Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 181 records · Page 10Linked to original sources

PubMed1999

Stimulant effect of nitric oxide generator and roxatidine on mucin biosynthesis of rat gastric oxyntic mucosa.

Although the involvement of nitric oxide (NO) in an increasing gastric mucus metabolism has been reported, information on whether or not its activation is limited to the specific mucus-producing cells is lacking. In this paper, we report the effect of the exogenous NO-donor, isosorbide dinitrate (ISDN), and second-generation histamine H2 receptor antagonist roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]propyl)acetamide hydrochloride) which is demonstrated to accelerate the mucin metabolism mediated by endogenous NO, on the mucin biosynthesis in distinct sites and layers of the rat gastric mucosa using an organ culture technique. Radiolabeled mucin was obtained from the tissue of full-thickness and the deep corpus layer, and the antrum of the rat stomach incubated for 5 hr with [3H]glucosamine(GlcN) in vitro. With the addition of ISDN to the culture medium, 3H-labeled mucin in the full-thickness corpus mucosa increased to 124-145% of the control (p<0.05), but not in the antrum. This stimulation of the mucin synthesis disappeared by the removal treatment of the surface mucous cell layer which has immunoreactivity of neuronal NO synthase. Similarly, roxatidine stimulated the mucin biosynthesis in the full-thickness corpus mucosa, but not in the gland mucous cell layer. These results suggest that the stimulation of the mucin biosynthesis mediated by NO is restricted to the surface mucous cells of the rat gastric oxyntic mucosa.

Animals↗

PubMed1999

Modification of polysulfone with phospholipid polymer for improvement of the blood compatibility. Part 2. Protein adsorption and platelet adhesion.

Protein adsorption and platelet adhesion from human plasma on polysulfone (PSf) membranes modified with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer were studied. The modification was carried out by blending of the MPC polymer in the PSf. The amount of protein adsorbed on the PSf/MPC polymer blend membrane was significantly decreased with an increase in the composition of the blended MPC polymer. The distribution of the specific proteins adsorbed on the membrane surface was also determined by a gold-colloid immunoassay. Albumin, gamma-globulin and fibrinogen were observed on every membrane surface after contact with plasma. However, in the case of the blended membrane, the density of the adsorbed proteins decreased compared with that of original PSf membrane. That is, the MPC polymer blended in the membrane could function as a protein-adsorption-resistant additive. The number of platelets adhered on the PSf membrane was reduced, and change in the morphology of adherent platelets was also suppressed by the modification with the MPC polymer. Therefore, the PSf/MPC polymer blend membrane had improved blood compatibility compared with the PSf membrane.

Adsorption↗

PubMed1999

Modification of polysulfone with phospholipid polymer for improvement of the blood compatibility. Part 1. Surface characterization.

To improve the surface blood compatibility of polysulfone (PSf) membranes, we prepared novel polymeric additives which have suitable blood compatibility. They were polymers with a phosphorylcholine group, a 2-methacryloyloxyethyl phosphorylcholine (MPC) unit. The MPC polymer could be blended with polysulfone by a solvent evaporation method during membrane processing, and a transparent membrane could be obtained. The mechanical properties of the blend membrane were similar to that of the original PSf membrane. Surface analysis of the blend membrane by X-ray photoelectron spectroscopy and dynamic contact angle measurement revealed that the MPC unit in the polymeric additive was concentrated on the surface of the membrane. The blend membrane significantly reduced plasma protein adsorption compared with that of the PSf membrane.

Adsorption↗

PubMed1999

The effect of the chemical structure of the phospholipid polymer on fibronectin adsorption and fibroblast adhesion on the gradient phospholipid surface.

The interaction between biocomponents and the polyethylene (PE) surface modified with poly[omega-methacryloyloxyalkyl phosphorylcholine (MAPC)] was considered taking into account the surface characteristics, i.e., density, mobility, and orientation of the poly(MAPC). The PE surface, grafted gradually with the poly(MAPC) was prepared by corona irradiation method. The amount of peroxide produced on the PE surface which was determined with 1,1-diphenyl-2-picryl-hydrazyl, increased with an increase in the energy of the corona. The surface density of the poly(MAPC) was increased with an increase in the amount of the peroxides produced by the corona irradiation. The orientation and mobility of the poly(MAPC) grafted on the PE surface was evaluated with 1,6-diphenyl-1,3,5-hexatriene. The orientation of the poly[6-methacryloyloxyhexyl phosphorylcholine (MHPC)] which has six methylene chains between the phospholipid polar group and the backbone was higher than that of other poly(MAPC)s. The mobility of the poly(MAPC) decreased with an increase in the methylene chain length in the MAPC unit. The fibronectin adsorption on the gradient PE sheet grafted with poly(MAPC) was determined with enzyme-labeled immunoassay. The amount of adsorbed fibronectin on the PE grafted with poly[2-methacryloyloxyethyl phospohorylcholine(MPC)] and poly(MHPC) decreased with an increase in their surface density. Especially, the PE sheet grafted with the poly(MHPC) was effectively reduced compared with other poly(MAPC)s. On the poly[10-methacryloyloxydecyl phosphorylcholine (MDPC)], there is a minimum amount of adsorbed fibronectin. The fibronectin adsorption pattern on the PE sheet grafted with poly(MAPC) was quite different from the chemical structure of the MAPC unit. The human normal diploid fibroblasts (WI-38 cells) were cultured on the gradient PE sheet grafted with poly(MAPC) changing the concentration of seeded WI-38 cells. The adhesion behavior of the WI-38 cells was different depending on the concentration of the seeded WI-38 cells. When the concentration was low, the number of the adherent WI-38 cells had the same tendency as fibronectin adsorption. The gradient PE sheet grafted with the poly(MHPC) effectively reduced WI-38 cells adhesion even when the concentration of the WI-38 cells was high. The biocompatibility of polymer surfaces can be improved by highly oriented phosphorylcholine group.

Adsorption↗

PubMed1999

Low frequency of neutralizing antibodies against natural interferon-beta during adjuvant therapy for Japanese patients with melanoma.

The incidence of therapy-induced neutralizing interferon-beta (IFN-beta) antibodies was investigated in 41 Japanese patients with melanoma treated with a combination of chemotherapy and subcutaneous injections of natural IFN-beta. Only one patient (2.4%) developed anti-IFN-beta antibodies. This finding differs from those of previous studies with Caucasian patients in which subcutaneous injections of natural IFN-beta resulted in a high incidence of anti-IFN-beta antibodies. This difference may be related to ethnic group of patients, treatment schedule, pharmacological preparation of IFN-beta and/or technical assay system used in each study.

Adult↗

PubMed1999

Degradation of pectic substances by two pectate lyases from a human intestinal bacterium, Clostridium butyricum-beijerinckii group.

Clostridium butyricum-beijerinckii group, an anaerobic human intestinal bacterium, produced exo-pectate lyase, endo-pectate lyase, and pectin methylesterase, but not polygalacturonase. The production of the two pectate lyases was strongly influenced by the composition of the carbon sources added to the medium. The enzymes secreted by the bacterium into the human large intestine cooperatively digested pectic substances, producing mainly 4,5-unsaturated digalacturonic acid with the participation of the pectin methylesterase. The findings suggest that in the human intestine the bacterium contributes to the digestion of ingested pectic substances.

Journal Article↗

PubMed1999

Lipase-catalyzed direct and regioselective acylation of flavonoid glucoside for mechanistic investigation of stable plant pigments.

One-step and regioselective acylation of flavonoid glucosides was achieved by lipase-catalyzed transesterification in dry organic media. For example, isoquercitrin (quercetin 3-O-glucoside), one of the flavonol monoglucosides, was converted efficiently to the corresponding aromatic acid ester (isoquercitrin 6''-O-cinnamate) by a lipase with vinyl cinnamate as an acyl donor. The method described, which is the first allowing the direct synthesis of aromatic acid esters of flavonoid glucosides, can be applied to the acylation of other glucosides, including naringin, rutin, callistephin, and chrysanthemin.

Journal Article↗

PubMed1999

Multifunctional biocompatible membrane and its application to fabricate a miniaturized glucose sensor with potential for use in vivo.

A multifunctional membrane with biocompatibility, diffusion-limiting effect, and the ability to curtail the responses of an H(2)O(2) electrode to ascorbate and urate was prepared. It was composed of MB, AB, and CTA, where MB is the copolymer of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butylmethacrylate (BMA), AB is the copolymer of acrylamide-2-methylpropane sulfonic acid (AMPS) and BMA, CTA is cellulose triacetate. Investigation of the biocompatibility of this membrane showed that, compared with CTA, relatively few platelets bound to it. The membrane was coated onto the working electrode of a needle-type glucose sensor on which immobilized glucose oxidase membrane has been coated. The sensor did not respond to ascorbate and urate at their concentration normally encountered in blood. Its response was not inhibited by metal ions in blood at usual concentration. The sensor exhibited superior thermostability in addition to a rapid response (<90 seconds in batch operation), good reproducibility (RE<5%), good stability (more than 36 hours continuously in heparinized whole blood), and a wide dynamic range (5-650 mg/dl glucose). The sensor was used to determine glucose in serum. The data obtained from the sensor showed good agreement with that from a clinical autoanalyzer (R=0.973).

Journal Article↗

PubMed1999

Novel carboxamide derivative (IS-741) attenuates lung injury in rats with cerulein-induced pancreatitis complicated by endotoxemia.

The therapeutic effects of an intravenously injected carboxamide derivative (IS-741) on lung injury were studied in rats with cerulein-induced pancreatitis complicated by endotoxemia. Pancreatitis was induced by four intramuscular injections of cerulein (50 microg/kg at 1-hr intervals). Pancreatitis rats were injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) 6 hr following the first cerulein injection as a challenge of endotoxemia. Rats were divided into four groups: group I, pancreatitis with LPS; group II, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 0.03 mg/kg/hr); group III, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 0.3 mg/kg/hr); and group IV, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 3 mg/kg/hr). IS-741 was administered 30 min before the endotoxemia challenge. Intense mononuclear cell infiltration and lung hemorrhage occurred in untreated pancreatitis rats with LPS (group I), but hemorrhage was not seen in group IV rats receiving a continuous injection of IS-741 shortly before the induction of endotoxemia. The IS-741-treated rats (groups II, III, and IV) had lower serum concentrations of cytokine-induced neutrophil chemoattractant (CINC), as well as fewer pulmonary infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). The number of neutrophils infiltrating the lung in groups II, III, and IV was significantly lower than that of group I. Conversely, CINC production by bronchoalveolar macrophages in vitro were stimulated by LPS but were reduced by the presence of IS-741. The carboxamide derivative IS-741 effectively prevented pancreatitis-associated lung injury following the challenge of endotoxemia.

Acute Disease↗

PubMed1999

A synthetic selective inhibitor of factor Xa, DX-9065a, reduces monocyte chemoattractant protein-1 expression after ischemia-reperfusion injury in rat liver.

Activated factor X (FXa) is a trypsinlike serine protease involved in the cascade of blood coagulation. The monocyte chemoattractant protein-1 (MCP-1) may be important in the pathophysiology of liver ischemia-reperfusion injury. We investigated the effects of a selective FXa inhibitor, DX-9065a, on MCP-1 expression after ischemia-reperfusion in the rat liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. DX-9065a was injected intravenously 5 min before vascular clamping. Serum concentrations of MCP-1 were measured by enzyme-linked immunosorbent assay. The levels of MCP-1 mRNA in the liver after reperfusion were determined by northern blot analysis. In vitro MCP-1 production by peritoneal macrophages in response to alpha-thrombin was examined. Serum concentrations of MCP-1 increased and peaked at 6 hr after reperfusion. However, pretreatment of animals with DX-9065a resulted in significantly smaller increases in the serum concentration of MCP-1 after reperfusion in a dose-dependent manner. Pretreatment with DX-9065a significantly reduced MCP-1 mRNA levels in the liver after ischemia-reperfusion. In vitro MCP-1 production by peritoneal macrophages was enhanced by alpha-thrombin. In addition, DX-9065a significantly reduced tissue factor mRNA levels in peripheral monocytes after ischemia-reperfusion, compared to untreated animals. In conclusion, a selective inhibitor of FXa, DX-9065a, limited MCP-1 production after ischemia-reperfusion of the rat liver.

Animals↗

PubMed1999

The effect of 2-h sleep reduction by a delayed bedtime on daytime sleepiness in children.

The purpose of the present study was to investigate the effect of acute 2h sleep reduction by a delayed bedtime on daytime sleepiness. Three children were evaluated over three consecutive days: two control days and a 2h sleep reduction day. A sleep latency test was conducted five times each day at 2h intervals from 10.00 h. The results showed that the effects of sleep loss generally increased daytime sleepiness, in particular, at 10.00 h, and suggested that the intensity of morning sleepiness may become a useful measure which reflects sleep loss.

Child↗

PubMed1999

Classification of the sleeping pattern of normal adults.

A questionnaire concerning their sleep-related lifestyle and mental health was mailed to people aged in their twenties to fifties living in the Fukushima (North East), Tokyo (Central, Metropolitan) and Okayama (West) areas of Japan. We classified the sleeping pattern of 3642 people (1702 men, 1940 women; mean age 41.3+/-10.67) by multivariational analyses (factor analysis and cluster analysis). They were classified into six groups and defined as 'poor sleeper group' (30.0%), 'good sleeper group' (28.3%), 'long sleeper group' (8.2%), 'short sleeper group' (18.5%), 'irregular sleeper group' (11.3%), and 'Delayed Sleep Phase Syndrome group' (3.7%) based on their characteristics of the factor pattern.

Adult↗

PubMed1999

Hepatic fatty acid oxidation enzyme activities are stimulated in rats fed the brown seaweed, Undaria pinnatifida (wakame).

The activities of hepatic enzymes involved in fatty acid synthesis and oxidation were compared in rats fed diets containing different proportions of dried powder of the brown seaweed, Undaria pinnatifida (wakame). Rats were fed diets containing 0, 0.5, 1.0, 2. 0, 5.0 and 10 g/100 g of dried wakame powder. Experimental diets were adjusted to provide consistent amounts of most nutrients, but mineral concentrations were not standardized. After the 21-d feeding period, serum and liver triacylglycerol levels in rats fed diets in which wakame constituted at least 2% were significantly lower than those in rats fed the control diet. The activity of glucose-6-phosphate dehydrogenase was significantly lower in rats fed the 5 and 10% wakame diets than in rats fed the control diet. In contrast, 10% wakame diet increased activities of enzymes involved in the beta-oxidation pathway including hepatic carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, enoyl-CoA hydratase and 2,4-dienoyl-CoA reductase. Some differences were detected in rats fed 5% wakame as well. These results suggest that alterations of the activities of enzymes involved in fatty acid metabolism in the liver are responsible for the serum triacylglycerol-lowering effect of dietary wakame. Thus, wakame may be useful as a food to prevent hyperlipidemia.

Animal Feed↗

PubMed1999

Rat gastric mucins recognized by monoclonal antibodies RGM21 and HIK1083: isolation of mucin species characteristic of the surface and glandular mucosa.

Whole mucins and reduced subunits were extracted from the corpus of the rat stomach. After purification by Sepharose CL-4B chromatography followed by cesium trifluoroacetate equilibrium centrifugation, they were analyzed by Sepharose CL-2B chromatography, rate-zonal sedimentation centrifugation, and Q-Sepharose chromatography. Monoclonal antibodies RGM21 and HIK1083, which histochemically stained mucins in the surface and glandular mucosa of the rat stomach, respectively, were used to detect the site-specific mucins. Although RGM21- and HIK1083-reactive mucins both had a multimerized structure, the density and size of both the whole mucins and reduced subunits differed, thus indicating the presence of distinct mucin species in the surface and glandular mucosa. The mucin subunits were separated into four fractions, UB, B1, B2a, and B2b, by Q-Sepharose chromatography. HIK1083 reacted mainly with UB, while RGM21 reacted with B1, B2a, and B2b. These results, combined with dot-blot, amino acid, and carbohydrate composition analyses, showed that the surface mucins may consist of three kinds of subunits. In contrast, the glandular mucins may consist of one kind of subunit which differs from that of surface mucins.

Amino Acids↗

PubMed1999

Long-term quality of life in patients after total gastrectomy.

This study used a questionnaire survey to evaluate the long-term quality of life (QOL) in 51 patients who underwent total gastrectomy. Activities of daily living (ADL) were good in 20, relatively good in 9, relatively poor in 13, and poor in 6 patients. The other 3 patients were treated on an inpatient basis. Of 38 patients who had been employed before surgery, 18 (47%) resumed working. Physically, body weight increased or showed no changes in 38 patients (74%), but decreased in the other 13 patients, of whom 3 showed a 15% or more decrease. Dumping symptoms developed in 13 patients (26%), 2 of whom had a severe condition. Clear decreases in physical strength and mental strength (spiritual energy) were reported by 10 and 8 patients, respectively. Comprehensive QOL was good in 20, slightly poor in 17, and poor in 14 patients. Quality of life was poor in 12 (41%) of the 29 patients with good ADL. The following were suggested as necessary for patients and their families: sufficient preoperative explanation about pathophysiology and nutritional management after total gastrectomy; execution of a continued patient education program until after discharge; and explanations in specific terms about cooking methods, nutritional management, exercise therapy, periodic medical checks, and patients' associations using pamphlets and food models to describe daily living of the patients after discharge.

Activities of Daily Living↗

PubMed1999

Monoclonal antibody to human midkine reveals increased midkine expression in human brain tumors.

We produced a rat IgG2a monoclonal antibody against the carboxyl terminal region of human midkine (MK), a novel growth factor. This monoclonal antibody was used in immunohistochemical studies to compare the expression of MK, proliferating cell nuclear antigen (PCNA) and p53 protein in 133 primary brain tumors and 21 carcinoma metastases to the central nervous system. Approximately half of the glioblastomas multiforme (GBMs) (19/32), medulloblastomas (8/14), primitive neuroectodermal tumors (PNETs) (5/11), breast carcinoma metastases (Br-Mts) (6/10) and lung carcinoma metastases (L-Mts) (5/11) as well as some astrocytomas (2/14) had tumor cells that expressed MK; however, oligodendrogliomas, ependymomas, schwannomas, meningiomas, and pituitary adenomas did not express MK. The values of the PCNA-labeling index were statistically higher in GBMs, medulloblastomas, PNETs, Br-Mts, and L-Mts that expressed MK than in those that did not (Wilcoxon rank-sum test, p < 0.05). There was no correlation between MK and p53 protein in all tumor types. Normal and non-neoplastic brain tissues were negative for MK, PCNA, and p53 protein. We conclude that primary and metastatic tumors of the brain express MK and that the MK expression in brain tumors may depend, in part, on the proliferating potential.

Animals↗

PubMed1999

Platelet-activating factor antagonist (TCV-309) attenuates the priming effects of bronchoalveolar macrophages in cerulein-induced pancreatitis rats.

We investigated the role of platelet-activating factor (PAF) as a priming signal for cytokine-induced neutrophil chemoattractant (CINC) expression by bronchoalveolar macrophages in acute pancreatitis. Pancreatitis was induced by four intramuscular injections of cerulein (50 micrograms/kg at 1-h intervals) in Wistar rats. The animals were injected intraperitoneally with 10 micrograms/kg of lipopolysaccharide (LPS) as a septic challenge. Pancreatitis rats were treated with a bolus intravenous injection of TCV-309 (3 or 30 micrograms/kg) 30 min before the septic challenge. Intense mononuclear cell infiltration and lung hemorrhage occurred in pancreatitis rats complicated with sepsis but were not seen in pancreatitis rats receiving a bolus TCV-309. Pancreatitis rats treated with TCV-309 had lower serum concentrations of CINC after septic challenge and lower levels of CINC messenger RNA (mRNA) in the lung, as well as fewer pulmonary infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). In vitro CINC production in response to LPS by bronchoalveolar macrophages obtained from pancreatitis rats 6 h after the first cerulein injection, immediately before septic challenge, was enhanced but was significantly reduced in a TCV-309-sensitive manner. LPS-stimulated in vitro CINC production by naive bronchoalveolar macrophages was significantly enhanced by pretreatment with PAF. TMB-8 (an inhibitor of calcium release from endoplasmic reticulum) or W7 (calmodulin antagonist) completely abrogated the chemoattractant production by bronchoalveolar macrophages pretreated with PAF after LPS stimulation. Altered intracellular calcium, due to Ca2+ efflux from intracellular stores, may be involved in the "priming" of bronchoalveolar macrophages to release CINC after triggering with LPS during acute cerulein-induced pancreatitis. The PAF antagonist TCV-309 effectively prevented hyperactivity of bronchoalveolar macrophages and pancreatitis-associated lung injury after the septic challenge.

Animals↗

PubMed1999

Specific microbial colonizations in the periodontal sites of HIV-infected subjects.

The purpose of this study was to examine colonization by specific organisms at periodontal sites in HIV-seropositive [HIV(+)] subjects. A total of 67 HIV(+) and 32 HIV(--) subjects were investigated. The specific pathogens included black-pigmented anaerobic rods (BPAR), Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Candida albicans and mycoplasma species. P. gingivalis was present in the HIV(+) subjects more frequently than in the HIV(--) periodontitis patients (P < 0.01). The cell numbers of BPAR and P. gingivalis and percentages as the total of CFUs on blood agar cultured in an anaerobic chamber were statistically higher in periodontal pocket samples from HIV(+) than from HIV(--). A. actinomycetemcomitans was also detected at a high rate (41.8%) in HIV(+) patients. The average cell numbers of C. albicans were higher in samples from the HIV(+) group (P < 0.05). The detection rate of mycoplasma species in the HIV(+) patients was significantly lower than that in HIV(--) subjects (P < 0.05), and most isolated mycoplasma strains were Mycoplasma salivarium.

Adolescent↗