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Biomedical subjects

Y Ando

Publications and source records attributed to Y Ando.

At least 199 records · Page 11Linked to original sources
PubMed1998

Histochemical detection of 4-hydroxynonenal protein in Alzheimer amyloid.

The presence of lipid peroxidation product in amyloid deposits from seven patients with Alzheimer disease and nine with non-Alzheimer disease was examined immunohistochemically by means of an affinity purified anti-HNE antibody to hydroxynonenal (HNE), a marker of lipid peroxidation. A positive reaction was found in amyloid deposits in all the specimens examined: most of the perivascular areas (89%) where amyloid deposition was confirmed by Congo red staining, showed immunoreactivity with the antibody in the specimens of Alzheimer disease. Twenty-one percent of senile plaques which were also stained by Congo red staining reacted with this antibody. Several perivascular cells were also stained by anti-HNE antibody. In other neurons both in Alzheimer and non-Alzheimer disease patients, only a few percent reacted with this antibody and no statistical difference was observed between them. These results verify that lipid peroxidation via free radical injury occurs in amyloid deposits in Alzheimer amyloid. Since HNE has been identified as a cytotoxic metabolite of free radical injury, amyloid deposits in the tissue may exhibit a toxic effect during the generation process of HNE.

Aged↗
PubMed1998

New system for linear accelerator radiosurgery with a gantry-mounted video camera.

PURPOSE: We developed a positioning method that does not depend on the positioning mechanism originally annexed to the linac and investigated the positioning errors of the system. METHODS AND MATERIALS: A small video camera was placed at a location optically identical to the linac x-ray source. A target pointer comprising a convex lens and bull's eye was attached to the arc of the Leksell stereotactic system so that the lens would form a virtual image of the bull's eye (virtual target) at the position of the center of the arc. The linac gantry and target pointer were placed at the side and top to adjust the arc center to the isocenter by referring the virtual target. Coincidence of the target and the isocenter could be confirmed in any combination of the couch and gantry rotation. In order to evaluate the accuracy of the positioning, a tungsten ball was attached to the stereotactic frame as a simulated target, which was repeatedly localized and repositioned to estimate the magnitude of the error. The center of the circular field defined by the collimator was marked on the film. RESULTS: The differences between the marked centers of the circular field and the centers of the shadow of the simulated target were less than 0.3 mm.

Computer Terminals↗
PubMed1998

Visceral orthostatic hypotension in patients with severe autonomic dysfunction.

Although changes in the blood flow of the cerebral vessels and the peripheral vessels in the extremities after changing body postures have been well examined in patients with orthostatic hypotension (OH), such changes in visceral vessels have not been well investigated. To elucidate the effect of autonomic dysfunctions on changes in the abdominal blood flow, the blood flow velocity of the portal vein was measured by Doppler ultrasonography in 11 patients with familial amyloidotic polyneuropathy (FAP) (Met30), 3 with pandysautonomia, 1 with Shy-Drager syndrome, and 10 healthy controls, in the supine and at the upright position. Among the 15 patients with the above-mentioned autonomic disorders, 5 of the patients showed a marked decrease in blood flow after standing, and one of these 5 patients exhibited transient hepatic and intestinal ischemia during intensive rehabilitation because of a severe decrease in visceral blood flow. Another 7 patients exhibited moderate decreases in the blood flow after standing. In contrast, no such change was observed in the 10 healthy controls. The FAP patients with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) administration showed no significant correlation between the degree of OH and the decrease in the blood flow of the portal vein, and the patients without the drug exhibited a weak correlation. On the contrary, the pandysautonomia and Shy-Drager syndrome patients exhibited a linear positive correlation. These results suggest that FAP is a disease for which this kind of ultrasonographic examination should be applied, and that Doppler ultrasonography may be a helpful tool to evaluate visceral OH.

Adult↗
PubMed1998

Liver transplantation in familial amyloidotic polyneuropathy (FAP). A comparative study of transplanted and non-transplanted patient's survival.

The purpose of the present study was to evaluate the impact of liver transplantation on familial amyloidotic polyneuropathy (FAP met-30) patients' survival. Forty-five FAP patients were involved in the study; 15 non-transplanted FAP patients and 30 liver-transplanted patients. All patients' records were scrutinised for information on disease duration. Preoperative nutritional status was evaluated in all patients. No difference in survival was observed for transplanted patients overall compared to historical controls. However, for cases in good nutritional status, an increased survival can be expected as a significantly increased mortality rate for malnourished patients was observed (P < 0.05). Increased survival has so far not been found for transplanted FAP patients. However, none of the transplanted cases has yet reached the expected survival time for nontransplanted FAP control patients. which is 14 years. A high fatality rate of malnourished patients transplanted late in the course of the disease contributed significantly to the mortality among transplanted patients.

Adult↗
PubMed1998

Preclinical approach for identifying drug interactions.

Pharmacokinetic drug interactions may be divided into two categories: induction and inhibition of enzymes involved in the metabolism of a drug. The induction and inhibition of such enzymes result in decreases or increases in the blood concentrations of the drug, causing drug effects to be altered. Cytochrome P450 (P450 or CYP) is an enzyme responsible for the metabolism of a wide variety of drugs, including some anticancer agents. If a drug with a high affinity to bind to a specific form of P450 is given to a patient in combination with other drugs mainly metabolized by this enzyme, the former may potentiate the pharmacological actions of the latter by preventing their metabolism and thus increasing their serum concentration. Alternatively, if a drug inhibits or inactivates essentially all forms of P450 nonspecifically, it may be possible that the pharmacological effects of other drugs used in combination with it will be enhanced. CYP3A4 is one of the major forms of P450 in human liver microsomes. In previous studies using human liver microsomes, docetaxel was determined to be metabolized mainly by this isozyme. Thus it was assumed that inducers and inhibitors of CYP3A4 might affect the pharmacokinetics of docetaxel. In our studies, administration of dexamethasone, a known inducer of CYP3A, to mice resulted in decreases in serum docetaxel concentrations. In contrast, ketoconazole, an inhibitor of CYP3A, is assumed to increase the serum and hepatic concentrations of docetaxel. As an example of a drug which might inhibit the metabolism of other drugs, we found that bis-aceto-ammine-dichloro-cyclohexylamine platinum(IV) (JM216), which is currently being developed as a potential anticancer agent, inhibits essentially all major forms of P450 present in human liver microsomes. Since its inhibition potency is relatively high, careful assessment of the effects of this drug on the metabolism of other drugs appears to be necessary.

Animals↗
PubMed1998

Familial amyloidotic polyneuropathy type I with extracellular superoxide dismutase mutation: a case report.

We report an autopsy case of familial amyloidotic polyneuropathy (FAP) Type I with mutations in both transthyretin (TTR) and extracellular superoxide dismutase (EC-SOD). This patient started to develop peripheral neuropathy at age 25, followed by cardiac, renal, and autonomic nervous system failure due to massive amyloid deposition. Thirteen years after the initial symptoms, he died of septic shock. Autopsy revealed suppurative peritonitis, multiple abscesses in the bile ducts and urinary tract, and more marked amyloid deposition than commonly seen in FAP. Amyloid deposition occurred in various organs and tissues, especially prominently around blood vessels and in interstitial tissues, and was demonstrated immunohistochemically to be composed of TTR but not amyloid A (AA) and not amyloid L (AL) proteins. The serum EC-SOD content of the patient was 10 fold higher than those seen often in other FAP patients and in healthy controls. Genetic analysis demonstrated the single amino acid substitutions in Val30Met TIR and Arg213Gly EC-SOD. Since these data suggest the dissociation of EC-SOD from the vascular wall, massive amyloid deposition in the present case may be related to increased oxidative stress in loco.

Adult↗
PubMed1998

Comparison of the effects of hydrogen peroxide, 4-hydroxy-2-nonenal and beta-amyloid (25-35) upon calcium signalling.

The neurotoxic beta-amyloid (Abeta) peptide fragment Abeta(25-35) has been suggested to exert its deleterious effects on cells via production of hydrogen peroxide. In human platelets and in the presence of DMSO to prevent production of hydroxyl radicals from hydrogen peroxide, both Abeta(25-35) and hydrogen peroxide were found to increase intracellular calcium levels. Hydrogen peroxide in addition reduced the calcium response to thrombin, whereas this was not seen with Abeta(25-35). A similar pattern of effects to those seen with hydrogen peroxide were also seen with the neurotoxic aldehyde lipid peroxidation product 4-hydroxy-2-nonenal (HNE). The initial increase in calcium produced by hydrogen peroxide was not affected by EGTA, but was partially prevented by dithiothreitol. The calcium response to Abeta(25-35) [which was also seen with Abeta(1-40) and Abeta(1-42) but not with the inactive peptide Abeta(40-1)] consisted of an EGTA-sensitive and an EGTA-resistant component, of which the latter was also sensitive to DTT. Hydrogen peroxide increased basal phosphoinositide breakdown in rat brain miniprisms and decreased the responses to noradrenaline, carbachol and veratrine. The specific binding of [3H]inositol-1,4,5-trisphosphate ([3H]Ins(1,4,5)P3) to its receptor recognition site in human platelet membranes was increased by Abeta(25-35) but remained unchanged following hydrogen peroxide treatment. It is concluded that under conditions where production of hydroxyl radicals from hydrogen peroxide is blocked, hydrogen peroxide and Abeta(25-35) produce their effects on calcium by affecting the mobilisation of intracellular calcium. The qualitative differences in the calcium responses of these two agents can be explained (a) by an additional effect of Abeta(25-35) upon calcium entry and (b) by differences in their effects upon the Ins(1,4,5)P3 receptor.

Aldehydes↗
PubMed1998

Taurin-conjugated ursodeoxycholic acid has a reversible inhibitory effect on human keratinocyte growth.

Tauroursodeoxycholic acid (TUDC) is one of the most hydrophilic taurin conjugated bile acids. TUDC has a suppressive effect on DNA synthesis in primary cultured rat hepatocytes. In this study, we investigated the growth inhibitory effect of TUDC on cultured human keratinocytes. TUDC suppressed the proliferation of keratinocytes in a dose dependent fashion, as measured by both cell counts and 5-bromo-2'-deoxyuridine (BrdU) uptake. Keratinocytes reproliferated and reached almost the same cell number as control after removal of TUDC from the medium. TUDC (1 mM) had no effect on the cell viability, as measured by the dye exclusion test. Epidermal sheets stratified in the presence of TUDC appeared thinner than those stratified without TUDC. These results suggest that TUDC has a reversible growth suppressive effect on human keratinocytes through the mechanism other than cytotoxicity and would be applicable for the treatment of hyperproliferative skin disorders such as psoriasis.

Animals↗
PubMed1998

MERIT-9: a patient information exchange guideline using MML, HL7 and DICOM.

To realize clinical data exchange between healthcare providers, there must be many standards in many layers. Terms and codes should be standardized, syntax to wrap the data must be mutually parsable, then transfer protocol or exchange media should be agreed. Among many standards for the syntax, HL7 and DICOM are most successful. However, everything could not be handled by HL7 solely. DICOM is good for radiology images, but, other clinical images are already handled by other 'lighter' data formats like JPEG, TIFF. So, it is not realistic to use only one standard for every area of clinical information. For description of medical records, especially for narrative information, an standard generalized mark-up language, document type definition (SGML DTD) for medical information, called MML (medical markup language) had been created in Japan. It is already implemented in more than ten healthcare providers. However, it is again not realistic to use MML solely for clinical information in various level of detail. Therefore, we proposed a guideline for use of available medical standards to facilitate clinical information exchange between healthcare providers. It is called MERIT-9 (Medical Records, Images, Texts, -Information Exchange). A typical use is HL7 messages, DICOM files, referred from an MML file in a patient record, as external entities. Both MML and MERIT-9 have been research projects of Japanese Ministry of Health and Welfare and the purpose is to facilitate clinical data exchanges. They are becoming to be used in technical specifications for new hospital information systems in Japan.

Community Networks↗
PubMed1998

UGT1A1 genotypes and glucuronidation of SN-38, the active metabolite of irinotecan.

BACKGROUND: Irinotecan (CPT-11) is metabolized by esterase to form a SN-38, which is further conjugated by UGT1A1. Genetic polymorphism has been shown in a promoter region of UGT1A1 and is related to its activity. We investigated whether there might be an inter-individual difference in pharmacokinetics of SN-38 and its glucuronide, depending on the genotypes of UGT1A1. PATIENTS AND METHODS: Nine male patients with lung cancer were treated with irinotecan (50 mg/m2) and carboplatin. Pharmacokinetic parameters were calculated with full sampling plasma data. Genotypes were determined by analyzing the sequence of TATA box of UGT1A1 of genomic DNA from the patients. RESULTS: The genotyping analysis revealed one heterozygote (6/7) and one homozygote (7/7) for (TA)7TAA allele (UGT1A1*28). The remaining seven patients were homozygote for (TA)6TAA allele (6/6, wild type). The metabolic ratios (SN-38/SN-38 glucuronide) in the patient with 7/7 genotype were uncharacteristically higher than those in the patients with other genotypes (6/6 and 6/7). Biliary index was 6980 versus 2180 +/- 1110 (range 840-3730) in patients with 7/7 versus 6/6 genotypes, respectively. CONCLUSION: These results support the idea that the patient with 7/7 genotype has an impaired capacity for glucuronidation of SN-38.

Aged↗
PubMed1998

Potent and non-specific inhibition of cytochrome P450 by JM216, a new oral platinum agent.

Bis-acetato-ammine-dichloro-cyclohexylamine-platinum (IV), JM216, is the first antineoplastic platinum compound that can be given to patients orally. Several phase II clinical trials of JM216 monotherapy have already been reported. However, no information on the potential drug interactions caused by JM216 is available. In this study, the capacity of JM216 to inhibit cytochrome P450 (CYP) in human liver microsomes was investigated by measuring the inhibition potential (IC50 and Ki) on prototype reactions. Specific substrates of CYP included testosterone (catalysed by CYP3A4), paclitaxel (CYP2C8), 7-ethoxyresorufin (CYP1A1, CYP1A2), coumarin (CYP2A6), aniline (CYP2E1) and (+/-)-bufuralol (CYP2D6). JM216 inhibited the catalytic activities of CYP isozymes. The IC50 values were between 0.3 microM and 10 microM, indicating strong and non-specific inhibitory effects of JM216. The inhibition occurred in a non-competitive manner, and the Ki value was 1.0 and 0.9 microM for metabolite formation of testosterone and paclitaxel respectively. Therefore, some in vivo studies should be conducted to determine whether or not there is a correlation between in vivo and in vitro results.

Antineoplastic Agents↗