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Biomedical subjects

Y Mitsui

Publications and source records attributed to Y Mitsui.

At least 19 recordsLinked to original sources
PubMed2004

Delayed macrofilaricidal activity of diethylcarbamazine against Brugia pahangi in Mongolian jirds.

The macrofilaricidal activity of diethylcarbamazine (DEC) was confirmed in jirds infected with Brugia pahangi. Seventy jirds were inoculated subcutaneously with 100 infective larvae. At 20 weeks post-infection, the microfilaraemic jirds were divided into two groups, untreated and treated. For the treated group, 200 mg kg(-1) of DEC was injected intraperitoneally for 5 consecutive days. One, 4, 8, 12, 16 and 27 weeks after the final treatment, 4-7 jirds in each group were sacrificed to measure adult worm burdens. The number of adult worms recovered from treated jirds was comparable to controls at earlier necropsy (1 and 4 weeks post-treatment). However, at late necropsy (8 weeks and later) the recovery rate of adult worms in treated jirds was significantly lower than that in untreated controls, indicating an adultcidal effect of DEC. The present study demonstrates that DEC requires 8 weeks to kill B. pahangi adult worms in jirds and that the Mongolian jird is a useful model for screening antifilarial activity.

Animals↗
PubMed2004

The effects of topical application of phytonadione, retinol and vitamins C and E on infraorbital dark circles and wrinkles of the lower eyelids.

BACKGROUND: Infraorbital dark circles and wrinkles of the lower eyelids are a cosmetic problem, especially with age. AIMS: To determine whether a gel containing 2% phytonadione, 0.1% retinol and 0.1% vitamins C and E is effective in reducing dark under-eye circles and wrinkles of the lower eyelids in healthy Japanese adults. PATIENTS/METHODS: Fifty-seven adult Japanese volunteers with dark under-eye circles and wrinkles were enrolled in an open label study. The gel formulation was applied twice daily to the lower eyelid site for 8 weeks. Haemostasis, pigmentation and wrinkles were evaluated by a physician and by the patients themselves, using a digital camera and a visual analogue scale respectively, after 4 and 8 weeks of treatment. RESULTS: Topical application of the gel decreased not only haemostasis but also wrinkles after 8 weeks of treatment. Of 57 patients, 27 (47%) had reductions in haemostasis. Wrinkles were also decreased in some patients. However, pigmentation was not clearly removed by this gel. CONCLUSIONS: Topical application of the gel containing 2% phytonadione, 0.1% retinol, 0.1% vitamin C and 0.1% vitamin E was fairly or moderately effective in reducing dark under-eye circles, especially in cases of haemostasis, over a short treatment period in healthy Japanese adults. This treatment also slightly decreased wrinkles.

Journal Article↗
PubMed2001

Endothelin-1 stimulates cardiomyocyte injury during mitochondrial dysfunction in culture.

To understand the pathophysiological role of endothelin-1 in the failing heart, we constructed a cellular mitochondrial impairment model and demonstrated the effect of endothelin-1. Primary cultured cardiomyocytes from neonatal rats were pretreated with rotenone, a mitochondrial complex I inhibitor, and the cytotoxic effect of endothelin-1 on the cardiomyocytes was demonstrated. Rotenone gradually decreased the pH of the culture medium with incubation time and caused slight cell injury. Endothelin-1 markedly enhanced the effect of rotenone that decreased the pH of the medium and enhanced cellular injury. The enhancement of the decrease in pH and cell injury induced by endothelin-1 was counteracted by the endothelin ET(A) receptor antagonist BQ123 or by maintaining the pH of the medium by the addition of 50 mM HEPES. Endothelin-1 markedly increased the uptake of 2-deoxyglucose and lactic acid production when the cardiomyocytes were pretreated with rotenone. These findings suggest that the stimulation of glucose uptake and anaerobic glycolysis followed by the increase in lactic acid accumulation in cardiomyocytes under the condition of mitochondrial impairment may be involved, at least in part, in the cellular injury by endothelin-1. Moreover, these findings suggest the possibility that the effect of endothelin-1 on myocardium is reversed by the condition of the mitochondria, and endogenous endothelin-1 may deteriorate cardiac failure with mitochondrial dysfunction. This may contribute to clarify the beneficial effect of endothelin receptor blockade in improving heart failures.

Animals↗
PubMed2001

Effect of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow in experimental diabetic neuropathy of rat.

The effects of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow (NBF) were explored in streptozotocin-induced diabetic rats. Rats were maintained on a diet of containing 0.09% zenarestat for 8 weeks, then NBF in the sciatic nerve was measured using microelectrode hydrogen polarography. NBF in the diabetic control rats was significantly lower than values in age-matched control rats, however, NBF was not significantly altered in diabetic rats treated with zenarestat. Direct application of nitric oxide synthase inhibitor, NG-nitro-L-arginine, did not affect NBF in diabetic control rats, whereas this application significantly reduced NBF both in age-matched control and zenarestat treated diabetic rats. Considerable levels of zenarestat were confirmed in the sciatic nerve in the drug treated rats. These data suggest that aldose reductase, such as zenarestat, might restore or prevent the alteration of endoneurial blood flow resulting from an impairment of nitric oxide function.

Aldehyde Reductase↗
PubMed2001

Identification and characterization of molecular interactions between glucose-regulated proteins (GRPs) mortalin/GRP75/peptide-binding protein 74 (PBP74) and GRP94.

A heat-shock protein (hsp) 70 family member mortalin/glucose-regulated protein (GRP) 75/peptide-binding protein 74 (PBP74) has been localized to various cellular compartments including mitochondria, endoplasmic reticulum and cytoplasmic vesicles. Here we describe its interactions with an endoplasmic reticulum protein GRP94, a member of the hsp90 family of GRPs. Interactions were identified, confirmed and characterized by far-Western screening, in vivo reporter and co-immunoprecipitation assays. Interacting domains of the two proteins were also characterized by mutational analysis. Such interactions of these two GRPs may be important for function of either or both and therefore provide important information for further studies.

Animals↗
PubMed2001

Crystal structure of 2-hydroxyl-6-oxo-6-phenylhexa-2,4-dienoic acid (HPDA) hydrolase (BphD enzyme) from the Rhodococcus sp. strain RHA1 of the PCB degradation pathway.

2-Hydroxyl-6-oxo-6-phenylhexa-2,4-dienoic acid (HPDA) hydrolase (the BphD enzyme) hydrolyzes a ring-cleavage product of an aromatic compound generated in a biphenyl/polychlorinated biphenyl (PCB) degradation pathway of bacteria. The crystal structure of the BphD enzyme has been determined at 2.4 A resolution by the multiple isomorphous replacement method. The final refined model of the BphD enzyme yields an R-factor of 17.5 % at 2.4 A resolution with reasonable geometry. The BphD enzyme is an octameric enzyme with a 422 point-group symmetry. The subunit can be divided into core and lid domains. The active site of the enzyme is situated in the substrate-binding pocket, which is located between the two domains. The substrate-binding pocket can be divided into hydrophobic and hydrophilic regions. This feature of the pocket seems to be necessary for substrate binding, as the substrate is composed of hydrophilic and hydrophobic parts. The proposed orientation of the substrate seems to be consistent with the general catalytic mechanism of alpha/beta-hydrolases.

Amino Acid Sequence↗
PubMed2001

Expression of telomerase reverse transcriptase and telomere elongation during sexual maturation in Paramecium caudatum.

Paramecium caudatum has a sexually immature period that lasts for about 60 fissions. To examine the possibility that telomere length is one of the determining factors of the duration of immaturity, we cloned the telomerase reverse transcriptase (TERT) gene from P. caudatum, and analyzed its expression levels at mRNA, telomerase activity, and telomere length during the course of clonal division. Paramecium TERT (Pc_TERT) cDNA encodes a basic protein of 107 kDa that harbors conserved RT motifs, T motif, CP motif, and N motif. Pc_TERT mRNA is expressed at very low levels only detectable by RT-PCR, but constitutively, during immature and mature periods, exhibiting abundant telomerase activity. No clear phase shift in Pc_TERT expression, telomerase activity, or telomere length was observed at the point of maturation in P. caudatum. Instead, the telomere elongates successively as cells divide in P. caudatum, although a close species, P. tetraurelia, was reported to keep the length constant. We discuss possible mechanisms for the expression of sexual activity associated with telomere length in P. caudatum.

Amino Acid Sequence↗
PubMed2001

A small dose of the immunosuppressive agent FK506 (tacrolimus) protects peripheral nerve from ischemic fiber degeneration.

The immunosuppressant agent FK506 (tacrolimus) has proven to be neuroprotective against brain ischemia, but there are no data on potential neuroprotective effects of FK506 in peripheral nerve ischemia. We examined the potential effects of two doses of FK506 in protecting peripheral nerve from ischemic fiber degeneration. Ischemia in the left sciatic nerve of the rat was produced by injecting 2 x 10(6) microspheres (14 microm) into the left femoral, hypogastric, and superior gluteal arteries in proportions of 47%, 37%, and 17%, respectively. After embolization, FK506 was injected into the left femoral, hypogastric, and superior gluteal arteries in doses of 9.4, 7.4, and 3.4 microg, respectively, for the high-dose group and 4.7, 3.7, and 1.7 microg, respectively, for the low-dose group. The control rats were injected with saline. FK506 treatment resulted in dramatic behavioral improvement in nerve function, in the number of functioning nerve fibers, and in the salvage of a majority of nerve fibers from ischemic fiber degeneration in a dose-dependent fashion. These results suggest that a small dose of FK506 protects peripheral nerve from ischemic fiber degeneration and that it may have potential in the treatment of ischemic neuropathy.

Action Potentials↗
PubMed2001

Pro- and anti-inflammatory cytokine gene expression in rat sciatic nerve chronic constriction injury model of neuropathic pain.

Cytokines may be pathophysiologically involved in hyperalgesia. Uncertainty exists about the types of cytokines and their site of action. To study the role of key pro- and anti-inflammatory cytokines in a chronic constriction model of neuropathic pain, mRNA expression of TNF, IL-1beta, IL-6, and IL-10 was quantified using competitive RT-PCR. Each cytokine mRNA in rat sciatic nerve was examined at days 3, 7, 14, and 45 after chronic constriction injury (CCI). We also undertook behavioral testing of these rats. Thermal warming and touch thresholds were significantly reduced at days 3, 7, and 14 in the CCI group, compared with the sham-operated group. Cytokine gene expression in sciatic nerve was significantly increased at day 7 for IL-1beta and IL-6 and at day 14 for TNF. Expression of IL-10 underwent a gradual and progressive increase, reaching statistical significance at day 45.

Animals↗
PubMed2001

Sex determination without the Y chromosome in two Japanese rodents Tokudaia osimensis osimensis and Tokudaia osimensis spp.

Both males and females of the species of spinous country-rats (Tokudaia osimensis osimensis, T.o.o., Rodentia: Muridae), which live on Amami Oshima Island, a southern Japanese island, have 25 chromosomes. Another species of spinous country-rats (Tokudaia osimensis spp., T.o. spp., which live on Tokunoshima Island 40 km south of Amami Oshima Island, also have an odd number of chromosomes, 45. Karyotypes of males and females by the G-band method were indistinguishable in both populations. The lesser number of chromosomes (25) of T.o.o. is likely to be a result of Robertsonian fusions of 45 chromosomes of T.o. spp. that seem to be the offspring of another spinous country-rat Tokudaia osimensis muenninki (T.o.m.), which live on Okinawa Island and have 44 chromosomes including the X and Y Chrs. The lengths of the non-paired, putative X-Chr of T.o.o. and T.o. spp. occupied roughly 3.2% and 1.7% of the total lengths, respectively, hinting at translocation or exchange of a part of the X Chr and thus in violation of Ohno's Law. Southern blot analysis with murine Sry as a probe indicated that these two animals do not have Sry. When Zfx from T.o. spp. was used as a probe, both males and females of T.o.o. and T.o. spp. showed two bands, suggesting possible translocation of Zfy from the Y Chr. Comparison of physical characteristics, constituents of chromosomes, and sex-determination methods of these three Tokudaia country-rat populations suggests that each is endemic to each island and constitutes an independent species. These specialized species would provide us with clues to elucidate the mechanisms of primary sex determination and karyotype evolution in mammals.

Animals↗
PubMed2001

A direct competitive enzyme-linked immunosorbent assay (ELISA) for determination of praziquantel concentration in serum.

A simple and reproducible enzyme-linked immunosorbent assay (ELISA) for the determination of the concentration of praziquantel in the serum was developed. Since praziquantel has no functional group to conjugate with carrier protein, praziquantel was first converted to a compound with an amino group similar to praziquantel. This compound was then conjugated to bovine serum albumin for use as an immunogen, and to horseradish peroxidase, as enzyme-labeled praziquantel, respectively. The conjugate of praziquantel-bovine serum albumin conjugate was used to raise anti-praziquantel antiserum in mice. The direct competitive ELISA was conducted by simultaneously incubating praziquantel and horseradish peroxidase-labeled praziquantel conjugate with anti-praziquantel antiserum over a second antibody and the enzyme activity of the remaining horseradish peroxidase-labeled praziquantel conjugate was measured. The intra- and inter-assay coefficient of variation was < 10% in the range of 1.0 to 30 ng ml(-1), and the limit of the detection was 0.3 ng ml(-1). The cross reactivities of anti-praziquantel antibody with compounds related to praziquantel were negligible. Using this ELISA, serum levels of praziquantel were easily determined in male Wistar rats up to 8 h following a single intraperitoneal injection at 2 mg kg(-1) of body weight.

Animals↗
PubMed2001

Senescent cells are resistant to death despite low Bcl-2 level.

Cellular senescence may be an antioncogenic event. Bcl-2 is a product of the oncogene, bcl-2, but it may also participate in cellular senescence. To investigate the role of Bcl-2, we analyzed the level of Bcl-2 during aging of normal human fibroblasts by immunoblot analysis and found that its level was highly suppressed in four normal senescent fibroblast strains. This result suggests that senescent cells are more sensitive to induction of death than young cells. Nevertheless, senescent cells showed more resistance to death induced by hydrogen peroxide than young cells, according to LDH assay. Because the balance among antiapoptotic and proapoptotic proteins is an important factor for the determination of cell death, we examined levels of other Bcl-2 family and apoptosis-regulating proteins, but observed no reasonable change to explain the resistance. During the course of the death induction experiment, we obtained results showing that growth-arrested cells were also resistant to death, and this was further confirmed by a BrdU-labeling experiment. As senescent cells are stopped permanently in the G0/G1-phase of the cell cycle, our data strongly suggest that this is the cause of resistance to death in senescent cells.

Apoptosis↗
PubMed2001

Induction of senescence-associated genes by 5-bromodeoxyuridine in HeLa cells.

5-Bromodeoxyuridine (BrdU) universally induces a senescence-like phenomenon in mammalian cells. To assess this phenomenon at the level of gene expression, we constructed a PCR-based subtractive cDNA library enriched for mRNA species that immediately increase by administration of BrdU to HeLa cells. Candidate cDNA clones were isolated by differential colony hybridization, and then positive clones were identified by Northern blot analysis. Sequencing analysis revealed that the identified cDNA species were classified into three groups: widely used senescence-markers, known species whose relevance to senescence is yet to be reported, and known or novel ESTs. As expected, the majority of them showed an increase in expression in senescent human diploid fibroblasts. These results suggest that similar mechanisms operate in the regulation of BrdU-induced genes and senescence-associated genes.

Bromodeoxyuridine↗
PubMed2001

p53-independent upregulation of p21WAF1 in NIH 3T3 cells malignantly transformed by mot-2.

Mot-2 protein is shown to interact with p53 and inhibit its transcriptional activation function. Mot-2 overexpressing stable clones of NIH 3T3 cells were malignantly transformed, however, they had a high level of expression of a p53 downstream gene, p21WAF1. The present study was undertaken to elucidate possible molecular mechanism(s) of such upregulation. An increased level of p21WAF1 expression was detected in stable transfectants although an exogenous reporter gene driven by p21WAF1 promoter exhibited lower activity in these cells suggesting that some post-transcriptional mechanism contributes to upregulation. Western analyses of transient and stable clones revealed that upregulation of p21WAF1 in stable NIH 3T3/mot-2 cells may be mediated by cyclin D1 and cdk-2.

3T3 Cells↗
PubMed2001

Ca(2+)-regulated nitric oxide generation in rabbit parotid acinar cells.

In rabbit parotid acinar cells, the muscarinic cholinergic agonist methacholine induced an increase in the intracellular Ca(2+) concentration and provoked nitric oxide (NO) generation. Ca(2+)-mobilizing reagents such as thapsigargin and the Ca(2+) ionophore A23187 mimicked the effect of methacholine on NO generation. Methacholine-induced NO generation was inhibited by the removal of extracellular Ca(2+). Immunoblot analysis indicated that the antibody against the neuronal type of nitric oxide synthase (NOS) cross-reacted with NOS in the cytosol of rabbit parotid gland cells. Immunofluorescence testing showed that neuronal NOS is present in the cytosol of acinar cells but less in the ductal cells. NOS was purified approximately 8100-fold from the cytosolic fraction of rabbit parotid glands by chromatography on Sephacryl S-200, DEAE-Sephacel, and 29,59-ADP-Sepharose. The purified NOS was a NADPH- and tetrahydroxybiopterin-dependent enzyme and was activated by Ca(2+) within the physiological range in the presence of calmodulin. These results suggest that NO is generated by the activation of the neuronal type of NOS, which is regulated in rabbit parotid acinar cells by the increase in intracellular Ca(2+) levels induced by the activation of muscarinic receptors.

Animals↗
PubMed2001

Time-resolved acquisition technique for elemental mapping by energy-filtering TEM.

A time-resolved acquisition technique for elemental mapping has been investigated for the heavy element barium (Ba) in (Ba(0.5), Sr(0.5)TiO3 (BST) by energy-filtering transmission electron microscopy (EF-TEM). Based on the conventional three-window method, five images were separately acquired for each energy region (about 780 eV signal region, and pre-1 and pre-2 energy regions). After correcting for image shift, the five images were added to form a new processed image in each energy region. Then, Ba element mapping was performed by using the conventional three-window procedure. This time-resolved technique was found to improve signal-to-noise ratio for 100 s total exposure time without increasing the image blurring problem.

Journal Article↗
PubMed2001

Neurofibromatosis type 1 with basilar artery fusiform aneurysm manifesting Wallenberg's syndrome.

A case of neurofibromatosis type 1 (NF1) manifesting Wallenberg's syndrome and fusiform aneurysm of the basilar artery is reported. The patient suddenly developed dysarthria, walking difficulty and sensory disturbance. Neurological examination suggested Wallenberg's syndrome and MR imaging confirmed an ischemic lesion at the left lateral medulla oblongata. Cerebral angiography revealed a fusiform aneurysm at the middle portion of the basilar artery. However, there was no occlusive change in either the posterior inferior cerebellar artery or the vertebral artery. The clinical and radiological features are discussed together with a review of NF1 cases with intracranial aneurysms in the literature.

Diagnosis, Differential↗