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Biomedical subjects

S Tsuji

Publications and source records attributed to S Tsuji.

At least 181 records · Page 10Linked to original sources
PubMed2000

Synergistic effects of food colors on the toxicity of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) in primary cultured rat hepatocytes.

The synergistic effect of food additives or food colors on the toxicity of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was investigated using primary cultured rat hepatocytes. When hepatocytes from rats fed a standard diet were treated with a mixture of four major food additives (sorbitol, sodium L(+)-glutamate, benzoic acid, and propylene glycol) or a mixture of six typical artificial food colors (erythrosine, allura red, new coccine, brilliant blue, tertrazine, and fast green), the in vitro treated food-color mixture itself showed cytotoxicity: the reduction of cell viability and decreases in the activities of gluconeogenesis and ureogenesis. The food-color mixture enhanced cytotoxicity of Trp-P-1 obviously. We then investigated the effects of in vivo-dosed food additives or food colors on Trp-P-1-caused toxicity. Hepatocytes were isolated and cultured from rats fed a diet containing a mixture of food additives or a mixture of food colors with half the amount of their respective acceptable daily intake for 4 wk. Trp-P-1 was administered to the hepatocytes at various concentrations for 12 h. Synergistic effects of in vivo-dosed food additives and food colors were not observed on Trp-P-1-caused cytotoxicity as estimated by a loss of cell viability and the reductions of DNA and protein syntheses. On the contrary, we have observed that in vivo administered food colors synergistically facilitated to reduce the activities of gluconeogenesis and ureogenesis in Trp-P-1-treated hepatocytes. These results suggest that the daily intake of artificial food colors may impair hepatic functions such as gluconeogenesis and ureogenesis, when dietary carcinogens are exposed to the liver cells.

Animals↗
PubMed2000

Elongation factor-1alpha as a homologous complement activator of Jurkat cells.

Although increasing evidence exist suggesting that apoptotic cells activate homologous complement, the homologous complement activators are only poorly characterized. We found that cell lysate of Jurkat cells contained a homologous complement activator of 50 kDa. Digestion of the 50 kDa activator with lysylendopeptidase yielded peptide fragments, with sequences identical to those of EF-1alpha. The 50 kDa activator was removed by immunoadsorption with anti-EF-1alpha, suggesting that the 50 kDa activator is EF-1alpha. The homologous complement activation did not proceed with EGTA-serum. In addition, C4b, a fragment produced by activation of the classical or lectin pathways was found to bind with EF-1alpha. These results suggest that EF-1alpha activates the homologous complement through the classical or lectin pathway.

Amino Acid Sequence↗
PubMed2000

Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells.

Betacellulin (BTC) was identified in mouse pancreatic beta cell tumors as a member of the epidermal growth factor (EGF) family, and was found to bind and activate the EGF receptor. BTC is also expressed in some human malignancies and may have an important role in tumor growth progression. We examined whether BTC and EGF have a growth stimulatory effect on human pancreatic cancer cell lines both in vitro and in vivo. We also investigated the BTC expression and autonomous induction of BTC in pancreatic cancer cells. in vitro, both BTC and EGF had almost the same proliferative effect on Panc-1, MIA PaCa-2 and AsPC-1. in vivo, in a Panc-1 inoculated athymic mice model, BTC-treated tumors grew approximately five times larger than in control. Immunocytochemistry showed that BTC expression occurred in three pancreatic cancer cell lines, with MIA PaCa-2 showing the strongest intensity. Semi-quantitative RT-PCR of MIA Paca-2 showed that mRNA levels of BTC gradually increased after treatment with 1 nM BTC. Immunocytochemistry also demonstrated that the intensity of BTC-like immunoreactivity was increased when treated with 1 nM BTC but was reduced after treatment with 100 nM of AG1478, an EGF receptor tyrosine kinase inhibitor. BTC has thus a significant growth stimulatory effect on pancreatic cancer cells and might function as an autocrine and paracrine growth factor. BTC expression in pancreatic cancer cells is, at least in part, controlled by an auto-induction mechanism.

Animals↗
PubMed2000

Synphilin-1 is present in Lewy bodies in Parkinson's disease.

Alpha-synuclein is believed to play an important role in Parkinson's disease (PD). Mutations in the alpha-synuclein gene are responsible for familial forms of PD and alpha-synuclein protein is a major component of Lewy bodies in patients with sporadic PD. Synphilin-1 is a novel protein that we have previously found to associate in vivo with alpha-synuclein. We now show that synphilin-1 is present in Lewy bodies of patients with PD. Our data suggest that synphilin-1 could play a role in Lewy body formation and the pathogenesis of PD.

Aged↗
PubMed2000

[A case of portal-systemic encephalopathy associated with Sheehan's syndrome].

A 66-year-old woman had had recurrent episodes of disturbed consciousness whenever she had been constipated or dehydrated. She had been inactive and afflicted with obstinate constipation since she had menopause at age of 32. She underwent gastrectomy for gastric ulcer at age of 37. Laboratory examination showed marked hyperammonemia, reduction in Fisher ratio, and poor excretion of ICG. Furthermore, hypopituitarism and secondary hypothyroidism were found. She was diagnosed as Sheehan's syndrome. A T1-weighted MRI demonstrated symmetrical high intensity in the bilateral globus pallidus and empty sella. The histological examination of the liver revealed a mild lymphocytic infiltration without liver cirrhosis. Abdominal angiography showed a large shunt vessel between the splenic vein and the left renal vein. After embolization of the shunt vessel, hyperammonemia and neurological impairment improved. Additionally multiple hormones replacement has been useful to reduce the drugs of standard therapy for hepatic coma. In this case, we speculated that Sheehan's syndrome accelerated the constipation and worsened the shunt encephalopathy.

Aged↗
PubMed2000

[A case of Charcot-Marie-Tooth disease 1 B with Val 146Phe mutation of myelin protein zero showing a severe clinical phenotype].

A 15-year-old boy had complaints of progressive gait disturbance and foot deformity. He started to walk at the age of 18 months. Since two years of age, he had noticed unstable gait. He showed evident scoliosis and enlarged great auricular nerves. Moderate to slight degrees of muscular atrophy and weakness of distal upper, and proximal and distal lower limbs were observed. Pes equinovarus deformity of both feet was obvious. Muscle stretch reflexes were absent in both limbs except decreased triceps brachii reflex. Vibratory sensation was decreased severely in the toes and mildly in the fingers. In cerebrospinal fluid, protein was mildly elevated. Median nerve motor conduction velocity was 5.0 m/sec. On sural nerve biopsy, both demyelinated and remyelinated axons and onion-bulbs without hypomyelination were observed. Therefore, the diagnosis of Charcot-Marie-Tooth disease 1 was made. The direct sequencing of the genomic DNA encoding the Po gene revealed a mutant allele, a guanine to thymine substitution of nucleotide position 436, which caused a substitution of phenylalanine for valine at amino acid position 146. This type of Po mutation is different from any type of Po mutation reported in the literature.

Adolescent↗
PubMed2000

Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15A13-15.

To date, three loci for autosomal recessive hereditary spastic paraplegia (ARHSP) linked to chromosomes 8p12-q13, 16qter, and 15q13-15 have been characterized. We have clinically characterized 13 Japanese ARHSP families and performed genetic linkage analyses. All 13 families were classified as having the "complicated" form, which manifests with mental impairment and thin corpus callosum. Linkage to the 8p12-q13 and 16qter loci was excluded, although 10 of the 13 families showed marker data consistent with linkage to the 15q13-15 locus. The multipoint LOD score of the 10 families linked to chromosome 15 was above 9.00 in the 3-centimorgan segment flanked by D15S994 and D15S659, with a maximum multipoint LOD score of 9.68 at a position 1.2 centimorgans telomeric from D15S994 to D15S659. We have shown that ARHSP with thin corpus callosum, a subtype of recessive spastic paraplegia, maps to chromosome 15q13-15.

Adolescent↗
PubMed2000

Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism.

Autosomal recessive juvenile parkinsonism is a hereditary neurodegenerative disorder, usually beginning before the age of 40. We found three exonic deletions and two novel point mutations (Arg33Stop and Cys431Phe) in six families with autosomal recessive juvenile parkinsonism. In 1 family, in which an autosomal dominant mode of inheritance was suspected, multiple mutant alleles were identified. Although a wide range of ages at onset was observed, there was no correlation between age at onset and genotype.

Adolescent↗
PubMed2000

Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression.

To examine the expression of the stromal cell-derived factor 1 (SDF-1)/CXCR4 receptor ligand system in pancreatic cancer cells and endothelial cells, we performed immunohistochemical analysis for 52 pancreatic cancer tissue samples with anti-CXCR4 antibody and reverse transcription-PCR analysis for CXCR4 and SDF-1 in five pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, HPAC, and PANC-1), an endothelial cell line (HUVEC), and eight pancreatic cancer tissues. We then performed cell migration assay on AsPC-1 cells, HUVECs, and CFPAC-1 cells in the presence of SDF-1 or MRC-9 fibroblast cells. Immunoreactive CXCR4 was found mainly in pancreatic cancer cells and endothelial cells of relatively large vessels around a tumorous lesion. The immunopositive ratio in the pancreatic cancer was 71.2%. There was no statistically significant correlation with clinicopathological features. SDF-1 mRNA expressions were detected in all pancreatic cancer tissues but not in pancreatic cancer cell lines and HUVECs; meanwhile, CXCR4 mRNA was detected in all pancreatic cancer tissues, cancer cell lines, and HUVECs. The results indicate that the paracrine mechanism is involved in the SDF-1/CXCR4 receptor ligand system in pancreatic cancer. In vitro studies demonstrated that SDF-1 significantly increased the migration ability of AsPC-1 and HUVECs, and these effects were inhibited by CXCR4 antagonist T22, and that the coculture system with MRC-9 also increased the migration ability of CFPAC-1 cells, and this effect was significantly inhibited by T22. Our results suggested that the SDF-1/CXCR4 receptor ligand system may have a possible role in the pancreatic cancer progression through tumor cell migration and angiogenesis.

Adult↗
PubMed2000

[Monitoring of the cryptococcus count in the cerebrospinal fluid with negative cultures in two cases of serious cryptococcal meningitis].

We monitored the cryptococcus count in the cerebrospinal fluid(CSF) using the filter technique in two cases of serious cryptococcal meningitis during the course of treatment with antifungal agents. Lumbar puncture was performed once a week, and 1 ml of CSF was filtered through a Millipore filter(5.0-micron pore for cells), followed by staining of the filters with Alcian blue. All of the cryptococci on the filter were counted under a light microscope at a magnification of x 100. More than 500/ml and 2,000/ml of cryptococci were still observed in the CFS in Cases 1 and 2, respectively, in whom CFS cultures for Cryptococcus neoformans became negative after 4 weeks of treatment. Even though the treatment with antifungal agents were continued in these cases, cryptococci could still be observed for 5 weeks and 60 weeks on the filter preparations of Cases 1 and 2, respectively, after the CSF cultures became negative. The cryptococcal antigen could also be detected in the CSF during the positive filter preparations in these cases. At autopsy in Case 2, patchy lepromeningeal inflammatory lesions with the characteristic capsules of cryptococci were observed in the subarachnoid space. These observations suggest that cryptococci, which persisted in the CSF despite the negative cultures, were responsible for the lesions in the subarachnoid space and protracted clinical course in the two cases of cryptococcal meningitis.

Aged↗
PubMed2000

Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent.

Recent studies indicate an expression of mitogen-inducible cyclooxygenase (COX-2) in gastric mucosa. Rebamipide, a mucoprotective agent enhances prostaglandin (PG) synthesis. The present study was designed to clarify the mechanism for rebamipide-induced mucosal protection. Male Sprague-Dawley rats were administered 5, 15, or 50 mg/kg/day rebamipide for 14 days. The expression of constitutive cyclooxygenase (COX-1) and COX-2 in gastric mucosa was determined using Western blot analysis. Another series of rats was used to examine 1) the levels of PGE(2) in stomach with and without pretreatment with a COX-2 inhibitor; 2) the protective action of rebamipide against gastric damage caused by 0.6 N HCl; and 3) the effects of a COX-2 inhibitor on rebamipide-induced gastric mucosal protection. COX-2 expression was enhanced, whereas COX-1 expression did not change significantly in the gastric mucosa of rats after treatment with rebamipide. The gastric mucosal PGE(2) was higher in the rebamipide groups than in the vehicle-treated group. Rebamipide also suppressed gastric damage induced by HCl in a dose-dependent manner. A COX-2 inhibitor blocked the rebamipide-induced increase in mucosal PGE(2), and mucosal protection induced by rebamipide. The results indicate that rebamipide induces COX-2 expression, increases PGE(2) levels, and enhances gastric mucosal defense in a COX-2-dependent manner. Thus, COX-2 has an important role in the effects of rebamipide on gastric mucosal protection.

Alanine↗
PubMed2000

[A case of NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) with a T-to-C point mutation at nt 8993 of mitochondrial DNA].

We report a case of NARP with a T-to-C point mutation at nt 8993 of mitochondrial DNA. A 37-year old man with mild mental retardation, retinitis pigmentosa, and clonic-tonic seizure was admitted to our hospital. The neurological examination revealed scanning speech, dystonic neck turning to the left side, and pyramidal tract signs. Serum-, CSF-lactate and pyruvate level were slightly elevated. Brain MRI findings showed cerebral atrophy, cerebellar cortical atrophy accompanied with dilation of forth ventricle, and high intensity lesions in the bilateral lenticular nuclei on T2 weighted images. Nucleotide sequence analysis of the mitochondrial DNA in the leukocytes demonstrated a T-to-C point mutation at nt 8993. To our knowledge, this is the first report of a Japanese patient with NARP associated with the T-to-C mutation at nt 8993 of mt DNA. Mitochondrial DNA analysis should be considered in the differential diagnosis of patients with retinitis pigmentosa and various neurological signs.

Adult↗
PubMed2000

[A patient with motor neuron syndrome clinically similar to amyotrophic lateral sclerosis, presenting spontaneous recovery].

We report a patient with motor neuron syndrome similar to amyotrophic lateral sclerosis (ALS) and with spontaneous recovery. At the age 40, the woman developed progressive muscular weakness, atrophy and fasciculation in extremities. She also noted a dyspnea, tongue atrophy and dysphagia. A neurological examination 6 months after onset revealed i) a tongue atrophy and fasciculation, ii) diffuse muscule weakness and atrophy in face, neck and extremities, and iii) marked hyperreflexia in the four limbs and bilateral Babinski reflex, but iv) neither sensory disturbance nor ophthalmoplegia. Electromyogram (EMG) detected such denervation potentials as fibrillation potentials, fasciculation potentials, positive sharp waves and polyphasic or giant MUPs diffusely in the limb muscles. Peripheral nerve conduction study detected neither conduction block nor delay. Thus, she was diagnosed as suffering from ALS. However, since approximate 1 year after onset, her muscle weakness has gradually been getting better. Simultaneously, the dyspnea and dysphagia gradually improved. Two years after onset, an EMG examination detected chronic denervation potentials in the left musculus sternocleidomastoideus and a few on-going denervation potentials in the left musculus extensor carpi radialis, but no denervation potentials in other limb muscles. Fasciculation potentials were found in tongue muscles. Thus, the present case was thought to have a reversible motor neuron syndrome clinically quite similar to ALS. A mild increase in IgE (346 U/ml) and a low-titer IgM-class anti-GM1 antibody were found in her serum though its pathological significance was uncertain. Any immunological aberrance may account for the pathogenesis. It should be noted that clinically diagnosed cases of ALS may rarely recover spontaneously.

Adult↗
PubMed2000

[Dentatorubral-pallidoluysian atrophy (DRPLA)--discovery of the disease, DRPLA gene and the pathophysiology].

The clinical entity of dentatorubral-pallidoluysian atrophy (DRPLA) was discovered and established in Japan. The characteristic clinical genetic features of DRPLA including prominent anticipation prompted us to search the genes carrying CAG repeats as the candidate genes for DRPLA. Based on this approach, the DRPLA gene was discovered by two independent Japanese groups in 1994. Given that DRPLA is caused by expansion of CAG repeats, the molecular mechanisms of the anticipation and the broad clinical presentations of DRPLA depending on the age at onset are clearly understood as a function of the size and the instability of the CAG repeats. Recent studies have suggested that mutant proteins with expanded polyglutamine stretches have "gain-of-toxic" functions to neuronal cells. The molecular mechanisms of the "toxic" functions, however, have not been identified. Based on the recent findings that nuclear transport of the mutant proteins carrying expanded polyglutamine stretches is important in the pathogenesis, we screened nuclear proteins which bind to expanded polyglutamine stretches. We found that expanded polyglutamine stretches bind to TAFII130, a TATA-binding protein-associated factor, and interfere with CREB-dependent transcriptional activation. Since CREB-dependent transcriptional activation plays essential roles in neuronal survival and plasticity, such interference is expected to lead to neuronal dysfunction.

Animals↗
PubMed2000

[Studies on procedure for sample preparation of ellagic acid in several kinds of foodstuffs].

A sample preparation for ellagic acid in several kinds of foodstuffs, which is included in the List of Existing Food Additives as natural antioxidants in Japan, functioning as an antioxidant, was studied. The solid samples were refluxed with methanol, and then the extract was refined using a solid-phase cartridge. The liquid samples were directly pretreated by solid-phase extraction. On the other hand, test solutions for cooking oils and fats were inapplicable to solid-phase extraction in this work, because the recovery tests from samples spiked with ellagic acid gave low recoveries. Consequently, they were prepared by modified frozen method using methanol or acetonitrile-2-propanol-ethanol (2:1:1). The recoveries from tested foodstuffs spiked with ellagic acid (50 micrograms/g) were 75.2-96.9%. The limits of quantification for ellagic acid were 0.05 microgram/g by the proposed method.

Antioxidants↗