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Biomedical subjects

S Miyake

Publications and source records attributed to S Miyake.

At least 91 records · Page 5Linked to original sources

Neutral carrier-type ion sensors based on sol-gel-derived membranes incorporating a bis(crown ether) derivative by covalent bonding.

Sol-gel-derived membranes incorporating crown ether neutral carriers by covalent bonding have been designed for durable, nontoxic neutral carrier-type ion sensors by sol-gel processing using tetraethoxysilane, diethoxydimethylsilane, and their corresponding alkoxysilylated neutral carriers. A tetraphenylborate anion was also bound chemically to the neutral carrier-type sol-gel-derived membranes for suppressing anion interference and membrane impedance. Ion-sensitive field effect transistors (ISFETs) based on the sol-gel-derived membranes modified chemically by crown ether derivatives, such as 16-crown-5 and bis(12-crown-4) derivatives, showed high performance, high sensitivity in wide cation activity ranges, short response time, and high electrode durability. Specifically, high ion selectivities of practical use in biological systems were attained in the sodium ISFETs based on the chemically modified bis(12-crown-4), which has been successfully applied to sodium assay in blood sera.

Ethers, Cyclic↗

A light-independent oscillatory gene mPer3 in mouse SCN and OVLT.

A new member of the mammalian period gene family, mPer3, was isolated and its expression pattern characterized in the mouse brain. Like mPer1, mPer2 and Drosophila period, mPer3 has a dimerization PAS domain and a cytoplasmic localization domain. mPer3 transcripts showed a clear circadian rhythm in the suprachiasmatic nucleus (SCN). Expression of mPer3 was not induced by exposure to light at any phase of the clock, distinguishing this gene from mPer1 and mPer2. Cycling expression of mPer3 was also found outside the SCN in the organum vasculosum lamina terminalis (OVLT), a potentially key region regulating rhythmic gonadotropin production and pyrogen-induced febrile phenomena. Thus, mPer3 may contribute to pacemaker functions both inside and outside the SCN.

Amino Acid Sequence↗

The tyrosine kinase regulator Cbl enhances the ubiquitination and degradation of the platelet-derived growth factor receptor alpha.

The Cbl protooncogene product has emerged as a negative regulator of receptor and nonreceptor tyrosine kinases. We recently demonstrated that oncogenic Cbl mutants upregulate the endogenous tyrosine kinase signaling machinery when expressed in the NIH 3T3 cells, and identified the platelet-derived growth factor receptor-alpha (PDGFRalpha) as one of the tyrosine kinases targeted by these oncogenes. These findings suggested a role for the normal Cbl protein in negative regulation of the PDGFRalpha. However, the mechanism of such negative regulation remained to be determined. Here we show that overexpression of the wild-type Cbl enhances the ligand-induced ubiquitination of the PDGFRalpha. Concomitantly, the PDGFRalpha in Cbl-overexpressing cells undergoes a faster ligand-induced degradation compared with that in the control cells. These results identify a role for Cbl in the regulation of ligand-induced ubiquitination and degradation of receptor tyrosine kinases and suggest one potential mechanism for evolutionarily conserved negative regulatory influence of Cbl on tyrosine kinases.

3T3 Cells↗

Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth.

The retinoblastoma tumor suppressor protein (pRB) can inhibit cell cycle progression and promote differentiation. pRB interacts with a variety of transcription factors, including members of the E2F and C-EBP protein families and MyoD, and can either repress or activate transcription depending on the promoter under study. These biological and biochemical activities of pRB have been mapped previously to a core domain, referred to as the pRB pocket. Using a panel of synthetic pRB pocket mutants, we found that the acute induction of a G1/S block by pRB is linked to its ability to both bind to E2F and to repress transcription. In contrast, these functions were not required for pRB to promote differentiation, which correlated with its ability to activate transcription in concert with fate-determining proteins such as MyoD. All tumor-derived pRB mutants tested to date failed to bind to E2F and did not repress transcription. Despite an inability to bind to E2F, pRB mutants associated with a low risk of retinoblastoma, unlike high-risk mutants, retained the ability to activate transcription and promote differentiation. Thus, the pRB pocket participates in dual tumor suppressor functions, one linked to cell cycle progression and the other to differentiation control, and these functions can be genetically and mechanistically dissociated.

Carrier Proteins↗

Liquefied aftercataract: a complication of continuous curvilinear capsulorhexis and intraocular lens implantation in the lens capsule.

PURPOSE: To describe a new type of aftercataract that contains a liquefied, milky white substance between the lens optic and the posterior lens capsule. METHOD: We reviewed the medical records of 41 patients identified as having this type of aftercataract. RESULTS: All 41 eyes (41 patients) underwent uneventful phacoemulsification after continuous curvilinear capsulorhexis and implantation of a posterior chamber intraocular lens made from polymethylmethacrylate. Two months to 6 years after surgery (average+/-SD, 3.8+/-1.7 years), fibrosis was noted evenly along the entire circumference and between the anterior surface of the intraocular lens optic and the edge of the capsular opening created by continuous curvilinear capsulorhexis. This led to formation of a closed chamber between the intraocular lens and the posterior lens capsule, which then accumulated a liquefied, milky white substance. Twenty-three of the 41 eyes showed liquefied aftercataract in conjunction with other types of aftercataract: in 12 eyes with fibrosis, in 11 eyes with Elschnig pearls, and in one eye with a Soemmering ring. None of the eyes had any signs of inflammation; six of the 41 eyes had reduced visual acuity caused exclusively by the liquefied aftercataract. Before cataract surgery, 14 eyes were diagnosed with diabetic retinopathy, four with glaucoma, and two with uveitis. CONCLUSION: We report a new type of aftercataract characterized by a liquefied, milky white substance that accumulates between the lens optic and the posterior lens capsule when the anterior capsular opening, originally created by continuous curvilinear capsulorhexis, becomes occluded with the lens optic.

Adult↗

Power spectral analysis of heart rate variability in type A females during a psychomotor task.

This study investigated changes in autonomic nervous activities due to psychological stress in Type A females. Eight Type A and eight Type B females performed a psychomotor task for 30 minutes. Power spectral analysis of heart rate variability (HRV) was used to examine the autonomic nervous activities. Results showed the low frequency (LF) component and LF/HF ratio in Type A females increased after the onset of the task. There were no significant differences in task performance between Type A and Type B females. The subjective mental workload increased gradually in Type A females during the tasks, whereas in Type B females this parameter did not change in a consistent manner. The results suggest that the sympathetic nervous system in Type A females was more stimulated by the task and Type A females felt a greater subjective mental workload than did Type B females.

Adult↗

New classification of capsular block syndrome.

PURPOSE: To propose a new classification of capsular block syndrome (CBS) to improve understanding of the etiology and provide effective treatment. SETTING: Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, and Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan. METHODS: Three groups of eyes with CBS were reviewed: eyes originally reported and diagnosed as having CBS; eyes experiencing CBS after hydrodissection and luxation of the lens nucleus; and eyes with CBS accompanying liquefied aftercataract or capsulorhexis-related lacteocrumenasia. RESULTS: In all 3 groups, the CBS occurred in eyes with a continuous curvilinear capsulorhexis (CCC). It was characterized by accumulation of a liquefied substance within a closed chamber inside the capsular bag, formed because the lens nucleus or the posterior chamber intraocular lens (IOL) optic occluded the anterior capsular opening created by the CCC. Depending on the time of onset, CBS can be classified as intraoperative (CBS seen at the time of lens luxation following hydrodissection), early postoperative (original CBS), and late postoperative (CBS with liquefied aftercataract or lacteocrumenasia). The etiology of the accumulated substance and the method of treatment are different in each type. CONCLUSION: Capsular block syndrome is a complication of cataract/IOL surgery that can occur during and after surgery. Correctly identifying the type of CBS is crucial to understanding the nature and effective treatment of this disorder.

Capsulorhexis↗

The c-Cbl oncoprotein.

Cbl has emerged as a novel signal transducing protein downstream of a number of cell surface receptors coupled to tyrosine kinases. Identified as the protein product of the c-cbl proto-oncogene, the cellular homolog to the transforming gene of a murine retrovirus, Cbl comprises an N-terminal transforming region (Cbl-N), which contains a phosphotyrosine binding (PTB) domain, and a C-terminal modular region (Cbl-C) containing a RING finger motif, a large proline-rich region and a leucine zipper. Deletion of Cbl-C or small deletions N-terminal to the RING finger render Cbl oncogenic, whereas wild type Cbl is non-transforming, even if overexpressed. Cbl serves as a substrate of both receptor and non-receptor tyrosine kinases, and binds to adaptor proteins Grb2, Crk and the p85 subunit of PI-3-kinase. Additionally, both Caenorhabditis elegans and Drosophila Cbl homologs, SLI-1 and D-Cbl, respectively, have been identified as negative regulators of the LET-23/DER receptor tyrosine kinases. Finally, oncogenic mutants of Cbl, when expressed in fibroblasts, upregulate the signaling cascade downstream of the platelet-derived growth factor receptor alpha in a Cbl-PTB domain-dependent manner. Together, these findings position Cbl as a central player in the regulation of tyrosine kinase signaling pathways. Identification of the Cbl-PTB domain binding motifs on tyrosine kinases and elucidation of the mechanisms of Cbl's negative regulatory effect may provide a new avenue to control tyrosine kinases for therapeutic purposes.

Animals↗

Identification of sna41 gene, which is the suppressor of nda4 mutation and is involved in DNA replication in Schizosaccharomyces pombe.

BACKGROUND: The replication licensing factor limits DNA replication to once in a cell cycle and is thought to contain MCM proteins as its component parts. Six MCM subtypes have been identified in various species. These MCM proteins are thought to bind each other to make a heteromeric complex. The Nda4 protein of Schizosaccharomyces pombe is one of the MCM proteins and is involved in DNA replication. RESULTS: The suppressor mutant of nda4 was isolated and the mutant gene was named sna41. The sna41-912 mutant demonstrated the ts phenotype, with an elongated cell shape at the restrictive temperature. Cells with 1C DNA content accumulated 2 h after shifting up to the restrictive temperature. This result suggests that sna41 is also involved in DNA replication. The sna41 genomic clone was isolated by a complementation of the ts phenotype of the mutant strain and was sequenced. The sna41 gene encodes a protein of 638 amino acids, which has low homology with CDC45 in S. cerevisiae. The gene disruption analysis showed that sna41 gene is essential for viability. CONCLUSIONS: The S. pombe sna41 mutation suppresses the nda4-108 mutation. Sna41 is involved in DNA replication and may play some roles in the regulation of DNA replication by the MCM proteins.

Amino Acid Sequence↗

Removal of low-density lipoprotein from plasma by adsorption increases bradykinin and plasma nitric oxide levels in patients with peripheral atherosclerosis.

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose column is brought about by electrostatic binding between the positive charges of apolipoprotein B in LDL and the negative charges of dextran sulfate cellulose. There is general agreement that the initial contact phase in the coagulation pathway may be activated by a negatively charged surface such as dextran sulfate cellulose, resulting in the generation of bradykinin. We investigated whether the increase in the generation of bradykinin during LDL adsorption is accompanied by the activation of endogenous production of nitric oxide (NO) in patients with peripheral atherosclerosis. LDL adsorption therapy was repeated ten times over a period of 3 months in ten peripheral atherosclerosis patients. Treatment significantly reduced serum total cholesterol and LDL cholesterol levels. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured the kinin-kallikrein system and plasma levels of NO in the same patients. The results showed that coagulation factors of the intrinsic pathway including high-molecular-weight kininogen and prekallikrein decreased markedly after initial adsorption compared with the levels before treatment. There was a marked increase in bradykinin and NO concentrations after the initial adsorption, compared with their levels before adsorption. Our results suggest that the generation of bradykinin and increased plasma levels of NO may contribute to the improvement in peripheral circulation after LDL adsorption in peripheral atherosclerosis patients.

Adsorption↗

A longitudinal study of the development of daytime sleepiness in children.

This study aims to (i) investigate longitudinally developmental changes of diurnal variations of body temperature and sleepiness in preschool and school-age children and (ii) investigate the effect of acute 2 h sleep reduction on daytime sleepiness over a 3 year period. Three subjects were evaluated over three consecutive days: two control days and one 2 h sleep reduction day. A sleep latency test was conducted five times each day at 2 h intervals from 10.00 h, and oral temperature measured every hour. The results showed that (i) daytime sleepiness was high and decreased with increasing age, (ii) an afternoon dip occurred with pubertal development, (iii) effects of sleep loss generally increased daytime sleepiness, in particular at 10.00 h, and (iv) temperature acrophase was delayed with age.

Body Temperature Regulation↗

Interferon therapy for chronic hepatitis C in hemodialysis patients: increased serum levels of interferon.

BACKGROUND/AIMS: The efficacy and side effects of interferon (IFN) therapy have not been well clarified in hemodialysis patients with chronic hepatitis C. METHODS: In 6 of 9 hemodialysis patients with chronic hepatitis C, 3 million units (MU) or 6 MU of recombinant IFN-alpha2b or natural IFN-alpha were administered intramuscularly daily for the first 2 weeks, followed by three times a week for 22 weeks. In the remaining 3 patients, 3 MU of IFN-alpha2b were given three times a week for 24 weeks. Serum concentrations of IFN-alpha2b were measured sequentially after the injection of interferon. Responders were defined as the patients with normal serum aminotransferase and negative serum HCV RNA 6 months after the cessation of IFN therapy. RESULTS: Three of the 6 patients who were administered IFN daily in the first 2 weeks were responders, while the other 3 withdrew from the therapy due to serious adverse events such as depression, loss of consciousness and persistence of high-grade fever. Serious adverse events were not observed in the 3 patients without daily administration. Half-lives of IFN-alpha2b in hemodialysis patients were significantly longer than those in nonuremic patients (10.0 vs. 6.0 h, p < 0.05). Moreover, the areas under the serum concentration curve of the hemodialysis patients were significantly larger than those of nonuremic patients (756 +/- 223 vs. 324 +/- 223 IU.h/ml, p < 0.05), despite the fact that the dose of IFN-alpha administered to hemodialysis patients was half that administered to nonuremic patients. CONCLUSIONS: In hemodialysis patients with chronic hepatitis C, pharmacokinetic parameters of IFN may be different from those in nonuremic patients, and daily or high-dose administration of IFN may lead to serious adverse events in those patients.

Adult↗

Effects of a neutrophil elastase inhibitor (ONO-5046) on acute pulmonary injury induced by tumor necrosis factor alpha (TNFalpha) and activated neutrophils in isolated perfused rabbit lungs.

The aim of this study was to examine the effect of ONO-5046, a neutrophil elastase (NE) inhibitor, on a model of acute lung injury induced by tumor necrosis factor alpha (TNFalpha) and phorbol myristate acetate (PMA)-activated neutrophils in isolated perfused rabbit lungs. 120 min after TNFalpha (4,000 JRU/ml) was injected into the pulmonary artery (PA), 5 x 10(7) PMA-stimulated neutrophils were infused into the PA together with 1251-rabbit serum albumin (RSA). In the ONO-5046-treated group (ONO), ONO-5046 (20 mg/kg/h) was continuously infused during the experimental period from 30 min prior to neutrophil administration. Saline, the ONO-5046 vehicle, was infused instead of ONO-5046 in the positive control group (ALD) and nonactivated neutrophils were infused without TNFalpha in the negative control group (Cont). PA pressure was monitored over a 240 min period, and bronchoalveolar lavage (BAL) was performed at the end of the experiment. Lung tissues were examined immunohistochemically for the expression of thrombomodulin (TM). The levels of TM in the perfusate were also measured by ELISA and the radioactivities in the BAL fluid, lung tissue and perfusate were determined to calculate the permeability index (PI) as an indicator of alveolar septal or vascular endothelial damage. The rabbit lungs infused with ONO-5046 showed slower and less increases in PA pressure compared with ALD group. The PI was significantly higher in ALD group (PI[BAL] = 0.028 +/- 0.014, PI[LUNG] = 0.04 +/- 0.003) than Cont (PI[BAL] = 0.002 +/- 0.001, PI[LUNG] = 0.015 +/- 0.003) and ONO group (PI[BAL] = 0.004 +/- 0.003, PI[LUNG] = 0.028 +/- 0.003 (p < 0.05). ALD group had higher TM levels in the perfusate and showed decreased expression of TM on the vascular endothelium compared to Cont and ONO group, suggesting that there was shedding of TM on endothelium and ONO-5046 attenuated a shedding of TM. In conclusion, ONO-5046 attenuated acute lung injury by inhibiting the alveolar epithelial and vascular endothelial injury triggered by activated neutrophils. NE appears to play an important role in the neutrophil-induced increase of pulmonary epithelial and microvascular permeability observed in acute lung injury.

Animals↗

Effectiveness of polyclonal and monoclonal antibodies prepared for an immunoassay of the etofenprox insecticide.

Two polyclonal antibodies and three monoclonal antibodies specific to the etofenprox insecticide were prepared from rabbits and mice, respectively. The monoclonal antibodies were more reactive with etofenprox than the polyclonal antibodies by C-ELISA. Monoclonal antibody cl 205-65 was found to be the most tolerant to methanol, most highly reactive and most specific to etofenprox among the antibodies tested.

Animals↗

Pulmonary pseudallescherioma associated with systemic lupus erythematosus.

We report a case of fungus ball due to Pseudallescheria boydii (pseudallescherioma) associated with systemic lupus erythematosus. Direct microscopical examination revealed a fungus with broad septate hyphae resembling Aspergillus and the fungus was identified as P. boydii on culture. Surgical resection was required to control episodes of hemoptysis. Cases of pulmonary pseudallescheriasis are rare, especially in Japan. However, some cases previously diagnosed as pulmonary aspergillosis may have been found to be caused by P. boydii, if adequate culture studies had been conducted. Unlike Aspergillus, P. boydii is resistant to amphotericin B. Therefore, we emphasize the importance of a correct diagnosis based on culture examination.

Adult↗

Sarcoid reactions scattered in the tumor-bearing lung parenchyma and regional lymph nodes associated with pulmonary carcinoid.

A 77-year-old woman was admitted to our hospital because of a mass lesion in the left lung. The tumor was pulmonary carcinoid associated with sarcoid reactions in the regional lymph nodes and scattered in the resected lung parenchyma. Pulmonary carcinoid with sarcoid reactions is extremely rare. This appears to be the first case report in which tumor-related sarcoid reactions were studded within the tumor-existing lung parenchyma and confirmed not to be within the uninvolved right lung.

Aged↗