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Biomedical subjects

K Miyamoto

Publications and source records attributed to K Miyamoto.

At least 163 records · Page 9Linked to original sources

Effects of anticonvulsants on local anaesthetic-induced neurotoxicity in rats.

The effects of various anticonvulsants on local anaesthetics procaine- and lidocaine-induced convulsions were investigated in rats. Pretreatment with diazepam (2.5-5 mg/kg, intraperitoneally) and clonazepam (5-10 mg/kg, intraperitoneally) completely protected the rats against both local anaesthetic-induced convulsions. Phenobarbital (12.5-50 mg/kg, subcutaneously) also significantly decreased the incidence of both convulsions and prolonged their latencies. Carbabazepine (10-40 mg/kg, intraperitoneally) did not completely repress both convulsions, but it prolonged their latencies. Phenytoin (5-20 mg/kg, intraperitoneally) and primidone (30-60 mg/kg, intraperitoneally) markedly enhanced both local anaesthetic-induced convulsions, as shown by shortening of latency and increase in mortality. Valproate (100-200 mg/kg, intraperitoneally) produced a protective effect against procaine-induced convulsions, while it strongly enhanced lidocaine-induced convulsions. These results suggest that the benzodiazepines are effective drugs to prevent neurotoxicity induced by local anaesthetics, while phenytoin and primidone potentiate them.

Anesthetics, Local↗

Spermatogenic disturbance induced by di-(2-ethylhexyl) phthalate is significantly prevented by treatment with antioxidant vitamins in the rat.

Phthalate esters, now regarded as endocrine disruptors, are widely used in the plastics industry. In particular, di-(2-ethylhexyl) phthalate (DEHP) is produced in large quantities, and is used in blood storage bags, catheters and haemodialysis instruments. Previous studies have demonstrated that treatment of rats with DEHP induces testicular atrophy with liver enlargement, although the precise nature and mechanism of the action of DEHP on these organs remains unclear. In the present study, we produced an experimental model of DEHP-induced spermatogenic disturbance in rats by feeding them a DEHP-containing diet. Liver enlargement occurred in rats fed either a 1 or 2% DEHP-containing diet. However, testicular atrophy accompanied by aspermatogenesis was induced by feeding with the 2% but not with the 1% DEHP-containing diet. This suggests that the critical DEHP dose for gonadotoxicity is higher than that for hepatotoxicity. Using the 2% DEHP-dose, the effect of simultaneous administration of antioxidant vitamins (= vitamins C and E) was next examined. It was found that the vitamin supplementation significantly prevented the testicular injury. The results suggest that antioxidant vitamins can protect the testes from DEHP-toxicity.

Animals↗

Studies on hemodynamic instability in paroxysmal supraventricular tachycardia: noninvasive evaluations by head-up tilt testing and power spectrum analysis on electrocardiographic RR variation.

Hemodynamic instability is a crucial determinant of the best therapeutic option in paroxysmal supraventricular tachycardia (PSVT). However, it is still unclear if hemodynamic instability is tachycardia dependent or independent. We performed frequency-domain analysis of electrocardiographic RR variations during induced PSVT and head-up tilt tests after successful ablation to investigate the role of autonomic vasomotor function in hemodynamic instability during PSVT. Thirty-six patients with (syncope group, n = 18) and without (nonsyncope group, n = 18) syncope and/or presyncope during PSVT were enrolled in this study. Serial blood pressure, heart rate, and variations in heart rate during induced PSVT and head-up tilt tests were examined. Initial blood pressure fall and heart rate changes during induced PSVT were greater in the syncope group than in the nonsyncope group. A significant positive linear relationship was found between these two. Delayed blood pressure fall was observed in the syncope group, independent of heart rate changes. Syncope in PSVT could be predicted from the results of head-up tilt tests with 82% accuracy. Heart rate responses after isoproterenol infusion were significantly greater in the syncope group than in the nonsyncope group. The changes in low frequency to high frequency (LF:HF) values during induced PSVT and head-up tilt tests were significantly greater in the syncope group than in the nonsyncope group, and an exponential correlation was found between LF:HF changes in both tests. We conclude that PSVT rate and vasomotor reaction are related with hemodynamic instability during PSVT and head-up tilt testing is a useful method for determining if patients will have syncope during PSVT.

Adolescent↗

Outbreak of human parvovirus B19 in hospital workers.

We report an outbreak of human parvovirus B19 (HPV B19) infection affecting five nursing staff, four hospital office workers and one physiotherapist and its possible transmission between hospital staff. We investigated the presence of the virus in serum specimens using a nested PCR assay to confirm HPV B19 infection. The viral genome was detected in serum specimens from a nurse with a rash and arthralgia and from three hospital office workers with a febrile illness. The DNA sequence of the PCR products from three staff members was identical. Our findings suggest that transmission of HPV B19 between hospital staff members occurred.

Adult↗

Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells: possible association with Na(+), K(+)-ATPase.

Previously, we showed that expression of nm23-H1 is associated inversely with sensitivity to cisplatin in human oesophageal squamous cell carcinoma (OSCC). The present study was undertaken to investigate the association of nm23-H1 expression with cisplatin-induced DNA damage in OSCC using antisense nm23-H1 transfectants. YES-2/AS-12, an antisense nm23-H1-transfected OSCC cell line, showed significantly reduced expression of intracellular nm23-H1 protein compared with that in parental YES-2 cells and YES-2/Neo transfectants. Surface expression of nm23-H1 protein was not observed in any of the three cell lines. PCR analysis for DNA damage demonstrated that YES-2/AS-12 cells were more resistant to nuclear and mitochondrial DNA damage by cisplatin than were YES-2/Neo cells. In addition, mitochondrial membrane potentials and DNA fragmentation assays confirmed that YES-2/AS-12 was more resistant than YES-2/Neo to apoptosis induced by cisplatin. In contrast, YES-2/AS-12 was more sensitive to ouabain, a selective inhibitor of Na(+), K(+)-ATPase, than YES-2 and YES-2/Neo. Pre-treatment with ouabain resulted in no differences in cisplatin sensitivity between the three cell lines examined. Intracellular platinum level in YES-2/AS-12 was significantly lower than that in YES-2 and YES-2/Neo following incubation with cisplatin, whereas ouabain pre-treatment resulted in no differences in intracellular platinum accumulations between the three cell lines. Our data support the conclusion that reduced expression of intracellular nm23-H1 in OSCC cells is associated with cisplatin resistance via the prevention of both nuclear and mitochondrial DNA damage and suggest that it may be related to Na(+), K(+)-ATPase activity, which is responsible for intracellular cisplatin accumulation.

Antineoplastic Agents↗

Masticatory muscle activity in children and adults with different facial types.

The purpose of this study was to examine the relationship between the duration of masticatory muscle activity during daytime and vertical craniofacial morphology in children and adults. Thirty children (12 boys and 18 girls) and 30 adults (20 men and 10 women) with normal anteroposterior skeletal relations, acceptable occlusions, and without any temporomandibular joint disorders, were selected as subjects. Activities of the masseter, temporal, and digastric muscles were recorded for 3 hours during daytime, excluding the periods for meals, sleep, and hard-exercise, using a portable electromyogram recording system. A lateral cephalogram was taken of each subject at the intercuspal position to divide the subjects into 3 different facial types, ie, low, average, and high angle groups. Masseter, temporal, and digastric muscle activities mainly consisted of low-amplitude bursts during daytime. Children exhibited longer duration of temporal muscle activity, whereas the masseter muscle presented longer duration of activity in adults. The activities of masseter and digastric muscles were significantly related with the vertical facial type in both children and adults, although temporal muscle activity presented no significant relationship with the craniofacial morphology. The duration of masticatory muscle activity during daytime showed a significant difference between children and adults, indicating a close association with vertical craniofacial morphology in children and adults.

Adult↗

The salience of visuospatial and organizational skills in reproducing the Rey-Osterreith Complex Figure in subjects with high and low IQs.

The salience of visuospatial and organizational skills in copying the Rey-Osterreith Complex Figure (ROCF) was examined in 44 adults diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). Subjects were divided into a high average and above IQ group (n = 21) and an average and below IQ group (n = 23). Multiple regressions were conducted for both groups, with the ROCF copy as the dependent variable and WAIS-R Block Design and Stern Fragmentation scores as predictor variables. Results indicated that, for the high IQ group, visuospatial skills were more salient in predicting ROCF copy scores. By contrast, for the low IQ group, organizational skills were more salient for predicting ROCF copy score. Our findings are discussed in relation to the Boston Process Approach.

Adult↗

Identification and functional analysis of three isoforms for the Na+-dependent phosphate co-transporter (NaPi-2) in rat kidney.

We have isolated three unique NaPi-2-related protein cDNAs (NaPi-2alpha, NaPi-2beta and NaPi-2gamma) from a rat kidney library. NaPi-2alpha cDNA encodes 337 amino acids which have high homology to the N-terminal half of NaPi-2 containing three transmembrane domains. NaPi-2beta encodes 327 amino acids which are identical to the N-terminal region of NaPi-2 containing four transmembrane domains, whereas the 146 amino acids in the C-terminal region are completely different. In contrast, NaPi-2gamma encodes 268 amino acids which are identical to the C-terminal half of NaPi-2. An analysis of phage and cosmid clones indicated that the three related proteins were produced by alternative splicing in the NaPi-2 gene. In a rabbit reticulocyte lysate system, NaPi-2alpha, beta and gamma were found to be 36, 36 and 29 kDa polypeptides, respectively. NaPi-2alpha and NaPi-2gamma were glycosylated and revealed to be 45 and 35 kDa proteins, respectively. A functional analysis demonstrated that NaPi-2gamma and alpha markedly inhibited NaPi-2 activity in Xenopus oocytes. The results suggest that these short isoforms may function as a dominant-negative inhibitor of the full-length transporter.

Animals↗

A role of insulin-like growth factor I for follicle-stimulating hormone receptor expression in rat granulosa cells.

The present study was undertaken to identify the mechanisms underlying the effect of insulin-like growth factor I (IGF-I) on FSH receptor (FSHR) in rat granulosa cells. Treatment with FSH produced a substantial increase in FSHR mRNA level, as was expected, while concurrent treatment with increasing concentrations of IGF-I brought about dose-dependent increases in FSH-induced FSHR mRNA, with a maximal response 2.8-fold greater than that induced by FSH alone. IGF-I, either alone or in combination with FSH, did not affect intracellular cAMP levels, whereas it enhanced the effect of 8-bromo (Br)-cAMP on FSHR mRNA production. Taken together, these findings suggest that the ability of IGF-I to enhance FSH action concerning the induction of FSHR is exerted at sites distal to cAMP generation. We then investigated whether the effect of IGF-I and FSH on FSHR mRNA levels was the result of increased transcription and/or altered mRNA stability. The rates of FSHR mRNA gene transcription, assessed by nuclear run-on transcription assay, were not increased by the addition of IGF-I. On the other hand, the decay curves for the 2. 4-kilobase (kb) FSHR mRNA transcript in primary granulosa cells significantly altered the slope of the FSHR mRNA decay curve in the presence of IGF-I and increased the half-life of the FSHR mRNA transcript. These data suggest a possible role for changes in FSHR mRNA stability in the IGF-I-induced regulation of FSHR in rat granulosa cells. Treatment with activin produced a substantial increase in FSHR mRNA level, as was expected, and concurrent treatment with IGF-I did not affect activin-induced FSHR mRNA. Our data suggest that the IGF-I effect on FSHR expression is related to cAMP production induced by FSH and may maintain FSHR mRNA level because of prolonged FSHR mRNA stability.

8-Bromo Cyclic Adenosine Monophosphate↗

Free water 3H concentration in diet samples collected from 1969 to 1988 in Akita, Japan.

Fallout 3H concentrations in diet samples collected from 1969 to 1988 in Akita Prefecture are reported. Since the data for samples from the 1960's and 1970's are important to understand the long-term movement of 3H in the environment, we searched for old diet samples. Recently, diet samples collected in Akita Prefecture during 1969-1982 were found and subjected to 3H analysis. The samples were originally gathered for nutrition survey programs and had been stored in a refrigerated warehouse at -20 degrees C until we located them. The free water 3H concentrations in the samples were measured and are reported here. The present results are combined with already published data; together they show 3H concentrations exponentially decrease from 1969 to 1988 with an apparent half time of 5.9 y. Levels of diet free water 3H concentrations are also similar to measured and estimated precipitation 3H concentrations in Akita City.

Diet Surveys↗

Effects of 1-methyl-3-propyl-7-butylxanthine (MPBX) on idarubicin-induced antitumor activity and bone marrow suppression.

The effects of 1-methyl-3-propyl-7-butylxanthine (MPBX), a xanthine derivative, on idarubicin (IDA)-induced antitumor activity against P388 leukemia cells (P388) and bone marrow suppression were examined. In P388 tumor-bearing mice, the combination of MPBX with IDA increased the antitumor activity of IDA. The IDA concentration in the tumors in the MPBX combination group increased by 2.0-fold compared to the level in the IDA-alone group. On the other hand, as regards IDA-induced bone marrow suppression, the combination of MPBX with IDA reduced the decrease in the bone marrow cell number by 30% compared to that in the IDA-alone group. In addition, the IDA concentration in the bone marrow cells was decreased by the combination of MPBX with IDA. An in vitro experiment showed that MPBX facilitated IDA influx and suppressed IDA efflux in P388 cells. In conclusion, the combination of MPBX with IDA increased the antitumor activity and decreased the bone marrow suppression. Therefore, we expect that the combination of MPBX with IDA will be useful for leukemia chemotherapy.

Animals↗

Faropenem transport across the renal epithelial luminal membrane via inorganic phosphate transporter Npt1.

We previously showed that the mouse inorganic phosphate transporter Npt1 operates in the hepatic sinusoidal membrane transport of anionic drugs such as benzylpenicillin and mevalonic acid. In the present study, the mechanism of renal secretion of penem antibiotics was examined by using a Xenopus oocyte expression system. Faropenem (an oral penem antibiotic) was transported via Npt1 with a Michaelis-Menten constant of 0.77 +/- 0.34 mM in a sodium-independent but chloride ion-sensitive manner. When the concentration of chloride ions was increased, the transport activity of faropenem by Npt1 was decreased. Since the concentration gradient of chloride ions is in the lumen-to-intracellular direction, faropenem is expected to be transported from inside proximal tubular cells to the lumen. So, we tested the release of faropenem from Xenopus oocytes. The rate of efflux of faropenem from Npt1-expressing oocytes was about 9.5 times faster than that from control water-injected Xenopus oocytes. Faropenem transport by Npt1 was significantly inhibited by beta-lactam antibiotics such as benzylpenicillin, ampicillin, cephalexin, and cefazolin to 24.9, 40. 5, 54.4, and 26.2% of that for the control, respectively. Zwitterionic beta-lactam antibiotics showed lesser inhibitory effects on faropenem uptake than anionic derivatives, indicating that Npt1 preferentially transports anionic compounds. Other anionic compounds, such as indomethacin and furosemide, and the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid significantly inhibited faropenem uptake mediated by Npt1. In conclusion, our results suggest that Npt1 participates in the renal secretion of penem antibiotics.

Animals↗

A serine protease-encoding gene (aprII) of Alteromonas sp. Strain O-7 is regulated by the iron uptake regulator (Fur) protein.

The ferric uptake regulator (Fur) box-like sequence was located upstream of the serine protease-encoding gene (aprII) from a marine bacterium, Alteromonas sp. strain O-7. To clarify whether the production of AprII (the gene product of aprII) is regulated by the environmental iron concentrations, this strain was cultured under iron-depleted or iron-rich conditions and the level of AprII in the culture supernatant was analyzed by Western blotting. The production of AprII was significantly repressed under iron-rich conditions. Northern hybridization analysis demonstrated that AprII biosynthesis was regulated by iron through the control of transcription. These results indicate that aprII is a new member of the iron regulon and plays an important role in the iron acquisition system of the strain. Furthermore, the gene encoding Fur was cloned and sequenced. The deduced amino acid sequence of the cloned Fur showed high sequence similarity with that from gram-negative bacteria.

Alteromonas↗

Decline in FEV(1) in community-based older volunteers with higher levels of neutrophil elastase in bronchoalveolar lavage fluid.

BACKGROUND: Neutrophil elastase (NE) is thought to be one of the key proteinases in the development of chronic obstructive pulmonary disease (COPD). Previously, we have shown that the NE-alpha1-proteinase inhibitor (NE-alpha1PI) complex in bronchoalveolar lavage (BAL) fluid was markedly elevated in asymptomatic smokers who had subclinical emphysema on CT scans. We proposed that excessive NE-alpha1PI complex in BAL fluid was a factor which might differentiate smokers who were developing emphysema from others. OBJECTIVE: In this study, we addressed the question of whether elevated levels of the NE-alpha1PI complex in BAL fluid are linked to the accelerated decline in pulmonary functions in those subjects. METHODS: We conducted a follow-up study to analyze the decline in FEV(1) for 4.3 years on average for 26 community-based volunteers who had received pulmonary function tests, CT scans and BAL. The levels of the NE-alpha1PI complex in BAL fluid and in plasma was measured. RESULTS: Neither pulmonary function measurements nor the presence of emphysema on CT scans could predict the decline in FEV(1). The number of inflammatory cells in BAL fluid was also not an indicator of progression. By contrast, subjects with higher levels of the NE-alpha1PI complex in BAL fluid had a significantly accelerated decline in FEV(1) compared to those with lower levels. CONCLUSION: These data seem to support the hypothesis that NE in the lung is related to the onset and/or progression of COPD.

Aged↗