Biomedical subjects
Publications and source records attributed to S Tsuji.
The authors report on four DRPLA patients who manifested delusions. All patients demonstrated autosomal dominant DRPLA confirmed by standard gene analysis. Patients with DRPLA can exhibit a variety of psychiatric symptoms in addition to extrapyramidal and cerebellar symptoms.
The present study was undertaken to determine the possible deleterious role played by poly(adenosine diphosphate-ribose) synthetase (PARS) in cochlear ischemia-reperfusion injury. Transient ischemia of the cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by pressing the labyrinthine artery at the porus acusticus internus. The animals were given intravenous 3-aminobenzamide (a PARS inhibitor) or physiological saline solution I minute before the onset of reperfusion. The compound action potential thresholds were measured before the onset of ischemia and 4 hours after the onset of reperfusion. A statistically significant reduction in the postischemic compound action potential threshold shift was observed in the animals treated with 3-aminobenzamide after 15 or 30 minutes of ischemia, whereas no statistical difference was found after 60 minutes of ischemia. These results suggest that excessive activation of PARS exerts deleterious effects on the cochlear injury induced by transient ischemia.
The level of understanding of taking medicine was examined at the start and the end of medicine-taking guidance, based on the estimation by pharmacists and inpatients. Six items for the estimation, such as "the way of taking medicines" were evaluated using a five-grade system. The significant improvement was observed in all items, suggesting that inpatients' understanding is improved by the guidance. A markedly positive correlation was found between the estimation by inpatients and that by pharmacists (p < 0.001). This confirms the appropriateness of estimation by pharmacists. Inpatients whose estimation was significantly different from that by pharmacists (difference of two grades or more) were examined to identify clear and potential problems with taking medicine. The problems were classified into such seven categories as "types of medicine". For each item with differences in estimation (two grades or more), problems were biased in some specific categories. On the basis of such a bias, a flow chart was prepared to clarify problems. In addition, a standard pharmaceutical management and guidance services program was drafted, in which measures in observation, treatment and education against problems by pharmacists were described according to the frequency of occurrence. Information about the program available on the Internet enables its use by other hospitals.
Modification of HPLC conditions for the determinations of raw materials, intermediates and subsidiary colors (organic impurities) in 5 kinds of food azo colors were studied in order to analyze them simply and rapidly. The organic impurities were determined by HPLC using L-column ODS and a gradient system (0.02 mol/L ammonium acetate solution for 10 min, and a gradient with a mixture of acetonitrile and water (7:3)). The organic impurities in 163 samples of azo colors subjected to inspection in fiscal year 1999 were determined under the proposed HPLC conditions. It was found that the contents of organic impurities in 163 samples were less than the limit of Japan's Specifications and Standards for Food Additives, 7th Edition.
One of eight Food Blue No. 1 aluminum lakes (B-1Als) used in the official inspection of coal-tar colors in fiscal year 1999 had a violet sub-spot during paper chromatography and was rejected. To clarify the orgin of the sub-spot, the violet subsidiary color (Sub-V) was isolated from the sample. On the basis of NMR and MS analyses and ion chromatography, the structure of the subsidiary color was elucidated to be 2-[[4-[N-ethyl-N-(3- sulfophenylmethyl)amino]phenyl][4-hydroxyphenyl]methylio]benzenesulfonic acid. The relative content of Sub-V to that of m,m-B-1 in the rejected sample was determined to be 39.5% by HPLC. The relative contents in other submitted samples of B-1Al were in the range of 1.1-3.6%.
The HPLC determination of organic impurities in Food Red No. 40 aluminum lakes (R-40Als) as directed by Japan's Specifications and Standards for Food Additives, 7th Ed. (JSFA-VII), has problems, such as reproducibility and low recovery. ICP analyses suggested that the problem was caused by the aluminum in the test solution. In the improved method for preparation of the test solution, aluminum was precipitated as a hydroxide gel by boiling with 1% aqueous ammonia. After centrifugation, the supernatant was used for the HPLC analysis of the organic impurities in the lakes. Recoveries of organic impurities were more than 85% from R-40Al spiked at the 0.1 and 1.0% levels of R-40. The proposed method was also adapted for Food Yellow No. 5 aluminum lakes.
In Japan, The new triple therapy was opened for Helicobacter pylori (HP) eradication from Nov. 1, 2000. The Japanese Society for Helicobacter Research presented a guideline for HP eradication. It recommended that HP infection should be checked at least 4 weeks after the treatment for peptic ulcer and HP infection using HPIgG antibody, rapid urease test, urea breath test, histology and/or culture. However, it did not state the best way and suitable timing to check HP infection after the eradication therapy. In this study, we investigated the accuracy of PyloriTek test(a 1-h rapid urease test) and tried to establish the suitable timing for checking HP infection after eradication therapy. In conclusion, when patients are examined more than 4 months after eradication therapy, the use of PyloriTek alone may be sufficient for correctly diagnosing HP infection.
The present paper reviews current concepts on the role of cyclooxygenase (COX) in the development of malignant tumors. An inducible isoform of cyclooxygenase is expressed in neoplastic, pre-neoplastic, and peri-neoplastic cells by mutation of oncogenes (such as ras), tumor promoters, mitogens, cytokines, their receptors, and pathogenic factors such as Helicobacter. Cells overexpressing cox-2 escape apoptosis, have abnormal cell-to-cell interactions, and acquire invasive phenotypes. On the other hand, angiogenesis plays a key role in the development of malignant tumors. Both in vitro and in vivo studies indicate that cox-2 overexpression upregulates angiogenic factors in neoplastic cells and promotes tumor angiogenesis. It is also possible that cox-2 expression upregulates angiogenic factors in peri-neoplastic cells that express the isozyme. Interestingly, cox-1, the other isozyme that is expressed in tumor vascular endothelia, participates in tumor angiogenesis, because an anti-sense oligonucleotide of cox-1 suppresses in vitro angiogenesis induced by cox-2-overexpressing cells. A non-specific COX inhibitor, not a specific COX-2 inhibitor, reduced growth and angiogenesis in cancer xenografts by inhibition of COX-1 in vascular endothelial cells, even when the tumor did not express COX-2. These results demonstrate that COX inhibitors suppress angiogenesis and tumor growth by inhibiting expression of angiogenic factors and vascular endothelial cell migration. Furthermore, another concept is emerging to indicate that prostaglandins (COX-2 products and mediators of classic inflammation) suppress host immunity against tumors. This evidence supports the hypothesis that COX is an important perigenetic factor in the development of cancer growth, and offers a new strategy against cancer using COX inhibitors (nonsteroidal anti-inflammatory drugs).
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At least nine neurodegenerative diseases are known to be caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches have been suggested, the molecular mechanisms of neurodegeneration remain unclear. We demonstrated that the nuclear translocation of mutant proteins containing expanded polyQ stretches is a prerequisite for the expression of their cytotoxicity. Hypothesizing that nuclear proteins that interact with mutant proteins, particularly, those that bind to the expanded polyQ stretches, are involved in the pathogenetic mechanisms underlying neurodegeneration, we screened nuclear proteins for their capability of binding to expanded polyQ stretches. We found that expanded polyQ stretches preferentially bind to TAF[symbol: see text]130, a coactivator involved in CREB-dependent transcriptional activation. The binding of TAF[symbol: see text]130 with expanded polyQ stretches strongly suppress CREB-dependent transcriptional activation, suggesting that interference with transcription due to the binding of expanded polyQ stretches with TAF[symbol: see text]130 and redistribution of TAF[symbol: see text]130 are involved in the pathogenetic mechanisms underlying neurodegeneration.
We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.
Activation of the innate immune system is a prerequisite for the maturation of dendritic cells (DC) and macrophages (Mphi) followed by clonal expansion of the lymphocytes, targeting cells expressing "non-self' antigens. Microbes usually have a component competent to activate DC/Mphi for antigen presentation. This component has been called adjuvant, but recently renamed "pathogen-associated molecular pattern" (PAMP) or modulin based on its molecular identification. Here, we propose the hypothesis that DC/Mphi express two sorts of receptors for PAMP, whose signaling pathways lead to a sufficient antigen (Ag)-presenting state. In bacterial infection, a Toll-like receptor (TLR) and an uptake receptor participate in DC maturation and Mphi activation. Likewise, with a number of viruses, two of the receptors, with short consensus repeats (SCR), immunoglobulin-like domains or chemokine receptor-like motifs etc. induce functional modulation of DC/Mphi. In immune therapy for cancer, primary activation of the innate system would be essential for tumor Ag-specific T cell augmentation. Cancer cells express tumor-associated Ag but barely co-express PAMP, which situation does not allow for the activation of innate immune responses. Supplementing tumor-associated Ag with PAMP may be an effective therapy for patients with cancer. Here, we discuss the possibility of an innate immune therapy for cancer with reference to bacillus Culmet Guillen cell-wall skeleton (BCG-CWS).
PURPOSE: METH-1/hADAMTS-1 and METH-2/hADAMTS-8 are recently identified genes that inhibit angiogenesis, and the murine homologue, ADAMTS-1, shows metalloproteinase function. Because the significance of METH-1 and METH-2 has not been determined in solid tumors, we examined the mRNA expressions of these molecules in pancreatic cancer and hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: METH-1 and METH-2 mRNA expressions were identified in six pancreatic cancer cell lines and were quantified by TaqMan reverse transcription-PCR in 18 paired samples of pancreatic cancer and surrounding noncancerous pancreas, and in 14 samples of pancreatic cancer. METH-1 mRNA expression was also examined in 16 pairs of HCC and cirrhotic liver. Vascularity was estimated by CD34 staining. The correlation between clinicopathological factors and METH-1 expression was additionally analyzed. RESULTS: Four of six pancreatic cancer cell lines expressed METH-1, and 1/6 expressed METH-2. METH-1 was substantially expressed in both pancreatic cancer and noncancerous pancreas, but METH-2 was not. METH-1 expression in pancreatic cancer tissue was significantly lower than that in noncancerous pancreas (P = 0.002), and a similar result was obtained between HCC and cirrhotic liver (P = 0.003). METH-1 expression did not show a significant correlation with vascularity in pancreatic cancer or in HCC. However, pancreatic cancer with higher expression of METH-1 showed significantly severe lymph node metastasis or retroperitoneal invasion (P = 0.033 and P = 0.018, respectively) and worse prognosis (P = 0.038). CONCLUSIONS: METH-1, which was initially reported to have a potent antiangiogenic effect, does not seem to be a predominant determinant of tumor vascularity in pancreatic cancer. Rather, METH-1 seems to be involved in progression of pancreatic cancer through local invasion and lymph node metastasis.
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There were 176 official inspections of tar colors and their lakes in fiscal year 2000, and 175 samples were qualified. The quantity of tar colors that passed inspection in Japan in fiscal year 2000 reached 137.5 tons. Tar color production is estimated by month and by manufacturer. The food tar color produced in the largest quantity was Food Yellow No. 4, accounting for 43.4% during this period.
One out of two sunset yellow FCF aluminum lakes (Y-5Als) did not comply with the specifications in JSFA-VII in the official inspection of tar colors in fiscal year 2000. A sub-spot was detected in the paper chromatography test. This rejected sample was analyzed by HPLC for the subsidiary color, raw materials and intermEdiates in Y-5. The sub-spot was identified as sulfanilic acid azo R salt color, and its content was estimated at 4.5% as the content of Y-5 in Y-5Al being 100.0%.
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by various combinations of cerebellar ataxia, choreoathetosis, myoclonus, epilepsy, dementia and psychiatric symptoms. With the discovery of the gene for DRPLA in 1994, molecular mechanisms of neurodegeneration has been intensively investigated. Expression of truncated DRPLA proteins in cultured cell has been shown to result in aggregate body formation and apoptosis. We have developed transgenic mice for DRPLA (Q129 mice). The Q129 mice showed a severe neurological phenotype characterized by ataxia, myoclonus and seizures. Although numerous neuronal intranuclear inclusions (NIIs) were observed in the brain, obvious neuronal loss was not observed. NIIs, however, appeared much later than the phenotypic presentations, and intranuclear accumulation (diffuse nuclear staining) of mutant proteins was the earliest phenomenon. These results suggest that "neuronal dysfunction", but not "neuronal cell death", is responsible for the phenotypes. Hypothesizing that nuclear proteins interacting with expanded polyglutamine stretches are involved in the pathogenesis, we found that that expanded polyglutamine stretches preferentially bind to TAF130, a cofactor involved in CREB-dependent transcriptional activation, and strongly suppressed CREB-dependent transcriptional activation. Taken together, these findings suggest that the interference of CREB-dependent transcription by expanded polyglutamine stretches is involved in the neuronal dysfunction in polyglutamine diseases.
Status epilepticus (SE) is a condition requiring emergency care. There are convulsive SE, non-convulsive SE including complex partial status and absence status, non-convulsive electric SE and pseudostatus epilepticus, although convulsive SE is the most common. Diagnosis of status epilepticus of complex partial seizures (CPS) and absence seizures was significantly delayed because delays in seeking medical attention were common. The seizures were generalized convulsive SE in 84% and CPS status in 16%, and the overall mortality rate was 15% in 41 SE patients of our study. EEG monitoring is important to make or exclude the diagnosis of SE. Diazepam is the first choice medication and effective in the management of SE, and lately, lorazepam, midazolam, propofol and pentobarbital etc as emergency therapy. Phenytoin is also considered first-line agent in the emergency management of SE. Repetitive transcranial magnetic stimulation (rTMS) led to a prolonged latency for seizure induction after an intraperitoneal injection of pentylenetetrazol (PTZ) and effectively prevented the development of status epilepticus of PTZ-induced convulsions in the rats. Our data suggest that rTMS has suppressive effects on the neuronal excitability in rats. These effects are anticonvulsive and suggest the possibility of therapeutic use of rTMS in the patients with refractory seizures.