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Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 595 records · Page 33Linked to original sources

Active oxygen species generation and cellular damage by additives of parenteral preparations: selenium and sulfhydryl compounds.

We investigated the relationship between active oxygen species (AOS) generation and cultured vascular endothelial cellular damage caused by simultaneous exposure to selenium compounds and sulfhydryl compounds such as cysteine (Cys) or reduced glutathione (GSH). Selenium compounds, selenite, selenate or selenomethionine (SeMet), are added to total parenteral nutrition (TPN) and intravenously administered. We confirmed by luminol dependent chemiluminescence, an indicator of AOS generation, that selenite generates AOS in the presence of clinical concentrations of sulfhydryl compounds, 0.5 mM Cys or 0.5 mM GSH, and that the amount of AOS generated reaches the maximum when their mole ratio is 1:50. However, AOS generation was not observed after simultaneous administration of various concentrations of selenate or SeMet with sulfhydryl compounds. Moreover, simultaneous exposure to 10 microM selenite and sulfhydryl compounds was found to result in significant increases in the [3H]-adenine and lactate dehydrogenase (LDH) release rates from cells, a significant decrease in the amount of cellular protein, and enhancement of cellular damage as compared with after exposure to selenite alone. However, simultaneous exposure to 10 microM selenate or 10 microM SeMet together with sulfhydryl compounds did not induce cellular damage. These findings revealed that selenite generates AOS and causes cellular damage in the presence of sulfhydryl compounds. Accordingly, it seems better to choose selenate or SeMet instead of selenite when a selenium compound is to be added to TPN.

Adenine↗

Efficacy of NND-502, a novel imidazole antimycotic agent, in experimental models of Candida albicans and Aspergillus fumigatus infections.

In vitro and in vivo anti-Candida albicans and anti-Aspergillus fumigatus activities of NND-502, a new imidazole-antimycotic, were compared with those of fluconazole (FCZ), itraconazole (ITZ) and/or amphotericin B (AmB). NND-502 exhibited strong in vitro antifungal activity against both fungal species; its MIC against C. albicans was 1-4 times lower than that of FCZ, and its MIC against A. fumigatus was at least 60-2000 times lower than that of ITZ and AmB. In vivo antifungal treatments with each drug were initiated 1 h after inoculation in the experimental models, so that antifungal potential reflected prophylactic activity rather than therapeutic activity. The oral regimen of NND-502 in a murine model of systemic C. albicans infection was much less effective than that of FCZ. In vivo anti-A. fumigatus activity of oral NND-502 in a murine model of systemic infection was apparently superior to that of FCZ and ITZ in terms of prolonging survival. In addition to the murine model of systemic aspergillosis, intravenous NND-502 was shown to be highly effective in a rat model of pulmonary aspergillosis compared with intravenous AmB; 90% of animals survived at a dose of 2.5 mg/kg per day of NND-502 while only 30% of animals escaped death when 5 mg/kg per day of AmB was used. This potent efficacy of NND-502 was also confirmed in a sublethal challenge study in which the administration of the agent at a dose as low as 1.25 mg/kg per day resulted in the significant reduction of organisms in the lung; no comparable effect of AmB was found.

Amphotericin B↗

The formation of two layers detectable by intraoperative echocardiography is a reliable predictor of late thrombosis within the false lumen of a dissected aorta.

The subjects consisted of one patient with chronic type A and three patients with chronic type B aortic dissection, who underwent replacement of an aorta obliterating distal false lumen. After the repair, the formation of two layers was detected by direct scanning echocardiography within the false lumen even during heparinization. In all cases, postoperative computed tomography confirmed complete thrombosis of the false lumen. The formation of two layers was considered to be a reliable predictor of late thrombosis.

Adult↗

Expression of multidrug resistance-associated protein in endometrial carcinomas: correlation with clinicopathology and prognosis.

The objective of the study reported here was to investigate the expression of multidrug resistance-associated protein (MRP) in endometrial carcinomas and to evaluate the relationship between its expression and clinical data. Using immunohistochemistry, we examined MRP expression in 15 normal endometria, 10 cases of endometrial hyperplasia, and 64 cases of endometrial carcinoma. The normal endometrial glands were weakly immunopositive throughout the menstrual cycle. In addition, we found a progressive increase in the MRP expression of the endometrial hyperplasias. Of the 64 cases of endometrial carcinoma, 62 (97%) expressed MRP. Of these 62 cases, 34 (55%) showed strong immunostaining (>/=50%) and 28 (45%) showed weak immunostaining (<50%). In particular, the intensity of the immunostaining was very strong in 25 (71%) of the 35 grade 1 carcinomas. There was a significant difference in MRP expression between the grade 1 carcinomas and the more poorly differentiated carcinomas (grade 2 or grade 3) (P <.01), especially at stages 1a and 1b (P <.001). However, beyond stage 1c, there was no significant difference in MRP immunoreactivity between the histologic differentiations. Furthermore, beyond stage 1c, those patients with strongly MRP-positive carcinomas had a relatively poorer survival rate than those with weakly MRP-positive carcinomas (P <.05). We concluded that MRP immunoreactivity was already present in normal endometrium and showed a progressive increase from endometrial hyperplasia to well-differentiated carcinoma. Beyond stage 1c, strongly MRP-positive carcinoma indicated a poorer survival rate.

ATP-Binding Cassette Transporters↗

A case of Diphyllobothrium nihonkaiense infection successfully treated by oral administration of Gastrografin.

A diphyllobothriid cestode infection found in a 54-year-old male residing in Oita, Japan, was successfully treated by oral administration of Gastrografin in combination with a intramuscular injection of Vagostigmin. The strobila expelled was 6.14 m long with a scolex, and morphologically identical with Diphyllobothrium nihonkaiense except unusual ovaries of which posterior horns were confluent in each proglottid. This is the first case of treatment of cestode infection by oral administration of Gastrografin.

Administration, Oral↗

A retrospective study of ocular toxocariasis in Japan: correlation with antibody prevalence and ophthalmological findings of patients with uveitis.

To classify the clinical characteristic of ocular toxocariasis in Japan, the prevalence of antibodies to Toxocara antigens was examined in patients with uveitis of unknown aetiology. From 1982 to 1993, serum specimens of 383 cases and intraocular fluid samples of 22 cases were serologically screened for Toxocara infection with five immunodiagnostic tests. Fifty-five sera and 11 intravitreous fluid samples were estimated to have significantly high antibody levels against larval excretory-secretory (ES) antigens of T. canis. Eight cases were positive in both serum and vitreous fluid, and three were positive only in the vitreous fluid. Among the 58 antibody positive samples, 20 cases were omitted due to a lack of detailed description of ocular findings. The remaining 38 cases are described in this study. Of these 38 cases, 34 (89%) were older than 20 years of age. Ocular lesions were located in the posterior fundus in 11 cases, in the peripheral fundus in 18 cases, and in both areas in seven cases. Of the eight cases in which papillary oedema or redness was observed, chorioretinal lesions were also present in seven of them. Tractional retinal detachment was present in five cases. These observations suggest that ocular toxocariasis in Japan has a different clinical profile compared with those in the other countries, and indicate a need for revised classification of ocular toxocariasis.

Adolescent↗

Dihydrochalcones and flavonolignans from Iryanthera lancifolia.

An extract from the pericarps of I. lancifolia afforded two dihydrochalcones (1 and 2) and two flavonolignans (3 and 4), with compounds 2-4 being of novel structure. The antioxidant activities of compounds 1-4 were evaluated through the measurement of malondialdehyde production, and Q(1/2) (concentration necessary for 50% inhibition of autoxidation) data were calculated. The Q(1/2) values obtained for 1-4 and the standard compounds alpha-tocopherol and quercetin were 6.9, 4.7, 5.5, 4.8, 12.1, and 7.6 microg/mL, respectively.

Animals↗

Introduction of plasmid DNA and oligonucleotides into lung epithelial cells by the hemagglutinating virus of Japan (HVJ)-liposome method.

The hemagglutinating virus of Japan (HVJ) fused with liposomes provides a unique transfection vehicle with characteristics of both virus vector and liposome. Here we investigate the efficiency and safety of the HVJ-liposome technique in delivering foreign genes and oligonucleotides into the lung of the Wistar rat. A plasmid vector containing the Escherichia coli beta-galactosidase (beta-gal) gene and the chicken beta-actin promoter was transfected via the trachea using the HVJ-liposome method. Cytochemical staining showed expression of exogenous beta-gal activity in airway epithelial cells, alveolar macrophages, and alveolar type II cells. This activity persisted at least 28 days after administration of the genes. FITC-labeled oligonucleotides also were introduced into the same types of lung cells as those expressing beta-gal. After instillation of HVJ-liposome, anti-HVJ antibodies were detected in the sera of the rats, but even after repeated administration of HVJ-liposome, no marked histopathologic change was observed while exogenous beta-gal expression was detected in pulmonary cells.

Actins↗

Effects of GABA on noradrenaline release and vasoconstriction induced by renal nerve stimulation in isolated perfused rat kidney.

We examined effects of gamma-aminobutyric acid (GABA) on vasoconstriction and noradrenaline (NA) release induced by electrical renal nerve stimulation (RNS) in the isolated pump-perfused rat kidney. RNS (1 and 2 Hz for 2.5 min each, 0.5-ms duration, supramaximal voltage) increased renal perfusion pressure (PP) and renal NA efflux. GABA (3, 10 and 100 microM) attenuated the RNS-induced increases in PP by 10-40% (P<0.01) and NA efflux by 10-30% (P<0.01). GABA did not affect exogenous NA (40 and 60 nM)-induced increases in PP. The selective GABA(B) agonist baclofen (3, 10 and 100 microM) also attenuated the RNS-induced increases in PP and NA efflux, whereas the RNS-induced responses were relatively resistant to the selective GABA(A) agonist muscimol (3, 10 and 100 microM). The selective GABA(B) antagonist 2-hydroxysaclofen (50 microM), but not the selective GABA(A) antagonist bicuculline (50 microM), abolished the inhibitory effects of GABA (10 microM) on the RNS-induced responses. The selective alpha2-adrenoceptor antagonist rauwolscine (10 nM) enhanced the RNS-induced responses. GABA (3, 10 and 100 microM) potently attenuated the RNS-induced increases in PP by 40-60% (P<0.01) and NA efflux by 20-50% (P<0.01) in the presence of rauwolscine. Prazosin (10 and 30 nM) suppressed the RNS-induced increases in PP by about 70-80%. Neither rauwolscine (10 nM) nor GABA (10 microM) suppressed the residual prazosin-resistant PP response. These results suggest that GABA suppresses sympathetic neurotransmitter release via presynaptic GABA(B) receptors, and thereby attenuates adrenergically induced vasoconstriction in the rat kidney.

Adrenergic alpha-2 Receptor Antagonists↗

Neurological complications after stem cell transplantation in childhood.

We analyzed the incidence of neurological complications in 77 patients receiving stem cell transplantation (SCT), and 12 patients (15.8%) had the following symptoms: convulsions, intracranial hemorrhage, and leukoencephalopathy. Although statistically not significant, neurological complications were seen more frequently in patients after allogeneic transplantation, and in those with acute graft-versus-host disease (GVHD) exceeding grade II. The most significant risk factor for neurological complications was identified as unrelated donor allogenic transplantation (P = 0.016). Complications were categorized into three groups, based on time of onset and symptoms: (1) convulsions during the conditioning period, (2) intracranial hemorrhage during the period of granulocyte recovery, and (3) leukoencephalopathy at around 2 months after SCT. We propose awareness of the risks of neurological complications in each period after SCT so that immediate and effective treatment of patients can be instigated.

Adolescent↗

Interaction between dexamethasone and butyrate in apoptosis induction: non-additive in thymocytes and synergistic in a T cell-derived leukemia cell line.

In thymocytes butyrate and trichostatin A are unable to augment dexamethasone-induced apoptosis. In cultured rat thymocytes the extent of apoptosis induced by dexamethasone alone did not increase by addition of 0.1 - 10 mM butyrate. Even more pronounced was the non-additive interrelationship between dexamethasone and trichostatin A, as trichostatin A-induced apoptosis was not only blocked by the presence of dexamethasone but dexamethasone-induced apoptosis was also partially inhibited in the presence of 0.1 - 0.5 microM trichostatin A. The fact that the non-additive relationship with dexamethasone for apoptosis induction was observed with both histone deacetylase inhibitors suggests that in thymocytes this phenomenon is related to histone acetylation. In contrast to this, in the human T cell-derived leukemia cell line CEM-C7H2, dexamethasone did not block butyrate- or trichostatin A-induced apoptosis; moreover, butyrate, in the concentration range of 0.1 - 1 mM, had a marked synergistic effect on dexamethasone-induced apoptosis. This synergism, however, was not mimicked by trichostatin A, indicating that the effect is not related to histone acetylation but rather due to a pleiotropic effect of butyrate. Furthermore, in CEM-C7H2 cells, at higher concentrations of butyrate (5 - 10 mM) or trichostatin A (0.4 - 0.8 microM), there was a minor but reproducible antagonistic effect of dexamethasone on apoptosis induced by each of the two histone deacetylase inhibitors, suggesting that this antagonistic effect too, is related to histone hyperacetylation.

Animals↗

Detection of inducible nitric oxide synthase (iNOS) mRNA by RT-PCR in ATL patients and HTLV-I infected cell lines: clinical features and apoptosis by NOS inhibitor.

Various tumors have been reported to express an inducible form of nitric oxide synthase (iNOS), and nitric oxide (NO) may affect the clinicopathological features of these tumors. Previously, Burkitt's lymphoma and Epstein-Barr virus (EBV)-infected cells were shown to express iNOS constitutively at a low level. We analyzed iNOS expression by the reverse transcriptase-polymerase reaction method (RT-PCR) in eight HTLV-I-infected cell lines (five were ATL-derived lines and there were in vitro transformed lines), nine ATL patients (three were chronic, two were acute, and four were lymphoma type), and an HTLV-I-negative T cell line (CEM). In four ATL derived and in all three in vitro transformed cell lines, iNOS was expressed constitutively, but it was not expressed in CEM cells. Four out of nine ATL patients also showed iNOS expression. The expression of iNOS was found in all subtypes of ATL. Three of four iNOS-positive patients had infiltration of ATL cells to organs such as skin, lung, or liver. In NOS inhibitor (NG-monomethyl-L-arginine: L-NMMA)-containing medium, an iNOS-positive ATL cell line (K3T) showed growth inhibition and DNA ladder. Although only a limited number of patients was analyzed, our results suggest that NO may be involved in the invasive character of ATL cells. The NOS inhibitor can induce apoptosis in an ATL cell line, as it does in EBV-infected cell lines.

Apoptosis↗

Expression of PRAD1/cyclin D1 in plasma cell malignancy: incidence and prognostic aspects.

We analysed PRAD1/cyclin D1 expression in 20 patients with plasma cell malignancy by Northern analysis. 6/17 multiple myeloma patients and 3/3 plasma cell leukaemia patients showed PRAD1/cyclin D1 expression. This incidence appeared to be higher than the expected incidence based on previous studies. Southern analysis did not show rearrangement of the bcl-1 region. Although there was no statistical difference, the PRAD1/cyclin D1 negative group showed a 1-year survival of 81.8%, 3-year survival of 45.5% and 5-year survival of 22.7%, and those for the PRAD1/cyclin D1 positive group were 63.5%, 16.9% and 16.9%, respectively. Further study is required to determine whether PRAD1/cyclin D1 expression is a prognostic factor.

Aged↗

Involvement of CRM1, a nuclear export receptor, in mRNA export in mammalian cells and fission yeast.

BACKGROUND: CRM1, an evolutionarily conserved protein, was shown to be a receptor for leucine-rich nuclear export signal (NES)-dependent protein transport. In lower eukaryotes CRM1 is reported to be required for the export of mRNA, however, involvement of the NES-dependent transport pathway in mRNA export in higher eukaryotes has not been established. RESULTS: We have found that treatment of mammalian cells with leptomycin B (LMB), a specific inhibitor of CRM1, induces the nuclear accumulation of endogenous mRNA, probably due to the inhibition of its export. In fission yeasts, the nuclear accumulation of mRNA also occurred in cells treated with LMB or in a temperature-sensitive crm1 mutant at a restrictive temperature. A synthetic mRNA that was injected into the nucleus of mammalian cultured cells was exported from the nucleus within 5 h. This export was inhibited by both wheat germ agglutinin and a temperature of 4 degrees C. Importantly, this mRNA export was inhibited by LMB or by an excess amount of the NES peptide-conjugates. LMB treatment, on the other hand, rapidly induced the nuclear entry of RanBP1, a factor involved in the active nucleocytoplasmic transport, although the treatment did not interfere with a nuclear localization signal-dependent transport system within 7 h. CONCLUSION: These results suggest that CRM1 is involved in mRNA export in eukaryotic cells.

Animals↗

The noncatalytic site-deficient alpha3beta3gamma subcomplex and FoF1-ATP synthase can continuously catalyse ATP hydrolysis when Pi is present.

We investigated ATP hydrolysis by a mutant (DeltaNC) alpha3beta3gamma subcomplex of F0F1-ATP synthase from the thermophilic Bacillus PS3 that is defective in the noncatalytic nucleotide binding sites. This mutant subcomplex was activated by inorganic phosphate ions (Pi) and did not show continuous ATP hydrolysis activity in the absence of Pi. Pi also activated the wild-type alpha3beta3gamma subcomplex in a similar manner. Sulphate activated wild-type alpha3beta3gamma but not DeltaNC alpha3beta3gamma, indicating that Pi activation did not involve noncatalytic sites but that sulphate activation did. Pi also activated ATP hydrolysis and coupled proton translocation by the wild-type and DeltaNC F0F1-ATP synthases reconstituted into vesicle membranes.

Adenosine Triphosphate↗

Inhibitory effect of nitric oxide on the renin-angiotensin system in Dahl salt-sensitive rats.

1. To explore the role of nitric oxide (NO) in the regulation of the renin-angiotensin system (RAS) in Dahl salt-sensitive (DS) rats, the effects of NG-nitro-L-arginine methyl ester (L-NAME) on plasma renin activity (PRA), and concentrations of angiotensin (Ang)I and AngII in the plasma, aorta and kidney were investigated in DS and Dahl salt-resistant (DR) rats. 2. NG-Nitro-L-arginine methyl ester (12-18 mg/kg per day) administration for 1 week increased mean arterial pressure (MAP) in DS and DR rats fed a 0.3% NaCl diet and in DR rats fed an 8% NaCl diet compared with corresponding vehicle (water)-treated groups. However, L-NAME administration did not change MAP in DS rats fed an 8% NaCl diet. 3. NG-Nitro-L-arginine methyl ester administration increased PRA in DS rats fed an 8% NaCl diet, but not in DR rats fed an 8% NaCl diet. NG-Nitro-L-arginine methyl ester administration increased AngI and AngII concentrations in plasma, aorta and kidney only in DS rats fed an 8% NaCl diet. The ratio of AngI to AngII did not change following L-NAME administration in any rats. 4. These results suggest that NO has an inhibitory role on renin release in DS rats fed a high-salt diet.

Animals↗

Intraportal perfusion of prostaglandin E1 attenuates hepatic postischaemic microcirculatory impairments in rats.

BACKGROUND: The efficacy of intraportal perfusion with prostaglandin E1(PGE1) in decreasing postischaemic hepatic microcirculatory damage was studied in rats. METHODS: An extrahepatic portosystemic shunt was created by attaching the spleen to a subcutaneous site on the left lateral wall of the abdomen in male Wistar rats weighing between 200 and 350 g. Four weeks later, when the shunt was mature, the portal vein and hepatic artery were occluded for 60 min. The animals were divided into the following three groups according to the type of intraportal perfusion during the ischaemic phase: group 1 consisted of untreated animals; group 2, animals perfused with lactated Ringer's solution; and group 3, animals perfused with PGE1 (0.1 microg/kg per min). The hepatic microcirculation was observed under an inverted intravital microscope after the injection of fluorescent dyes to label leucocytes and damaged cells 30 and 60 min after reperfusion. The liver was removed 60 min after reperfusion and stained immunohistochemically using 1A29, an anti-rat intercellular adhesion molecule-1 (ICAM-1) antibody. RESULTS: The leucocyte velocity during reperfusion was lowest in group 1 and highest in group 3. Of the three groups, group 3 showed the least leucocyte adhesion to the sinusoidal walls and terminal venules, the lowest damaged cell count and the lowest ICAM-1 expression on the sinusoidal walls. CONCLUSION: The results of this study suggest that hepatic perfusion with PGE1 markedly alleviates microcirculatory damage associated with ischaemia and reperfusion through the inhibition of leucocyte-endothelium interactions.

Alprostadil↗