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Biomedical subjects

M Ueda

Publications and source records attributed to M Ueda.

At least 523 records · Page 29Linked to original sources
PubMed1997

Effect of chronic administration of alcoholic beverages and seasoning containing alcohol on hepatic ethanol metabolism in mice.

Five-week-old male mice, C3H/HeNCrj (C3H/He), were given a 5% (v/v) ethanol solution, commercial alcoholic beverages (Japanese sake (sake) or red wine) or a Japanese seasoning (mirin [containing ethanol and a large amount of glucose]) ad libitum for 45 d, and were then examined for changes in the hepatic enzymes related to ethanol metabolism 2 h after oral administration of 5 g of ethanol/kg body weight. The specific activity of aniline hydroxylase (ANH) in the hepatic microsome increased significantly in all groups chronically administered ethanol solution, sake, red wine or mirin, and the greatest increase was in the hepatic microsome of mirin-administered mice. The cytochrome P-450 (CYP) 2E1 increased in the hepatic microsome of the mice administered ethanol solution, red wine or mirin where accompanied by high ANH activity. The immunoreactive band for CYP1A1 showed high specificity in the microsome of mice given sake, red wine or mirin. It was assumed that CYP1A1 was induced by unknown component(s) other than ethanol in these solutions. In the cytosolic fraction, following the chronic administration of sake and mirin, the total aldehyde dehydrogenase (A1DH) activity with high-Km decreased significantly. In the mitochondrial fraction, the activity of high-Km A1DH increased significantly in the mirin-administered mice which drank a large amount of ethanol, whereas that in the red wine-administered group tended to decrease. These results indicate that the enzyme activities related to the oxidation of both ethanol and acetaldehyde in the cytosolic, mitochondrial and microsomal fractions of the liver were affected by either the action of ethanol or its interaction with other constituents of sake, red wine and mirin.

Alcohol Dehydrogenase↗
PubMed1997

Activation of the erythropoietin promoter by a point mutation from GATA to TATA in the -30 region.

We show here a role of the highly conserved GATA motif in the -30 region of the erythropoietin (Epo) promoter. Epo production is reduced in normoxia and activated in hypoxia to control the oxygen supply through erythropoiesis. Although the hypoxic inducibility has been analyzed, the molecular mechanism for the low basal activity in normoxia remained unclear. The GATA motif in the -30 region upstream of the transcription initiation site is highly conserved among the species. In many genes, the consensus motif in the -30 region is TATA. The GATA motif of the Epo promoter was mutated to TATA. The transcriptional activity of the mutant was enhanced even in normoxia. Binding assays showed that TATA-binding protein (TBP) could weakly bind to the wild-type GATA motif whereas TBP bound to the mutant TATA motif with high affinity. These results indicate that the highly conserved GATA motif in the -30 region of the Epo promoter can avoid binding and activation by TBP. This evidence is considered to be the molecular basis for the low physiological expression from the Epo promoter in normoxia.

Animals↗
PubMed1997

[Abnormally distributed regional cerebral blood flow in brain malformations detected by single photon emission computed tomography].

Brain malformations are rare congenital anomalies caused by neuronal migration disorders or cerebral tissue destruction during gestation. And epileptic disorders and psychomotor retardation are sometimes induced by them. Previous understanding of these anomalies was derived from pathologic studies after autopsy. The recent advancement of neuroimaging techniques, such as magnetic resonance imaging (MRI), has allowed us to achieve a high diagnostic capability of these malformations. These abnormalities have been more widely recognized morphologically. However, cerebral function in these cases has been rarely described. To evaluate the cerebral functional state in these anomalies, 123I-N-isopropyl-p-iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) was performed in 3 cases with brain malformations and 22 normal controls. Several regions of interest (ROI) in the cortex were determined, and the radioactivity at each ROI was counted. The regional cerebral blood flow (rCBF) distribution was evaluated semiquantitatively by calculating the cortico-cerebellar ratios at each ROI. A 23-year-old female with schizencephaly (Case-1) and a 21-year-old male (Case-2) with polymicrogyria showed increased rCBF in their abnormal cortices. And a 39-year-old male with porencephaly (Case-3) demonstrated severely decreased rCBF in his abnormal cortex with gliosis which was considered to be a result from a secondarily disturbed neuronal migration after tissue destruction during gestation. Furthermore, abnormal rCBF distribution was observed in their morphologically normal cortices in addition to their abnormal cortices compared to normal controls. Case-2 showed decreased cerebral perfusion in the morphologically normal cortex around his abnormal cortex with increased rCBF, suggesting surrounding suppression associated with epileptic foci. In contrast, the lesions with decreased rCBF in Case-1 were not around the abnormal cortices. In the cortices with decreased rCBF, despite morphologically normal imaging, of Case-3, the decrement was considered to be diaschisis, since these lesions were located in the ipsilateral hemisphere of the tissue defect. We concluded that brain malformations show various rCBF abnormalities, and these are spread over a larger area than detected by MRI. Therefore, SPECT is a valuable examination method for the determination of abnormal areas and the assessment of pathologic functional state in patients with brain malformations.

Adolescent↗
PubMed1997

[The effect of hypothermia on CSD propagation in rats].

In the cortical zone surrounding an ischemic or traumatic focus, CSD is a transient phenomenon involving interstitial ions, blood flow and metabolism and is believed to be completely reversible. However, it may extend to secondary brain injuries because CSD releases excitatory amino acids into the extracellular space. In order to prevent secondary brain injuries, it may be effective to block repeated CSD. This study was designed to determine whether hypothermia can block CSD propagation and whether this study is a potentially useful means for preventing secondary brain injuries. Male wistar rats weighing 270 g on average were used for the experiments. The animals were divided into two groups: hypothermic rats (33.5-34 degrees C, rectal temp.) and normothermic rats (37-37.5 degrees C). The changes in rCBF (regional Cerebral Blood Flow) were monitored in order to observe CSD. LDF (Laser Doppler Flowmetry) was used to measure rCBF. The two LDF probes were placed on the parietal cortex (4 mm apart). To elicit CSD, a needle stab injury was made on the cortex or a piece of paper soaked with 10% KCl was applied on the cortex. The velocity of CSD propagation was more prolonged in the hypothermic rats than in the normothermic rats (p < 0.01). There were smaller numbers of repeated CSD in the hypothermic rats than in the normothermic rats. Histological examination of the cerebral cortex revealed shrinkage neurons more distinctly in the normothermic rats than in hypothermic rats. From these results, we can speculate that hypothermic may block CSD propagation and that hypothermic therapy has the potential to prevent secondary brain injuries.

Animals↗
PubMed1997

Quantitative detection of ultraviolet-specific p53 mutations in normal skin from Japanese patients.

We have previously developed sensitive methods to detect UV-specific p53 mutations (CC to TT tandem mutations) and have reported that such mutations could be found in the normal skin cell populations of sun-exposed body sites, but not in those of covered sites, in Australian cancer patients. We have now further refined our allele-specific PCR method for detecting CC to TT mutations at codons 247/248 of the p53 gene to allow quantitative measurements. Using DNA containing this mutation from a tumor as a standard for calibration and 5 micrograms of genomic DNA/PCR reaction, we could detect 1 mutant allele in about 10(6) wild-type alleles. It is essential to use purified primers and 64 degrees C as the annealing temperature for PCR. Our method has been applied in a study of the correlation of sun exposure and accumulation of CC to TT mutations in normal skin biopsies from Japanese patients. There were more p53 mutations in samples taken from sites that were chronically exposed to the sun than in those from covered sites. A significant trend of increased p53 mutation frequency with increase in age of subjects was found, suggesting the cumulative nature of the mutation. On the other hand, the p53 mutation frequency was higher in patients with premalignant tumors or nonmelanocytic skin cancer than in patients with only benign tumors. These results confirm the utility of PCR-based p53 gene mutation assays for the measurement of exposure to UV as well as for predicting the risk of UV-associated skin cancer.

Adult↗
PubMed1997

Development of microchimerism in pediatric patients after living-related liver transplantation.

Microchimerism has been suggested to play an important role in the long-term acceptance of allogeneic organ grafts by transplant patients and for the maintenance of a state of donor-specific low responsiveness. In order to elucidate the kinetics of the development of chimerism we have performed a follow-up analysis in 10 pediatric patients with living-related liver transplantation (LRLTx). Blood samples obtained during the first 6 months and at 18 months post-transplant and skin biopsies taken at one month were analysed for the presence of donor cells by PCR using donor-specific HLA-DRB1 primer pairs or primers for a Y chromosome-specific sequence. Furthermore 13 long-term patients more than 2 yr after LRLTx were studied at two different time points. In the follow-up studies donor cells could be demonstrated in the blood of all patients immediately after transplantation. After a gradual decline all patients became chimerism-negative for several weeks or months. At 6 months, however, in five of eight patients tested and at 18 months in six of nine patients donor cells had reappeared. This biphasic pattern in the development of chimerism is proposed to reflect the occurrence of different donor-derived cell populations in the recipient. The population giving rise to the first wave of chimerism probably represents matured cells with a limited lifespan which are released from the graft into the circulation of the recipient during the first weeks after transplantation. The population of cells occurring with the second wave of chimerism is likely to have been generated by donor-derived cells with stem cell potential located either in the graft or in the hematopoetic organs of the recipient after emigration from the graft. This model may be able to explain fluctuations in the incidence and degree of microchimerism described in other patient populations during the first year post-transplant. Of the 13 long-term patients, chimerism could be demonstrated in 11. In seven patients it was detected in both blood and skin, in three patients the results obtained for blood and skin were discordant. In one patient only blood was analysed. It is not clear whether the negative results really reflected the absence of chimerism or whether the number of donor cells was below the level of detectability.

Adolescent↗
PubMed1997

Increased level of c-erbB-2/neu/HER-2 protein in cutaneous squamous cell carcinoma.

Overexpression of c-erbB-2/neu/HER-2 oncoprotein, a receptor tyrosine kinase, has been demonstrated in a variety of human cancers. To elucidate the involvement of c-erbB-2 in human skin carcinogenesis, we examined expression of the protein in skin samples from five cases of keratoacanthoma (KA), 10 of actinic keratosis (AK), 24 of squamous cell carcinoma (SCC) and 10 of basal cell carcinoma (BCC) and five samples of normal epidermis, using an immunohistochemical method on formalin-fixed, paraffin-embedded sections. Expression of c-erbB-2 was also examined in cultured SCC cell lines, a premalignant cell line and in cultured normal keratinocytes. Normal epidermal cells showed no or very little c-erbB-2 protein, but the covering epidermal layer of some tumours showed a few strongly positive cells. Samples of KA and AK showed barely detectable c-erbB-2 protein in only a few cases. Twenty of the 24 cases of SCC had elevated expression of c-erbB-2 protein, with a tendency to more positive cells in metastatic lesions. Five of the 10 cases of BCC stained for c-erbB-2 but more weakly than those of SCC. Reaction products of the positive cells were seen in the cytoplasm. All three cultured SCC cell lines stained for c-erbB-2 protein more strongly than the premalignant HaCaT or normal keratinocytes. Our results indicate the possible involvement of c-erbB-2 overexpression in the malignant conversion of keratinocytes.

Basal Cell Carcinoma↗
PubMed1997

[Sudden cardiac tamponade due to hemorrhagic myocarditis after preconditioning marrow transplantation with cyclophosphamide in a patient with aplastic anemia].

A 28-year-old male was diagnosed as aplastic anemia in 1983. He maintained on corticosterone with a large transfusion requirement for being resistant to other therapies, and combined with hemochromatosis at 20-year-old. In February 1994, he was admitted to the hospital for consideration of BMT. Echocardiogram was normal on admission. He was transplanted with bone marrow from his HLA-matched MLC negative sister following contained of TLI (7.5 Gy) and CY 50 mg/kg for four days on March 10 1994. Disturbance of consciousness appeared, an echocardiogram showed severe pericardial effusion on day 1 after BMT. He was diagnosed cardiac tamponade, pericardiocentesis was done immediately and 100 ml pericardial effusion was removed. Transiently he became alert, however, irreversible cardiac arrest occurred on day 2. Postmortem examination revealed thickened left ventricles with intramyocardial hemorrhage. It seems necessary to reduce CY, or substitute it with anti-thymocyte globulin (ATG) or TBI etc. for BMT in aplastic anemia accompanied by hemochromatosis.

Adult↗
PubMed1997

Detection of cytokine mRNA in unfractionated peripheral blood by reverse transcriptase polymerase chain reaction.

OBJECTIVE: To detect cytokine gene expression in unfractionated peripheral blood by reverse transcriptase-polymerase chain reaction (RT-PCR). DESIGN: Prospective study. SETTING: University hospital, Japan. SUBJECTS: 3 healthy volunteers and 3 severely infected patients. INTERVENTIONS: Peripheral blood was obtained and total RNA was extracted from 0.5 ml unfractionated whole blood with a 4 M guanidinium isothiocyanate mixture, 0.2 M sodium acetate, phenol, and chloroform. The mRNA was reverse transcripted, and interleukin-1 beta (IL-1beta) and tumour necrosis factor (TNF) cDNA were selectively amplified by synthetic primers with PCR. MAIN OUTCOME MEASURES: Establishment of cytokine gene expression in unfractionated peripheral blood. RESULTS: About 10 microg of total RNA was obtained from a 0.5 ml sample of blood. IL-1beta and TNF mRNA were not detected in blood from healthy volunteers, though they were detected in patients with severe infection. CONCLUSION: This method avoids artefactual gene activation and may be applicable to monitoring cytokine gene expression in various pathophysiological states.

Adult↗
PubMed1997

[A clinical investigation of Bentall's operation for annuloaortic ectasia in the elderly].

Although Bentall's operation has become a routine procedure for annuloaortic ectasia (AAE), few reports on its effects on operative mortality in elderly patients have been published. The results of Bentall's operation for AAE on 4 elderly patients were reviewed. There were two males and two females in the series. The ages ranged 71 to 77 years with an average of 73. The etiology of aneurysms was syphilitic in three and arteriosclerotic in one patients. All patients had AAE, aortic regurgitation and ascending aortic aneurysms. Of all these patients, 1 had a subacute Type A dissecting aneurysm, 1 had a proximal arch aneurysm and 1 had an aortic arch aneurysm plus a sacciform descending aortic aneurysm. All patients had composite graft replacement with coronary reimplantation. Three patients received the concomitant operative procedures including aortic arch replacement and CABG to right coronary artery with saphenous vein graft. All patients survived operation. Postoperative CTR and NYHA classification showed remarkable improvement and serious complications were not found in spite of old age. In the late postoperative period, all patients were alive and well from 4 to 6 years after operation. Bentall's operation can be performed in elderly patients with AAE.

Age Factors↗
PubMed1997

Antigenic analysis of influenza viruses isolated in Thailand between 1991 and 1994.

We studied the epidemiology of influenza viruses in Thailand by isolating them and comparing their antigenic features with those of Japanese isolates. Between 1991 and 1994, 32 strains were isolated from 186 throat swab specimens. Twenty-one of the 32 isolates were of type A, subtype H3N2, and 11 strains were type B. It was suggested that the isolates of type A, subtype H3N2, drifted antigenically from A/Beijing/352/89-like to A/Kitakyusyu/159/93-like variants used as reference strains for comparison. The type B isolates in 1991 were suspected to be antigenically different from those of B/Bangkok/163/90, Thailand, in HI tests. These 1991 isolates were similar to B/Mie/1/93, which was isolated in the latter half of the epidemic in Japan in winter 1992/1993.

Animals↗
PubMed1997

[Epstein-Barr virus-infected T-cell malignancy in an adult patient with Behçet's disease-like symptoms].

A 20-year-old woman was hospitalized on November 11, 1994 with Behçet's disease-like symptoms (fever, genital ulcer and aphtha in the oral cavity). Bilateral cervical lymph node swelling was also noted and diagnosed as lymphadenitis on biopsy. Chronic active Epstein-Barr virus infection (CAEBV) was diagnosed based on the high titer of antibodies to the EBV capsid antigen, early antigen, and nuclear antigen. She was treated with prednisolone and acyclovir and all symptoms improved. However, ten months after onset of symptoms, T-cell malignancy was diagnosed on bone marrow aspiration, which revealed 34.9% blast cells that had rearrangement of TCR-beta. She died on May 8, 1995, despite anticancer therapy. In analyzing the blast cells, the monoclonal junctional DNA structure of the EBV terminal repeat was analyzed by Southern blotting and provided definitive evidence for the monoclonality of EBV-infected T cells. These findings strongly suggest that EBV plays a pathogenic role in T-cell malignancy. EBV-infected T-cell malignancy, such as this case, is very rare in Japan, especially in adult.

Adult↗
PubMed1997

Inhibitory effects of ubenimex (bestatin) on the invasion of uterine cervical carcinoma cells and their production and activation of gelatinase A.

The present study was undertaken to investigate the effects of the aminopeptidase inhibitor ubenimex (bestatin) on the invasive activity of cultured human uterine cervical carcinoma cells. The invasion of squamous cell carcinoma OMC-1 and SKG-IIIb cells, and adenocarcinoma OMC-4 and CAC-1 cells into reconstituted basement membrane (Matrigel) was inhibited by the presence of bestatin in a concentration-dependent manner. However, bestatin did not have any effect on tumor cell proliferation or migration. Immunoblot analysis of tumor-conditioned medium showed that the treatment of tumor cells with bestatin resulted in the reduction of the 72 kDa gelatinase level (gelatinase A, latent form) in the four cell lines examined, and the reduction of the 68 kDa gelatinase level (gelatinase A, active form) in SKG-IIIb cells. Bestatin inhibited hydrolyzing activities towards substrates of aminopeptidases in tumor cells, but did not directly inhibit gelatinase A. These results suggest that bestatin may inhibit the invasion of uterine cervical carcinoma cells possibly through the inhibitory mechanisms for production and activation of gelatinase A modulated by tumor aminopeptidases.

Aminopeptidases↗
PubMed1997

Kinetics in parasite abundance in susceptible and resistant mice infected with an avirulent strain of Toxoplasma gondii by using quantitative competitive PCR.

The kinetics of changes in Toxoplasma gondii abundance were evaluated with a quantitative competitive (QC)-polymerase chain reaction (PCR) assay at various sites in both C57BL/6 and BALB/c mice. Higher mortality was apparent in C57BL/6 mice than in BALB/c mice when infected with a high dose of cysts. There were significant differences in cyst number when infected with a low dose of cysts, although there was no significant difference in mortality between the 2 mouse strains. One day after infection with a low dose of an avirulent Fukaya strain, T. gondii was detected in peripheral blood, mesenteric lymph nodes, spleen, lungs, and brain. Two weeks after infection, the number of T. gondii in the brain greatly increased in C57BL/6 mice but not in BALB/c mice. Thus, it would appear that the first to second week after infection is a critical period in determining T. gondii abundance. QC PCR allows the detection of low numbers of T. gondii at an early stage of infection in the murine model. This is useful for the early diagnosis of toxoplasmosis and to understand reactivation of toxoplasmosis.

Animals↗
PubMed1997

[Small increase of CR1 and CR3 by C5a-receptors on polymorphonuclear leukocytes in systemic lupus erythematosus].

One of the anaphylatoxins, C5a, is known to increase the expression of the complement receptors, CR1 and CR3, on PMNs which play important roles in the phagocytosis. We measured the expression of these receptors before and after the stimulation with C5a and C5a-receptors (C5aR) on PMNs in patients with systemic lupus erythematosus (SLE). PMNs from 16 patients and 11 normal controls were tested. All the patients with SLE were administered with prednisolone orally and were in the inactive stage. The CR1 expression in SLE was significantly weak (p < 0.01) before and after stimulation with 4.55 nM (50 micrograms/ml) of C5a. There was no significant difference of CR3 expression before stimulation. However, after the stimulation with C5a, the increase of CR3 on PMNs from SLE was significantly small (p < 0.01). C5aR on PMNs showed no difference between the two groups. However, the expression of C5aR was significantly suppressed in patients treated with a high dosage of prednisolone (> = 10 mg/day) compared to those with a low dosage of prednisolone (< 10 mg/day). There was no significant difference of CR1 and CR3 expression between these groups. It is concluded that the increase of CR1 and CR3 on PMNs by C5a in small in SLE, of which impaired increase is not due to C5aR on PMNs, and that the expression of C5aR is suppressed by prednisolone.

Antigens, CD↗
PubMed1997

[Usefulness and early detection of acute exacerbation by peak expiratory flow rate in the management of asthma].

The monitoring of peak expiratory flow (PEF) and maintenance of a symptom diary have been proposed as means to monitor asthma severity. This study assessed via longitudinal analysis, the usefulness and limitation of daily PEF monitoring (amplitude percent mean) as an index for asthma severity, and the usefulness of recording daily intake of beta-agonists as a measure of symptom severity. Nine subjects with moderate to severe asthma were treated with inhaled beclomethasone dipropionate (BDP). Sustained-release theophylline and oral corticosteroids supplemented inhaled BDP according to both individual symptom prevalence and PEF measurements. The patients kept records four times daily of their PEF and asthmatic symptoms (cough, sputum and number of attacks), from the beginning to the end of treatment. They also recorded the daily frequency of beta-agonist inhalation (as needed for symptomatic relief). Minimum daily PEF (expressed as percent best) correlated significantly with symptom scores: cough (r = -0.69), sputum (r = -0.69) and attack (r = -0.69). Minimum PEF correlated strongly with the daily frequency of beta agonist inhalation (r = 0.76). Each symptom score and the daily frequency of beta-agonist inhalation was zero when the minimum PEF was approximately 80%. We evaluated the correlation between minimum PEF and daily PEF variability in all data (r = -0.72): for a minimum PEF > or = 20% (r = -0.72), a minimum PEF > or = 30% (r = -0.77), a minimum PEF > or = 40% (r = -0.82) and a minimum PEF > or = 50% (r = -0.80). We determined the correlation between minimum PEFs of > or = 35 to 45% in 1% increments and daily PEF variability in relation to the severity of asthma. With a minimum PEF > or = 40%, the strongest correlation was demonstrated between minimum PEF and daily PEF variability. Daily PEF variability was a reliable indicator for the management of asthma when the PEF > or = 40%. When the minimum PEF was 80%, daily PEF variability was approximately 10%. When the minimum PEF was 40%, daily PEF variability was 46%, and the daily frequency of beta-agonist inhalation was 2.6. We concluded that, 1) The target values of minimum PEF and daily PEF variability are 80% and 10% respectively in the treatment of asthmatic patients, 2) The daily frequency of beta-agonist inhalation is recommended as an indicator for the severity of asthmatic symptoms, and 3) Daily PEF variability in combination with the daily frequency of beta-agonist inhalation is very useful in the management and early detection of acute asthma.

Adolescent↗
PubMed1997

[Neurosarcoidosis with an alternating and recurrent external ophthalmoplegia].

We report a 62-year-old woman who was admitted to our hospital because of abrupt onset of ptosis, and alternating and recurrent bilateral external ophthalmoplegia in a short period without pupillary sphincter muscle abnormality. She had been suffering from uveitis of unknown origin for four years before admission, which was improved with the local administration of steroid. Her brain CT and MRI showed a parasellar mass lesion, and cerebral angiography revealed total occlusion of the right internal carotid artery with little arteriosclerotic change in other blood vessels. She was diagnosed as having sarcoidosis because of elevated serum creatinine kinase and lysozyme levels, and the pathological finding of granuloma in muscle biopsy. The oral administration of prednisolone resulted in disappearance of her external ophthalmoplegia completely in ten months. We postulate that in this patient, the alternating and recurrent external ophthalmoplegia in a short period was related to ischemic neuropathy caused by vascular lesion of neurosarcoidosis.

Cranial Nerve Diseases↗