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Biomedical subjects

E Nakano

Publications and source records attributed to E Nakano.

At least 19 recordsLinked to original sources

Quantitative examinations of internal representations for arm trajectory planning: minimum commanded torque change model.

Quantitative examinations of internal representations for arm trajectory planning: minimum commanded torque change model. A number of invariant features of multijoint planar reaching movements have been observed in measured hand trajectories. These features include roughly straight hand paths and bell-shaped speed profiles where the trajectory curvatures between transverse and radial movements have been found to be different. For quantitative and statistical investigations, we obtained a large amount of trajectory data within a wide range of the workspace in the horizontal and sagittal planes (400 trajectories for each subject). A pair of movements within the horizontal and sagittal planes was set to be equivalent in the elbow and shoulder flexion/extension. The trajectory curvatures of the corresponding pair in these planes were almost the same. Moreover, these curvatures can be accurately reproduced with a linear regression from the summation of rotations in the elbow and shoulder joints. This means that trajectory curvatures systematically depend on the movement location and direction represented in the intrinsic body coordinates. We then examined the following four candidates as planning spaces and the four corresponding computational models for trajectory planning. The candidates were as follows: the minimum hand jerk model in an extrinsic-kinematic space, the minimum angle jerk model in an intrinsic-kinematic space, the minimum torque change model in an intrinsic-dynamic-mechanical space, and the minimum commanded torque change model in an intrinsic-dynamic-neural space. The minimum commanded torque change model, which is proposed here as a computable version of the minimum motor command change model, reproduced actual trajectories best for curvature, position, velocity, acceleration, and torque. The model's prediction that the longer the duration of the movement the larger the trajectory curvature was also confirmed. Movements passing through via-points in the horizontal plane were also measured, and they converged to those predicted by the minimum commanded torque change model with training. Our results indicated that the brain may plan, and learn to plan, the optimal trajectory in the intrinsic coordinates considering arm and muscle dynamics and using representations for motor commands controlling muscle tensions.

Adult

Cloning and expression of a cDNA encoding the laccase from Schizophyllum commune.

We cloned and analyzed the nucleotide sequence of a cDNA that encodes polyphenol oxidase (laccase) from the white-rot basidiomycete Schizophyllum commune. The nucleotide sequence of the full-length cDNA contained a 1554-base open reading frame that encoded a polypeptide of 518 amino acid residues, including a putative signal peptide of 16 residues. It contained four highly similar regions that are conserved in the deduced amino acid sequences of other laccases, including the region thought to be involved in copper binding. Aspergillus sojae strain 1860 (which has low protease levels) was transformed with the plasmid lacAL/pTPT, which contained the laccase gene under the control of the tannase promoter from Aspergillus oryzae. Laccase was secreted into the medium when transformants A1 and A2 were cultured in tannic acid-containing medium.

Amino Acid Sequence

Ectoderm cell--ECM interaction is essential for sea urchin embryo skeletogenesis.

Paracentrotus lividus sea urchin nectin (Pl-nectin) is an extracellular matrix (ECM) protein of the sea urchin embryo on the apical surface of the ectoderm and has been shown to be an adhesive substrate for embryonic cells. A monoclonal antibody (McAb) to Pl-nectin was generated that inhibits the adhesion of blastula cells to Pl-nectin-coated substrates in an in vitro functional assay. To examine for possible in vivo functions of Pl-nectin, Fab fragments (Fabs) of Pl-nectin McAb were added to early blastulae. Ingression of primary mesenchyme cells was not affected by Fabs. As control embryos reached the pluteus stage, treated embryos showed a severe inhibition of skeletal elongation and patterning. When the Fabs were injected directly into the blastocoel, even at higher concentration than was applied externally, skeletogenesis was normal. Therefore, the effect of the antibody on spiculogenesis was indirect. The treatment was partially reversible as embryos eventually seemed to recover and elongate spicules, although with an incorrect patterning. Migration of pigment cells was also affected by the Fabs, since they did not disperse throughout the ectoderm but remained clustered in ectopic areas. In contrast, the development of endoderm structures was not affected. Our results indicate that in the sea urchin embryo the appropriate contact of ectodermal cells with outer ECM components is essential for the correct morphogenesis of inner mesodermal structures.

Animals

A protein of the basal lamina of the sea urchin embryo.

The purification, biochemical characterization and functional features of a novel extracellular matrix protein are described. This protein is a component of the basal lamina found in embryos from the sea urchin species Paracentrotus lividus and Hemicentrotus pulcherrimus. The protein has been named Pl-200K or Hp-200K, respectively, because of the species from which it was isolated and its apparent molecular weight in SDS-PAGE under reducing conditions. It has been purified from unfertilized eggs where it is found packed within cytoplasmic granules, and has different binding affinities to type I collagen and heparin, as assessed by affinity chromatography columns. By indirect immunofluorescence experiments it was shown that, upon fertilization, the protein becomes extracellular, polarized at the basal surface of ectoderm cells, and on the surface of primary mesenchyme cells at the blastula and gastrula stages. The protein serves as an adhesive substrate, as shown by an in vitro binding assay where cells dissociated from blastula embryos were settled on 200K protein-coated substrates. To examine the involvement of the protein in morphogenesis of sea urchin embryo, early blastula embryos were microinjected with anti-200K Fab fragments and further development was followed. When control embryos reached the pluteus stage, microinjected embryos showed severe abnormalities in arms and skeleton elongation and patterning. On the basis of current results, it was proposed that 200K protein is involved in the regulation of sea urchin embryo skeletogenesis.

Animals

[Successful preoperative interferon-alpha therapy of renal cell carcinoma with tumor thrombus extending into the inferior vena cava--case report].

We report a case of renal cell carcinoma in whom preoperative interferon-alpha therapy was successful in reducing the primary lesion and the tumor thrombus extending into the inferior vena cava. A 67-year-old man was referred to our hospital because of his right renal mass. We made a diagnosis of a right renal tumor with tumor thrombus by imaging examinations. Because his performance status was 3, a radical operation was considered risky. So we started interferon-alpha therapy. Four months after the start of interferon-alpha therapy, the primary lesion and the tumor thrombus reduced in their size, and the clinical response was evaluated as partial response by the response criteria for urological cancer treatment. Because of improving the performance status and reducing the tumor size, radical nephrectomy and tumor thrombectomy could be performed. Pathological examinations revealed that viable renal cell carcinomas were found only in some small parts of the primary lesion, but not in the tumor thrombus. Postoperatively, no recurrence and metastasis of renal cell carcinoma of the patient have been detected in these two and a half years.

Aged

[The association between autoantibodies to enzyme and diseases--with special reference to antibodies to pyruvate dehydrogenase complex (PDH)].

A serological feature of primary biliary cirrhosis (PBC) is the presence of high-titer antimitochondrial autoantibodies (AMA) in patient sera. Five different target mitochondrial autoantigens recognized by sera from PBC patients have been identified as subunits of the 2-oxoacid dehydrogenase complex (2-OADC), of which pyruvate dehydrogenase complex-E2 (PDH-E2) is the most prominent antigenic component. Extensive molecular and immunological studies in PBC such as cloning of mitochondrial autoantigens, mapping of both T and B cell epitopes and immunohistochemical studies have provided valuable reagents in the understanding of immunopathogenesis of PBC. We mapped the epitope recognized by AMA specific to 2-oxoglutarate dehydrogenase complex-E2 (OGDC-E2) in patients with PBC using full-length rat OGDC-E2 cDNA and a series of expression clones spanning the entire molecule. It appears that the epitope is dependent on conformation and includes the lipoic acid-binding region. Furthermore we have taken advantage of the antigenic mapping studies of PDC-E2, OGDC-E2 and branched chain 2-oxoacid dehydrogenase complex-E2 (BCOADC-E2) subunits and designed a hybrid clone, pML-MIT3, that expressed three different immunodominant epitopes. Our results indicate that an immunoassay using recombinant, cloned autoantigen is a powerful and very specific method for detecting AMA in PBC.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)

[Ocular complications of atopic dermatitis].

We examined the frequency and types of ocular complications that developed in 560 eyes of 280 patients with atopic dermatitis at the Department of Dermatology, Tokyo Medical College Hospital. Mild ocular involvement included blepharitis in 294 eyes (52.5%), conjunctivitis in 221 eyes (39.5%), and superficial punctate keratopathy in 65 eyes (11.6%). More serious ocular complications leading to decreased visual function occurred in 133 eyes (23.8%) that developed lens opacities, and 34 eyes (6.0%) that developed retinal break or retinal detachment. Because of the presence of abnormalities in the peripheral retina, we believe that a pathogenic factor may have been present in the vitreous of these atopic dermatitis patients. Many of our patients with atopic dermatitis had serious ocular complications in the absence of ocular symptoms. Thus it is important to conduct a thorough ophthalmological examination in the early period of disease in atopic dermatitis patients, both for the management of early but serious ocular complications, as well as for the preservation of visual function.

Adolescent

[A randomized study on intravesical pirarubicin (THP) chemoprophylaxis of recurrence after transurethral resection of superficial bladder cancer].

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of tetrahydropyranyladriamycin (THP) following complete transurethral resection (TUR) of superficial bladder cancer. A total of 80 patients were randomized into "THP" or "control" group. In the THP group, 20 mg of THP dissolved in 40 ml saline (or 5% dextrose) was administered intravesically once a week for 10 weeks, starting from about 7 days after TUR. In the control group, 40 ml saline was given with the same schedule. The patients were followed up by cystoscopy and urinary cytology every 3 months. The number of evaluable patients was 36 for the THP group and 37 for the control group. The non-recurrence rates in the THP group and control group were 79.4% versus 63.2% at 1 year and 69.8% versus 47.4% at 3 to 5 years, respectively. These figures were not statistically significant. However, THP instillation significantly reduced tumor recurrence rates for multiple tumors, and also tended to decrease recurrence rates for primary and pT1 tumors. Adverse effects were observed in 53.6% of the patients in the THP group, but they were tolerable. Our results suggest that intravesical THP instillation would not be effective for all patients with superficial bladder cancer. Further study is warranted in a selected group of patients.

Administration, Intravesical

Evaluation of the genotoxic potential of flumethrin in mouse bone marrow by chromosomal analysis and micronucleus test.

The genotoxic potential of the pyrethroid flumethrin was evaluated by using the combined protocol of metaphase analysis and micronucleus test in vivo in mouse bone marrow. The dermal route was tested in a single treatment and the intraperitoneal (i.p.) route in a single and a multiple treatment. Flumethrin showed a cytotoxic effect on both myelopoiesis and erythropoiesis, as evidenced by a reduction in the mitotic index and in polychromatic erythrocyte values. An increase in the frequency of gaps after the dermal exposure and of breaks only at the highest dose tested in the i.p. treatment indicates a weak clastogenic potential of the compound. A significant increase in the frequency of micronucleated polychromatic erythrocytes was observed after single and multiple i.p. treatments. In the latter, the induction of micronuclei was highly significant but not accompanied by an increase in breaks. This may indicate that the clastogenic effect might not account by itself for the induction of micronuclei, which could also have arisen from an aneugenic potential of flumethrin.

Administration, Topical

Cloning, sequence analysis, and expression in Escherichia coli of the gene encoding the Candida utilis urate oxidase (uricase).

A urate oxidase (uricase) gene was cloned from Candida utilis with an oligonucleotide probe based on the amino acid sequence of cyanogen bromide-cleaved uricase. The uricase gene contains 909 base pairs and encodes a protein with a predicted mass of 34,193 Da. Candida uricase was similar (49% match in amino acid sequence) to the uricase from Aspergillus flavus. The uricase from Candida utilis has four cysteines and one of them, Cys168, participates in the enzyme activity. This enzyme was expressed to a level of about 20% of total cellular protein in an Escherichia coli cell as a soluble and functional form.

Amino Acid Sequence

[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer].

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

Administration, Oral

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

Administration, Oral

Left ventricular-coronary sinus shunt through a septal aneurysm after mitral valve re-replacement.

We describe a case in which a left ventricular-coronary sinus communication through a dissecting ventricular septal aneurysm developed after a redo mitral valve replacement. The outlet orifice of the communication was located in the side wall of the ostium of the coronary sinus. Both the communication and the aneurysm were successfully dealt with by performing a right atriotomy and by opening the aneurysm from its outlet orifice.

Aged

Neuroleptic malignant syndrome in striatonigral degeneration.

A 6-year-old boy with striatonigral degeneration had an episode of neuroleptic malignant syndrome after an upper respiratory infection. Dantrolene treatment was successful. Some reports have demonstrated that anesthetic and antipsychotic agents lead to neuroleptic malignant syndrome in disorders of the basal ganglia. However, neuroleptic malignant syndrome attributable to a respiratory infection has not previously been reported. Our patient illustrates the potential morbidity of neuroleptic malignant syndrome in patients with striatonigral degeneration.

Child

[Prealbumin].

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Adolescent

Nucleotide sequence of the phosphotransacetylase gene of Escherichia coli strain K12.

The phosphotransacetylase gene (pta) from Escherichia coli strain K-12 1100 was identified in a cloned fragment of chromosomal DNA (Yamamoto-Otake, H., Matsuyama, A. and Nakano, A. (1990) Appl. Microbiol. Biotechnol. 33, 680-682). Overexpression in E. coli confirmed the presence of the pta gene within the cloned fragment. DNA sequence analysis of the cloned pta gene indicates that the predicted phosphotransacetylase polypeptide chain is 713 amino acids in length. The carboxyterminal region of the E. coli phosphotransacetylase shows 42.6% sequence identity with the corresponding enzyme from Methanosarcina thermophila (142 out of 333 residues in corresponding positions are identical). Several short regions of high sequence identity may be structurally or functionally important for enzymic activity.

Amino Acid Sequence

Elucidation of the thermal stability of the neutral proteinase II from Aspergillus oryzae.

The neutral proteinase II from Aspergillus oryzae (NpII) is a zinc proteinase with three intramolecular disulfide bonds. NpII is most unstable after 10 min at about 75 degrees C, but regains stability beyond this temperature and is relatively stable at 100 degrees C. We analyzed the thermal stability of wild-type NpII and apo NpII. The results suggested that NpII unfolds reversibly upon incubation up to 100 degrees C, and that the irreversible inactivation observed is mainly due to autoproteolysis. To further understand the stability, a mutant NpII (Cys78-->Ala) lacking one of the disulfide bonds, was produced in a heterologous yeast expression system. The mutant NpII showed a similar stability profile, but the most unstable temperature and the most catalytically active temperature decreased to the same extent (around 10 degrees C), confirming that autoproteolysis is the main cause of the irreversible inactivation. Several lines of evidence presented in this study demonstrated that the thermal stability of o++NpII is attributed to reversible thermal unfolding and autoproteolysis.

Aspergillus oryzae