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Biomedical subjects

I Miyamoto

Publications and source records attributed to I Miyamoto.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacokinetic properties of a novel tissue-type plasminogen activator pamiteplase after single intravenous administration to rats, dogs, and monkeys.

The pharmacokinetics of pamiteplase and recombinant tissue-type plasminogen activator (rt-PA) in rats, dogs, and monkeys were examined using a newly developed enzyme-linked immunosorbent assay (ELISA). Plasma concentrations after intravenous administration of pamiteplase to rats declined in a triphasic manner. Plasma concentrations after intravenous administration of pamiteplase to dogs or monkeys declined in a biphasic manner. The area under the plasma concentration-time curve from zero to infinity (AUC(0-->infinity)) in rats and dogs increased with increasing dose. The half-life and mean residence time of pamiteplase in rats, dogs, and monkeys were shown to be longer than those of rt-PA. Total clearance (CL(total)) of pamiteplase was only 7-16% that of rt-PAs, suggesting that concentrations of pamiteplase in plasma were higher and more continuous than those of rt-PA in these experimental animals. The data suggest that a bolus administration of pamiteplase shows the same thrombolytic activity as continuous infusion of rt-PA in experimentally induced thrombosis in rats and dogs. The pharmacokinetic parameters distribution volume at the steady state and CL(total) calculated by immunoreactive concentration after administration of pamiteplase to rats, dogs, and monkeys show high correlation with body weights (r(2)=.7728 and .9039).

Animals↗
PubMed2000

Determination, pharmacokinetics and protein binding of a novel tissue-type plasminogen activator, pamiteplase in human plasma.

1. An enzyme-linked immunosorbent assay (ELISA) and functional bioassay to determine immunoreactive and bioactive concentrations of pamiteplase, a novel thrombolytic agent, in human plasma were developed. The ELISA and functional bioassay showed satisfactory accuracy and precision within a concentration range of 0.5-25 ng.ml(-1) and of 0.127-16.2 ng.ml(-1) respectively. 2. The pharmacokinetics of pamiteplase in healthy human subjects were evaluated using the ELISA and functional bioassay. Irrespective of the method used, plasma concentrations declined bi-exponentially. Half-lives in the beta phase were 1.25 and 0.78 h, and AUCs were 507.9 and 286.4 ng.h.ml(-1) respectively. Total clearances of pamiteplase decreased to 19 and 31% of those of the wild-type tissue-type plasminogen activator. 3. The protein binding of pamiteplase in human plasma was investigated by gel filtration chromatography. Pamiteplase formed three high molecular weight complexes with alpha2-macroglobulin, C1-esterase inhibitor and alpha2-plasmin inhibitor in human plasma. This complex formation was relatively slow, and was thought to be irreversible and covalently bounded. Furthermore, this protein binding in humans resulted in the termination of biological action.

Adult↗
PubMed1999

Atomic force microscopic study of commercially available implant abutments.

BACKGROUND: Clinical studies have reported a correlation between the surface roughness of implant abutments and the rate of supragingival and subgingival plaque formation. In order to maintain periimplant health, it is important to understand the relationship between abutment surface characteristics and plaque formation. PURPOSE: The aim of this study was to use high image resolution imaging techniques for analysis of implant abutment surface topography. MATERIALS AND METHODS: Five commercially available implant abutments (Brånemark, Nobel Biocide, AB, Goteborg, Sweden, Astra, Astra Tech AB, Mondal, Sweden, IMZ, Friatec AG, Mannheim, Germany, Steri-Oss, Denar Corp, Anaheim, Calif, USA, and POI, Kyocera Corp, Kyoto, Japan) were visually and quantitatively characterized using an atomic force microscope. RESULTS: Statistical analysis by analysis of variance and Fishers's Protected Least Significant Differences showed significant differences (p < .05) between arithmetic mean deviation values of surface relative to the center plane (Sa). Power spectral density analysis also was effective as a spacing parameter. Sectional profiles measured the exact length, depth, or height of the specific features on the images. CONCLUSIONS: Within the limits of this study, the Brånemark, Astra and IMZ abutments displayed turning marks in x direction from the procedure. The Steri-Oss abutment showed smoothest surface among the five abutments tested.

Analysis of Variance↗
PubMed1999

Adrenocortical insufficiency associated with long-term high-dose fosfestrol therapy for prostatic carcinoma.

A 59-year-old man was admitted to our hospital because of muscular pain, weakness, and anorexia. He had been treated with 600 mg/day of fosfestrol, a synthetic estrogen, for 10 years for prostatic carcinoma. Endocrinological studies demonstrated adrenocortical insufficiency due to inadequate ACTH secretion. After initiation of glucocorticoid replacement therapy, his symptoms subsided rapidly. To our knowledge, an association between estrogenic agents, including fosfestrol, and secondary adrenocortical insufficiency has not been previously reported. Physicians who treat patients with long-term and high-dose strong estrogenic agents should be cautious about the possible emergence of secondary adrenocortical insufficiency.

Adrenal Insufficiency↗
PubMed1999

[Fetal megacystis with idiopathic intestinal pseudo-obstruction syndrome: a case report].

A 2,510 g female newborn was delivered by Cesarean section at 33 weeks gestation due to increasing volume of her huge bladder and bilateral hydronephrosis. Just after birth 190 ml of urine was drainaged by catheterization without difficulty. Voiding cystourethrography showed no VUR. She had no ureteral dilation, either. Urodynamic study revealed large bladder capacity and detrusor hypocontractility. Neither neurological nor gastrointestinal abnormality was detected neonatally. Clean intermitted catheterization was performed every 4 hours. At 12 months of her age she had no history of urinary tract infection. However, as she grew up with normal diet, severe constipation became apparent. This is a case of idiopathic intestinal pseudo-obstruction syndrome whose gastrointestinal symptom was masked in the newborn period. Attention should be paid for gastrointestinal tract as well as urinary tract when the body has congenital megacystis with unknown etiology.

Female↗
PubMed1998

Elevated serum levels of soluble vascular cell adhesion molecule-1 in NIDDM patients with proliferative diabetic retinopathy.

We studied 68 Japanese NIDDM patients (38 men and 30 women), aged 56.9+/-1.2 years (range 33-75 years), with a BMI of 23.1+/-0.5 kg/m2 without hypertension, dyslipidemia, and diabetic macroangiopathy for evaluating the relationship between serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and the severity of diabetic retinopathy. Fundus examination was performed by an ophthalmologist using an ophthalmoscope, and the findings were graded as: (1) no signs of diabetic retinopathy (NDR), (2) background diabetic retinopathy (BDR), or (3) proliferative diabetic retinopathy (PDR). Serum sVCAM-1 levels were measured in duplicate by enzyme-linked immunosorbent assay using the soluble VCAM-1 KIT (R&D Systems Ltd., Ablingdon, Oxfordshire, UK). There was no difference in serum sVCAM-1 levels between patients with BDR (n = 17) and patients with NDR (n = 40) (1035.3+/-104.4 and 978.8+/-48.9 ng/ml, respectively, P = 0.8), but patients with PDR (n = 11) showed a significant increase of serum sVCAM-1 levels compared with patients with NDR (1281.8+/-166.3 and 978.8+/-48.9 ng/ml, respectively, P = 0.02). Although serum sVCAM-1 levels were correlated, not only with age but also with the known diabetic duration (r = 0.39, P = 0.001, and r = 0.40, P = 0.0007, respectively), age-adjusted sVCAM-1 levels were still significantly higher in the PDR group than in the NDR group. In contrast. serum sVCAM-1 levels were not related to the presence of diabetic nephropathy or HbA1c levels. Our results suggest that sVCAM-1 might be implicated in the development of the diabetic retinopathy, and measurement of serum sVCAM-1 levels in NIDDM patients maybe clinically useful for assessing the severity and possibly the activity of diabetic retinopathy.

Adult↗
PubMed1998

Lower urinary tract problems in patients with enuresis.

OBJECTIVE(S): Two hundred and thirty-eight children (170 males, and 68 females) with nocturnal enuresis were retrospectively studied for lower urinary tract problems. Surgical correction of subclinical organic obstruction in the lower urinary tract was evaluated for the improvement of bed-wetting. METHODS: One hundred and fifty-five micturating cystourethrography (MCU), and 89 urodynamic studies were performed. Optic internal urethrotomy was done in a boy, and meatoplasty in a girl for urethral 'ring' stenosis (URS). RESULTS: Nocturnal enuresis was found in 153 cases and nocturnal enuresis associated with daytime enuresis in 67 cases. Vesicoureteral reflux was found in 30, URS in 42, and posterior urethral valve in 3 cases on MCU. Detrusor instability was recognized in 39.4% of 38 cases of nocturnal enuresis associated with daytime enuresis and in 25.0% of 51 cases of nocturnal enuresis. Surgery brought 73.8% improvement of bed-wetting in 42 cases. CONCLUSIONS: Surgical correction of subclinical obstruction in the lower urinary tract might contribute to the earlier resolution of bed-wetting in children with nocturnal and/or diurnal enuresis.

Adolescent↗
PubMed1997

Pharmacological and pharmacokinetic characteristics of YM435, a novel dopamine DA1-receptor agonist, in anaesthetized dogs.

Time-course of plasma concentration of unchanged drug of the dopamine DA1-receptor agonist (-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy-1,2,3,4- tetrahydroisoquinoline hydrochloride hydrate (YM435), and its effects on blood pressure and renal blood flow were investigated in anaesthetized dogs. Continuous intravenous infusion of YM435 (0.1-3 micrograms kg-1 min-1) rapidly increased renal blood flow and lowered blood pressure in a dose-dependent manner. These effects remained generally stable throughout the infusion period. Following the start of infusion, plasma concentration of unchanged drug also rose rapidly and dose-dependently and remained virtually constant throughout the infusion period. A significant correlation was observed between log YM435 plasma concentration and the increase in renal blood flow (r = 0.93, P < 0.0001) and between the former and the reduction in blood pressure (r = 0.93, P < 0.0001). The present results indicate that YM435 produces renal vasodilatation and lowering of blood pressure in a dose-dependent manner and with rapid onset following continuous intravenous infusion, and that these effects are generally stable throughout the period of infusion. These haemodynamic effects of YM435 were in good agreement with the time-course of plasma concentration of unchanged drug.

Animals↗
PubMed1996

[Peculiar cemental lesion of the jaws--its pathological entity and natural history].

Two hundred fifty-five solitary and 42 multiple cases of fibro-osseous lesions of the jaws, and 74 cases of sclerosing osteomyelitis were studied clinico-pathologically, in order to discuss the entity of peculiar cemental lesion with sequester-like appearance, which occurs mainly in the mandibular molar area of over middle-aged females. Four allied lesions, including the sequester-like cemental lesion, were revealed. They were provisionally designated sequestrated cemental masses, cemental masses, focal cemento-osseous dysplasia, and periapical cemental masses respectively, because no entities that were consistent with them could be found in the classifications of World Health Organization (WHO). The above- mentioned peculiar cemental lesion was equivalent to sequestrated cemental masses, which consist of sclerotic cementum and/or osteocementum with inflammation. Cemental masses and periapical cemental masses were related to sequestrated cemental masses. Focal cemento- osseous dysplasia was considered to be a counterpart of lesion which had been recently reported by Summerlin et al. In consideration of similarity and continuity of the histological and clinical findings, the four allied lesions were thought to be arranged in a continuous spectrum of fibro-cemento-osseous dysplasia of the jaws, along with periapical cemental dysplasia and florid cemento-osseous dysplasia that are mentioned in the WHO classification.

Dental Cementum↗
PubMed1994

Asymptomatic vesicoureteral reflux in children.

Between 1973 and 1992, a routine voiding cystourethrography screening was performed in all children attending our urological clinic. A total of 1023 children were diagnosed as cases of primary vesicoureteral reflux; 166 (210 renal units) of them were asymptomatic and were studied retrospectively. Ninety-one patients presented with enuresis, 39 with hypospadias, 14 with undescended testis, 8 with asymptomatic proteinuria and 14 had other manifestations such as intersexuality, inguinoscrotal swelling, abnormal external genitalia, etc. We documented high-grade reflux (IV-V) in 16.2% and renal scarring in 16.7% of the 210 renal units. None of the children showed features of urinary tract infection (UTI) or had a definite history in the past, but 23.5% of the 166 cases developed UTI during their follow-up period. Spontaneous resolution of reflux was observed in 52.7% of the 150 renal units and progression of renal scarring in 20% during follow-up. Antireflux operation was performed in 15 cases (26 renal units). In 9 children (5.4%) we found gross renal damage which progressed in two cases to end-stage renal disease followed by renal transplantation. A small kidney was noted in 5 patients and hypertension in two. It is concluded that the natural history of asymptomatic reflux is almost the same as in symptomatic reflux. Thus, routine voiding cystourethrography is suggested in all children attending a urological clinic in order to detect reflux as early as possible.

Adolescent↗
PubMed1994

The XPA protein is a zinc metalloprotein with an ability to recognize various kinds of DNA damage.

The XPA (xeroderma pigmentosum group A) gene encodes a protein of 273 amino acids with a zinc finger motif. The human XPA cDNA was placed in an Escherichia coli expression vector for the synthesis of the recombinant XPA protein. The molecular weight of the wild-type protein was about 40 kDa in SDS-PAGE. Microinjection of the wild-type protein specifically restored the defect of UV-induced unscheduled DNA synthesis in XP-A cells. Thus, the bacterially expressed XPA protein retains biochemical properties identical to those of natural sources. The wild-type protein binds preferentially to UV-, cis-diamminedichloroplatinum(II) (cisplatin)- or osmium tetroxide (OsO4)-damaged DNA as assayed by retention on nitrocellulose filters. In addition, the data from atomic absorption and UV-CD spectra revealed that the wild-type protein is a zinc metalloprotein with secondary structure. Furthermore, the mutant protein, of which the cysteine-103 residue in the zinc finger motif was replaced with serine, has a vastly different protein conformation resulting in a loss of XP-A correcting and DNA-binding activities. These findings indicate that the XPA protein is a zinc-binding protein with affinity for various DNA damages, and a cysteine residue in the C4-type zinc finger motif is indispensable for normal protein conformation.

Amino Acids↗
PubMed1993

Isolation of a Drosophila gene encoding a head-specific guanylyl cyclase.

We have isolated and characterized a new guanylyl cyclase gene (dgc1) in Drosophila. The deduced amino acid sequence (683 amino acids) most closely resembled the mammalian soluble-type guanylyl cyclase alpha subunit. The cyclase catalytic domain was highly conserved between the mammalian and Drosophila guanylyl cyclases. The dgc1 mRNA was detected in wild-type heads but not in bodies, and its level was reduced in the mutant eyes absent (eya), indicating that dgc1 is preferentially expressed in the CNS and in the eye. The enriched distribution in the eye suggests that dgc1 may have a role in phototransduction.

Amino Acid Sequence↗
PubMed1993

Flavin-photosensitized monomerization of dimethylthymine cyclobutane dimer in the presence of magnesium perchlorate.

We have investigated the photosensitized monomerization of the cis,syn-cyclobutane dimer of 1,3-dimethylthymine using riboflavin tetraacetate and a 5-deazaflavin derivative as photosensitizer. Although little monomerization of the dimer is induced by photoexcitation of the flavins in the absence of any additives, the flavins can function as an efficient photosensitizer in the presence of magnesium perchlorate. Mechanistic studies involving spectroscopic, quantum-yield and flash-photolysis measurements demonstrated that the photosensitized monomerization exclusively proceeds through electron transfer from the dimer to the triplet flavins complexed with Mg2+. The effects of magnesium perchlorate are compared with those on the chloranil-photosensitized monomerization and also with the effects of HClO4 on the flavin-photosensitized reaction.

Flavins↗
PubMed1993

[Liver impairment in kidney transplant recipients. 1. Prevalence and clinical significance of hepatitis C].

The prevalence and the clinical significance of hepatitis C (HCV) infection in recipients of kidney transplantation was assessed using second generation anti-HCV antibody (anti-HCV-2). Out of 88 patients whose preoperative sera were available for anti-HCV-2 determination, 27 patients (30.7%) were positive. Transfusion units were significantly larger and the duration of hemodialysis was significantly longer in the patients with anti-HCV-2 than those without. In 10 patients whose preoperative sera were negative for anti-HCV-2, seroconversion was documented after the operation, so that the postoperative positive rate of anti-HCV-2 increased to 42.9% (39/91). Seroconversion from positive to negative was observed in only one patient. Out of 91 patients who were followed-up at least 3 months after operation, 66 patients (72.5%) developed liver dysfunction. According to the criteria of non-A, non-B post-transfusion hepatitis established by the Japanese Society of Digestive Disease, 31 of 66 patients (34.1%) were diagnosed as "definite", 21 patients (23.1%) as "suspicious". The anti-HCV-2 positive rate was 90.3% in the "definite" group, which was significantly higher than the other groups. Liver dysfunction in the patients with anti-HCV-2 had a tendency for a chronic or prolonged course. Out of 20 patients in whom liver dysfunction continued for more than 1 year, 18 patients were positive for anti-HCV-2. It is concluded from this study that the prevalence of hepatitis C is very high in kidney transplant recipients with HCV as the main and most important etiologic factor of liver dysfunction, especially in chronic liver impairment.

Adolescent↗
PubMed1992

Mutational analysis of the structure and function of the xeroderma pigmentosum group A complementing protein. Identification of essential domains for nuclear localization and DNA excision repair.

We showed previously that the xeroderma pigmentosum group A complementing (XPAC) protein involved in the DNA excision repair pathway contains a zinc-finger motif and is localized in the nucleus of normal human cells. For detailed structural and functional analyses of the XPAC protein, we constructed various XPAC cDNAs by site-directed mutagenesis and isolated permanent cell lines expressing mutant proteins. Immunofluorescent analysis of these lines indicated that the nuclear localization signal is located in the region encoded by Exon 1, especially centered at amino acids 30-42. A UV survival study showed that regions from Exons 2 through 6 were essential for DNA repair function, but that Exon 1 was not. Interestingly, deletion of the glutamic acid cluster in the region encoded by Exon 2 resulted in a dramatic loss of DNA repair activity. Furthermore, replacements of each of the 4 cysteines supposed to form a zinc-finger structure in the region encoded by Exon 3 by serine or glycine resulted in similar levels of loss of repair activity. These results suggest that all 4 cysteines forming a zinc-finger structure and also the glutamic acid cluster are important for DNA repair function.

Amino Acid Sequence↗
PubMed1992

Characterization of the insulin resistance in liver cirrhosis: a comparison with non-insulin dependent diabetes mellitus.

To characterize the mechanisms of insulin resistance in liver cirrhosis (LC), we estimated the peripheral tissue sensitivity and responsiveness to insulin using the euglycemic clamp technique and determined the insulin binding to erythrocytes in patients with compensated LC as well as in patients with non-insulin dependent diabetes mellitus (NIDDM). The insulin dose-response curves of the glucose metabolic clearance rates (MCR) were shifted to the right and downward both in patients with LC and NIDDM, indicating a reduced sensitivity and responsiveness to insulin. In the cirrhotics, MCR at the maximally effective insulin level, an index of insulin responsiveness, was correlated with fasting insulin levels (r = -0.57, P < 0.01) and sigma BG in 75 gOGTT (r = -0.43, P < 0.05), but no correlations were found between them and the diabetics. Although specific insulin bindings to erythrocytes were significantly lower in patients both with LC and NIDDM, Scatchard analysis revealed a significant decrease in the number of insulin receptors in the cirrhotics, and a decrease in the empty-site affinity in the diabetics. These findings suggest that insulin resistance in LC consists of a combination of binding and postbinding defects. The latter defect may be caused by basal hyperinsulinemia and contribute to the development of glucose intolerance. Although binding and postbinding abnormalities are also found in NIDDM, the mechanisms of insulin resistance in LC and NIDDM may be different.

C-Peptide↗