Biomedical subjects

K Sakurai

Publications and source records attributed to K Sakurai.

At least 91 records · Page 5Linked to original sources

PubMed1999

New sensitive agents for detecting singlet oxygen by electron spin resonance spectroscopy.

Free radicals are well-established transient intermediates in chemical and biological processes. Singlet oxygen, though not a free radical, is also a fairly common reactive chemical species. It is rare that singlet oxygen is studied with the electron spin resonance (ESR) technique in biological systems, because there are few suitable detecting agents. We have recently researched some semiquinone radicals. Specifically, our focus has been on bipyrazole derivatives, which slowly convert to semiquinone radicals in DMSO solution in the presence of potassium tert-butoxide and oxygen. These bipyrazole derivatives are dimers of 3-methyl-1-phenyl-2-pyrazolin-5-one and have anti-ischemic activities and free radical scavenging properties. In this work, we synthesized a new bipyrazole derivative, 4,4'-bis(1p-carboxyphenyl-3-methyl-5-hydroxyl)-pyrazole, DRD156. The resulting semiquinone radical, formed by reaction with singlet oxygen, was characterized by ESR spectroscopy. DRD156 gave no ESR signals from hydroxyl radical, superoxide, and hydrogen peroxide. DRD156, though, gives an ESR response with hypochlorite. This agent, nevertheless, has a much higher ability to detect singlet oxygen than traditional agents with the ESR technique.

Dimethyl Sulfoxide↗

PubMed1999

Benign mesenchymoma of the cheek: report of a case and review of the literature.

Benign mesenchymoma is a soft tissue neoplasm that contains 2 or more differentiated mesenchymal components in addition to fibrous tissue. A rare case of benign mesenchymoma of the cheek in a 6-year-old boy is presented. The literature pertaining to mesenchymoma in the head and neck region is reviewed and discussed.

Cheek↗

PubMed1999

Role of Na+/Ca2+ exchange in endothelin-1-induced increases in Ca2+ transient and contractility in rabbit ventricular myocytes: pharmacological analysis with KB-R7943.

1. The effects of endothelin-1 (ET-1) on intracellular Ca2+ ion level and cell contraction were simultaneously investigated in rabbit ventricular cardiac myocytes loaded with indo-1/A1. The role of Na+/Ca2+ exchange in ET-1-induced positive inotropic effect (PIE) was examined by using KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate), a selective inhibitor of reverse mode Na+/Ca2+ exchange. 2. ET-1 at 0.3 pM - 1 nM increased cell contraction and Ca2+ transient (CaT) with EC50 values of 2.9 pM and 1.2 pM, respectively, and the increase in amplitude of CaT was much smaller relative to the PIE: ET-1 at 1 nM increased peak cell shortening by 237%, while it increased peak CaT by 167%. For a given level of PIE, ET-1-induced increase in CaT was much smaller than that induced by elevation of [Ca2+]o and by isoprenaline. Therefore, ET-1 shifted the relationship between peak CaT and cell shortening to the left relative to the relationship for increase in [Ca2+]o, an indication that ET-1 increased myofibrillar Ca2+ sensitivity. 3. KB-R7943 at 0.1 microM and higher inhibited contraction and CaT induced by 0.1 nM ET-1 and at 0.3 microM it abolished the increase in CaT while inhibiting the PIE by 48.1%. Over concentration range of 0.1-0.3 microM, KB-R7943 neither inhibited baseline contraction and CaT nor the isoprenaline-induced response, although at 1 microM and higher it had a significant inhibitory action on these responses. 4. These results indicate that in rabbit ventricular myocytes both increases in CaT and myofibrillar Ca2+ sensitivity contribute to the ET-induced PIE, and the activation of reverse mode Na+/Ca2+ exchange may play a crucial role in increase in CaT induced by ET-1 in rabbit ventricular cardiac myocytes.

Animals↗

PubMed1999

Indomethacin-induced gastric antral damage in hamsters: are neutrophils involved?

BACKGROUND: A direct role for neutrophils in the pathophysiology of indomethacin-induced gastric damage is controversial. Therefore, such damage was evaluated in hamsters. METHODS: Gastric antral damage was evaluated 4 h after the oro-gastric administration of indomethacin (30 mg/kg). Prior to indomethacin, hamsters were treated with various pharmacological agents: rebamipide, methotrexate or anti-neutrophil serum (ANS). The number of circulating neutrophils was determined from Wright-Giemsa stained blood smears. Myeloperoxidase (MPO) activity was measured as a marker of gastric antral neutrophil infiltration. RESULTS: Indomethacin caused primarily gastric antral damage. By histology, this damage did not penetrate the muscularis mucosa. A significant increase in gastric antral MPO activity was also found in indomethacin-treated hamsters. Rebamipide decreased macroscopic gastric antral damage in a dose-related fashion. Methotrexate treatment reduced the circulating blood neutrophil number by 38-44%, but did not affect gastric damage. ANS treatment resulted in near complete neutropenia, and also in a substantial reduction (84%) in gastric antral MPO activity. However, gastric antral damage was not significantly altered by ANS. CONCLUSIONS: Neutrophils are not directly involved in the pathophysiology of indomethacin-induced damage to the hamster gastric antrum.

Alanine↗

PubMed1999

Effect of naproxen on the hamster gastric antrum: ulceration, adaptation and efficacy of anti-ulcer drugs.

BACKGROUND: Various animal models of non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulceration exist. These models have limitations, which make them less relevant to the human situation. AIM: : To develop a more simple and more relevant model of NSAID-induced gastric ulceration and adaptation. METHODS: Gastric ulceration was evaluated following the orogastric administration of naproxen (80 mg/kg b.d.) to hamsters. The effects of misoprostol and famotidine on gastric acid secretion and ulceration were also determined. Gastric adaptation was evaluated by proliferating cell nuclear antigen (PCNA) immunohistochemistry, in hamsters given naproxen for 3 weeks. Antral resistance to acute injury by NSAIDs and ethanol was also determined in these animals. RESULTS: Naproxen caused primarily gastric antral ulceration, which decreased from day 3 to day 21. This gastric adaptation was accompanied by an increase in PCNA positive cells, particularly on days 7 and 14. The adapted gastric antral mucosa was resistant to acute damage by various agents. Misoprostol (1 or 100 microg/kg) prevented antral ulceration, without affecting gastric acid secretion. Despite decreasing acid output by> 90%, famotidine (30 mg/kg) failed to prevent ulceration. CONCLUSION: The administration of naproxen (80 mg/kg b.d.) to hamsters is a simple, reliable and relevant method for evaluating NSAID-induced gastric antral ulceration and adaptation.

Adaptation, Physiological↗

PubMed1999

Comparison of the effects of cilostazol and milrinone on intracellular cAMP levels and cellular function in platelets and cardiac cells.

Cilostazol is a potent cyclic nucleotide phosphodiesterase (PDE) type 3 (PDE3) inhibitor that was recently approved by the Food and Drug Administration (FDA) for the treatment of intermittent claudication. Its efficacy is presumed to be due to its vasodilatory and platelet activation inhibitory activities. Compared with those treated with placebo, patients treated with cilostazol showed a minimal increase in cardiac adverse events. Because of its PDE3 inhibitory activity, however, the possibility that cilostazol exerts positive cardiac inotropic effects is a safety concern. Therefore we compared the effects of cilostazol with those of milrinone, a selective PDE3 inhibitor, on intracellular cyclic adenosine monophosphate (cAMP) levels in platelets, cardiac ventricular myocytes, and coronary smooth muscle cells. We also compared the corresponding functional changes in these cells. Cilostazol and milrinone both caused a concentration-dependent increase in the cAMP level in rabbit and human platelets with similar potency. Furthermore, cilostazol and milrinone were equally effective in inhibiting human platelet aggregation with a median inhibitory concentration (IC50) of 0.9 and 2 microM, respectively. In rabbit ventricular myocytes, however, cilostazol elevated cAMP levels to a significantly lesser extent (p < 0.05 vs. milrinone). By using isolated rabbit hearts with a Langendorff preparation, we showed that milrinone is a very potent cardiotonic agent; it concentration-dependently increased left ventricular developed pressure (LVDP) and contractility. Cilostazol was less effective in increasing LVDP and contractility (p < 0.05 vs. milrinone), which is consistent with the cardiac cAMP levels. The cardiac effect of OPC-13015, a metabolite of cilostazol with about sevenfold higher PDE3 inhibition, was similar to cilostazol. Whereas milrinone concentration-dependently increased cAMP in rabbit coronary smooth muscle cells, cilostazol did not have such an effect. However, both compounds increased coronary flow equally in rabbit hearts. Our results show that although cilostazol and milrinone both inhibit PDE3, cilostazol preferentially acts on vascular elements (platelets and flow). This unique profile of cilostazol is consistent with its beneficial and safe clinical outcomes in patients with intermittent claudication.

Animals↗

PubMed1999

Co-increase of nerve fibers and HLA-DR- and/or factor-XIIIa-expressing dendritic cells in dentinal caries-affected regions of the human dental pulp: an immunohistochemical study.

Neuro-immune interaction has been suggested to play some modulatory role in the immunodefense of the dentin/pulp complex. In this study, we performed a simultaneous immunohistochemical observation of neural elements and pulpal dendritic cells (PDCs) on human carious teeth, to obtain morphological evidence for neuro-immune interaction in response to dentinal tubule-derived carious stimuli. Human third molars bearing a pulp-exposure-free caries lesion were studied. Immunoperoxidase staining was performed with anti-HLA-DR, anti-coagulation factor XIIIa, and anti-CD14 as PDC markers, and anti-low-affinity nerve growth factor receptor (NGFR), anti-protein gene products 9.5, and anti-calcitonin gene-related peptide as nerve markers. The carious teeth usually exhibited localized accumulation of both PDCs and nerve fibers immunoreactive to each marker, in the para-odontoblastic region corresponding to the pulpal end of carious dentinal tubules. Semi-quantitative digital densitometry revealed that pixel numbers corresponding to factor-XIIIa- and NGFR-immunoreactivity were significantly higher in the carious regions than those in the non-carious regions of the same teeth as well as those in the corresponding regions of intact teeth. Classification of specimens with respect to caries depth showed that the co-increase was most apparent in teeth with superficial caries. The increase of PDCs was less pronounced in carious teeth with reparative dentin. These findings suggest that both pulpal nerves and PDCs respond promptly and actively to dentinal tubule-derived carious stimuli. The synchronized accumulation of the two structures suggests an increased opportunity for neuro-immune interaction that may be of significance in the modulation of pathological processes in the dental pulp.

Dendritic Cells↗

PubMed1999

Relationship between aging and recovery of the underlying mucosa immediately after removal of pressure: the first molar region in the mandible.

To investigate changes in the characteristics of edentulous mucosa in the alveolar ridge with aging, we applied pressure to the mucosa of the alveolar ridge in subjects of various ages and evaluated the recovery amount and time after the pressure was removed. Twenty-three subjects ranging from 23 to 79 years of age, who had lost the first mandibular molar tooth, were selected. Displacing pressure was applied to the mucosa corresponding to the mandibular first molar region. After release the pressure, we measured the recovery amount of mucosa from its displacement, which was expressed as the movement of a target which had been placed on the mucosa as measured by an indirect displacement measurement device. The levels of displacement were set at 0.1 mm, 0.2 mm and 0.3 mm, and the time to achieve the selected displacement level was set at 1 second. The initial recovery of the mucosa immediately after the pressure has been released was designated as the initial recovery amount, and the time needed for recovering to 90% of the previous state was designated as the final recovery time. Then we investigated the relationships between the measures of the initial recovery amount, the final recovery time, and the subjects' ages. The initial recovery amount of mucosa was lower and the final recovery time was longer in older subjects, and this tendency was exaggerated when the displacement was increased.

Adult↗

PubMed1999

Buccal mucosa ridging and tongue indentation: incidence and associated factors.

Buccal mucosa ridging and tongue indentation have been considered as one of the visible and reliable signs of bruxism. However, there have not been any reports justifying this relationship scientifically. Moreover, there have not been any studies reporting specific procedures to assess them. Thus, the purpose of the present study was to determine the clinical incidence of buccal mucosa ridging and tongue indentation and assess the possible relationship between certain factors that can influence their occurrence. A total of 244 (178 males and 66 females) dentulous adults from 20 to 59 years of age, who were employees at the Bank of Yokohama, were randomly selected. At first, the buccal mucosa ridging and tongue indentation were classified into three groups based in their intensity: none, mild, and severe. The incidence of both conditions in the different age groups, as well as the incidence by gender was evaluated. Furthermore, the possible relationships between buccal mucosa ridging and tongue indentation and age, gender, clenching awareness, grinding awareness, headache, neck stiffness, vertical dimension, temporomandibular joint (TMJ) pain to palpation, masticatory muscle tenderness to palpation, and the presence of premature contacts were evaluated using the chi-square test. A positive relationship was found between the occurrence of buccal mucosa ridging and tongue indentation and gender (p < 0.01); both conditions were observed more frequently in females than in males. A positive relationship was also found to age; the group between 20-29 years old showed the highest incidence. The vertical dimension had a positive relationship with the occurrence of both buccal mucosa ridging and tongue indentation. Other factors evaluated did not show any correlation.

Adult↗

PubMed1999

[Importance of drug selection and the use of sensitivity tests for the eradication therapy for Helicobacter pylori].

Drug selection for eradication therapy of H. pylori, considering their drug resistance was evaluated. The measurement of resistant colonies was performed in blood agar plates using the MIC method and the criteria for resistance was as follows: MIC > 1 mg/l with AMPC, MIC > 2 mg/l with CAM and MIC > 8 mg/l with MNZ. Primary resistant colonies were found in 0% with AMPC, 8.9% with CAM and 5.9% with MNZ. Secondary resistant colonies were found in 0% with AMPC, 50.0% with CAM and 54.5% with MNZ. CAM and MNZ showed high resistance rate and among them, colonies resistant to CAM were also highly resistant to MNZ. But colonies resistant to MNZ (acquired after CAM) were all sensitive to AMPC. Considering this issue and the absence of resistance to AMPC, we considered the triple therapy with AMPC, MNZ and a PPI as the best option for the eradication of H. pylori.

Amoxicillin↗

PubMed1999

[Immunohistochemical study of p16MTS1/INK4a and Ki-67 expression in esophageal squamous cell carcinomas].

We evaluated the clinical significance of p16 and Ki-67 expressions in esophageal squamous cell carcinomas. Operative specimens obtained from 64 patients with esophageal squamous cell carcinomas were investigated by staining with antibodies against p16 and Ki-67. The possible correlations among p16 and Ki-67 expression, clinicopathologic factors and prognosis were studied. The expression of p16 was observed in 68.9%, and it related to histologic classification, lymphatic invasion and clinicopathological stage. Survival rate was significantly better in the patients with p16 positive tumors than in those with p16 negative tumors. Ki-67 positive index (Ki-67-PI) related to only histologic classification. It is suggested that immunohistochemical assessment on the p16 expressions would be useful to select more suitable treatment of squamous cell carcinoma of the esophagus.

Aged↗

PubMed1999

Proton MR spectroscopy of Sjögren-Larsson's syndrome.

We performed single-voxel proton MR spectroscopy (1H-MRS) in two children with Sjögren-Larsson's syndrome (SLS). Both patients showed two abnormal spectral peaks at 1.3 ppm and 0.9 ppm that were obtained with short echo times. These two abnormal spectral peaks were seen in high-intensity areas on T2-weighted images and also in basal ganglia of normal intensities. 1H-MRS may be useful for establishing the diagnosis and investigating the natural history of SLS, and for evaluating the efficacy of therapeutic approaches to SLS.

Aldehyde Oxidoreductases↗

PubMed1998

Molecular cloning of rat Pax4: identification of four isoforms in rat insulinoma cells.

Molecular cloning of rat Pax4 cDNA from a rat insulinoma cell line, RINm5F, library by PCR-based cloning strategy revealed four isoforms of the protein. Analysis of tissue distribution using Northern blotting and RT-PCR showed specific expression of Pax4 mRNA in pancreatic islets and RIN cells. RT-PCR confirmed that the mRNAs of four isoforms are expressed in RIN cells. These Pax4 variants may regulate the transcriptional activity of Pax4 during the development of pancreatic islets.

Amino Acid Sequence↗

PubMed1998

A grazing-incidence reflectometer for BL-39XU at SPring-8.

A new grazing-incidence reflectometer has been designed for the X-ray undulator beamline BL-39XU at SPring-8. It will be used for analytical applications, especially ultra-trace-level determination by total reflection X-ray fluorescence (TXRF), nanometer-scale surface topography by specular/non-specular X-ray reflection, and thin-film interface studies by combined measurements of X-ray fluorescence and X-ray reflection. The requirements for the instrument and the solutions in the present design are discussed. A prototype has been developed to test the feasibility of the design. It has been confirmed that the measurements planned at the beamline are achievable with this reflectometer.

Journal Article↗

PubMed1998

Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells.

Xylose forms the direct carbohydrate-protein link in extra- or pericellular proteoglycans (PGs) that are substituted with either chondroitin sulfate (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying HS are important regulators of cell growth. Xylose coupled to an aromatic compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS synthesis, depending on the nature of the aromatic adduct. Here, we show that 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside, which can prime both types of glycan chains, inhibits growth of a set of normal and transformed cells. Transformed cells are preferentially inhibited, and at a concentration of 0.15-0.20 mM xyloside, transformed cells are totally growth arrested, whereas normal cells are only < or = 50% inhibited. No inhibition of growth is observed with the stereoisomeric 2-(6-hydroxynaphthyl)-O-beta-L-xylopyranoside, which does not prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O-beta-D-xylopyranoside, which only primes CS/DS synthesis under these conditions; or with p-nitrophenyl-O-beta-D-xylopyranoside, which is known to prime only CS/DS synthesis. We conclude that growth inhibition is due to priming of HS and/or CS/DS synthesis, which may either lead to the formation of specific antiproliferative glycans or glycan fragments or to interference with endogenous PG synthesis and turnover.

3T3 Cells↗

PubMed1998

Hepatitis G virus infection from needle-stick injuries in hospital employees.

A new RNA virus, hepatitis G virus (HGV) is known to be transmissible by blood transfusion. The aim of this study was to assess whether HGV is an occupational risk to hospital employees as a result of exposure to needle-stick injuries. Among 220 cases of needle-stick injuries, 21 employees were contaminated with HGV. Initially none of the 21 recipients were HGV positive. Fourteen of the 21 recipients were followed up and further tested for HGV RNA and serum anti-envelope (E2) specific antibody. None of the 21 recipients exposed to HGV developed liver function abnormalities, but one of the 14 recipients became positive for HGV RNA after the injury. Anti-E2 was negative in all recipients tested. These findings suggests a low clinical risk of occupational exposure to HGV in hospital employees. Nevertheless HGV is transmissible by needle-stick injury.

Acute Disease↗

PubMed1998

Primary squamous cell carcinoma of accessory parotid gland duct epithelium: report of a case.

A rare case of primary squamous cell carcinoma surrounding Stensen's duct in a 75-year-old man is presented. The tumor was a relatively well-defined, hard, subcutaneous mass, measuring 18 x 14 x 9 mm and situated in the right cheek. Microscopic examination of an excisional biopsy specimen revealed tumor cells showing squamous differentiation, a papillary growth pattern, and ductal structures with comedo necrosis. Immunohistochemical studies showed positive reactivity for KL-1 (cytokeratin, monoclonal), epithelial membrane antigen, and carcinoembryonic antigen in some tumor cells. The origin of the tumor was thought to be the accessory parotid gland duct epithelium.

Aged↗

PubMed1998

Isolation and characterisation of radioresistant human KB carcinoma cells in vitro.

In order to investigate the radioresistance mechanism in human carcinoma cells, we isolated the radioresistant cells from a human KB carcinoma cell line by various methods. Although the radioresistant cells were not isolated by the repeated X-irradiation method, pretreatment of the cells with mutagens including N-methyl-N'nitro-N-nitrosoguanidine and 4-nitroquinoline 1-oxide induced radioresistance of 1.50 to 3.75-fold, as judged by the D0 ratio to parental KB cells. When three representative radioresistant cell clones with stable growth isolated by a different method were examined for cross-resistance to anticancer drugs, each cell clone exhibited resistance to one, five and two anticancer drugs, including mitomycin C, bleomycin and methotrexate, respectively. Among them, the cell line N10, showing stable plating efficiency and population doubling time, was further characterised. Consequently, immunocytochemistry, Western blotting and flow cytometry revealed that N10 expressed a higher level of mutant p53 protein than did parental KB, suggesting the involvement of mutant p53 protein in radioresistance of N10.

Antineoplastic Agents↗