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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 415 records · Page 23Linked to original sources
PubMed1996

Pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment: effects of alpha 1-acid glycoprotein.

The pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment were compared with those in healthy volunteers, and the factors that influenced plasma levels of tamsulosin were elucidated. A single oral dose of 0.2 mg of tamsulosin was given and blood and urine samples were obtained for 36 hours after administration. Unbound plasma concentration of tamsulosin was measured by a combination of equilibrium dialysis and liquid chromatography tandem mass spectrometry methods to examine the effect of protein binding on the pharmacokinetics of tamsulosin. Mean values for maximum concentration (Cmax) and area under the concentration-time curve (AUC) of total drug (Cmax,t and AUC1) in patients with renal impairment were 73% and 211% greater, respectively, than those in healthy volunteers. Mean Cmax and AUC of unbound drug (Cmax,u and AUCu), however, were almost the same in the two groups. A high correlation was found between alpha 1-acid glycoprotein (alpha 1-AGP) concentration and AUCt, but no correlation was found between alpha 1-AGP concentration and AUCu,0-36) or between creatinine clearance (ClCR) and AUCu,0-36). These results show that in patients with renal impairment, the pharmacokinetics of tamsulosin are affected by the change in protein binding that is associated with alteration of plasma alpha 1-AGP concentration, but are not largely affected by the decrease in the renal excretion. Although total tamsulosin levels increased as plasma protein binding increased, unbound tamsulosin levels (which are directly associated with the pharmacologic effects) remained unchanged in these patients.

Adrenergic alpha-Antagonists↗
PubMed1996

Pharmacodynamics and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) after administration of a rectal dosage vehicle.

The pharmacodynamic activities (leukopoietic effect) and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered rectally in various doses as hollow-type suppositories were investigated in rabbits. Three kinds of rhG-CSF hollow-type suppositories were employed: suppository I containing rhG-CSF (100-1000 micrograms/kg) in 10 mM acetate buffer solution (ABS) at pH 4.0, suppository II containing rhG-CSF in ABS with alpha-cyclodextrin (alpha-CyD) as an absorption-enhancing agent, and suppository III containing lyophilized rhG-CSF powder. We found that the total count of leukocytes in peripheral blood (total blood leukocyte count) and serum granulocyte colony-stimulating factor (G-CSF) concentration showed a dose-dependent increase. Consequently, the area under the increased total blood leukocyte count-time curve (AUI), an index of pharmacodynamic activity, and the area under the serum G-CSF concentration-time curve (AUC), a pharmacokinetic parameter, increased with an increase in the rhG-CSF dose administered rectally. Good correlation was found between AUL and AUC; thus, it is concluded that an increase in AUC leads to an increase in the effect of rhG-CSF in inducing leukopoiesis in rabbits following rectal administration. We report for the first time the rectal absorption of rhG-CSF using a new rectal dosage vehicle (rhG-CSF hollow-type suppository) and its leukopoietic effect. The rhG-CSF hollow-type suppository is found to be a promising drug delivery system.

Administration, Rectal↗
PubMed1996

Intraglomerular C3 synthesis in human kidney detected by in situ hybridization.

Complements 3 and 4 are known to be synthesized in diseased renal tissue and the mRNA of these complements has been demonstrated, using polymerase chain reaction, in renal biopsies from nephritic patients. However, the types of cells producing the complements in intact renal tissue have not been defined. To identify the renal cellular components involved in complement synthesis, we analyzed the expression of C3 mRNA in renal tissues from patients with immune-complex glomerulonephritis by a high-resolution in situ hybridization using digoxigenin-labeled oligonucleotide. Renal tissues from 15 patients with immunoglobulin (Ig) A nephropathy (IgAN), five with lupus nephritis (LN), and five with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidney with tumors served as normal controls. C3 mRNA was detected in mesangial cells, glomerular epithelial cells, and Bowman's capsule in IgAN and LN. In the interstitium, some tubules and some infiltrating mononuclear cells were positively stained for C3 mRNA. C3 mRNA was not detected in MCNS and control tissues. Our results confirm that the glomerular resident cells can synthesize C3 in immune-mediated glomerulonephritis and suggest that locally synthesized complement may be involved in tissue injury in glomerulonephritis.

Biopsy↗
PubMed1996

Spheroid cultures of human hepatoblastoma cells (HuH-6 line) and their application for cytotoxicity assay of alcohols.

Spheroid cultures of human hepatoblastoma cells (HuH-6 line) were established by rotating 3 x 10(6) cells/3 ml culture medium in 25-ml Erlenmeyer flasks on a gyratory shaker. The size of the spheroids rapidly increased until 4 days of culture, and thereafter their size gradually increased until 8 days of culture. A considerable amount of lactate dehydrogenase (LDH) was detected in the culture medium at 24h after seeding because of cell damage by subculturing, but thereafter the amount released was small, indicating that the spheroids were in healthy condition. Albumin production, one of the differentiated functions of hepatocytes, was higher in spheroid cultures than in monolayer cultures. Using this spheroid culture model, the cytotoxic effects of alcohols on HuH-6 cells were studied by measuring the activity of LDH released in the medium from damaged cells. The results indicate that the increasing order of toxicity of the alcohols was as follows: methanol < ethanol < propanol.

Albumins↗
PubMed1996

[Von Siebold's prescriptions (2)].

I have interpreted and explained 20 of von Siebold's prescriptions 4 times. Of the 20 prescriptions, 6 were stored at the Siebold's Memorial Museum (questionable 1 was excluded) and 14 at the Municipal Museum of Ohzu City, Ehime Prefecture. The 20 prescriptions used 39 types of drugs (different forms of the same drug such as crude glycyrrhiza, glycyrrhiza extract, and glycyrrhiza powder were regarded as 3 types). The prescriptions were classified according to the drug form: powders, 6 prescriptions; pills, 3; decoctions 2; confections, 2; eye drops, 2; drugs for internal and external use, 2; applications, 1; solutions (?), 1; and unknown 1. There were 2 prescriptions that use oil-sugars as correctives. The classification of the prescriptions according to drug efficacy and disease was difficult because one drug had various effects, or some diseases could be considered depending on symptoms. However, the following classification was done: digestives, 4 prescriptions; drugs for syphilis-suppuration, 3; drugs for eye diseases, 3; cathartics, 2; alteractives and resolvents, 2; drugs for scrofula, 1; drugs for scabies, 1; antitussives and expectorants, 1; rubefacients, 1; diuretics-antiphlogistic-laxative (niter), 1; and unknown, 1. Siebold's medical activities were performed mainly in the last days of the Tokugawa shogunate in Japan. Therefore, there may be only a few prescriptions remaining in other countries. Such important cultural heritage should be carefully stored.

Drug Prescriptions↗
PubMed1996

Increased levels of human hepatocyte growth factor in serum and peritoneal fluid after partial hepatectomy.

OBJECTIVE/METHOD: It has been reported that inflammatory cytokines up-regulate human hepatocyte growth factor synthesis in vitro. To demonstrate the relation of this growth factor to interleukin-6 and tumor necrosis factor alpha, the changes in the levels of these cytokines were measured in serum and peritoneal fluid in 22 patients after partial hepatectomy. RESULTS: Serum and fluids levels of cytokines showed a maximum within 3 days after surgery. Cytokines concentrations were much higher in fluid than in serum (p < 0.05). The maximum serum levels of human hepatocyte growth factor were significantly correlated with those of interleukin-6, intraoperative blood loss, and operating time (p < 0.05) but not resected liver weights. In fluid level, the growth factor was also correlated with interleukin-6 (p < 0.05) but with tumor necrosis factor alpha. CONCLUSIONS: These results suggest that human hepatocyte growth factor might be locally produced in the injured tissue associated with interleukin-6 and independently of resected liver weights.

Aged↗
PubMed1996

Detection of cytokine mRNA-expressing cells in peripheral blood of patients with IgA nephropathy using non-radioactive in situ hybridization.

IgA nephropathy (IgA-N) is considered to be an immune-mediated disorder and several immunological abnormalities have been observed. In the present study, we optimized non-radioactive in situ hybridization and applied this technique to evaluate the degree of expression of various cytokine mRNAs in peripheral blood mononuclear cells (PBMC) taken from patients with IgA-N on cytospin preparation. Using this method, together with image analysis, we examined the expression of mRNA in cells which secrete cytokines, such as IL-2, interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-6. The expression of these mRNAs was clearly observed in monocytes and lymphocytes at a single-cell level. Compared with healthy adults, the expression of IL-4 mRNA, IL-5 mRNA and IL-6 mRNA, but not IL-2 mRNA or IFN-gamma mRNA, was significantly enhanced. Our results indicate that non-radioactive in situ hybridization method is a powerful technique for analysis of cytokine mRNAs in PBMC at a cellular level. Our results also suggest that mRNA expression of IL-4, IL-5 and IL-6, produced by Th2 cells, is increased in patients with IgA-N. The abnormal regulatory process involved in cytokine expression may play an important immunopathologic role in IgA-N.

Adult↗
PubMed1996

Dentin bonding system. Part I: Literature review.

Currently, clinicians face choices of restoration including amalgams (mercury-based, gallium-based alloys, or mercury-free silver-based substitutes), composite resins, ceramics, and gold alloy. In order to choose an appropriate restorative material, many parameters are involved; they include preparation time requirements, finishing and polishing, marginal integrity, anatomy and contours, chipping and fracture, sensitivity, microleakage, wear resistance, and corrosion resistance. It is generally believed that amalgams are still evaluated as the best of all restorative materials as far as the aforementioned parameters are concerned. It is claimed that the amalgams exhibit in the range of 10 to 25 service years, while the composite resin exhibits ranging between 7 and 11 service years. When a composite resin requires a mass large enough for indirect fabrication, a bonding system is demanded with which this restoration should form an instantaneous, impervious, and stable bond to the tooth structure. Roughly a quarter century has passed since the research and development of a promising dentin bonding system was initiated. We are now in the fifth generation of the dentin bonding system, during the research and development of which various types of bonding agents as well as bonding models have been introduced. In this article, the history of development of the bonding agents and the understanding of the bonding mechanism will be reviewed.

Composite Resins↗
PubMed1996

Dentin bonding system. Part II: Effect of crosshead speed.

Dentin bond strengths are normally evaluated by conducting mechanical tests in tensile and/or shear mode at a certain level of crosshead speed. According to the literature review, crosshead speed is varied in a relatively wide range from 0.1 mm/min to 10.0 mm/min (with the exception of a few studies conducted above 10.0 mm/min). It was also found that crosshead speeds of 0.5, 1.0, 2.0 and 5.0 mm/min were commonly employed to evaluate dentin bond strengths for both tensile and shear modes, although no rationale for selecting the crosshead speed was described in the articles. For testing dentin bond strengths, no plastic deformation should be involved, and fracture only should take place during the fracturing process. With the Scotchbond Multiple-Purpose/Z100 bonding system, tensile bond strengths were evaluated at crosshead speeds of 0.1, 0.5, 1.0, 5.0 and 10.0 mm/min. It was found that (i) there was no strain rate sensitivity when the test was conducted below the 1.0 mm/min crosshead speed, and (ii) if the crosshead speed exceeded 1.0 mm/min, a strain rate dependency of the tensile bond strengths was observed. Knowledge that the composite resin (Z100) did not exhibit strain rate dependency influenced the conclusion that (iii) the above observed strain rate dependency was solely due to the mechanical response from the bonding interface region.

Bias↗
PubMed1996

[Epidural catheterization dose not meet our expectation].

According to the roentgenographically confirmed intervertebral space at which an epidural catheter was placed, 241 patients who underwent abdominal or orthopedic hip surgery were allocated into 3 groups. Groups A, B, and C received epidural catheterization at Th7-10, Th10-L1, and L1-4, respectively. In each group, we examined the intervertebral space, which the anesthesiologist who had placed epidural catheter had determined, and the one which had been confirmed roentgenographically. We also investigated the catheter movement during the postoperative period. Catheters were barely placed at the same intervertebral space which had been confirmed roentgenographically. Considering the iliac crest as a landmark of L3-4 intervertebral space, the puncture point agreed with the roentgenographically confirmed intervertebral space with a percentage of 33 in group A. The extent of agreement increased up to 47 and 55 percent, in groups B and C, respectively. In contrast, when we counted down from the cervical prominent vertebra, a landmark of C7, the agreement was better in group A (55%) than in group C (33%). In the postoperative period, catheters came out more frequently in groups A and B than in group C, resulting from the early ambulation in abdominal surgery groups. There results suggest that, to place the epidural catheter more properly, (1) we should start to count from the landmark which is close to the puncture point and (2) we should keep it in mind that catheters come out accidently in patients who are encouraged to ambulate in the early postoperative period.

Aged↗
PubMed1996

[Intraoperative ST-T depression during extreme hemodilution].

A 45 year old woman undergoing a removal of cerebral arterio-venous malformation, suffered an unexpected massive bleeding. With transfusion of plasma constituents, her hemoglobin concentration decreased to about 5 g.dl-1, but her hemodynamic parameters remained unchanged. Electrocardiogram showed a depressed ST segment, indicating myocardial ischemia, when hemoglobin concentration decreased to 2.2 g.dl-1. Accompanied with the ECG change, her blood pressure fell down from 110/70 mmHg to 70/40 mmHg and an elevation of CVP was observed. With rapid transfusion of concentrated red cell and whole blood, hemodynamic parameters as well as ECG change were restored to normal. With hemodilutional myocardial ischemia which is caused by acute massive bleeding, hemoglobin concentration of about 2 g.dl-1 would be critical.

Anesthesia, General↗
PubMed1996

[Magnetic resonance studies of dentato-rubro-pallido-luysian atrophy--correlation with clinical severity and age of onset].

Dentato-rubro-pallido-luysian atrophy (DRP-LA) is a rare autosomal dominant neurodegenerative disorder. Recently the genetic abnormality has become clear. We encountered four patients with DRPLA (including a 14-year-old boy and his father) in whom the final diagnosis was made by DNA analysis. In addition to performing conventional MRI, we quantified brain metabolites by proton MR spectroscopy. We also compared the expanded repeat size of CAG trinucleotide in a gene on the short arm of chromosome 12 to the MR findings which consisted of the findings of clinical severity and age of onset. The method reported by Nagafuchi et al. was used to determine the size of the CAG repeat on the focus chromosome. Repeat size was closely correlated with age at onset and disease severity. The MR studies were performed with a Magnetum H-15SP (Siemens, 1.5 Tesla) equipped with a C-P type head coil. Axial T2-WIs (TR = 2000 ms, TE = 90 ms) and T1-WIs (TR = 200 ms, TE = 15 ms) were measured. Atrophy of the brainstem, the tegmentum, and the cerebellum, and periventricular hyperintensity could be seen. The sequence for 1H-MRS was PRESS, voxel size was 8 ml, and regions of interest were placed on right basal ganglia and right parietal white matter. After compensating the observed signals, we obtained metabolite concentrations by using compensated water intensity as an internal standard. Despite the absence of abnormalities of the basal ganglia on MRI, NAA concentrations differed from patient to patient and were low in severe clinical cases. We propose that the CAG repeat size of the focus chromosome and NAA concentration quantified by 1H-MRS are closely correlated with clinical severity and age of onset. In conclusion, DNA analysis may be useful in early diagnosis and 1H-MRS can detect metabolic abnormalities non-invasively even when no markedly abnormal findings can be detected with other clinical modalities.

Adolescent↗
PubMed1996

[The spread of contrast medium in the epidural space and the analgesic area in epidural anesthesia in elderly patients].

We evaluated the relationship between the spread of contrast medium in epidural space and the analgesia area in epidural anesthesia in elderly patients. The spread of contrast medium was examined radiographically after the injection of iotrolan 5 ml through the epidural catheter and the analgesia area was examined by pin prick following the epidural injection of the same volume of 1% lidocaine. In lumbar group (group L) (n = 10), the radiographic spread was 10.4 (4-17) segments (mean, minimum-maximum) and the analgesic area was 8.5 (4-15) dermatomes. In cervical or thoracic group (group C/T) (n = 10), the radiographic spread was 12.4 (8-17) segments and the analgesic area was 10.4 (6-15) dermatomes. The dose of local anesthetics required to get analgesia per. one dermatome was 0.7 (0.3-1.3) ml in group L and 0.5 (0.3-0.8) ml in group C/T. The spread of contrast medium correlated well with the analgesic area in both groups (group L:Y = 0.79X + 0.31, r = 0.92, group C/ T:Y = 0.80X + 0.52, r = 0.79). The mean dose of local anesthetics required for analgesia was smaller than that of previous reports although individual variations were large. We conclude that the spread of contrast medium is useful for predicting the spread of epidural block.

Aged↗
PubMed1996

[Immunohistochemical study of PCNA, p53 gene product and c-erbB-2 gene product in endometrial carcinoma].

I have investigated 84 endometrial specimens (from 15 cases of normal endometrium, 20 cass of hyperplasia and 49 cases of endometrial carcinoma) to determine the relationship between three proteins (proliferating cell nuclear antigen (PCNA), p53 gene product and c-erB-2 gene product) and endometrial carcinoma by immuno-histochemical staining. In 49 cases of endometrial carcinoma, the positive rates for PCNA, p53 protein (mutant type) and c-erbB-2 protein were 65.3%, 59.2% and 22.4%. I could not find the expression of p53 protein besides endometrial carcinoma. And I could find the expression of c-erbB-2 protein in 11 cases of endometrial carcinoma and 1 case of atypical hyperplasia, but not in normal endometrium. p53 protein was more common in such a case, as with lymphnode metastasis, deep myometral invasion and undifferentiated adenocarcinoma. c-erbB-2 was also more common in a case with deep myometrial invasion. In conclusion, PCNA, p53 protein and c-erbB-2 protein are related to the proliferation of endometrial carcinoma. So they can be useful factors in making the prognosis.

Adult↗
PubMed1996

Body mass index is a determinant of blood pressure in young adults with essential hypertensive parents. Health Care Programme of University of Tokyo.

We analysed blood pressure (BP) and various parameters related to glucose metabolism in 10,867 Japanese university students aged 19.22 +/- 0.01 years, and investigated the relationship between the subject's own BP and hypertension in close relatives. After 2 years we also examined a subset of these students enrolled in 1993. BP levels in subjects having hypertensive parents were normotensive, but significantly higher than those in subjects without hypertensive relatives or only with hypertensive grandparents. The close the genetic relationship was, the higher the subject's own BP levels. In subjects with hypertensive parents, the subject's own mean BP levels correlated significantly with the subject's own body mass indices. This correlation was much weaker in subjects without hypertensive relatives and those having only second degree relatives with hypertension. In addition, the BP levels in the offspring of hypertensive parents correlated with glutamyl-oxaloacetic transaminase. In the follow-up study in 1995, the correlation between BP levels and body mass index (BMI) was observed in this subgroup. Moreover, the subjects with hypertensive parents tended to have a higher plasma insulin level than those without hypertensive relatives. It is suggested that BP is more likely to be determined by BMI in the individuals with a genetic predisposition to hypertension.

Adult↗
PubMed1995

PTB domains of IRS-1 and Shc have distinct but overlapping binding specificities.

PTB domains are non-Src homology 2 (SH2) phosphotyrosine binding domains originally described in the receptor tyrosine kinase substrate, Shc. By serial truncation, we show that a 174-residue region of Shc p52 (33-206) has full PTB activity. We also show that a 173-residue region of insulin receptor substrate-1 (IRS-1; residues 144-316) has related PTB activity. In vitro both domains bind directly to activated insulin receptors. Binding is abrogated by substitution of Tyr-960 and selectively inhibited by phosphopeptides containing NPXY sequences. Phosphopeptide assays developed to compare PTB domain specificities show that the Shc PTB domain binds with highest affinity to psi XN beta 1 beta 2 pY motifs derived from middle T (mT), TrkA, ErbB4, or epidermal growth factor receptors (psi = hydrophobic, beta = beta-turn forming); the IRS-1 PTB domain does not bind with this motif. In contrast, both the Shc and IRS-1 PTB domains bind psi psi psi XXN beta 1 beta 2pY sequences derived from insulin and interleukin 4 receptors, although specificities vary in detail. Shc and IRS-1 are phosphorylated by distinct but overlapping sets of receptor-linked tyrosine kinases. These differences may be accounted for by the inherent specificities of their respective PTB domains.

3T3 Cells↗
PubMed1995

The effect of fatigue caused by electrical induction or voluntary contraction on Ia inhibition in human soleus muscle.

A comparison of the effect of fatigue caused by electrical induction or voluntary contraction on Ia inhibition in human soleus muscle was investigated in fourteen healthy male subjects. The Hoffmann reflex (H reflex) was employed to elucidate the contribution of fatigue induced contraction to the Ia inhibition. A statistically significant difference (P < 0.05) in H reflex amplitude between the intermittent stimulation at 15 Hz and voluntary contraction was observed. Our study suggested that Ia inhibition in human soleus muscle, caused by electrically induced or voluntary contraction, induced differences in the number of impulses in the group Ia fibers, between the two conditions.

Adult↗