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Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 235 records · Page 13Linked to original sources
PubMed1997

[Neuroradiological findings on cerebral blood flow and metabolism of a case of adult onset sialidosis].

We examined a patient with adult onset sialidosis using N-isopropyl-p-123I-iodoamphetamine single photon emission computed tomography (SPECT) and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (PET). A 41-year-old [correction of 47] man was admitted to our hospital because of the involuntary movement of his extremities and gait disturbance. On admission, he exhibited action myoclonus in his face and extremities with cerebellar ataxia. Ophthalmoscopy revealed cherry-red spots on his retina. Enzymological analysis of his leucocytes and skin fibroblasts revealed primary sialidase deficit. Brain MRI showed no abnormal findings. Brain SPECT showed decreased cerebral blood flow in the cortex of bilateral occipital lobes, and PET study revealed decreased glucose metabolism in the cortex of bilateral occipital lobes. This case is the thirteenth patient of adult onset sialidosis in Japan. As far as we know, there are no previous reports of SPECT or PET on sialidosis patients. Why the cerebral blood flow and glucose metabolism was decreased in the occipital lobe region remains obscure. From the literatures, we suppose that the onset time of neuronal tissue degeneration or the sensitivity to cumulative metabolites in the occipital region may be different from those in other regions. Further studies are required to confirm abnormalities of cerebral blood flow and metabolism in sialidosis.

Adult↗
PubMed1997

Relationship of epidermal growth factor binding capacity to histopathologic features and prognosis in human renal cell carcinoma.

We studied the association between epidermal growth factor (EGF) binding capacity and histopathologic features or prognosis in human renal cell carcinoma (RCC) by Scatchard analysis in 67 patients. EGF binding capacity was significantly greater in metastatic than in nonmetastatic tumors, and in nuclear grade 3 than nuclear grade 1 tumors. Multivariate analysis revealed that tumor stage, nuclear grade, EGF binding capacity, and tumor size significantly correlated with overall survival. These results suggest that EGF binding may be an important determinant of prognosis in patients with RCC.

Adult↗
PubMed1996

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level.

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.

Animals↗
PubMed1996

Thermolabile beta-2 macroglycoprotein (Hakata antigen) in liver disease: biochemical and immunohistochemical study.

Thermolabile beta-2 macroglycoprotein is a novel serum protein that was detected by an autoantibody in sera of a Japanese woman with systemic lupus erythematosus. We developed an enzyme-linked immunosorbent assay for this glycoprotein and measured its serum levels in patients with chronic liver disease. There were significant correlations between serum levels of this glycoprotein and those of albumin and cholinesterase. The serum levels of TL beta 2MG decreased with increasing severity of cirrhosis. Immunohistochemical staining using monoclonal anti-thermolabile beta-2 macroglycoprotein antibody revealed positive staining in the cytoplasm of the hepatocytes. These data strongly suggested that hepatocyte may be one of the production sites of this glycoprotein. Measurement of serum levels of this glycoprotein was useful for evaluation of hepatic function in chronic liver disease.

Adult↗
PubMed1996

Novel AMPA receptor antagonists: synthesis and structure-activity relationships of 1-hydroxy-7-(1H-imidazol-1-yl)-6-nitro-2,3(1H,4H)- quinoxalinedione and related compounds.

As part of our study of novel antagonists at the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype of excitatory amino acid (EAA) receptors and the pharmacophoric requirements of the receptor, we designed and synthesized a series of 1-substituted 6-imidazolyl-7-nitro-, and 7-imidazolyl-6-nitroquinoxalinediones, as well as related compounds, 6a-j, 7, 11a-e, 15, and 17, which are 1- and 4-substituted analogues of 1 (YM90K), and evaluated their activity to inhibit [3H]AMPA binding from rat whole brain. On the basis of their structure-activity relationships (SAR), we deduced that the amide proton of the imidazolyl-near side of the quinoxalinedione nucleus is not essential for AMPA receptor binding, whereas that of the imidazolyl-far amide is. Further, the receptors possess size-limited bulk tolerance for their N-substituents on the imidazolyl-near amide portion. Moreover, we found that introduction of a hydroxyl group at the imidazolyl-near amide portion causes a severalfold improvement in AMPA receptor affinity over unsubstituted derivatives. Among the compounds, 1-hydroxy-7-(1H-imidazol-1-yl)-6-nitro-2,3(1H,4H)-quinoxalinedione (11a) showed high affinity for AMPA receptor with a Ki value of 0.021 microM, which is severalfold greater than that of 1 and NBQX (2) (1,Ki = 0.084 microM; 2,Ki = 0.060 microM). Compound 11a also showed over 100-fold selectivity for the AMPA receptor than for the N-methyl-D-aspartate (NMDA) receptor and the glycine site on NMDA receptor.

Animals↗
PubMed1996

Dopamine D3 and D4 receptor antagonists: synthesis and structure--activity relationships of (S)-(+)-N-(1-Benzyl-3-pyrrolidinyl)-5-chloro-4- [(cyclopropylcarbonyl) amino]-2-methoxybenzamide (YM-43611) and related compounds.

In this study, we synthesized a series of (S)-N-(3-pyrrolidinyl)benzamide derivatives, 1, 2a-d, 5a-1, and 7, and their enantiomers, (R)-1 and (R)-5c-e, and evaluated their binding affinity for cloned dopamine D2, D3, and D4 receptors and their inhibitory activity against apomorphine-induced climbing behavior in mice. The results indicate that D2, D3, and D4 receptors have different bulk tolerance (D4 > D3 > D2) for the substituent of the 4-amino group (R1) on the benzamide nuclei and that cyclopropyl-, cyclobutyl-, and cyclopentylcarbonyl groups likely possess adequate bulkiness with respect to D3 and D4 affinity and selectivity over D2 receptors in this series. The results also suggested that the N-substituent (R2) on the pyrrolidin-3-yl group performs an important role in expressing affinity for D2, D3, and D4 receptors and selectivity among the respective subtypes. One of the compounds, (S)-(+)-N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-[(cyclopropylcarbonyl+ ++) amino]-2-methoxybenzamide (5c) (YM-43611), showed high affinity for D3 and D4 receptors (Ki values of 21 and 2.1 nM, respectively) with 110-fold D4 selectivity and 10-fold D3 preference over D2 receptors and weak or negligible affinity for representative neurotransmitter receptors. Compound 5c displayed potent antipsychotic activity in inhibiting apomorphine-induced climbing behavior in mice (ED50 value, 0.32 mg/kg sc).

Animals↗
PubMed1996

Subtype selectivity of a new alpha 1-adrenoceptor antagonist, JTH-601: comparison with prazosin.

The existence of alpha 1-adrenoceptors with low affinity for prazosin (alpha 1L group: alpha 1L and alpha 1N subtypes) has been proposed in addition to alpha 1-adrenoceptor subtypes with high affinity for prazosin (alpha 1H group: alpha 1A, alpha 1B and alpha 1D subtypes). A newly synthesized alpha 1-adrenoceptor antagonist, JTH-601 (N-(3-hydroxy-6-methoxy-2,4,5-trimethylbenzyl)-N-methyl-2-(4-hydro xy-2-isopropyl-5-methyl-phenoxy) ethylamine hemifumarate) showed approximately a 10 times higher affinity for the alpha 1L group, a similar affinity for the alpha 1A subtype, but a more than 10 times lower affinity for the alpha 1B and alpha 1D subtypes when compared with prazosin. These results provide a further pharmacological evidence that alpha 1-adrenoceptors with low affinity for prazosin exist in addition to those with high affinity for prazosin, suggesting that JTH-601 may be useful for characterising the alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Antagonists↗
PubMed1996

Novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonists: synthesis and structure-activity relationships of 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione and related compounds.

We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-substituted 2,3(1H,4H)-pyrido[2,3-b]pyrazinedione derivatives 4, 7-1-, 13, 15 and 16 showed some differences in comparison with those of the corresponding substituted quinoxalinediones, including 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione (1) (YM90K). The X-ray study exhibited that conformation of the 7-nitro group of 1.HCl was nearly coplanar with the quinoxaline ring, whereas the 6-imidazol-1-yl group was rotated with respect to the aromatic ring. From the glycine site on NMDA receptor binding study, it is indicated that bulkiness of 6-substituents on pyridopyrazinediones may be responsible for the selectivity against the glycine site. Among the series of azaquinoxalinediones, 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione (8c) exhibited a combination of the best affinity to AMPA receptors with a Ki value of 0.14 microM and selectivity against the glycine site (no affinity at 10 microM). In vivo, 8c also protected against sound-induced seizure in DBA/2 mice (minimum effective dose, 10 mg/kg ip).

Animals↗
PubMed1996

Hopelessness in a community population in Japan.

The Japanese version of the Beck Hopelessness Scale was administered to a total of 154 community residents. The internal consistency (KR-20) was .86. The mean BHS score was 8.6 (SD = 3.9), approximately one standard deviation higher than the reported mean for an Irish general population. The BHS scores were found to be significantly correlated with the age and the number of people living together. Significant negative correlations were found with subjective physical fitness, self-confidence, satisfaction with accommodation and marital state, and adjustment in the work place. The mean BHS score was significantly higher among those individuals who had experienced early maternal or paternal death than those who had not.

Adult↗
PubMed1996

Subcapsular hematoma of the liver and pylethrombosis in the setting of cholestatic liver injury.

We describe a subcapsular hematoma of the liver and pylethrombosis in a patient who developed cholestasis 4 days after severe burn injury. On the 44th hospital day, severe anemia suddenly appeared with no determinable cause. This was the initial manifestation of hepatic hematoma. Cholestatic liver injury of unknown cause lasted throughout the clinical course. The patient subsequently died of hepatic failure 27 months after the burn injury. An autopsy confirmed pylephlebitis and pylethrombosis, which were considered to have contributed to the hepatic failure. This was a rare case of hepatic hematoma and pylephlebitis and pylethrombosis that developed after burn injury.

Aged↗
PubMed1996

Efficient production of Thermus protease aqualysin I in Escherichia coli: effects of cloned gene structure and two-stage culture.

The DNA sequence encoding Thermus protease aqualysin I was inserted downstream from a bacteriophage T7 promoter in an expression vector. In the T7 expression system, using a strain lacking an F' episome, aqualysin I was produced in soluble form without chemical induction. The deletions of part (30 amino acid residues) or all (105 residues) of the C-terminal pro-sequence from the C terminus significantly affected both cellular growth and the production of the enzyme. Complete deletion adversely affected both. In contrast, the 30-residue deletion markedly improved productivity by approximately four times compared to non-deletion, and shortened the time needed for the activation of a precursor to active enzyme. The concentration of inducer isopropyl beta-D-thiogalactopyrano-side (IPTG) was varied to examine its effects, and it was found that a low concentration of IPTG improved aqualysin I production. To avoid the inhibitory effects of acetic acid accumulation in the culture medium, the use of other carbon sources besides glucose was examined. When cells were cultivated with glycerol, the acetic acid level remained relatively low, and both good cellular growth and a high level of production were attained. The aqualysin I productivity for a fed-batch culture using two carbon sources, glucose and glycerol, reached more than 150 kU/ml enzymatically active aqualysin I.

Bacteriophage T7↗
PubMed1996

Chronic effect of hyperprolactinemia on blood glucose and lipid levels in mice.

We studied the chronic effects of hyperprolactinemia, induced by ectopic pituitary grafting, on blood glucose and lipid levels in adult male mice. For one year after pituitary grafting, we measured the blood levels of prolactin, growth hormone (GH), insulin, glucose and free fatty acid (FFA) at various intervals. The graft caused consistent hyperprolactinemia without changes in the serum GH levels. Hypoglycemia developed at 1 and 3 months after grafting but was not accompanied by any changes of the serum insulin levels. Thereafter, the blood glucose and serum insulin levels began to increase in the pituitary-grafted (PG) mice, and at 12 months after the operation, both levels became significantly higher in PG mice than controls. The serum FFA levels and the weight of epididymal fat bodies were significantly lower in PG mice than controls from 3-12 months after the grafting. Thus, hyperprolactinemia leads to persistent hypolipidemia and biphasic changes in the blood glucose level.

Adipose Tissue↗
PubMed1996

Occurrence of tetrodotoxin in Alexandrium tamarense, a causative dinoflagellate of paralytic shellfish poisoning.

A significant amount of tetrodotoxin was identified in the cultured cells of Alexandrium tamarense, a causative dinoflagellate of paralytic shellfish poisoning. This result supports the hypothesis that both tetrodotoxin and paralytic shellfish toxins can be detected in organisms which possess either of them, although their proportion is different individually. The present result also supports our previous finding that A. tamarense is the origin of tetrodotoxin detected in the highly toxic scallop Patinopecten yessoensis during the bloom of A. tamarense.

Animals↗
PubMed1996

Gene analysis of reassortant influenza virus by RT-PCR followed by restriction enzyme digestion.

An amplification system for nearly full length cDNA coding the eight influenza virus segments of A type (H1N1, H2N2, H3N2) and B type influenza viruses is described. Each of the segments of PB1, PB2, PA, NP, M, and NS can be amplified using one 5' primer and one 3' primer for A-type influenza viruses. The RT-PCR amplification system was applied to define the gene composition of three subtype cold-recombinant, live attenuated influenza viruses. Each segment of the attenuated influenza virus could be identified as deriving from segments of the Ca donor or wild virus by comparing the representative restriction enzyme digestion patterns of the three PCR products obtained from the Ca donor, the cold-live attenuated influenza viruses and the wild virus. This RT-PCR method, using RT-PCR followed by digestion of PCR products with restriction enzymes, was very beneficial for analyzing the genome of reassortant influenza viruses.

Base Sequence↗
PubMed1996

Side effects of high-dose interferon therapy for chronic hepatitis C.

BACKGROUND/AIMS: Various side effects have been reported in patients treated with alpha interferon, but their incidence and prognosis remain unknown. METHODS: Nine hundred and eighty-seven patients with chronic active hepatitis C received 6 to 10 MU of alpha interferon per day for 2 weeks and 3 times per week for 22 weeks. Autoantibodies, thyroid function tests, and fasting plasma glucose concentrations were evaluated prior to alpha interferon therapy. RESULTS: Of the 987 patients, 310 were required reduction in the dose of alpha interferon to 3 MU/day or cessation of alpha interferon therapy because of adverse reactions such as flu-like symptoms, leukopenia, and thrombocytopenia. Of the remaining 677, five developed diabetes mellitus, 12 had hyperthyroidism, and six acquired hypothyroidism. Of the 18 with thyroid disorders, five demonstrated antimicrosomal antibodies before therapy. Forty-four patients revealed high or low concentrations of thyroid stimulating hormone at the end of alpha interferon therapy. Three patients developed interstitial pneumonia, one acquired systemic lupus erythematosus-like syndrome, two had autoimmune hepatitis, two developed rheumatoid arthritis, and one developed autoimmune thrombocytopenic purpura. No patients had a history of an autoimmune disorder. One patient experienced sudden hearing impairment and one had retinal detachment. Melena was seen in three patients; two of these cases were compatible with ischemic colitis. Symptoms of depression were seen in 23 patients, and one patient manifested memory loss. CONCLUSION: High-dose alpha interferon therapy induces various adverse effects. Most of the side effects cannot be predicted, but are reversible.

Adult↗
PubMed1996

Effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: a prospective randomized study.

BACKGROUND/AIMS: Although ursodeoxycholic acid is effective for the treatment of primary biliary cirrhosis, some patients do not respond to this treatment. The objective of the present study was to investigate the effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. METHODS: Twenty-two patients with primary biliary cirrhosis treated with ursodeoxycholic acid (600 mg/day) for 30 months were randomly assigned to two groups: group 1, colchicine (1 mg/day) and ursodeoxycholic acid (n = 10); group 2, ursodeoxycholic acid alone (n = 12). RESULTS: In group 1, there were significant decreases in mean serum levels of alkaline phosphatase, total bilirubin, gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, and IgM, and these changes were more remarkable in those who responded poorly to ursodeoxycholic acid. In contrast, there were no significant changes in those values in group 2. CONCLUSIONS: Additional administration of colchicine to ursodeoxycholic acid may be beneficial for patients with primary biliary cirrhosis, especially those who respond poorly to ursodeoxycholic acid. It is necessary, however, to further confirm the efficacy of colchicine by examining histological changes and following the patients for longer periods.

Aged↗
PubMed1996

Values and fertility change in Japan.

This paper analyses how value change and economic and social change have jointly affected fertility in Japan since 1950, and especially since 1973 when fertility resumed declining after some 15 years at near-replacement level. The resumption of fertility decline since 1973 has been driven primarily by underlying economic and social changes. Value change has tended to lag behind fertility change, and this lag has tended to be larger in Japan than in other advanced nations, primarily because underlying economic and social conditions have evolved more rapidly in Japan, and because it takes time for values to adjust to changes in underlying conditions. Because of Japan's high degree of cultural homogeneity, values tend to be widely and quickly shared, so that under certain conditions value change tends to occur in spurts. In Japan, many of the more important value changes affecting fertility in recent decades are bound up with major educational and job gains by women, which have led to greater economic independence and more emphasis on values of individualism and equality between the sexes.

Fertility↗