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Biomedical subjects

M Uchida

Publications and source records attributed to M Uchida.

At least 145 records · Page 8Linked to original sources

Clinical features of relative focal hyperfusion in patients with intracerebral hemorrhage detected by contrast-enhanced xenon CT.

BACKGROUND AND PURPOSE: The prevalence and clinical features of relative focal hyperperfusion were investigated in 165 consecutive patients with intracerebral hemorrhage. METHODS: Contrast-enhanced xenon CT was used to observe regional cerebral blood flow in all patients (86 men and 79 women ranging in age from 25 to 89 years; mean age, 66 years). The clinical data of patients with and without relative focal hyperperfusion were compared to define distinguishing characteristics. RESULTS: Relative focal hyperperfusion was observed in 24 (23.5%) of 102 patients in the acute stage but in no patient in the subacute or chronic stages. Relative focal hyperperfusion was associated significantly more often with putaminal and subcortical hemorrhage than with thalamic and cerebellar hemorrhage. We found that patients with relative focal hyperperfusion had a lower mean age than those without it; a male dominance; and a more common history of intracerebral hemorrhage. CONCLUSION: Relative focal hyperperfusion occurs in the acute stage after intracerebral hemorrhage and does not persist for more than 30 days. The most common locations are the putamen and subcortical areas. Risk factors include male sex and previous bleeding in the same area.

Adult↗

[Two cases of functioning parathyroid cysts].

Two cases of functioning cysts are reported. The first patient was a 48-year-old man who underwent percutaneous cyst puncture for a palpable mass in the neck at another hospital. Hypercalcemic crisis brought the patient to Koga General Hospital. The second patient was a 69-year-old woman with the complaint of discomfort in the right neck of several years duration and with a palpable mass identified on physical examination at a local hospital. Both patients had high serum calcium and parathyroid hormone (PTH) levels and were diagnosed as having functioning parathyroid cysts by imaging studies including ultrasonography, computed tomographic scan, magnetic resonance imaging and scintigraphy. After parathyroidectomy, their serum calcium and PTH levels became normal, but calcium supplement was necessary in the first patient. To our knowledge, these are the 40th and 41st cases reported in the Japanese literature.

Aged↗

[2,8-dihydroxyadenine urolithiasis due to partial deficiency of adenine phosphoribosyltransferase: a case report].

A 35-year-old female was referred to our clinic with a complaint of left flank pain in 1993. Drip infusion pyelography showed a filling defect of 25 x 24 mm in size in the left ureteropelvic junction. Computed tomography and ultrasonography revealed it as the renal stone. Percutaneous nephroureterolithotomy and extracorporeal shock-were lithotomy were performed. The stone was composed of 2,8-dihydroxyadenine (DHA). The patient was diagnosed as having a partial deficiency of adenine phosphoribosyltransferase (APRT) from the low APRT activity and a genotype of a compound heterozygote APRT*J/APRT*Q0 by T-cell analysis. The urinary excretion of 2,8-DHA crystals disappeared by the postoperative treatment with allopurinol. Cases of 2,8-DHA urolithiasis reported in the Japanese literature are discussed.

Adenine↗

A distinct function of STAT proteins in erythropoietin signal transduction.

The Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway is an important signaling pathway of interferons and cytokines. We examined the activation of STAT proteins induced by interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin (EPO) using the human leukemia cell line, UT-7, which requires these cytokines for growth. IL-3, GM-CSF, and EPO induced DNA-binding activity to the oligonucleotides corresponding to the sis-inducible elements (SIE) of c-fos, in addition to the beta-casein promoter (beta-CAP), SIE- and beta-CAP-binding proteins were identical to Stat1alpha and Stat3 complex and to Stat5 protein, respectively. This indicates that IL-3, GM-CSF, and EPO commonly activated Stat1alpha, Stat3, and Stat5 proteins in UT-7. However, EPO hardly activated Stat1alpha and Stat3 in UT-7/GM, which is a subline of UT-7 that grows slightly in response to EPO. Transfection studies revealed that UT-7/GM cells constitutively expressing Stat1alpha, but not Stat3, can grow as well in response to EPO as GM-CSF, suggesting that Stat1alpha is involved in the EPO-induced proliferation of UT-7. Thus, although Stat1alpha, Stat3, and Stat5 proteins are activated by GM-CSF, IL-3, and EPO, our data suggest that each STAT protein has a distinctive role in the actions of cytokines.

Cell Division↗

The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice.

The present study was undertaken to investigate a mechanism of the inhibitory effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E feeding or indomethacin treatment suppressed the urethane-induced increase in ODC activity, while exogenous PGE2 overcame the effect of vitamin E on ODC activity. Furthermore, the amount of PGE, and the level of ODC activity were well correlated. These results indicate that the vitamin E-induced decrease in PGE2 level probably contributes to the inhibition of ODC induction and the prevention of tumor development in the lung.

Animals↗

In vitro development of erythroid and megakaryocytic cells from a UT-7 subline, UT-7/GM.

UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin (EPO) for growth and survival. We isolated a novel subline, UT-7/GM after long-term culture of UT-7 with GM-CSF. The hemoglobin concentration and gamma-globin and EPO-receptor mRNA levels were significantly higher in EPO-treated UT-7/GM cells than in untreated cells. In contrast, the platelet factor 4 and glycoprotein IIb mRNA levels were much higher in thrombopoietin (TPO)-treated UT-7/GM cells than in untreated cells. Some TPO-treated cells had morphologically mature megakaryocytic characteristics such as a developed demarcation membrane in the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM is a bipotential cell line that can be induced to differentiate into erythroid and megakaryocytic lineages by EPO and TPO, respectively. Moreover, a minority of UT-7/GM cells acquired a high hemoglobin concentration by treatment with TPO, suggesting that TPO in part induced the erythroid differentiation of the UT-7/GM cells. Interestingly, GM-CSF inhibited the EPO- or TPO-induced erythroid differentiation and the TPO-induced megakaryocytic differentiation of UT-7/GM cells. These results support the hypothesis that cytokines influence the programming of gene expression required for lineage commitment or differentiation.

Cell Differentiation↗

The inhibitory effect of vitamin E on pulmonary polyamine biosynthesis, cell proliferation and carcinogenesis in mice.

We investigated the modulating effect of vitamin E on pulmonary polyamine biosynthesis, cell proliferation and carcinogenesis in mice treated with urethane. Pulmonary ornithine decarboxylase induction and subsequent polyamine accumulation were observed during the initiation and promotion phases of the urethane-induced lung carcinogenesis in mice. The increases of ODC activity and polyamine level during both phases were almost inhibited when a high vitamin E diet was provided. The urethane-increased level of pulmonary proliferating cell nuclear antigen as a marker of cell proliferation during the carcinogenesis was inhibited by vitamin E treatment. Also, vitamin E suppressed the urethane-induced elevation of pulmonary cyclooxygenase activity as a marker of tumor promotion. In conjugation with these events, vitamin E reduced the development of lung tumors in mice treated with urethane. These results indicated that vitamin E could act as a useful chemopreventive agent against lung carcinogenesis in mice due to the regulation of cell proliferation.

Animals↗

The inhibitory effect of vitamin E on K-ras mutation at an early stage of lung carcinogenesis in mice.

In this study, we investigated the effect of vitamin E on the activation of the K-ras oncogene with a 61st codon A-->T mutation at an early stage of urethane-induced lung carcinogenesis in mice. Thirty days after urethane injection, the K-ras mutation was detected in 64% of lung samples tested by mutant-allele-specific amplification. The consumption of a supplemented diet with about 20-times more vitamin E than the control diet, only during the promotion phase or during both the initiation and promotion phases of lung carcinogenesis, reduced the frequency of the mutation to 36 and 18%, respectively. Also, vitamin E suppressed the level of proliferating cell nuclear antigen as a marker of cell proliferation in the lungs of mice treated with urethane. These results support the notion that vitamin E is a useful chemopreventive agent against lung cancer.

Animals↗

Male to male transmission of supernumerary nipples.

We report on a father and his son with supernumerary nipples. No male-to-male transmission has previously been described with this trait. This observation confirms that this trait is inherited in an autosomal dominant fashion.

Child, Preschool↗

Alcohol intake decreases brain Zonisamide concentration in inbred EL mice.

This study was undertaken to evaluate the effect of ethanol intake on the anticonvulsive effects of Zonisamide (ZNS), a sulfonamide derivative. EL mice, which are highly susceptible to seizures, were given a 10% ethanol solution ad lib for 1-4 weeks. In mice given ethanol for 4 weeks, seizures were not suppressed by ZNS at a dose of 75 mg kg-1, i.p. Serum ZNS concentrations following ethanol consumption for 1-4 weeks were higher than in untreated mice; however, brain ZNS concentrations following ethanol consumption were lower than those in untreated mice. These results suggest that alcohol intake decreases the brain concentration of ZNS, but not the serum concentration.

Animals↗

Localization of ectopic parathyroid glands using technetium-99m sestamibi imaging: comparison with magnetic resonance and computed tomographic imaging.

The aim of the study was to compare the accuracy of technetium-99m sestamibi imaging for localization of ectopic parathyroid glands in patients with hyperparathyroidism with that of magnetic resonance (MR) and computed tomographic (CT) imaging. Eleven patients with primary (n=3) or secondary (n=8) hyperparathyroidism were studied with 99mTc sestamibi parathyroid imaging CT and MR imaging. Images of the neck were acquired at 10 min and 2-3 after tracer injection. The three patients with primary hyperparathyroidism and five patients with secondary hyperparathyroidism underwent parathyroidectomy. The ectopic glands were confirmed by histopathological examination of the resected specimens. In respect of 20 parathyroid glands in the eight patients explored surgically, the sensitivity and specificity of sestamibi imaging were 70% (14/20) and 88%, respectively, those of CT, 40% (8/20) and 88%, and those of MR imaging, 60% (12/20) and 88%. Of these patients, three had parathyroid adenomas while five had hyperplasia (17 glands). Sestamibi imaging localized eight ectopic parathyroid glands, which were surgically confirmed (six were located in the thymus and two in the mediastinum). In one patient explored surgically, the ectopic gland was located outside the field of the MR coil. Although the remaining three cases of secondary hyperparathyroidism were not confirmed surgically, these patients demonstrated sestamibi uptake in five parathyroid glands, including three ectopic glands. MR images demonstrated abnormal parathyroid glands in the same regions as sestamibi imaging. Our data indicate that 99mTc-sestamibi imaging should be used initially to localize the ectopic parathyroid glands in patients with hyperparathyroidism for anatomical guidance prior to MR or CT imaging.

Choristoma↗

Metabolism of carteolol by cDNA-expressed human cytochrome P450.

OBJECTIVES: To determine human cytochrome P450 isoform(s) (CYPs) involved in the metabolism of carteolol, the biotransformation of the compound was investigated in vitro using ten isoforms of human cytochrome P450 expressed in human AHH-1 TK +/- cell lines. In addition, the inhibitory effects of carteolol on the activities of important CYP isoforms, namely, CYP1A2, 2C9, 2C19, 2E1, and 3A4, were examined. RESULTS: Carteolol was metabolised to 8-hydroxycarteolol by CYP 2D6 with KM and Vmax values of 183 mumoles.l-1 and 26.09 pmol.min-1.pmol-1 P450, respectively. CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2E1 and 3A4 were not involved in the metabolism of the compound. CYPD6-mediated carteolol 8-hydroxylase activity was inhibited by quinidine, propranolol, nortriptyline, dextromethorphan, sparteine, bufuralol, and biperiden. Biperiden competitively inhibited the catalytic reaction with a Ki value of 0.45 mumoles.l-1. Carteolol did not affect the following catalytic reactions: CYP1A2-mediated (R)-warfarin 6-hydroxylation, CYP2C9-mediated tolbutamide methylhydroxylation, CYP2C19-mediated (S)-mephenytoin 4-hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, and CYP3A4-mediated testosterone 6 beta-hydroxylation. CONCLUSION: 8-Hydroxylation is the only cytochrome P450-catalyzed metabolic reaction of carteolol by its expressed microsomes, and CYP2D6 is the principal isoform of the enzyme involved in the catalytic reaction. Carteolol has neither stimulative nor inhibitory effects on CYP1A2, 2C9, 2C19, 2E1, and 3A4 activities.

Carteolol↗

In vitro binding of vitamin D receptor occupied by 24R,25-dihydroxyvitamin D3 to vitamin D responsive element of human osteocalcin gene.

We previously reported that 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] activates the human osteocalcin gene (hOC) through vitamin D receptor (VDR) and vitamin D responsive element (VDRE) in the same manner as 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2 D3] [17]. In the present study, the interaction of 24R,25(OH)2D3-liganded VDR [24R,25(OH)2D3-VDR] with the hOC VDRE in vitro was investigated. The electrophoretic mobility shift assay (EMSA) revealed that the binding of 24R,25(OH)2D3-liganded VDR to the hOC VDRE was weak, even at concentrations of 24R,25(OH)2D3 10(5)-fold higher than 1 alpha,25(OH)2D3. The effect of the nuclear accessory factor (NAF), which is required for the high affinity interaction of the VDR to the VDRE, on the binding of the 24R,25(OH)2D3-VDR to the VDRE was studied using hOC VDRE affinity column chromatographic assays. In the absence of NAF, the 24R,25(OH)2D3-VDR associated weakly with the VDRE compared to the 1 alpha,25(OH)2D3-liganded VDR [1 alpha,25(OH)2D3-VDR], whereas the NAF enhanced the binding of the 24R,25(OH)2D3-VDR for the VDRE. In the absence of the hOC VDRE, the binding affinity of the 24R,25(OH)2D3-VDR for the NAF was weaker than that of 1 alpha,25(OH)2D3-VDR. These results suggest that the weak interaction of the 24R,25(OH)2D3-VDR with both NAF and hOC VDRE is responsible for the weak binding of the 24R,25(OH)2D3-VDR to the VDRE detected in EMSA. In terms of VDR function, 24R,25(OH)2D3 was more potent in transactivation than in vitro binding.

24,25-Dihydroxyvitamin D 3↗

A new Thermus-Escherichia coli shuttle integration vector system.

We established a Thermus thermophilus strain in which the pyrE gene (coding for orotate phosphoribosyltransferase of the pyrimidine biosynthetic pathway) was totally deleted. We also constructed an integration vector, which consisted of the Escherichia coli plasmid vector pBluescript and a 2.1-kb segment of the T. thermophilus leu operon sequence, for the integration of a foreign gene into a chromosome of the thermophile. pyrE and leuB genes were used as probes to test the integration vector. The integration vector pINV, bearing the pyrE gene, transformed the delta pyrE strain at a frequency of 6 x 10(-5) through a single crossover event. The leuB gene could also be used as another marker of the integration vector system. The vector could be integrated at the expected site. By digesting the chromosomal DNA of the T. thermophilus transformants with a unique restriction enzyme, the vector could be recovered into E. coli after the recircularization in vitro. The kanamycin nucleotidyltransferase gene could be successfully expressed in the thermophile by using pINV.

3-Isopropylmalate Dehydrogenase↗

Synthesis of a new potent anti-angiogenic agent, 17 alpha-acetoxy-9 alpha-fluoro-6 alpha-methylprogesterone (9 alpha-fluoromedroxyprogesterone acetate [FMPA]).

A new anti-angiogenic agent, 17 alpha-acetoxy-9 alpha-fluoro-6 alpha-methylprogesterone (9 alpha-fluoromedoroxyprogesterone acetate [FMPA, 9] was synthetized in a 10-step sequence. FMPA (9) had about two orders of magnitude stronger anti-angiogenic activity than medroxyprogesterone acetate (MPA), as estimated in a bioassay involving chorioallantoic membranes of growing chick embryos.

Animals↗

[Involvement of nitric oxide, which was synthesized by constitutive nitric oxide synthase, and prostaglandin on diarrhea induced by castor oil in rats].

To clarify the mechanism of castor oil-induced diarrhea, this study was performed by using rats in relation to nitric oxide (NO) and prostaglandin (PG). Castor oil induced diarrhea in all rats within 3 hr in the control group. The pretreatment of NG-nitro-L-arginine methyl ester prevented the diarrhea, and this effect was attenuated by the combined treatment of L-arginine. Amino-guanidine inhibiting inducible NO synthase had no effect on the diarrhea, but dexamethasone, an inhibitor of both inducible NO synthase and phospholipase A2 that synthesizes PGs, significantly prevented it. Indomethacin, an inhibitor of cyclooxygenase that synthesizes PGs, also significantly prevented diarrhea. Therefore, the mechanism of the preventive effect by dexamethazone on diarrhea was suggested to be the inhibition of PGs generation. From the above results, it became clear that PG and NO, especially that synthesized by constitutive NO synthase, are involved in the mechanism of diarrhea induction by castor oil in rats.

Animals↗