment. Maximum inhibitions of temiverine and RCC-36 were significantly greater than that of oxybutynin. CONCLUSION: Atropine, oxybutynin, temiverine, and RCC-36 have different efficacies and potencies of anticholinergic and calcium antagonistic activity on isolated human detrusor muscles. Furthermore, temiverine and RCC-36 have significant inhibitory actions toward the atropine-resistant part of contractions, which may be related to the calcium antagonistic actions of these compounds.

Acetylcholine↗
PubMed1998

Antimicrobial activity of novel furanonaphthoquinone analogs.

Analogs of furanonaphthoquinone (FNQ) from Tecoma ipe Mart had MICs ranging from 1.56 to 25 microg/ml against gram-positive bacteria. FNQ showed significantly lower MICs against methicillin-resistant Staphylococcus aureus than against methicillin-sensitive S. aureus. FNQ inhibited Helicobacter pylori with an MIC of 0.1 microg/ml. Fungi, including pathogenic species, were sensitive to FNQ with MICs similar to those of amphotericin B.

Aspergillus↗
PubMed1998

Replacement of loop II of VP1 of the DA strain with loop II of the GDVII strain of Theiler's murine encephalomyelitis virus alters neurovirulence, viral persistence, and demyelination.

Theiler's murine encephalomyelitis viruses, which are murine picornaviruses, can cause central nervous system inflammatory disease. To study the role of loop II in capsid protein VP1, two mutant viruses of strain DA in which DA loop II amino acids were replaced with strain GDVII amino acids were constructed. Infection of mice with the two mutant viruses led to dramatically different patterns of disease.

Animals↗
PubMed1998

Aberrant functional organization in schizophrenia: analysis of EEG coherence during rest and photic stimulation in drug-naive patients.

EEG coherence provides a measure of functional correlations between two EEG signals. The present study was conducted to examine intrahemispheric EEG coherence at rest and during photic stimulation (PS) in 18 drug-naive patients with paranoid schizophrenia and 30 control subjects. Compared with the controls, the schizophrenic patients had significantly higher intrahemispheric coherence of the resting EEG for the delta band, although no significant group differences were found for other frequency bands. EEG analysis during PS showed that the patients also had significantly higher EEG coherence over the left posterior regions. In this study, we also examined the changes in intrahemispheric coherence from rest to the stimulus condition (i.e., PS-related coherence reactivity); the patients were found to show significantly smaller changes, with significant group differences being also confined to the posterior regions in the left hemisphere. These findings provide evidence that schizophrenic patients have abnormal EEG coherence in both resting and stimulus conditions and suggest more diffuse, undifferentiated functional organization within hemispheres. In addition, diminished coherence reactivity suggests a failure of PS-related functional reorganization in schizophrenia.

Adult↗
PubMed1998

Properties of alpha-1-adrenergic receptors in the rat prostate: effect of experimental diabetes.

We studied the effects of 8 weeks of streptozotocin (STZ)-induced diabetes on the density and the pharmacological properties of alpha1-adrenoceptors in the rat prostate using receptor-binding experiments with [125I]iodo-2[beta-(4-hydroxyphenyl)-ethylaminomethyl]tetralone [125I]HEAT. Saturation experiments showed the presence of specific [125I]HEAT-binding sites in the control and diabetic rat prostate and that the induction of diabetes significantly decreased the density of [125I]HEAT-binding sites in the rat prostate. [125I]HEAT-binding sites in the prostate of both groups were inhibited by prazosin (nonselective), spiperone (alpha1B-selective), WB4101 and 5-methylurapidil (alpha1A-selective) and BMY7378 (alpha1D-selective) with the following rank order of Ki values: prazosin < WB4101 < 5-methylurapidil < spiperone < BMY7378, indicating a similar pharmacological profile of alpha1-adrenoceptor in the 2 groups. Comparing the Ki values of the rat prostate with those obtained from the rat submaxillary gland (alpha1A), rat spleen (alpha1B), rat vas deferens (alpha1A + alpha1B) and those reported for cloned alpha1D, indicates the predominance of the alpha1A + alpha1B or the alpha1A subtype in the rat prostate. The present study demonstrates that STZ-induced diabetes downregulates the expression of alpha1-adrenoceptor in the rat prostate, without significantly affecting the receptor subtype specificity.

Adrenergic alpha-Antagonists↗
PubMed1998

A study of growth pattern in giant condyloma acuminatum.

We report a case of giant condyloma acuminatum (CA) of the perianal region. Pathological diagnosis revealed a typical CA with no sign of atypia. In addition, HPV type 11 could be identified by Southern blot analysis. PCNA was highly positive immunohistochemically, but the positivity of p53 protein was not as high as compared with the other control cases. Thus, the high growth rate of tumor cells evaluated by PCNA staining seems to contribute to the marked increase in size, and not only the p53 mutation but also an other cascade may be implicated in cell proliferation.

Adult↗
PubMed1998

Population pharmacokinetics and pharmacodynamics of cisplatin in patients with cancer: analysis with the NONMEM program.

The population pharmacokinetics and pharmacodynamics of cisplatin (CDDP) were evaluated based on a mixed-effect model using the NONMEM program. Unchanged CDDP in plasma was measured as a biologically active platinum species during CDDP chemotherapy, using high-performance liquid chromatography. Plasma concentration measurements (157) of unchanged CDDP from 26 patients with cancer receiving 80 mg/m2 CDDP by infusion over 2 hours, 3.5 hours, or 4 hours were analyzed according to a one-compartment model. The influences of individual characteristics such as body weight, dose schedule, course, and clinical laboratory values (renal function markers, albumin) on total body clearance (Cl) and volume of distribution (Vd) were examined. In the final pharmacokinetic model, body surface area and dose schedule affected Cl of unchanged CDDP. The Cl of CDDP was increased by 27.3% after the 2-hour infusion schedule compared with Cl after the longer infusions. The Vd was estimated as 13.4 L/m2. The interindividual variability for Cl and Vd and residual variability were 22.9%, 30.9%, and 35.5%, respectively. The relationships between maximum concentration (Cmax) of unchanged CDDP and maximum blood urea nitrogen (BUNmax), or minimum creatinine clearance (ClCr,min) over a 1-month period after CDDP administration were evaluated according to linear, exponential, or maximum response (Emax) models. The linear or Emax model described pharmacodynamics most successfully, with relatively large interindividual variability for both slope and EC50 (more than 25%). Residual variability was 15.3% and 17.1% in BUNmax and Clcrmin, respectively. The population means and interindividual and residual variability of pharmacokinetics and pharmacodynamics of CDDP were evaluated using the NONMEM program. The results of this study show that the population pharmacokinetic and pharmacodynamic approach could be useful to manage CDDP nephrotoxicity using sparse data in a clinical setting.

Adult↗
PubMed1998

Acute inversion injury of the ankle: magnetic resonance imaging and clinical outcomes.

This study was undertaken to compare the clinical and magnetic resonance imaging results of 24 patients who had sustained ligament injuries after acute inversion injury of the ankle. On magnetic resonance imaging, the following lesions were detected: anterior talofibular ligament tear in 23 patients, calcaneofibular ligament lesion in 15, posterior talofibular ligament lesion in 11, interosseous talocalcaneal ligament lesion in 13, cervical ligament lesion in 12, and deltoid ligament lesion in 8. Compared with the clinical outcome at the follow-up study, there was a statistically significant relationship between interosseous talocalcaneal ligament lesion and each of giving way, pain, and limitation of ankle motion; between cervical ligament lesion and both giving way and pain; and between deltoid ligament lesion and giving way (P < 0.05).

Acute Disease↗
PubMed1998

Interhemispheric EEG coherence in never-medicated patients with paranoid schizophrenia: analysis at rest and during photic stimulation.

We assessed functional relationships between hemispheres by calculating interhemispheric EEG coherence at rest and during photic stimulation in 18 never-medicated patients with paranoid schizophrenia and 30 control subjects. Although no significant group differences were found in the resting EEG, the schizophrenic patients had significantly higher coherence on EEGs recorded during photic stimulation, compared to the control subjects. In this study, we also examined the changes in interhemispheric coherence from rest to the stimulus condition (i.e., stimulation-related coherence reactivity); the patients were found to show significantly greater coherence reactivity to photic stimulation. These findings provide further evidence that schizophrenic patients have a higher degree of interhemispheric functional connectivity and thus have less lateralized cerebral organization than normal subjects. Our results also suggest that schizophrenic patients have excessive functional reorganization between hemispheres in association with photic stimulation.

Adolescent↗
PubMed1998

Increased anticoagulant activity of recombinant thrombomodulin modified with glycosaminoglycan.

Thrombomodulin (TM) is a thrombin receptor on the endothelial cell surface, effective as an anticoagulant by changing procoagulant thrombin to an anticoagulant one. As rabbit TM with glycosaminoglycan (GAG) has a more potent anticoagulant activity than that without GAG, we expressed recombinant GAG-modified urinary thrombomodulin (GAG-UTM) in C-127 cells. The effect of an additional GAG chain on anticoagulant activity was investigated in comparison with unmodified recombinant UTM (r-UTM). In vitro, the activity of cleavage of fibrinogen by thrombin or prothrombinase activity was more potently depressed by GAG-UTM than by r-UTM, and the generation of activated protein C by TM-thrombin complex was accelerated by GAG modification. The acceleration of antithrombin III-dependent anticoagulant activity was shown only by GAG-UTM. Parameters like thrombin time, prothrombin time and activated partial thromboplastin time in human plasma were prolonged by GAG-UTM more than by r-UTM. In vivo, the effect of GAG-UTM and r-UTM in endotoxin-induced disseminated intravascular coagulation (DIC) rats was investigated using hematological parameters. GAG-UTM and r-UTM significantly reduced the decrease in fibrinogen and platelet number induced by endotoxin at the dosage of 0.1 and 1.0 mg/kg/h, respectively, suggesting that the antithrombotic effect of GAG-UTM in endotoxin-induced DIC rats was 10-fold as potent as that of r-UTM. GAG-UTM reduced the prolongation of the bleeding time induced by endotoxin, while r-UTM accelerated it. These results suggest that the addition of a GAG chain may increase availability as an anticoagulant.

Angiotensin III↗