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S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 163 records · Page 9Linked to original sources
PubMed2000

Excessive concentration of glucose during in vitro maturation impairs the developmental competence of bovine oocytes after in vitro fertilization: relevance to intracellular reactive oxygen species and glutathione contents.

The effect of glucose (0, 1.5, 5.6 or 20.0 mM) in synthetic oviduct fluid supplemented with 20 amino acids (SOFaa) on the developmental competence of bovine oocytes after in vitro fertilization was investigated. Intracellular reactive oxygen species (ROS) and the glutathione content of bovine oocytes matured in SOFaa containing 0-20.0 mM glucose were also examined. When oocytes were matured in SOFaa without glucose, the nuclear maturation rate was lower than that in oocytes matured in glucose-containing medium. The developmental competence to the blastocyst stage of oocytes matured in 1.5 mM glucose was higher than that of oocytes matured in 20.0 mM glucose. In addition, the intracellular ROS content of oocytes matured in 0, 1.5 or 5.6 mM glucose was lower than that of oocytes matured in 20.0 mM glucose. Furthermore, the intracellular glutathione content of oocytes matured in 0, 1.5 or 5.6 mM glucose was higher than that of oocytes matured in 20.0 mM glucose. These results show that excessive glucose in the medium for oocyte maturation impairs the development of bovine oocytes to the blastocyst stage, possibly due to the increase of ROS and the decrease in the intracellular glutathione content of bovine oocytes.

Amino Acids↗
PubMed2000

Low oxygen tension during in vitro maturation is beneficial for supporting the subsequent development of bovine cumulus-oocyte complexes.

The effects of carbohydrates on meiotic maturation and ATP content of bovine oocytes under low oxygen tension (5%) were investigated. Furthermore, the developmental competence or intracellular H(2)O(2) contents of the oocytes matured under 5% or 20% O(2) was assessed. In vitro maturation of bovine cumulus-oocyte complexes was performed in synthetic oviduct fluid (SOF) containing 20 amino acids and hormones (SOFaa). The proportion of the oocytes that matured to the metaphase II stage in SOFaa containing 1.5 mM glucose, 0.33 mM pyruvate, and 3.3 mM lactate under 5% O(2) was dramatically lower than that of oocytes matured under 20% O(2) (P < 0.01). Similarly, the ATP content of the oocytes that matured under 5% O(2) was much lower than that of oocytes matured under 20% O(2) (P < 0.05). Under 5% O(2) the proportion of metaphase II oocytes increased with increasing glucose concentration (0-20 mM) in SOFaa without pyruvate or lactate. In addition, the ATP content of oocytes cultured in 20 mM glucose was higher (P < 0.05) than that of oocytes cultured in 1. 5 mM glucose. Two glucose metabolites (pyruvate and lactate) and a nonmetabolizable glucose analog (2-deoxy-glucose), however, had no noticeable effects on meiotic maturation under 5% O(2). These results suggest that ATP production under 5% O(2) is not dependent on the TCA cycle. Addition of iodoacetate, a glycolytic inhibitor, to SOFaa containing 20 mM glucose significantly reduced (P < 0.01) the proportion of metaphase II and ATP content. Moreover, the proportion of the development to the blastocyst stage of oocytes matured under 5% O(2) was higher (P < 0.05) than that of oocytes matured under 20% O(2). H(2)O(2) contents of oocytes matured under 5% O(2) was lower (P < 0.05) than that of oocytes matured under 20% O(2). The results of the present study demonstrate that glucose plays important roles in supporting the completion of meiotic maturation in bovine cumulus-oocyte complexes under low oxygen tension and that low oxygen tension during in vitro maturation is beneficial for supporting the subsequent development of bovine oocytes.

Adenosine Triphosphate↗
PubMed2000

Properties of fucoidan from Cladosiphon okamuranus tokida in gastric mucosal protection.

To elucidate the anti-ulcer potential of Cladosiphon fucoidan, anti-peptic activity, bFGF stabilizing activity and inflammatory properties of this and related substances were investigated. Anti-peptic activity was observed with this and other sulfated polysaccharides such as dextran sulfate, carrageenan, and Fucus fucoidan. However, non-sulfated polysaccharides such as mannan and dextran did not exert the anti-peptic activity. The loss of bFGF bioactivity was prevented by all sulfated polysaccharides tested except chondroitin sulfate, at pH 7.4 and at pH 4.0. At pH 2.0, only heparin protected the bFGF activity. The generation of superoxide by macrophages and PMNs was stimulated by dextran sulfate, carrageenan, and Fucus fucoidan, whereas Cladosiphon fucoidan, heparin and chondroitin did not. Dextran sulfate, carrageenan, and Fucus fucoidan also stimulated the secretion of TNFalpha from macrophages, while Cladosiphon fucoidan did not. Thus, Cladosiphon fucoidan is a sulfated polysaccharide without inflammatory action. These results suggest that Cladosiphon fucoidan is a safe substance with potential for gastric protection.

Animals↗
PubMed2000

Increased concentrations of nitrate and nitrite in the cyst fluid suggesting increased nitric oxide synthesis in solitary bone cysts.

The etiology and treatment of a solitary bone cyst have remained undefined. Surgical treatments have not been encouraging, because a less invasive corticosteroid-injection treatment has afforded good results. However, there has been little scientific rationale supporting corticosteroid treatment. In recent reports, bone-resorbing factors, including matrix metalloproteinases, prostaglandins, interleukin-1, and oxygen free radicals, have been demonstrated in the cyst fluid. To better elucidate the pathophysiology of the solitary bone cyst, we examined the activities of nitric oxide and cytokines in the cyst fluid as well as in the cyst membrane. The levels of nitrate and nitrite were significantly higher in the cyst fluid than in serum. Immunostaining of cells in the stroma and lining cells of the cyst wall was strongly positive for inducible nitric synthase. The levels of interleukin-6 and interleukin-1beta in the cyst fluid were elevated, and cells in the cyst membrane were positive for tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. Cultured cells from the cyst membrane were induced in the production of nitrate and nitrite in response to cytokine treatment. These findings suggest that the solitary bone cyst was in a state favorable for the production of nitric oxide.

Adolescent↗
PubMed2000

Biological functions of extravasated serum IgG in rat brain.

During blood-brain barrier opening serum IgG could be extravasated. The function of intraparenchymal IgG, however, is unknown. Its biological effects in the acute phase were currently investigated. From rat autoserum IgG was purified and injected into the cortex. Similarly, IgG-Fab fragment was prepared and administered likewise. As for the control group, only vehicle was injected. Animals were sacrificed on days 1, 2 and 4 after the infusion and were histologically evaluated. On days 1 and 2, the infusion of IgG caused significant intraparenchymal infiltration of neutrophils which expressed LFA-1-alpha. It also induced CR3 up-regulation in microglia and endothelial ICAM-1 expression. On day 4, these findings had disappeared. HE stained brain sections and the TUNEL method did not reveal significant nerve cell death in IgG injected animals during the experiment as compared to the controls. IgG-Fab did not cause significant changes either. Extravasated IgG has been viewed to have biochemical functions. Its Fc fragment seemed to cause microglial and endothelial activation, followed by leukocytic infiltration. This sequence itself was not neurotoxic. Therefore, it is suggested that extravasated IgG is one of the inducers that modulate cellular responses in the acute phase of brain damage.

Acute-Phase Reaction↗
PubMed2000

A major metabolite of aceclofenac, 4'-hydroxy aceclofenac, suppresses the production of interstitial pro-collagenase/proMMP-1 and pro-stromelysin-1/proMMP-3 by human rheumatoid synovial cells.

OBJECTIVE AND DESIGN: We examined the effects of aceclofenac and its metabolites on the production of pro-collagenase-1/pro-matrix metalloproteinase-1 (proMMP-1), pro-gelatinase A/proMMP-2, pro-stromelysin-1/proMMP-3 and tissue inhibitor of metalloproteinases-1 (TIMP-1) by rheumatoid synovial cells. MATERIALS: Synovial cells were obtained from patients with rheumatoid arthritis. TREATMENT: Cultures of confluent cells were treated with interleukin-1beta (IL-1beta)(1 ng/ml) and/or test drugs (0.3-30 microM) for 48 h. METHODS: Production of proMMPs and TIMP-1 was monitored by Western blotting or gelatin zymography. Prostaglandin E2 (PGE2) was measured by an enzyme immunoassay. RESULTS: 4'-Hydroxy aceclofenac, a major metabolite of aceclofenac, down-regulated both basal and IL-1beta-induced production of proMMP-1 and proMMP-3 at a concentration sufficient to suppress PGE2 production without modulating proMMP-2 or TIMP-1, whereas aceclofenac itself had no marked effect on the production of proMMPs. CONCLUSIONS: Down-regulation of proMMP-1 and proMMP-3 production by 4'-hydroxy aceclofenac may contribute to the therapeutic effect of aceclofenac on rheumatoid arthritis and osteoarthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Modified irinotecan hydrochloride (CPT-11) administration schedule improves induction of delayed-onset diarrhea in rats.

PURPOSE: Clinically, diarrhea is the major dose-limiting toxicity of irinotecan hydrochloride (CPT-11). Using a rat model, we attempted to decrease the incidence of delayed-onset diarrhea by modifying the administration schedule of CPT-11, and studied the pharmacokinetics in this model in relation to the incidence of diarrhea. METHODS: CPT-11 (total dose, 240 mg/kg) was administered intravenously (i.v.) to rats according to various schedules, and the incidence of delayed-onset diarrhea was monitored. RESULTS: Administration of CPT-11 at a dose of 60 mg/kg once daily for four consecutive days induced severe diarrhea, while at 30 mg/kg twice daily at an interval of 9 h (daily dose 60 mg/kg) for four consecutive days alleviated the diarrheal symptoms, and at 30 or 40 mg/kg once daily for eight or six consecutive days, respectively. diarrhea was hardly induced. With the first schedule, mucosal impairment of the cecal epithelium was observed, including wall thickening, edema, decrease in crypt number and size, and formation of pseudomembrane-like substance, whereas these changes were less severe with the second schedule and were hardly observed with the other two schedules. The areas under the plasma and cecal tissue concentration-time curves (AUCpla and AUCcec), the maximum plasma concentrations (Cmax) and the biliary excretions of CPT-11 and its metabolites, 7-ethyl-10-hydroxycamptothecin (SN-38) and SN-38 glucuronide (SN-38G) in rats depended on the daily dose of CPT-11. Exceptionally, CPT-11 Cmax was significantly lower and SN-38 AUCcec was larger in the animals treated at 30 mg/kg twice daily than in those treated at 60 mg/kg once daily. CONCLUSION: These results suggested that the duration of exposure to both CPT-11 and SN-38 of the intestinal epithelium and CPT-11 plasma Cmax are closely related to the incidence and severity of CPT-11-induced delayed-onset diarrhea in rats.

Animals↗
PubMed2000

Neurotrophic effects of FPF-1070 (Cerebrolysin) on cultured neurons from chicken embryo dorsal root ganglia, ciliary ganglia, and sympathetic trunks.

We examined the effect of FPF-1070 (Cerebrolysin) on neurite outgrowth in explant cultures of dorsal root ganglia (DRG), sympathetic trunks (ST), and ciliary ganglia (CG) from 10- to 11-day chicken embryos. FPF-1070 significantly promoted neurite outgrowth in DRG and ST neurons at all concentrations examined, in comparison with phosphate buffered saline-treated negative controls; however, this effect on neurite outgrowth was not as significant as that observed for nerve growth factor-treated positive controls on DRG and ST neurons. Additionally, FPF-1070 exhibited an inverted U relationship between concentration and effectiveness in DRG and ST neurons. In contrast, FPF-1070 did not affect neurite outgrowth in CG neurons although ciliary neurotrophic factor-treated positive controls showed striking neurite outgrowth. Our results demonstrate that FPF-1070 has different neurotrophic effects depending on the subpopulation of neurons. This study clarifies a role for neurotrophic activity in the mechanism of action of FPF-1070.

Amino Acids↗
PubMed2000

Grepafloxacin inhibits tumor necrosis factor-alpha-induced interleukin-8 expression in human airway epithelial cells.

We examined the effect of grepafloxacin (GPFX), a new fluoroquinolone antimicrobial agent, on interleukin-8 (IL-8) expression in tumor necrosis factor-alpha (TNF-alpha)-stimulated human airway epithelial cells (AEC). GPFX inhibited IL-8 protein production as well as mRNA expression in a concentration-dependent manner (2.5 - 25 micro g/ml), but the inhibition of IL-8 expression by corresponding concentrations of GPFX to serum and airway lining fluids was not complete. We discuss the modulatory effect of GPFX on IL-8 production in the context of its efficacy on controlling chronic airway inflammatory diseases.

Anti-Infective Agents↗
PubMed2000

Elevated serum vitellogenin levels and gonadal abnormalities in wild male flounder (Pleuronectes yokohamae) from Tokyo Bay, Japan.

Concentrations of vitellogenin (VTG) in serum of wild male flounder (Pleuronectes yokohamae) were investigated, as a biomarker for environmental estrogens in marine waters, from January 1997 to May 1998 in Tokyo Bay, Japan (n = 130) and from a reference site in Hokkaido, Japan, far from urban areas (about 40 km from Hakodate city) from March 1997 to June 1998 (n = 62). Statistically higher concentrations of serum VTG were detected in wild male flounder collected in Tokyo Bay (range: 25-2200 ng ml-1) compared to fish from Hokkaido (range: 31-91 ng ml-1) throughout the entire sampling period. Three out of 20 males collected off Haneda, in the inner part of Tokyo Bay, showed testes containing small numbers of oocytes. This intersex condition was not found among males collected from the reference site. This study suggests that the abnormally high levels of VTG and the presence of oocytes in the testis of male flounder collected from Tokyo Bay could be the effect of environmental estrogens.

Animals↗
PubMed2000

The mechanism of geranylgeraniol-induced apoptosis involves activation, by a caspase-3-like protease, of a c-jun N-terminal kinase signaling cascade and differs from mechanisms of apoptosis induced by conventional chemotherapeutic drugs.

In the present study, we investigated the effects of geranylgeraniol (GGO), a potent inducer of apoptosis in various lines of human tumor cells, on signal transduction cascades involved in apoptosis in human leukemia cells. GGO strongly induced the activation of c-Jun N-terminal kinase (JNK/SAPK) within 2 h in U937 and K562 cells, while neither ERK nor p38 was activated to any considerable extent during GGO-induced apoptosis. Transient expression of a constitutively active mutant form of mitogen-activated protein kinase kinase 1 (MEKK1), deltaMEKK1, or of deltaMEKK1-green fluorescent protein (GFP) in K562 cells activated JNK, but not a caspase-3-like protease, and was insufficient to induce cell death but rendered cells susceptible to GGO-induced cell death. Stable expressions of deltaMEKK1-GFP in U937 cells gave similar results. In contrast to VP-16-induced apoptosis, GGO-induced activation of JNK was almost completely inhibited by benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (Z-DEVD) and by benzyloxycarbonyl-Asp-CH2OC[O]-2,6,-dichlorobenzene (Z-Asp), indicating that the JNK-activation step is located downstream of the caspase signaling pathway in GGO-induced apoptosis. Moreover, apoptosis induced by GGO was significantly inhibited in two lines of cells with a dominant-negative deletion mutation in c-Jun, indicating a requirement for JNK signaling. In addition, unlike the effects on other inducers of apoptosis, the activation of JNK and of the caspase-3-like protease by GGO was significantly delayed by 12-O-tetradecanoylphorbol-13-acetate (TPA), suggesting that the site of inhibition by TPA might be located upstream of the protease and JNK in the GGO-induced apoptotic signaling pathway.

Antineoplastic Agents↗
PubMed2000

Inhibition of L-leucine methyl ester mediated killing of THP-1, a human monocytic cell line, by a new anti-inflammatory drug, T614.

T614 (3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne) is a member of the family of methanesulfonanilide non-steroidal anti-inflammatory drugs (mNSAIDs), most of which act as cyclooxygenase (COX)-2 inhibitors. L-leucine methyl ester (Leu-OME) is a reagent which has been shown to kill phagocytes following interaction with intracellular proteases. There are two pathways whereby Leu-OME becomes cytotoxic to phagocytes. Within lysosomes, Leu-OME is converted into free Leu, which causes disruption of the lysosomes and subsequent cell necrosis. The other is the conversion of Leu-OME into (Leu-Leu)(n)-OME, which is associated with the induction of apoptosis. In the present study, we examined the action of T614 on Leu-OME mediated killing of THP-1, a human monocytic cell line. We revealed that T614 and phenylmethyl sulfonyl fluoride (PMSF), a serine protease inhibitor, inhibited Leu-OME mediated killing of THP-1 cells. All the other mNSAIDs, including nimesulide (NIM-03), fluosulide (CGP28238), FK3311 and NS398, also rescued THP-1 from Leu-OME mediated killing, although to a lesser degree. Of the classical NSAIDs tested, a protective effect was observed with diclofenac at high concentration, but not with naproxen or indomethacin. Unlike conventional lysosomal inhibitors, such as chloroquine and ammonium chloride (NH(4)Cl), T614 and PMSF did not raise lysosomal pH, as measured by flow cytometry using fluorescein isothiocyanate dextran (FITC-dextran). Therefore, the mechanism whereby T614 and PMSF inhibit Leu-OME killing is distinct from that of chloroquine or NH(4)Cl. Based on the similarity of T614 and PMSF, we suggest that, besides their roles as COX-2 inhibitors, T614 and other mNSAIDs may act as lysosomal protease inhibitors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

An integrated service digital network (ISDN)-based international telecommunication between Samsung Medical Center and Hokkaido University using telecommunication helped radiotherapy planning and information system (THERAPIS).

This study introduces the integrated service digital network (ISDN)-based international teleradiotherapy system (THERAPIS) in radiation oncology between hospitals in Seoul, South Korea and in Sapporo, Japan. THERAPIS has the following functions: (1) exchange of patient's image data, (2) real-time teleconference, and (3) communication of the treatment planning, dose calculation and distribution, and of portal verification images between the remote hospitals. Our preliminary results of applications on eight patients demonstrated that the international telecommunication using THERAPIS was clinically useful and satisfactory with sufficient bandwidth for the transfer of patient data for clinical use in radiation oncology.

Japan↗
PubMed2000

The role of radiotherapy in treating squamous cell carcinoma of the external auditory canal, especially in early stages of disease.

PURPOSE: Our intent was to investigate the role of radiotherapy in treating external auditory canal squamous cell carcinoma, especially in early stages of disease. MATERIALS AND METHODS: The treatment results for 20 patients treated between 1980 and 1998 were retrospectively analyzed. Radiotherapy was used as an initial treatment without surgery in eight patients and with surgery in 12 patients. The patients treated by radiotherapy alone received 65 Gy in 26 fractions over 6.5 weeks. The patients treated with radiotherapy perioperatively received 30-75 Gy in 12-30 fractions. The follow-up period for survivors including patients died of intercurrent disease ranged from 7 to 205 months (mean: 71 months). RESULTS: The 5-year survival rate calculated by the Kaplan-Meier method for all patients was 59%. According to Stell classification (Laryncol. Otol. 99 (1985) 847), the 5-year survival rates for eight patients with T1 disease and eight with T2 disease were 100 and 38%, respectively. In the eight patients with T1 disease, disease control was 100%. Local control with hearing preservation was achieved in five patients with T1 disease by radiotherapy alone. No late complications related to radiotherapy were observed. CONCLUSIONS: A precise diagnosis of the disease in terms of whether or not it has invaded the bone is important in order to predict the treatment outcome. Radiotherapy with or without surgery is the treatment of choice for patients with T1-stage disease. Surgery with radiotherapy is recommended as standard care for tumors with bony invasion.

Adult↗
PubMed2000

Ipsilateral irradiation for carcinomas of tonsillar region and soft palate based on computed tomographic simulation.

PURPOSE: To reduce xerostomia in selected patients with carcinomas of the tonsillar region and soft palate. METHODS AND MATERIALS: We evaluated the treatment results of 32 patients with tonsillar region and soft palate carcinoma treated by radical radiotherapy between May 1989 and December 1996. They have a unilateral tumor that did not cross midline and have no contralateral neck lymphnode metastasis and treated with an ipsilateral technique (an anterior oblique and a posterior oblique field). All patients were planned with computed tomographic (CT) simulation and given 65 Gy in 26 fractions in 6.5 weeks with or without 5-15 Gy boost irradiation. The median follow-up was 44 months (4-86 months). RESULTS: Five-year overall, cause-specific survival, local control, and regional control rate was 64, 79, 74 and 81%. No failure at the contralateral neck occurred. Moderate or severe symptomatic xerostomia was seen in 3 (9%) patients and ostero-radionecrosis requiring surgery occurred in one (3.3%) of 32 patients. CONCLUSION: It is suggested that the ipsilateral technique is indicated in patients who had an unilateral tonsillar region or soft palate carcinoma that did not cross midline and have no contralateral neck lymphnode metastasis.

Adult↗
PubMed2000

Morphologic changes in forearm flaps of the oral cavity.

PURPOSE: This study was undertaken to investigate the morphologic changes in the forearm flap in the oral environment. PATIENTS AND METHODS: Histologic evaluation of biopsy specimens from 20 forearm flaps was done 1 to 75 months after intraoral reconstruction after treatment of cancer. Hematoxylin and eosin and Azan were used to stain the deparaffinized sections. RESULTS: The clinical features of the grafted flap seemed to depend on the time since the operation. The cornified layer of the epidermis of the flaps showed thinning histologically. CONCLUSION: After 11 months of exposure to an intraoral environment, "mucosalization" of the forearm flap is evident.

Adult↗
PubMed2000

A guinea pig model of adhesive otitis media and the effect of tympanostomy.

OBJECTIVE: The pathophysiology and prevention strategies of adhesive otitis media were investigated using two animal otitis media models induced by the inoculation of a corrosive agent into the tympanic clefts of guinea pigs. METHODS: In the first experiment, KANSUI (consisting of potassium carbonate and sodium carbonate) solution was injected into the left tympanic cleft of the guinea pigs. Five groups of five animals were sacrificed at 2 weeks, and at 1, 3, 6, and 12 months after inoculation to observe the pathological changes with time. In the second experiment, a similar otitis media model was induced in 18 guinea pigs. Tympanostomy was performed at 1 and 2 weeks after induction of the otitis media to eliminate inflammatory exudate from the tympanic cleft. Three groups of six animals were sacrificed at 1, 3, and 6 months after the tympanostomy to compare the differences in pathological changes between the groups with and without tympanostomy. RESULTS: In the first experiment, severe mucosal injury to the middle ear mucosa was observed at 2 weeks, and at 1 and 3 months after inoculation, and the tympanic membrane (TM) had adhered to the promontorium at 3, 6 and 12 months after inoculation. In the second experiment, TM adhesion decreased following the tympanostomy. CONCLUSION: It is suggested that severe injury to the middle ear mucosa caused TM adhesion during the process of wound healing, and that tympanostomy is effective in preventing adhesive otitis media.

Animals↗