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Biomedical subjects

T Miyazaki

Publications and source records attributed to T Miyazaki.

At least 289 records · Page 16Linked to original sources
PubMed1997

[Long-term prognosis in patients with exercise-induced ST-segment elevation after myocardial infarction].

The present study investigated whether the exercise-induced ST-segment elevation can predict the prognosis for patients with myocardial infarction. Among 529 patients with myocardial infarction, 411 underwent treadmill exercise testing about 5 weeks after the onset. All patients were followed up (mean [+/-SD] 54 +/- 41 months) to compare the incidence of cardiac events. One hundred and eighteen patients (22%) could not perform the exercise test due to cardiac or noncardiac limitation. Ineligibility for exercise test was most useful for risk stratification. Multivariate analysis showed that elimination from the stress test with cardiac limitation was the most significant predictor for cardiac death. Excluding the 16 patients with bundle branch block, the 395 patients were classified into four groups of ST-segment elevation (107 cases, 27%), ST-segment elevation combined with depression (22 cases, 6%), ST-segment depression (106 cases, 27%), ST-segment unchanged (160 cases, 40%). Among the various stress test abnormalities, only low exercise duration was a predictor for cardiac death. ST-depression and ST-elevation combined with depression were independent risk predictors for all cardiac events. Most patients with ST-elevation had single-vessel disease with excellent exercise capacity and low incidence of cardiac events. ST-segment elevation during exercise 5 weeks after myocardial infarction is not associated with a poor prognosis.

Aged↗
PubMed1997

Metabolism substrate with negative myocardial uptake of iodine-123-BMIPP.

UNLABELLED: Iodine-123-BMIPP is an iodinated methyl-branched-chain fatty acid. Low uptake of BMIPP relative to thallium or other perfusion tracer indicates metabolically damaged but viable myocardium (for example, ischemic but viable myocardium). In some cases, however, negative myocardial uptake of BMIPP is observed. The main purposes of this study were to assess the frequency of such BMIPP findings and to clarify metabolism of such cases by using PET. METHODS: Among the 1258 patients who underwent BMIPP scintigraphy, 11 patients (0.9%) showed negative myocardial uptake of BMIPP. Under fasting condition, PET using [11C]palmitate, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [11C]acetate was performed in nine of these 11 patients. RESULTS: Global myocardial uptake of [11C]palmitate, expressed as the standardized uptake value, was significantly lower in the patients than in control (3.62 +/- 0.44 versus 5.49 +/- 1.62; p < 0.01). However, the early phase clearance rate of [11C]palmitate and oxidative metabolism was not significantly different. In the fasting state, PET studies showed increased FDG accumulation in seven of nine patients (high group) and decreased accumulation in two patients (low group). In the high group patients, glucose metabolism in the fasting state was similar to that in the normal volunteers after glucose loading (Kcomplex: 0.050 +/- 0.016 versus 0.038 +/- 0.015; p = ns). However, low glucose metabolism was noted in the low group patients (Kcomplex: 0.007 and 0.005). CONCLUSION: Negative myocardial uptake of BMIPP is occasionally, but not often, observed. Global uptake of [11C]palmitate was decreased in these patient. The majority of these patients showed "metabolic switching" from normal free fatty acid metabolism to abnormally enhanced glucose metabolism in the fasting state. However, some patients showed decreases in both exogenous glucose utilization and free fatty acid uptake in the fasting state.

Acetates↗
PubMed1997

[Aortic valve insufficiency caused by nonpenetrating chest trauma difficult to distinguish from infective endocarditis with transesophageal echocardiography: a case report].

A 58-year-old man was involved in an automobile accident and suffered remittent fever, leukocytosis and high C-reactive protein level. He developed a diastolic murmur 2 months after the accident. Transesophageal echocardiography showed severe aortic regurgitation with a vegetation-like echo image attached to the right coronary cusp leaflet, suggesting infective endocarditis. Intensive medical treatment for 11 months did not improve the vegetation-like echo-image, so aortic valve replacement was performed. Disruption of the right coronary cusp leaflet was confirmed surgically. Prolapse had occurred as a result of disruption during diastole. The vegetation-like echo-image was considered to be the tip of this leaflet.

Aortic Valve Insufficiency↗
PubMed1997

Quercetin, a bioflavonoid, inhibits the induction of interleukin 8 and monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha in cultured human synovial cells.

OBJECTIVE: Tumor necrosis factor (TNF)-alpha is present in synovial fluid of patients with rheumatoid arthritis. It induces the expression of proinflammatory cytokines in synovial cells. Based on our recent finding that reactive oxygen intermediates play important roles in mediating TNF-alpha action, we examined the effect of an antioxidant bioflavonoid, quercetin, on TNF-alpha induced expression of interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in cultured human synovial cells. METHODS: The amounts of mRNA for IL-8 and MCP-1 were determined by Northern blot analysis. Electrophoretic mobility shift assays (EMSA) were performed for the detection of a transcription factor, nuclear factor-kappa B (NF-kappa B). RESULTS: Addition of quercetin suppressed TNF-alpha induced increase in the mRNA for IL-8 and MCP-1 in a dose dependent manner. Quercetin did not affect the stability of these mRNA. H2O2 mediated induction of IL-8 and MCP-1 genes was also inhibited by quercetin. EMSA revealed that quercetin inhibited the activation of NF-kappa B by TNF-alpha. CONCLUSION: Quercetin suppresses TNF-alpha mediated stimulation of IL-8 and MCP-1 expression, at least in part, by inhibiting the activation of NF-kappa B.

Arthritis, Rheumatoid↗
PubMed1997

Studies on the antifungal activity of the new imidazole antimycotic lanoconazole in infected sites. Distribution in the skin and in vitro activity in the presence of stratum corneum.

To answer the question why topically applied lanoconazole (CAS 101530-10-3, NND-318) is so highly effective in the treatment of dermatomycoses in both animal models and human patients, the antifungal activity of lanoconazole in infected sites was investigated. 1. Distribution of lanoconazole in rat skin: The distribution of lanoconazole within the dorsal skin of rats was examined by measurement of radioactivity and microscopic autoradiography. 24 h after dermal application of 14C-lanoconazole cream formulation, 83% of the total radioactivity in the skin was recovered from the stratum corneum, and thereafter the radioactivity decreased gradually up to 96 h. Metabolite analysis showed that more than 94% of the extractable radioactivity was lanoconazole itself after 24 and 48 h. Microautoradiograms of the skin also supported the radioactivity distribution. 2. In vitro antifungal activity in stratum corneum-containing medium: Candida albicans TIMM 2640 was incubated for 10 days at 27 degrees C in a vitamin-supplemented yeast carbon base medium containing 5 mg/ml of human stratum corneum and different concentrations of lanoconazole or bifonazole (CAS 60628-96-8, reference agent). Compared with the control culture, lanoconazole strongly inhibited fungal growth in a concentration dependent manner at concentration above 0.1 microgram/ml, resulting in a reduction of viable cell recovery to less than 50% after 10 days. The inhibitory activity of bifonazole was clearly weaker than that of lanoconazole. At concentrations of 0.1-10 micrograms/ml lanoconazole reduced keratinolytic acid proteinase activity in the culture-supernate to 40-70% of the control value, while bifonazole showed 50% reduction of the activity at a concentration of 10 micrograms/ml. These results indicate that lanoconazole is mainly distributed and retained in the stratum corneum after topical application where it exerts strong antifungal activity.

Administration, Topical↗
PubMed1997

Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys.

We recently reported that the serum levels of indoxyl sulfate, a dietary protein metabolite, are increased in both uremic rats and patients, and that the administration of indoxyl sulfate to uremic rats accelerates the progression of glomerular sclerosis. Thus, we hypothesize that the overload of protein metabolites such as indoxyl sulfate on nephrons promotes the progression of chronic renal failure (CRF). Recent studies revealed that tubulointerstitial injury is of equal or greater importance than glomerular sclerosis in determining whether progressive renal dysfunction will ensue in various renal diseases. In the present study, to clarify the role of indoxyl sulfate in the progression of CRF, the expressions of genes related to tubulointerstitial fibrosis such as transforming growth factor (TGF)-beta 1, tissue inhibitor of metalloproteinases (TIMP-1) and pro-alpha 1(I) collagen were examined in the renal cortex of 5/6-nephrectomized uremic rats given indoxyl sulfate. In the first experiment, the administration of indoxyl sulfate for five weeks significantly increased the mRNA levels of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in the uremic rats given indoxyl sulfate compared with the control uremic rats, accompanied by a significant decline in renal function and worsening of glomerular sclerosis. In the second experiment, the administration of indoxyl sulfate for 2.5 weeks also increased the expression of the mRNA levels with no significant decline in the renal function. In conclusion, these findings indicate that the overload of the protein metabolite indoxyl sulfate on remnant nephrons is involved in the increased bioactivity of TGF-beta 1 in uremic kidneys, which enhances the renal expression of TIMP-1 and type 1 collagen, leading to the progression of CRF.

Administration, Oral↗
PubMed1997

The protein metabolite hypothesis, a model for the progression of renal failure: an oral adsorbent lowers indoxyl sulfate levels in undialyzed uremic patients.

We have recently demonstrated that indoxyl sulfate promotes the progression of glomerular sclerosis in uremic rats. In the present study, we determined whether an oral adsorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate and suppress the progression of chronic renal failure (CRF) in undialyzed uremic patients. Twenty-five undialyzed uremic patients were given AST-120 at a dose of 6 g/day for 6 months, while 10 undialyzed uremic patients were not given AST-120. The effects of the oral adsorbent on the slope of the 1/serum creatinine (Scr)-time plot, and the serum and urine levels of indoxyl sulfate were evaluated. Administration of AST-120 significantly decreased the serum and urine levels of indoxyl sulfate, and tended to improve the slope of the 1/SCr-time plot in the CRF patients. Among the patients in whom urinary excretion of indoxyl sulfate was reduced by AST-120, the oral adsorbent significantly improved the slope of the 1/SCr-time plot. The change in the slope of the 1/SCr-time plot showed a significant negative correlation with the change in the urine level of indoxyl sulfate. Thus, patients who showed a greater decrease of urinary indoxyl sulfate also showed more marked suppression of the progression of CRF. These results support the notion that indoxyl sulfate, a protein metabolite, is involved in the progression of CRF, and that an oral adsorbent can delay progression at least partly by reducing the serum and urine levels of indoxyl sulfate.

Administration, Oral↗
PubMed1997

Indoxyl sulfate and progression of renal failure: effects of a low-protein diet and oral sorbent on indoxyl sulfate production in uremic rats and undialyzed uremic patients.

We have previously demonstrated that indoxyl sulfate is a stimulating factor for the progression of glomerular sclerosis in uremic rats. In this study we determined if a low-protein diet or oral sorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate in 5/6-nephrectomized uremic rats and undialyzed uremic patients. The uremic rats were treated by fasting or AST-120 for 2 days. The serum and urine levels of indoxyl sulfate dramatically decreased 1-2 days after fasting or AST-120 treatment. We then measured the serum and urine levels of indoxyl sulfate and calculated protein intake from urinary amounts of urea nitrogen using Maroni's equation in 80 undialyzed uremic patients with creatinine clearance less than 30 ml/min. The serum and urine levels of indoxyl sulfate were significantly lower in the patients on a low-protein diet than in those in the normal-protein diet group. Administration of AST-120 significantly decreased serum and urine levels of indoxyl sulfate in 22 undialyzed uremic patients. In conclusion, a low-protein diet or AST-120 reduced the serum and urine levels of indoxyl sulfate, a stimulating factor for glomerular sclerosis, in both uremic rats and undialyzed uremic patients.

Administration, Oral↗
PubMed1997

Indoxyl sulfate stimulates renal synthesis of transforming growth factor-beta 1 and progression of renal failure.

We recently demonstrated that the administration of indoxyl sulfate (dietary protein metabolite) to 5/6-nephrectomized rats accelerated the progression of chronic renal failure by increasing the transforming growth factor (TGF)-beta 1 synthesis in the kidneys, which enhanced the renal expressions of tissue inhibitor of metalloproteinase (TIMP)-1 and type 1 collagen, leading to renal fibrosis. The aim of the present study was to clarify the mechanism by which the administration of indoxyl sulfate increases TGF-beta 1 in the kidneys of uremic rats. Since infiltrative monocytes are suggested to be an important source of TGF-beta 1 in tubulointerstitial fibrosis, we examined the effect of indoxyl sulfate administration to uremic rats on the renal gene expression of intercellular adhesion molecule (ICAM)-1, which is involved in the infiltration of monocytes to kidneys. Indoxyl sulfate administration was observed to enhance the mRNA levels of ICAM-1 as well as those of TGF-beta 1, TIMP-1 and pro alpha 1 (I) collagen in the renal cortex of 5/6-nephrectomized uremic rats. In addition, we demonstrated in vitro that the addition of indoxyl sulfate significantly increased the synthesis of TGF-beta 1 in cultured proximal tubular cells. Thus, the overload of indoxyl sulfate in uremic kidneys increased the infiltration of monocytes and directly increased the synthesis of TGF-beta 1 in proximal tubular cells.

Animals↗
PubMed1997

[Analysis of B-3 desamido insulin in human insulin preparations by HPLC].

The content of A-21 desamido insulin (A-21 DI) and B-3 desamido insulin (B-3 DI) in human insulin preparations was measured by new RP-HPLC method using a neutral eluent (pH 6.5). Sometimes the content of B-3 DI in human insulin preparations was about two times larger than that of A-21 DI. In particular, in the case of neutral insulin injection, the content of B-3 DI has increased remarkably as the increase of total desamido content. The content of B-3 DI obtained by the new RP-HPLC method will open the new aspect of the impurity test for insulin preparations.

Chromatography, High Pressure Liquid↗
PubMed1996

Voltage-dependent potassium currents of sympathetic preganglionic neurons in neonatal rat spinal cord thin slices.

Voltage-dependent potassium currents were analyzed in the visually identified sympathetic preganglionic neurons (SPNs) of neonatal rat spinal cord thin slices by the whole-cell patch-clamp technique. Some of the SPNs were identified by the presence of retrogradely transported fluorescent dye, DiI, injected into the superior cervical ganglion several days prior to experimentation. In a tetrodotoxin (TTX)-containing solution, a step depolarization from the holding potential of -72 mV generated a slow outward current that was suppressed by tetraethylammonium (TEA) and by Ca(2+)-free/2.5 ImM Co2+ solution. Ca(2+)-dependent current consisted of a transient and a sustained components. In a Ca(2+)-free (substituted with Mg2+) solution with TTX and TEA, a step depolarization from a hyperpolarized potential evoked a transient outward current that was blocked by 4-aminopyridine (4-AP). A step hyperpolarization evoked a voltage-dependent inward current, the conductance of which was dependent not only on the membrane potential, but also on the extracellular K+ concentration. Tail current analyses revealed that all of these currents were carried by K+ ions. These results indicate that SPN possesses at least five types of voltage-dependent K+ current, including the delayed rectifier current (IK), Ca(2+)-dependent transient current (IC), Ca(2+)-dependent sustained current (IAHP), A-current (IA) and inward rectifying current (Iu), which may be targets of putative transmitters released from various descending and segmental inputs impinging upon the SPN.

Animals↗
PubMed1996

Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain.

BAG-1 is a Bci-2-binding protein which functions in protection from apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-mediated upregulation of BAG-1 expression. In hematopoietic cell line BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c chain is sufficient to confer proliferation and cell survival responses to IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically induced by IL-2. The IL-2-mediated induction of BAG-1 expression required the activation of tyrosine kinase(s) and was sensitive to rapamycin as the induction of bcl-2 expression was. Analysis of the transfectants which express mutant IL-2R beta c chains or mutant Janus family protein tyrosine kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1 gene expression required the serinerich region within the IL-2R beta c chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1 gene expression thus highly resembles that for bcl-2 gene expression, strongly suggesting that their induction shares the same signaling pathway. In addition, deletion of the serine-rich region led to loss of IL-2-mediated protection from apoptotic cell death. Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system in follicular growth and ovulation.

The interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system (RAS) in follicular growth and ovulation were studied with the use of an isolated perfused rabbit ovary preparation. Ovulation failed to occur in either control ovaries or the experimental ovaries perfused with IGF-I in a concentration of 1, 10, or 100 ng/ml in the absence of gonadotropin. Exposure to IGF-I stimulated the secretion rate of angiotensin II-like immunoreactivity (Ang II-IR) in perfused rabbit ovaries in a dose-dependent manner. The percent increase in follicle diameter in ovaries perfused with IGF-I for 12 h was significantly correlated with the secretion rate of Ang II-IR at 12 h after exposure to IGF-I. The addition of IGFBP-3 to the perfusate did not induce ovulation in the absence of gonadotropin, but exposure to IGFBP-3 inhibited hCG-induced ovulation in a dose-dependent manner. In addition, IGFBP-3 significantly reduced the ovarian secretion rate of Ang II-IR and prostaglandins stimulated by hCG administration. Intrafollicular plasminogen activator (PA) activity significantly increased within 4 h after exposure to 100 ng/ml of IGF-I, compared with that in control ovaries perfused with medium alone. The concomitant addition of IGFBP-3 to the perfusate significantly reduced the IGF-I-stimulated PA activity in the preovulatory follicles at 4, 6, and 8 h after exposure to IGF-I. However, IGFBP-3 alone affected neither the ovarian secretion rate of Ang II-IR nor intrafollicular PA activity. Exposure to streptokinase, an exogenous PA, in vitro stimulated both follicular growth and the intrafollicular Ang II-IR content. In conclusion, IGF-I enhances both ovarian Ang II production and follicular development by stimulating intrafollicular PA activity.

Angiotensin II↗
PubMed1996

Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway.

Acute promyelocytic leukemia (APL) is associated with a chromosomal translocation t(15;17) and successfully differentiated by all-trans-retinoic acid (ATRA) in vivo as well as in vitro. The PML-retinoic acid receptor alpha (RARA) oncoprotein, which is generated by the translocation, blocks the differentiation, and ATRA is thought to modulate the dominant negative function of PML-RARA. However, the molecular effect of ATRA on PML-RARA is unknown. In this study, we showed by means of immunoblotting that the expression of PML-RARA decreased within 12 h in APL cells treated with ATRA at concentrations greater than 0.1 microM. The decrease of PML-RARA was associated with restoration of the normal subcellular PML localization. PML-RARA transcripts were not down-regulated by ATRA. However, lactacystin, a specific inhibitor of the proteasome, almost completely inhibited the decrease of PML-RARA. These data indicate that the PML-RARA degradation is accelerated by pharmacological concentrations of ATRA, suggesting that ATRA allows APL cells to differentiate by relieving the differentiation block.

Acetylcysteine↗
PubMed1996

Molecular cloning of a novel thyroid hormone-responsive gene, ZAKI-4, in human skin fibroblasts.

Utilizing a method called "differential display of mRNAs by means of polymerase chain reaction", the cDNA fragment of a thyroid hormone-responsive gene ZAKI-4 was cloned from cultured human skin fibroblasts. Northern blot analysis revealed that there were two ZAKI-4 mRNA species (3.4 and 1.4 kilobases (kb)), and they were up-regulated by a physiological concentration of triiodothyronine (T3). This T3 effect was abolished by the treatment with cycloheximide, indicating the possibility that gene ZAKI-4 is regulated by T3 in an indirect fashion, through an intermediate product of T3, rather directly by T3 itself. No effect of T3 on ZAKI-4 mRNA stability suggested that T3 induces the mRNA at the transcriptional level. Rapid amplification of cDNA ends confirmed the presence of two mRNA species. ZAKI-4 mRNA was detected in heart, brain, liver, and skeletal muscle but not in placenta, lung, kidney and pancreas. In skin fibroblasts and skeletal muscle, 3.4-kb mRNA was the major species, whereas 1.4-kb mRNA was dominant in heart, brain, and liver. The sequence analysis suggested that the two mRNA species arise from alternative polyadenylation and code a single protein of 192 amino acids. No homologous protein sequence was found in a data base. Elucidation of the function of ZAKI-4 gene product will provide new insights into an important role of T3 in various organs.

Adolescent↗
PubMed1996

Selective cooperation of HTLV-1-encoded p40tax-1 with cellular oncoproteins in the induction of hematopoietic cell proliferation.

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL). The virus-encoded p40tax-1, a nuclear oncoprotein, is known to promote transcription of its own as well as a variety of cellular genes. However, the mechanism by which p40tax-1 promotes lymphocyte transformation is not fully understood. In the present study, we examined whether p40tax-1 can induce hematopoietic cell proliferation by cooperating with the products of cellular proto-oncogenes; i.e. an activated form of the src-family protein tyrosine kinase p56lck (lck F505), c-Myc or Bcl-2. These oncoproteins are critical mediators of interleukin 2 (IL-2)-induced proliferative signals. We show that p40tax-1 alone cannot render the hematopoietic cell line, BAF-B03, able to proliferate in the absence of cytokines, but it can do so in cooperation with lckF505, or c-Myc but not with Bcl-2.

Animals↗