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Biomedical subjects

Y Fujimoto

Publications and source records attributed to Y Fujimoto.

At least 199 records · Page 11Linked to original sources

Forking genetic algorithms: GAs with search space division schemes.

In this article, we propose a new type of genetic algorithm (GA), the forking GA (fGA), which divides the whole search space into subspaces, depending on the convergence status of the population and the solutions obtained so far. The fGA is intended to deal with multimodal problems that are difficult to solve using conventional GAs. We use a multipopulation scheme that includes one parent population that explores one subspace and one or more child populations exploiting the other subspace. We consider two types of fGAs, depending on the method used to divide the search space. One is the genotypic fGA (g-fGA), which defines the search subspace for each subpopulation, depending on the salient schema within the genotypic search space. The other is the phenotypic fGA (p-fGA), which defines a search subspace by a neighborhood hypercube around the current best individual in the phenotypic feature space. Empirical results on complex function optimization problems show that both the g-fGA and p-fGA perform well compared to conventional GAs. Two additional utilities of the p-fGA are also studied briefly.

Algorithms↗

Spinocerebellar ataxia type 6. Molecular and clinical features of 35 Japanese patients including one homozygous for the CAG repeat expansion.

Spinocerebellar ataxia type 6 (SCA6) is a newly classified autosomal-dominant cerebellar ataxia (ADCA) associated with CAG repeat expansion. We screened 111 patients with cerebellar ataxia for the SCA6 mutation. Of these, 35 patients were found to have expanded CAG repeats in the SCA6 gene, indicating that second to SCA3, SCA6 is the most common ADCA in Japan. Expanded alleles ranged from 21 to 29 repeats, whereas normal alleles had seven to 17 repeats. There was no change in the CAG repeat length during meiosis. The age at onset was inversely correlated with the repeat length. The main clinical feature of the 35 patients with SCA6 was slowly progressive cerebellar ataxia; multisystem involvement was not common. The 35 patients included nine cases without apparent family history of cerebellar ataxia. The sporadic cases had smaller CAG repeats (21 or 22 repeats) and a later age at onset (64.9 +/- 4.9 years) than the other cases with established family history. We also identified one patient who was homozygous for the SCA6 repeat expansion. The homozygote showed an earlier age of onset and more severe clinical manifestations than her sister, a heterozygote carrying an expanded allele with the same repeat length as the homozygote. This finding suggests that the dosage of the CAG repeat expansion plays an important role in phenotypic expression in SCA6.

Adult↗

[Assessment of Swallowing Ability Scale for oral and oropharyngeal cancer patients].

The Swallowing Ability Scale (SAS) has been recently reported by us. This scale is a new method to assess dysphagia after therapy for oral and oropharyngeal cancer. The preliminary results on 23 patients showed that the scale was reliable and sensitive to functional differences across a broad spectrum of oropharyngeal dysphagia after therapy. This paper confirmed the above facts in 73 oral and oropharyngeal cancer patients who were treated in two hospitals between 1995 and 1996. As stated in the previous paper, SAS consists of a 2-step questionnaire: the MTF score and the Dysphagia score. The MTF score is a simple and practical assessment tool consisting of three subscales: 1) Method of intake, 2) Time of intake, and 3) Food. The Dysphagia score is a relevant assessment tool for defining patients' anatomic or physiologic swallowing disorders. In 40 patients with wide resection of the tongue, the Dysphagia score (p < 0.05) and the MTF score (p < 0.01) were significantly decreased. And we found a correlation between the MTF score and the Dysphagia score (r = 0.78, p < 0.001) in 73 patients. The usefulness of the SAS will be further studied for the assessment of rehabilitation to improve postoperative dysphagia.

Deglutition↗

[Sibling cases of opsoclonus-polymyoclonus syndrome].

We described a 34-year-old man who developed opsoclonus-polymyoclonus syndrome (OPS) associated with benign encephalitis. His older sister also suffered from the same syndrome 12 years ago. We examined HLA types in 6 patients with OPS who were admitted to our hospital, including these sibling cases. All 6 patients have type A2 antigen and statistical analysis suggested that there is a positive relationship between OPS and HLA A2 antigen. Considering the two facts that the existence of the sibling cases in this relatively rare disorder and sharing of HLA A2 antigen in our 6 cases, some genetic factors might be involved in the development of OPS.

Adult↗

Inhibition of rabbit gastric glucosamine synthetase activity by Cu2+, Zn2+ and Se4+.

The effects of Fe2+, Cu2+, Zn2+ and Se4+ on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, in rabbit gastric corporal mucosa were examined. Cu2+, Zn2+ and Se4+ inhibited the glucosamine synthetase activity at concentrations ranging from 1 to 10 microM (Cu2+, 8-98% inhibition; Zn2+, 10-99% inhibition; Se4+, 32-89% inhibition). The inhibitory effects of these three ions were much stronger than that of UDP-N-acetylglúcosamine known as a representative inhibitor of the glucosamine synthetase activity (10 microM, 52% inhibition). Fe2+ had no significant effect on the glucosamine synthetase activity up to 100 microM. These results suggest that Cu2+, Zn2+ and Se4+ can be potent inhibitors of gastric glucosamine synthetase activity.

Animals↗

Effect of 13-hydroperoxyoctadecadienoic acid on the glucosamine synthetase activity in rabbit gastric mucosa.

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, in rabbit gastric corporal mucosa was examined. 13-HPODE inhibited the glucosamine synthetase activity at concentrations ranging from 10 to 100 microM. The effect was concentration-dependent, and the concentration required for 50% inhibition was approximately 20 microM. Experiments utilizing Fe2+ and 13-hydroxyoctadecadienoic acid revealed that the inhibitory effect of 13-HPODE on the glucosamine synthetase activity is not due to the alcohol adduct and hydroxyl radical which are expected to be formed from 13-HPODE, and that the hydroperoxyl functional group is a prerequisite. The fact that tert-butyl hydroperoxide exhibited about 50 times weaker inhibition than 13-HPODE indicates the relative specificity of fatty acyl hydroperoxides in the modulation of the glucosamine synthetase activity. These results suggest that 13-HPODE has the potential to modulate the synthesis of gastric mucus by affecting the glucosamine synthetase activity.

Animals↗

[Clinical efficacy of post-TUR prophylactic chemotherapy for superficial bladder cancer--the result of co-operative prospective randomized trial].

We have performed a prospective randomized clinical trial of post-operative prophylactic therapy for superficial bladder cancer since October in 1991. The criteria were as follows; age < or = 80 y.o., Ta/T1, TCC G1/G2, without CIS lesion and resectable cancer by TUR. The therapeutic arm was divided into three as follows: arm A intracystic instillation with Epirubicin; arm B: oral administration with 5-FU; arm C: combination of arm A and arm B. The number of registered patients were 20 in arm A, 18 in arm B, and 18 in arm C. The patient characteristics in every group were not significantly different. The prophylactic efficacy of arm A was superior to that in the other two groups.

Administration, Intravesical↗

[Hallucination in opsoclonus-polymyoclonus syndrome].

Here we report 2 cases of opsoclonus-polymyoclonus syndrome (OPS) associated with viral encephalitis. They had sleep disturbance, and visual hallucination. Case 1 had auditory hallucination in addition, and case 2 had dreamlike behavior. Those hallucination, which were colorful and vivid, usually appeared at the bed time. Their hallucinations were similar to peduncular hallucinations and you may also call hypnagogic hallucinations, which are often seen in patients with narcolepsy. Dreamlike behavior is observed during REM sleep in patients with brainstem damage or sometimes in the healthy elderly people. The presence of sleep disturbance, hypnagogic hallucination, and dreamlike behavior suggests that there may be some relationship between OPS and REM sleep. Considering that REM sleep is suppressed by serotonergic projection of the dorsal raphe nucleus in addition to several reports about brainstem lesion with serotonergic abnormalities in this disorder, we considered that dysfunction of serotonergic neurons of the dorsal raphe nucleus might be related in the development of OPS.

Adolescent↗

[A case of chorea-acanthocytosis successfully treated with posteroventral pallidotomy].

We described a 41-year-old man with chorea-acanthocytosis, who presented severe choreoathetosis in all the limbs, neck, face and tongue. Especially, the oral area was affected most strikingly. He had difficulty in eating, because he pushed foods out of the mouth with the tongue. He received left posteroventral pallidotomy (PVP). His involuntary movements became much less enough for the patient to eat with a spoon in a sitting position by himself. Six months after the first operation, although involuntary movement on the right hand remained reduced, choreoballistic movement appeared on the left side. He received PVP on the right side. The choreoballistic movement was remarkably improved after the right PVP. No neurological aggravation has been found for 7 months after the second PVP. Bilateral PVP was fully effective as for the improvement of the activity of daily life. The output from the internal globus pallidus (GPi) is well-known to be inhibitory. Therefore, it is understandable that the coagulation of GPi results in improvement of hypokinesia and rigidity in patients with Parkinson's disease. However, some clinical reports, including ours, have described the significant reduction of hyperkinetic choreoballistic movement after PVP. The exact mechanism of these surgical effects has not been elucidated yet, and further clinical and basic studies are needed to answer this question.

Acanthocytes↗

Amitriptyline inhibits the G protein and K+ channel in the cloned thyroid cell line.

We have reported that thyroid K+ channel is activated by extracellular application of the thyroid-stimulating hormone (TSH) using single channel recording method performed on cloned normal rat thyroid cell (FRTL-5) membrane. Treatment of dibutyryladenosine cyclic monophosphate (Bt2 cAMP) also activated the TSH-dependent K+ channel. These findings indicate that the thyroid K+ channel is activated through the TSH-adenosine cyclic monophosphate (cAMP)-protein kinase A system. We examined the effects of amitriptyline on TSH-guanosine triphosphate binding protein (G protein)-adenylate cyclase-cAMP-K+ channel system in the cloned normal rat thyroid cell line FRTL-5. Amitriptyline inhibited the cAMP production induced by TSH. Amitriptyline also inhibited the cAMP production induced by cholera toxin, indicating that amitriptyline inhibited the thyroid G protein. Amitriptyline had no effect on TSH-receptor binding and cAMP production by forskolin (adenylate cyclase stimulator). Amitriptyline inhibited the K+ channel activation by cAMP, indicating that the suppressing mechanism is not the inhibition of TSH receptor or G protein but the direct suppression of K+ channel. It was concluded that amitriptyline inhibited the thyroid G protein and K+ channel.

Amitriptyline↗

Proadrenomedullin N-terminal 20 peptide is rapidly cleaved by neutral endopeptidase.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide which is processed from an adrenomedullin precursor. PAMP is rapidly cleaved by human neutral endopeptidase (NEP), a protease which plays a key role in the degradation of human atrial natriuretic peptide (ANP). A double reciprocal plot indicated that Km of NEP as a substrate of PAMP was 6.1 microM and V(max) was 3.1 mmol/min/mg of NEP. EDTA, phosphoramidon and thiorphan inhibit the proteolysis of PAMP by NEP. NEP cleaves at least 6 peptide bonds in human PAMP; Arg2-Leu3, Glu8-Phe9, Lys12-Trp13, Lys15-Trp16, Trp16-Ala17 and Ala17-Leu18. The present data suggest that NEP may be involved in the circulation control by degrading PAMP as well as ANP.

Adrenomedullin↗

15-Hydroperoxyeicosapentaenoic acid inhibits arachidonic acid metabolism in rabbit platelets more potently than eicosapentaenoic acid.

The effect of 15-hydroperoxy-5,8,11,13,15-eicosapentaenoic acid (15-HPEPE), a hydroperoxy adduct of eicosapentaenoic acid (EPA), on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane (TX) B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) from exogenous arachidonic acid in washed rabbit platelets was examined. 15-HPEPE inhibited 12-HETE, TXB2 and HHT formation at concentrations ranging from 2 to 8 microM. The inhibitory effect of 15-HPEPE was dose-dependent (12-HETE, 16.0-82.9% inhibition; TXB2, 16.7-57.2% inhibition; HHT, 4.6-52.0% inhibition). EPA inhibited the production of these three metabolites, but the inhibitory effect was kept low (20-100 microM: 12-HETE, 8.3-31.1% inhibition; TXB2, 18.9-49.5% inhibition; HHT, 12.5-41.7% inhibition) as compared with 15-HPEPE. Experiments utilizing 15-hydroxy-5,8,11,13,15-eicosapentaenoic acid and hydroxyl radical scavengers (dimethyl sulfoxide and mannitol) revealed that 15-HPEPE exerted its effect in the form of the hydroperoxy adduct. These results suggest that 15-HPEPE has the potential to modulate the activities of the cyclo-oxygenase and 12-lipoxygenase in platelets. This may also be one convincing mechanism for the anti-thrombotic and anti-atherosclerotic actions of EPA.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Effect of Prograf (FK506) on spermatogenesis in rats.

Prograf (FK506) was given to male mature rats in a daily subcutaneous dose of 1 or 3 mg/kg/day for 2 weeks to investigate its effect on spermatogenesis. Prograf dose-dependently sperm counts and motility, but did not affect testosterone level in the serum of rats. Histopathologically, there were no abnormal changes in the testis, seminal vesicle or prostate in any rats dosed with Prograf, but intra-ductal eosinophilic globules, probably degeneration of the sperm cells, were observed in the epididymis of the 3 mg/kg/day group. Sperm counts and motility returned to the control levels after stopping of the drug. The results indicate that Prograf decreased sperm counts and motility through direct action on the sperm in the epididymis, but not the production of sperm in the testis. Cyclosporine A (CsA) was used as the reference drug in the present study. Thirty mg/kg/day of CsA also decreased sperm counts and motility, and stopping of the drug led to the recovery of these changes. The males dosed with Prograf for 2 weeks were mated with non-dosed females to investigate its effect on the fertility potential of the males. Prograf did not affect copulation or fertility index, but a decrease in the number of live fetuses associated with implantation loss was observed in the 3 mg/kg/day group. The changes were considered to be due to the decrease of sperm counts and motility, although 1 mg/kg/day of Prograf, 5-10 times the clinical dose, did not affect any fertility parameters including implantation index.

Animals↗

Autosomal dominant cerebellar ataxias in the Kinki area of Japan.

The autosomal dominant cerebellar ataxias are a heterogeneous group of neurodegenerative disorders characterized by slowly progressive cerebellar ataxia. Recently, among the ataxias, spinocerebellar ataxia type 1 (SCA1), Machado-Joseph disease (MJD) and dentatorubral-pallidoluysian atrophy have been found to be caused by expansion of a CAG trinucleotide repeat in the coding region of the disease genes. We have analyzed the CAG repeats of 67 patients from 47 families with dominantly inherited ataxia who lived in the Kinki area of Japan. The following results were obtained. First, 31 patients from 22 families were found to be positive for the MJD repeat expansion, indicating that MJD is the most common dominantly inherited ataxia in the Kinki area of Japan. Second, no SCA1 repeat expansion was found among the families studied. This presents a striking contrast to the fact that there are many families with SCA1 in Hokkaido and the Tohoku area of Japan. These findings suggest geographic variation in autosomal dominant cerebellar ataxias in Japan.

Asian People↗

Appearance and disappearance of unilateral spatial neglect for an object: influence of attention-attracting peripheral stimuli.

We reported a dramatic phenomenon of appearance and disappearance of left unilateral spatial neglect for the same single object. In experiment 1, four patients with mild neglect who copied a single flower satisfactorily showed left neglect in copying of the same flower when it was accompanied with some peripheral stimuli. In experiment 2, we included three additional conditions to determine the stimulus component crucial for left neglect of the flower: a flower with a stem and a flower with either right or left peripheral stimuli were also used for copying. Overall results showed that neglect was most evident for the flower with the right peripheral stimuli. On the other hand, the presence of left stimuli provoked less severe neglect of the flower, which was as mild as that in the single flower condition. The results were explained in terms of an attentional mechanism underlying unilateral spatial neglect. When copying the flower with peripheral stimuli on both sides or on the right side, the stimuli on the right side might attract the patient's attention. Consequently, he exhibited left neglect on the central flower. On the other hand, neglect was less evident in the other conditions, since the figures did not include such attention-attracting stimuli on the right side.

Adult↗

Phloroglucinols from Baeckea frutescens.

Two new phloroglucinols, named BF-1 and BF-2, were isolated from the dried leaves of Baeckea frutescens. Their structures were determined by their 1H and 13C NMR and mass spectral data. BF-2 exhibited strong cytotoxic activity (IC50 = 5.0 micrograms ml-1) against leukaemia cells (L 1210) in tissue culture.

Antineoplastic Agents, Phytogenic↗

Effects of Fe(2+), Zn(2+), Cu(2+) and Se(4+) on the synthesis and catabolism of prostaglandins in rabbit gastric antral mucosa.

Effects of Fe(2+), Zn(2+), Cu(2+) and Se(4+) on the synthesis and catabolism of prostaglandins (PGs) in rabbit gastric antral mucosa were examined. Fe(2+) inhibited the cyclooxygenase activity in the microsomal fraction. Zn(2+) suppressed the endoperoxide E(2) isomerase activity in the microsomal fraction and the 15-hydroxy PG dehydrogenase (PGDH) activity in the cytosolic fraction. Cu(2+) stimulated the cyclooxygenase activity, inhibited the PGDH activity and possibly induced non-enzymatic reduction of PGG(2) or PGH(2) to PGF(2 alpha) Se(4+) possibly induced the non-enzymatic reduction of PGG(2) or PGH(2) to PGF(2 alpha), as well as Cu(2+). These results suggest that Fe(2+), Zn(2+), Cu(2+) and Se(4+) can be modulators of the gastric antral mucosal PG levels by affecting the PG synthesizing enzymes, PG catabolizing enzyme and/or non-enzymatic reduction of PGG or PGH to PGF.

Animals↗