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Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 307 records · Page 17Linked to original sources
PubMed2000

Synergistic effects of iontophoresis and jet injector pretreatment on the in-vitro skin permeation of diclofenac and angiotensin II.

A non-needle syringe (jet injector) was utilized to increase skin permeation of drugs by iontophoresis. Briefly, physiological saline was initially flushed by the injector to make a pore in the stratum corneum of excised hairless rat skin, and the iontophoretic skin permeation of two model compounds, sodium diclofenac and angiotensin II, was followed using a 2-chamber diffusion cell. Constant voltage and constant current iontophoresis treatments were evaluated. Pretreatment using the jet injector alone resulted in about 13- and 22-fold increases in the steady-state flux of diclofenac and angiotensin II, respectively, through the skin, compared with non-treated controls. Jet injector pretreatment with constant voltage iontophoresis further enhanced skin permeation of diclofenac and angiotensin II, and the enhancement was also greater than that by constant voltage iontophoresis alone. Thus, a synergistic effect was observed. The ratio of enhancement was greater compared with the control. Jet injector pretreatment with constant current iontophoresis, however, did not always yield higher skin permeation of the drugs than injector pretreatment alone, although the lag time was shortened. The difference in the enhancement between the constant voltage- and constant current iontophoresis can be explained by the electric current through the excised skin. Constant current iontophoresis after a short period of constant voltage iontophoresis with multiple jet injector pretreatments may be the best way to increase drug permeability while preventing severe skin damage.

Administration, Cutaneous↗
PubMed2000

Enhancing effect of tumor promoters, phorbol esters and teleocidins on nuclear receptor-mediated transcription.

Interaction between a tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), and ligands of nuclear receptors has been interpreted as the result of crosstalk between the nuclear receptors and oncogenic transcription factor AP-1. We examined the effects of various tumor promoters on transcription mediated by several nuclear receptors (RAR, TR, and ROR) by using thymidine kinase promoter-based reporter systems. TPA-type and other types of tumor promoters (okadaic acid, thapsigargin) enhanced reporter gene transcription independently of the cognate ligands for the receptors. Various kinds of TPA-type tumor promoters, teleocidine and its synthetic derivatives (indolactam, benzolactams) enhanced reporter gene transcription in proportion to their differentiation-inducing activities. Although TPA is known to activate protein kinase C (PKC), some PKC inhibitors did not inhibit the effect of TPA on reporter gene transcription. Interestingly, staurosporin, a strong PKC inhibitor and also a tumor promoter, enhanced the effect of TPA and weakly enhanced the reporter transcription itself. These results suggest this reporter system is useful for the evaluation of effects on the gene expression of various tumor promoters, including non-TPA type.

Animals↗
PubMed2000

Diagnostic usefulness of the post-exercise systolic blood pressure response for the detection of coronary artery disease in patients with diabetes mellitus.

Patients with diabetes mellitus (DM) often have a positive result on exercise testing despite a normal coronary arteriogram, which indicates that exercise-induced ST depression is not always an accurate indicator of the presence of coronary artery disease (CAD) in such patients. The present study evaluated the usefulness of the post-exercise systolic blood pressure (SBP) response for the detection of CAD in 47 consecutive patients with DM. Significant stenotic lesions were detected by angiography in 25 patients; 18 of these had true positive (TP) exercise testing results, and 7 had false negative (FN) results. No significant stenotic lesions were detected in the remaining 22 patients and of these 10 had true negative (TN) exercise testing results, and 12 had false positive (FP) results. The SBP ratio (SBP after 3 min of recovery divided by the SBP at peak exercise) was significantly higher in patients with coronary stenoses than in those without. Analysis of the relative cumulative frequency revealed that a SBP ratio greater than 0.87 was associated with significant stenoses. The sensitivity, specificity, and accuracy of ST change combined with a SBP ratio greater than 0.87 for detecting stenoses in patients with DM were 68%, 82%, and 74%, respectively. These results suggest that calculating the SBP ratio, in combination with monitoring for ST depression, improves the accuracy of treadmill exercise testing for the detection of CAD in patients with DM.

Adult↗
PubMed2000

Entrainment function in the suprachiasmatic nucleus of streptozotocin-induced diabetic rats.

The term for re-entrainment to a new light-dark cycle in streptozotocin (STZ)-induced diabetic rats was significantly longer than that in control rats. In STZ-induced diabetic rats, the same level of phase delay in the suprachiasmatic nucleus neuronal firing rhythm was observed in control rats after glutamate application. Therefore, 5-HT function in the hypothalamus is thought to be decreased in STZ-induced diabetic rats. These results suggest that postsynaptic neuronal function is still maintained in the suprachiasmatic nucleus of STZ-induced diabetic rats. Therefore, 5-HT mechanisms may play an important role in the maintenance of this function.

5-Hydroxytryptophan↗
PubMed2000

Characteristic changes in carbohydrate profile in the kidneys of hereditary nephrotic mice (ICGN strain).

The ICR-derived glomerulonephritis (ICGN) mice consist of heterozygous and homozygous groups and are considered to be a good model for human idiopathic nephrotic syndrome. To reveal changes in cell-surface carbohydrate construction, 24 lectins were applied to kidney sections of 10-, 30- and 50-week-old male heterozygous and homozygous ICGN mice and age-matched male ICR mice. Bandeiraea simplicifolia lectin-I (BSL-I), which specifically binds to alpha-D-galactopyranosyl groups, showed positive staining in the glomeruli of ICGN mice, but not in those of ICR mice. Positive BSL-I staining was observed only in distal tubules of homozygous ICGN mice. Lectin blotting for BSL-I demonstrated characteristic glycoproteins (45, 58 and 64 kD) in ICGN but not in ICR mice, and the levels of these molecules augmented in homozygous ICGN mice with the progression of renal failure. Moreover, succinylated wheat germ agglutinin, Dolichos biflorus agglutinin, Aleuria aurantia lectin and Ulex europaeus agglutinin-I showed positive staining only in the glomeruli of homozygous ICGN mice, but not in those of heterozygous ICGN or ICR mice. The staining intensities of Ricinus communis agglutinin-I, Phaseolus vulgaris agglutinin-E and -L, Lens culinaris agglutinin and Erythrina cristagalli agglutinin (ECL) in the glomeruli of homozygous ICGN mice were stronger than those of heterozygous ICGN and ICR mice. In conclusion, lectin histochemistry provided useful information for the diagnosis and prognosis of nephrotic lesions. Characteristic BSL-I binding glycoproteins may be pathogenic factors which cause renal disease in ICGN mice and are good tools to investigate the molecular mechanism of renal disorders in ICGN mice.

Animals↗
PubMed2000

Identical twins with long QT syndrome associated with a missense mutation in the S4 region of the HERG.

Familial long QT syndrome (LQTS) is caused by mutations in genes encoding ion channels important in determining ventricular repolarization. Mutations in at least five genes have been associated with the LQTS. Fire genes, KCNQ1, HERG, SCN5A, KCNE1, and KCNE2, have been identified. We have identified a missense mutation in the HERG gene in identical twins in a Japanese family with LQTS. The identical twins in our study had QT prolongation and the same missense mutation. However only the proband had a history of syncope. Although many mutations in LQT genes have been reported, there are few reports of twins with LQTS. This is the first report, to our knowledge, of identical twins with a HERG gene mutation.

Adult↗
PubMed2000

8-bromo-cyclicAMP stimulates glucose transporter-1 expression in a human choriocarcinoma cell line.

Facilitative glucose transporter-1 (GLUT1) is abundant in trophoblast cells and is responsible for glucose transport in the placenta. However, the change in GLUT expression in human placenta upon trophoblast differentiation remains to be clarified. Therefore, we first examined the localization of GLUT1 and GLUT3 using human first-trimester chorionic villi. We found that GLUT1 and GLUT3 were mainly localized to syncytiotrophoblast and cytotrophoblast cells respectively. We analyzed whether placental GLUT1 and GLUT3 expression changes during differentiation using a human choriocarcinoma (BeWo) cell line which is known to show functional and morphological differentiation in response to cAMP in culture. Treatment of BeWo cells with 8-bromo-cyclicAMP (8-bromo-cAMP) increased the level of hCG secretion and induced cell fusion leading to the formation of large syncytia. Treatment of BeWo cells with 8-bromo-cAMP also resulted in a significant increase in glucose uptake on days 2-3 of culture. The stimulating effect of 8-bromo-cAMP on glucose uptake was concentration dependent. Northern and immunoblot analyses revealed that the levels of mRNA and protein of GLUT1, but not of GLUT3, were significantly increased by 8-bromo-cAMP. These findings suggest that 8-bromo-cAMP stimulates GLUT1 expression with differentiation in BeWo cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 26). Detection of 1,3-dinitrobenzene-induced histopathological changes in testes and epididymides of rats with 2-week daily repeated dosing.

As part of a collaborative work, male rats were administered 1,3-dinitrobenzene (1,3-DNB) daily at 0, 25 and 50 mg/kg/day from the age of 6 weeks for 4 weeks (4-week exp.), or at 25, 50 and 75 mg/kg/day from the age of 8 weeks for 2 weeks (2-week exp.). After the end of each administration period, all survivors were sacrificed, and their testes and epididymides were removed, weighed and examined histopathologically. The following results were obtained. In the 4-week exp.: At 50 mg/kg/day, the weights of testes and epididymides showed decrease with macroscopic atrophy. The testicular spermatogenic epithelium showed decrease in the number of sperm-spermatocytes, degeneration/necrosis, giant cell formation and vacuolation, reduction in sperm counts also being evident in the ducts of the epididymides. In the 2-week exp.: At 50 and 75 mg/kg/day, the weights of testes and/or epididymides showed decrease with macroscopic atrophy. Several histopathological changes in the testes and epididymides were essentially the same changes as in the group given 50 mg/kg/day in the 4-week exp., with a clear relation. These results indicate that a 2-week administration period is sufficient to detect testicular and epididymal histopathological changes induced by 1,3-dinitrobenzene in male rats.

Administration, Oral↗
PubMed2000

Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers.

A positive association between hyperuricemia and cardiovascular disease has been reported, but no study has evidenced yet the precise role of serum uric acid in the development of cardiovascular disease. In addition, no epidemiological studies have so far documented a decreased risk of cancer among people with hyperuricemia, even though the antioxidant action of uric acid has recently been stressed to inhibit DNA damage. The present prospective cohort study investigates the relationship between hyperuricemia and health hazards in a Japanese working population. The subjects were 49,413 Japanese male railroad workers, aged 25-60 years at enrollment. Serum uric acid and other baseline data were provided by annual health-survey records from 1975 to 1982. The vital status of the subjects was traced until the end of 1985 for those who remained alive. During an average 5.4-year study period, 984 deaths were recorded. Those with serum uric acid over 8.5 mg/dl showed elevated relative risks (RRs) of death in all causes (RR 1.62, p<0.01), coronary heart disease ( RR 1.52), stroke (RR 2.33, p<0.01), hepatic disease (RR 3.58, p<0.01), and renal failure ( RR 8.52, p<0.01), as compared with those with serum uric acid levels of 5.0-6.4mg/dl. The RR of death in all causes still remains statistically significant when adjusted by age and serum total cholesterol (2.00, p<0.01), age and alcohol intake (1.85, p<0.001), age and smoking (1.69, p<0.001), age and gout treatment (1.61, p<0.05), and also age and BMI (1.50, p< 0.05). On the other hand, the RR of all causes decreased but was still above 1.0 when adjusted by age and blood glucose (1.62), age and systolic blood pressure (1.32), age and GOT (1.23), and also age and history of cardiovascular disease (1.17). These results showed that hyperuricemia has a strong association with the RRs of death in all causes, coronary heart disease, stroke, hepatic disease and renal failure, and indicated that serum uric acid seems to be a considerable risk factor for reduced life expectancy.

Adult↗
PubMed2000

Ovarian carcinoma in patients with endometriosis: MR imaging findings.

OBJECTIVE: Various types of malignancy can develop in patients with endometriosis. Enhancing mural nodules have been reported as an imaging characteristic of malignant transformations. We evaluated contrast-enhanced MR imaging to determine the optimum sequence to reveal mural nodules and other characteristics of malignant transformations. MATERIALS AND METHODS: We examined 10 patients with pathologically proven ovarian adenocarcinoma in endometriosis and 10 patients (the control group) with ovarian endometrioma suggestive of malignant transformation on the basis of sonographic findings. We analyzed the size and nature of the endometriomas in each patient. We compared four types of contrast-enhanced MR imaging to determine which sequence best revealed mural nodules. RESULTS: In the malignant and control groups, 80% of the cysts with findings suggestive of malignant transformation showed unilateral disease or larger endometrial cysts on the suggestive side than on the contralateral side. High signal intensity on T1-weighted images and low signal intensity on T2-weighted images relative to the myometrium were observed only in two of 10 malignant endometrial cysts and in all control cysts. All malignant endometriomas had small mural nodules with low signal intensity on T1-weighted contrast-enhanced images. Only three benign endometriomas had mural nodules and none of them enhanced. The enhancement of mural nodules was easily seen on dynamic subtraction imaging. CONCLUSION: On the basis of our findings, endometrial cysts with malignant transformation rarely show low signal intensity on T2-weighted images and usually have enhancing mural nodules. Because the enhancement of mural nodules is often difficult to evaluate on conventional T1-weighted images, dynamic subtraction imaging can be valuable.

Adenocarcinoma↗
PubMed2000

Including weight decay in the Rescorla-Wagner model avoids an unlikely prediction.

Weight decay is a common technique for improving generalization in the field of neural networks. If weight decay is added to the Rescorla-Wagner model, a desirable result emerges in that the effects of prior learning are not expected to be permanent. This revised model accommodates an experimental finding called unblocking that was claimed to refute the Rescorla-Wagner model.

Algorithms↗
PubMed2000

Coordinate regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 expression in human vascular smooth muscle cells.

The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by human vascular smooth muscle cells (SMC) was monitored as a function of the phenotypic modulation in vitro. Cell phenotype was manipulated by varying serum concentration and cell density. Synthetic phenotype was characterized by a minimum expression of the contractile proteins and a maximal proliferation rate. Contractile phenotype was quiescent and expressed a maximal level of contractile proteins. Synthetic cells expressed the highest levels of both MMP-1 and TIMP-1 and displayed maximal collagenolytic activity. No significant change was detected in MMP-2 expression or catalytic activity. Enzyme immunoassays revealed that MMP-1 expression fell by 77+/-2.4-95+/-0.5%, and that of TIMP-1 by 34+/-0.5-59+/-1.9%, as the cells acquired a contractile phenotype. The level of the MMP-1/TIMP-1 complex was similarly reduced by 78+/-2.9-85+/-1.6%. These data demonstrate that the expression of MMP-1 and TIMP-1 are coordinately regulated with SMC phenotype.

Adult↗
PubMed2000

Suppressive effect of genistein on rat bone osteoclasts: involvement of protein kinase inhibition and protein tyrosine phosphatase activation.

The suppressive effect of genistein on osteoclast-like multinucleated cells from rat femoral tissues was investigated. The bone cells isolated from rat femoral tissues were cultured for 48 h in an alpha-minimal essential medium (5% fetal bovine serum) containing either vehicle or genistein (10(-7)-10(-5) M). Osteoclasts were estimated by staining for tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts. The presence of genistein caused a significant decrease in the number of osteoclasts. Such a decrease was also seen in the presence of calcium choride (10(-5) M). Magnesium chloride (10(-5)-10(-3) M), a blocker of Ca2+ channels, had no effect on the number of osteoclasts. The effect of genistein (10(-5) M) or calcium (10(-3) M) in decreasing osteoclasts was significantly prevented by the presence of magnesium (10-3 M). Vanadate (10(-6)-10(-4) M), an inhibitor of protein tyrosine phosphatase activity, did not have an effect on the number of osteoclasts. The genistein's effect was not altered by vanadate. When isolated osteoclasts were cultured for 24 h in the presence of genistein (10(-7)-10(-5) M), protein kinase activity in the 5500 g supernatant of homogenate of the cells was significantly decreased, while protein tyrosine phosphatase activity was significantly elevated. Such an effect was also seen by the addition of genistein (10(-7)-10(-5) in the enzyme reaction mixture in vitro. The present study suggests that the suppressive effect of genistein on rat bone osteoclasts is partly involved in the inhibition of protein kinase and the activation of protein tyrosine phosphatase in osteoclasts.

Animals↗
PubMed2000

Anabolic effect of genistein in osteoblastic MC3T3-E1 cells.

Genistein is a natural isoflavone found in Leguminosae. The effect of genistein on osteoblastic MC3T3-E1 cells was investigated. Cells were cultured for 48 h in the presence of genistein (10(-7)-10(-5) M). Genistein (10(-6) and 10(-5) M) caused a significant elevation of protein content, alkaline phosphatase activity, and deoxyriboncleic acid (DNA) content in the cells. The effect of genistein (10-5 M) in increasing protein content, alkaline phosphatase activity and DNA content in the cells was completely prevented by the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis, suggesting that the isoflavone's effect results from a newly synthesized protein component. The effect of genistein (10(-5) M) in elevating cellular protein content and alkaline phosphatase activity was completely inhibited by the presence of trifluo-perazine (10(-5) M), staurosporine (10(-7) M) or vanadate (10(-6) M), various protein kinase inhibitors. Moreover, genistein (10(-5) M)-increased protein content and alkaline phosphatase activity in the cells was clearly abolished by the presence of anti-estrogen tamoxifen (10(-6) M). The effect of 17beta-estradiol (10(-9) M) in elevating protein and alkaline phosphatase activity in the cells was not enhanced by the presence of genistein (10(-5) M). Genistein's effect might be partly involved in estrogen action. The present study demonstrates that genistein has an anabolic effect on osteoblastic MC3T3-E1 cells.

Alkaline Phosphatase↗
PubMed2000

The gene of Ca2+-binding protein regucalcin is highly conserved in vertebrate species.

Regucalcin is a Ca2+-binding protein, which plays a regulatory role in liver cell functions related to Ca2+. In this study we have cloned cDNA for regucalcin from rabbit, bovine, chicken and toad livers by using rapid amplification of cDNA ends (RACE) method. The nucleotide and amino acid sequences of them are compared with published human, rat and mouse sequences. Comparison analysis revealed that the nucleotide sequences of regucalcin from seven vertebrate species were highly conserved in their coding region. The overall regucalcin proteins in these species consisted of 299 amino acids, and they had 69.9-91.3% identity. Furthermore, phylogenetic analysis showed that regucalcin in seven species appears to form a single cluster. This study demonstrates a great conservation of the regucalcin genes throughout evolution.

Amino Acid Sequence↗
PubMed2000

Suppressive effect of endogenous regucalcin on the enhancement of protein synthesis and aminoacyl-tRNA synthetase activity in regenerating rat liver.

The effect of regucalcin, which is a regulatory protein in Ca2+ signaling, on protein synthesis in regenerating rat liver was investigated. Protein synthesis was assayed in a reaction mixture containing the 5500 g supernatant fraction in the presence of [3H]leucine. The presence of anti-regucalcin monoclonal antibody (100 and 150 ng/ml) in the reaction mixture caused a significant elevation of in vitro protein synthesis. This elevation was completely prevented by the addition of regucalcin (1.0 microM). Regenerating liver after partial hepatectomy (HPX) induced a significant increase in protein synthesis. This increase was significantly enhanced by the presence of anti-regucalcin monoclonal antibody (100 ng/ ml). This enhancement was remarkable at 24 and 48 h after HPX. [3H]Leucyl-tRNA synthetase activity in the 105000 g supernatant fraction (cytosol) of the liver homogenate from normal rats was significantly raised by the presence of antibody (100 and 150 ng/ml) in the enzyme reaction mixture. Regenerating liver caused a significant elevation of the enzyme activity at 24, 48, and 72 h after HPX. This elevating was significantly enhanced in the presence of antibody (100 ng/ml). The present study suggests that endogenous regucalcin has a suppressive effect on the enhancement of protein synthesis in regenerating rat liver with a proliferative cells.

Amino Acyl-tRNA Synthetases↗
PubMed2000

Enhancement of protein tyrosine phosphatase activity in the proliferation of cloned rat hepatoma H4-II-E cells: suppressive role of endogenous regucalcin.

The role of endogenous regucalcin in the regulation of protein tyrosine phosphatase activity in the proliferation of the cloned rat H4-II-E hepatoma cells was investigated. Cells were cultured for 6 to 96 h in a medium containing 1.0 or 10% fetal bovine serum (FBS). Cell numbers were significantly raised by culture with 10% FBS in comparison with that of 1.0% FBS. Protein tyrosine phosphatase activity in the cells was significantly elevated by culture with 10% FBS for 24 to 96 h as compared with that of 1% FBS. Such an increase was not seen in protein phosphatase activity toward phosphoserine or phosphothreonine. The presence of anti-regucalcin monoclonal antibody (50 or 100 ng/ml) in the enzyme reaction mixture caused a remarkable elevation of protein tyrosine phosphatase activity in the cells obtained by culture with 1.0 or 10% FBS. This elevation was completely prevented by the addition of regucalcin (10-6 M). The effect of antibody in elevating protein tyrosine phosphatase activity in the cells was significantly inhibited by the addition of okadaic acid (10-6 M) or vanadate (10(-6) M), an inhibitor of protein phosphatase, in the reaction mixture. The present study suggests that protein tyrosine phosphatase activity in the cloned rat hepatoma cells is increased in serum-stimulated cell proliferation, and that endogenous regucalcin has a suppressive role in the enhancement of the enzyme activity in proliferative cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗