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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 199 records · Page 11Linked to original sources

[Multicenter screening of Chlamydia pneumoniae pneumonia by ELISA method].

We prospectively investigated the etiology of community-acquired pneumonia among adult patients admitted to three general hospitals over one year. Antibody titers to Chlamydia pneumoniae were also measured by ELISA method to investigate the incidence and clinical pictures of C. pneumoniae pneumonia in Japan. Two hundred and fourteen patients were enrolled in the study. Seventeen patients (7.9%) satisfied the criteria for diagnosis of acute infection due to C. pneumoniae by ELISA method. C. pneumoniae was the 3rd leading causative agent following Streptococcus pneumoniae (21.5%) and Haemophilus influenzae (8.4%). Preexisting antibodies were detected in 62.1% of the patients. Most of the patients with C. pneumoniae pneumonia were aged, and had comorbidities of respiratory system. Superinfection with bacterial pneumonia was recognized in some patients. Though there are several problems, ELISA method is thought to be useful to diagnose C. pneumoniae pneumonia, and is suitable for screening tests.

Aged↗

Influence of L-365,260, a CCK-B/gastrin receptor antagonist, on tetragastrin-stimulated mucin metabolism in rat gastric mucosa.

The effect of L-365,260, a CCK-B/gastrin receptor antagonist, on gastric mucus metabolism induced by tetragastrin was investigated in rats. In vivo application of L-365,260 at a dose of 3 mg/kg p.o. significantly reduced the tetragastrin (12 microg/kg s.c. )-stimulated gastric acid secretion, but 0.3 mg/kg of L-365,260 did not affect the gastric acid secretion induced by the tetragastrin administration. A single administration of 12 microg/kg of tetragastrin caused an increase in gastric mucin content in the soluble mucus (175% of control), the mucus gel (155% of control) and the surface mucosa (125% of control). L-365,260 at the doses of 0.3 and 3 mg/kg considerably inhibited the tetragastrin-induced mucus secretion in the soluble mucus (70-80% of tetragastrin) and the mucus gel (45-70% of tetragastrin) and resumed the mucus accumulated in the surface mucosa to the control situation (80% of tetragastrin). In the in vitro incubation system of rat gastric mucosa, L-365,260 (0.1-10 micromol/l) caused no significant change in gastric mucin synthesis. An in vivo study also showed that the increase in total gastric mucin content and the distributional changes in mucin content induced by 12 microg/kg of tetragastrin reverted with 3 mg/kg of L-365,260 pretreatment to the control situation. It is evident from these results that the CCK-B/gastrin receptor is involved in the mechanism of the stimulation of mucus secretion and/or mucus accumulation in rat gastric mucosa and not directly concerned with the action of gastrin-induced gastric acid secretion.

Animals↗

The novel carboxamide derivative IS-741 reduces neutrophil chemoattractant production by bronchoalveolar macrophages in rats with cerulein-induced pancreatitis complicated by sepsis.

BACKGROUND/AIMS: The priming mechanism of macrophages to secrete cytokines in acute pancreatitis is important for remote organ failure following septic complication. The effects of novel carboxamide derivative, IS-741, on neutrophil chemoattractant production by bronchoalveolar macrophages were studied in rats with cerulein-induced pancreatitis complicated by sepsis. METHODS: Pancreatitis was induced by four intramuscular injections of cerulein (50 microg/kg at 1-hour intervals). Pancreatitis rats were injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) 6 h following the first cerulein injection as a septic challenge. Pancreatitis rats received a continuous intravenous injection of IS-741 (3 mg/kg/h) 30 min before the septic challenge. RESULTS: Intense mononuclear cell infiltration and lung hemorrhage occurred in untreated pancreatitis rats complicated with sepsis, but hemorrhage was not seen in septic pancreatitis rats receiving a continuous intravenous injection of IS-741 shortly before sepsis induction. The IS-741-treated rats had lower serum concentrations of cytokine-induced neutrophil chemoattractant (CINC), as well as fewer the pulmonary neutrophils and infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). CONCLUSION: The novel carboxamide derivative IS-741 reduced CINC production by bronchoalveolar macrophages and effectively prevented pancreatitis-associated lung injury following the septic challenge.

Animals↗

Analysis of biological activities of recombinant rat interleukin-5.

We analyzed the biological activities of recombinant rat interleukin-5 (IL-5). Purified recombinant rat IL-5 promoted the proliferation of T88-M cells in a concentration-dependent manner, and its effect was inhibited by an anti-murine IL-5-neutralizing polyclonal antibody. When bone marrow cells from normal rats were incubated with recombinant rat IL-5 in medium containing methylcellulose, the colony formation by eosinophilic cells was induced. Furthermore, when rat peritoneal eosinophils were incubated with recombinant rat IL-5, the spontaneous decrease in eosinophil viability was inhibited in a time- and concentration-dependent manner. In addition, the recombinant rat IL-5-induced eosinophil survival was inhibited by an anti-murine IL-5-neutralizing polyclonal antibody. These findings suggest that rat IL-5 acts as B cell growth factor II, eosinophil differentiation factor, and eosinophil survival-enhancing factor.

Animals↗

Improvement of blood compatibility on cellulose hemodialysis membrane: IV. Phospholipid polymer bonded to the membrane surface.

To improve the surface blood compatibility on a cellulose hemodialysis membrane, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers with a phospholipid polar group were immobilized on the surface through covalent bonding. The MPC polymers had a carboxylic group, which can react with hydroxyl groups on the cellulose membrane, and were synthesized by conventional radical polymerization. The reaction between the MPC polymers and the cellulose membrane was carried out in a heterogeneous system using a condensation reagent. Surface analysis of the modified membrane by X-ray photoelectron spectroscopy revealed the immobilization of the MPC polymer on the surface. The mechanical strength and permeability for a solute of the membrane did not change even after the modification. The modified cellulose membrane was blood-compatible, as determined by the prevention of adhesion, deformation, and aggregation of platelets after contact with platelet-rich plasma. Based on these results, it is concluded that the MPC polymers may be a useful material for improving the blood compatibility of cellulose hemodialysis membranes.

Adsorption↗

Competitive adsorption between phospholipid and plasma protein on a phospholipid polymer surface.

The competitive adsorption of proteins and phospholipids on omega-methacryloyloxyalkyl phosphorylcholine (MAPC) polymer was evaluated in this study. Albumin, fibrinogen, and dimyrstoyl phosphatidylcholine (DMPC) were used as model components. The amount of DMPC adsorbed on the MAPC polymers increased with an increase in the MAPC unit composition of the polymer. The methylene chain length of the MAPC unit was another factor influencing the DMPC adsorption when the MAPC unit composition of the MAPC polymer was low. The state of albumin and DMPC liposome adsorbed on the 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was determined by dynamic contact angle (DCA) measurement. The adsorption strength of albumin on the MPC polymer was weaker than that on the poly[n-butyl methacrylate (BMA)], that is, the albumin was detached from the MPC polymer during the rinsing process. On the poly(BMA) surface, no difference in the shape of the DCA loops before and after contact with the DMPC liposomal suspension was observed. Fibrinogen adsorption on the MAPC polymer was detected by gold-colloid labeled immunoassay. The amount of fibrinogen adsorbed on every MAPC polymer surface was reduced by addition of the DMPC liposome in the fibrinogen solution. The number of platelets adhered on the MAPC polymer was also decreased when the DMPC liposome was present in the fibrinogen solution during pretreatment. We concluded that phospholipids were preferentially adsorbed on the MAPC polymer surface compared with plasma protein and that the adsorbed phospholipids played an important role in showing an excellent blood compatibility on the MAPC polymer.

Adsorption↗

Inhibition of fibroblast cell adhesion on substrate by coating with 2-methacryloyloxyethyl phosphorylcholine polymers.

Fibroblast adhesion and growth behavior were examined on various polymers coated on a poly(ethylene telephthalate) (PET) substrate. The polymers are poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylatel copolymer (PMB)s with different MPC unit compositions, and poly(2-hydroxyethyl methacrylate). Surface analysis by dynamic contact angle measurement revealed that the mobility of the polymer chain on the PET substrate depended on the MPC unit composition, but there was no significant difference between the PMBs with 3-10 mol% MPC units and poly(HEMA). Fibronectin adsorption on the polymer surface from a cell culture medium was determined by immunoassay. The adsorbed fibronection was evenly distrubuted in every polymer, however, the amount was reduced with an increase in the MPC unit composition in the PMB. This result suggested that the MPC unit could weaken the interaction between the polymer surface and proteins. When fibroblast L-929 cells, were cultured on the polymers, the cells adhered and the number of cells increased on not only the hydrophobic poly(BMA) but also on the hydrophilic poly(HEMA). However, the number of cells that adhered on the PMB surface decreased with an increase in the MPC unit composition. This was a result of the fibronectin adsorption behavior. Thus, it could be concluded that since the PMB could suppress cell adhesion proteins e.g. fibronectin, the PMB showed excellent cell adhesive resistance properties.

Adsorption↗

Effect of phospholipidic boundary lubrication in rigid and compliant hemiarthroplasty models.

Hemiarthroplasty may benefit from materials which produce lower friction and improved boundary lubrication protection during start-up conditions. The purpose of this study was to evaluate the effect of phospholipidic boundary lubrication in both rigid and compliant hemiarthroplasty. An in vitro model was designed to dissociate the relative contribution of implant material compliance and the presence of phospholipid to the overall friction of a hemiarthroplasty contact using bovine articular cartilage. Normal bovine articular cartilage was articulated against four flat materials using reciprocating motion: (a) borosilicate glass: (b) borosilicate glass coated with dipalmitoylphosphatidylcholine (DPPC); (c) polyurethane (PU) elastomer (Tecoflex SG93A, a medical-grade aliphatic thermoplastic PU, Thermedics Incorporated. Woburn, Massachusetts); and (d) surface-coated PU (Tecoflex SG93A substrate coated with lipid-attracting copolymer poly[methacryloyloxyethyl phosphorylcholine (MPC)-co-butyl methacrylate (BMA)]. Tests were conducted in physiologically simulated tribological conditions for a non-conformal point contact. Friction and lubrication analysis was performed using both static and kinetic coefficients of friction mu measured for each group as a function of time for a sliding distance of up to 60 m. Results showed that the inclusion of supplemental phospholipid, DPPC, on a rigid substrate significantly decreased mu in comparison with the control (cartilage-glass). Additionally, removal of phospholipid components from the articular cartilage surface produced a significantly greater start-up mu in comparison with normal cartilage at the test onset. The use of a material with a lower modulus resulted in lower mu for the entire duration of the test. Polyurethane elastomer coated with the lipid-attracting copolymer, poly(MPC-co-BMA), resulted in the lowest frictional response. As seen in this study, the improvement of low-modulus hemiarthroplasty may involve the optimization of chemical modification and incorporation of lipid-attracting MPC copolymers onto compliant materials. However, further tests are warranted to determine whether lipid-attracting MPC copolymers perform as well during long-time, in vivo wear studies.

1,2-Dipalmitoylphosphatidylcholine↗

Isolated primary chylopericardium.

A 16-year-old man was found to have an enlarged cardiac silhouette. Primary chylopericardium was diagnosed when pericardiocentesis yielded the characteristic milky-white fluid. The thoracic duct was easily identified by giving milk and butter and an injection of ethylene blue immediately before the operation. Intraoperative thoracic ductography showed no abnormal findings. Mass ligation of the thoracic duct above the diaphragm and partial pericardiectomy were successfully performed through a right thoracotomy approach. In addition, many of the lymphatics were ligated above the diaphragm. The right thoracotomy approach was a useful method for resection and ligation of the thoracic duct just above the diaphragm. Follow-up showed no accumulation of pericardial fluid or pleural effusion.

Adolescent↗

[The function of sigma receptors--electrophysiological approach].

The functions of sigma (sigma) receptors were reviewed based on electrophysiological studies. Systemic administration of sigma ligands reportedly produces a variety of effects on dopamine (DA) neurons. In the mesolimbic DA system, (+)SKF-10,047 suppressed activities of the ventral tegmental area. In the substantia nigra, DTG also suppressed these activities, while BMY-14802 increased the activity of neurons. In the cerebellum, however, activities of Purkinje cells were suppressed by locally applied DTG, with probable involvement of the catecholaminergic system. This effect on Purkinje cells may explain the action of sigma ligands on the motor system. In the hippocampus, neuronal activities were inhibited by SR31742A in vivo (CA3 region) and by (+)SKF10,047 in vitro (CA1 region). DTG at high concentration (1 mM) completely suppressed population spikes (PS) in the CA1 region of hippocampal slice preparations. In our experiments, a novel sigma ligand, OPC-24439, suppressed PS in CA1 at concentrations of 1-100 microM. However, NMDA-induced neuronal firings in CA3 in vivo were augmented by low doses of DTG in a haloperidol-sensitive manner, but high doses were ineffective. In contrast, non-NMDA responses were not affected by DTG. In addition, several sigma ligands having no effect on the NMDA response have been reported. In addition, endogenous ligands, neuropeptide Y and dehydroepiandrosterone, augmented the NMDA-induced firing. In whole-cell patch clamp recording, NMDA-induced currents were suppressed by a relatively higher concentration of DTG in a concentration-dependent manner, while non-NMDA responses were only slightly suppressed. These findings suggest that effects of sigma ligands on NMDA receptor responses are biphasic, and sigma ligands may modulate memory and learning and suppress neuronal death by anoxia. In addition, sigma ligands are also reported to suppress Ca2+ channels in hippocampal culture neurons and induce current by closing K+ channels in NCB-20 cells. Thus, sigma receptors may be involved in the modulation of a variety of neurons that relate to psychiatric function and plasticity.

Animals↗

[Effects of OPC-24439, a sigma ligand, on neuronal activities in the hippocampus].

Sigma receptors in the central nervous system have been considered to play an important role in the modulation of mental diseases and memory/learning. However, the physiological function of sigma receptors still remains unknown. To elucidate physiological functions of the sigma receptors in modulation of neuronal activities, the effects of OPC-24439 (a sigma receptor ligand) on neuronal activities in hippocampal slices were studied with electrophysiological methods. Hippocampal slices (thickness ca. 450 microns) were prepared from male Wistar rats (4-7 weeks of age). In extracellular recording, population spikes in the CA1 region evoked by stimulation applied to the Schaffer collateral/commissural fibers were suppressed by OPC-24439 (1-100 microM) in a dose-dependent manner. This inhibition was antagonized by simultaneously applied haloperidol at 1 microM. In intracellular recording experiments, OPC-24439 (100 microM) did not affect the resting membrane potentials of neurons recorded. In addition, OPC-24439 had no effects on depolarization and firing induced by glutamate. These results indicate that sigma receptor activation caused suppression of neuronal activities in the hippocampus via the sigma receptors. This inhibition probably mediated via the suppression of ion channels that are not related to membrane potentials on post-synaptic neurons and/or sigma receptors on pre-synaptic neurons or interneurons.

Animals↗

Mechanism underlying the therapeutic effects of electroconvulsive therapy (ECT) on depression.

Electroconvulsive therapy (ECT) is used to treat drug-resistant depressive disorders. The results of studies on the mechanism underlying the effectiveness of ECT on depression are still controversial. ECT stimulus is usually larger than the threshold of induction of seizures and activation of whole-brain is believed to be necessary to produce therapeutic effects. A single ECT session induces alterations of the electroencephalogram (EEG) including initial epileptic discharges, then slow waves, and finally flattened EEG. Repeated ECT results in an increasing number of slower waves in the EEG for as long as a month. ECT-induced changes in various neurotransmitter systems have also been reported. Serotonin (5-hydroxytryptamine, 5-HT) is one of the most important neurotransmitters involved in depressive illness, and ECT alters several 5-HT-receptor subtypes in the central nervous system. 5-HT1A receptors in post-synaptic neurons are sensitized by repeated ECT, but those in pre-synaptic neurons (auto-receptors) are not changed. In addition, our electrophysiological studies have shown that ECT increases sensitivity to 5-HT of 5-HT3 receptors in the hippocampus, resulting in an increase in release of neurotransmitters such as glutamate and gamma-aminobutyric acid. In contrast, ECT decreases the auto-receptor functions in noradrenergic and dopaminergic neurons in the locus coeruleus and substantia nigra, respectively, resulting in an increase in release of noradrenaline and dopamine. In conclusion, 5-HT1A-receptor sensitization may be important for explaining the effectiveness of ECT, as this change induces a decrease in the number of 5-HT2A receptors that are elevated in depressive patients. Facilitation of neurotransmitter releases due to 5-HT3-receptor sensitization by ECT may also play an important role in effective treatment of depressive patients refractory to therapeutic drugs.

Animals↗

Rat gastric mucous gel layer contains sialomucin not produced by the stomach.

The sialylated mucus components of the normal gastric mucosa and mucous gel layer of rats were studied by using various histochemical staining methods including Maackia amurensis II (MAL-II) and Sambucus nigra (SNA) lectins, alcian blue (AB) pH 2.5 -- periodic acid Schiff (PAS) and high iron diamine (HID) -- AB pH 2.5. The acidic and neutral mucins characterized by the AB-PAS staining were abundantly present in the mucous gel layer as well as in the gastric mucosa. The sialomucin characterized by HID-AB was barely found in either the mucous gel layer or the mucosa. The sialomucin positive to MAL-II and SNA, which react with the N-acetyl neuraminic acid residue linked to galactose via an alpha-linkage, was moderately detected only in the mucous gel layer, but not in the entire mucosal layer. Furthermore, in animals given surgery to form an esophageal fistula through which saliva was excluded or in animals subjected to salivectomy, the mucous gel layer stained with MAL-II and SNA lectins was markedly decreased. These results indicate that a part of the sialomucin containing-mucous gel layer covering normal rat gastric mucosa originates from the saliva and that MAL-II and SNA lectins are useful for detecting this specific sialomucin.

Animals↗

Further characterization of earthworm serine proteases: cleavage specificity against peptide substrates and on autolysis.

Cleavage specificity of two fibrinolytic enzymes from Lumbricus rubellus [Nakajima, N., et al., Biosci. Biotechnol. Biochem., 57, 1726-1730 (1993) and 60, 293-300 (1996)] was investigated using beta-amyloid 1-40 and oxidized insulin B-chain as peptide substrates. The serine protease, F-III-2, cleaved the former substrate at six sites, and the latter at five sites. F-II digested them at six and ten, respectively. The cleavage specificity of F-III-2 resembled those of both trypsin and chymotrypsin. F-II had a broader specificity than F-III-2 and preferred also the bonds consisting neutral or hydrophobic amino acids. Furthermore, F-III-2 itself was digested initially on the site of Arg(144)-Tyr(145) to produce two peptide fragments, when it was autolyzed regularly by heating.

Amino Acid Sequence↗

Enhancement of swimming endurance in mice by highly branched cyclic dextrin.

We investigated the ergogenic effect in mice of administering highly branched cyclic dextrin (HBCD), a new type of glucose polymer, on the swimming endurance in an adjustable-current swimming pool. Male Std ddY mice were administered a HBCD, a glucose solution or water via a stomach sonde 10 min before, 10 min after or 30 min after beginning swimming exercise, and were then obliged to swim in the pool. The total swimming period until exhaustion, an index of the swimming endurance, was measured. An ergogenic effect of HBCD was observed at a dose of 500 mg/kg of body weight, whereas it had no effect at a dose of 166 mg/kg of body wt (p < 0.05). The mice administered with the HBCD solution 10 min after starting the exercise were able to swim significantly longer (p < 0.05) than the mice who had ingested water or the glucose solution. The rise in mean blood glucose level in the mice administered with HBCD, which was measured 20 min after starting swimming, was significantly lower (p < 0.05) than that in the mice administered with glucose, although it was significantly higher (p < 0.05) than that in the mice administered with water. The mean blood insulin rise in the mice given HBCD was significantly lower (p < 0.05) than that in the mice given glucose. The mice administered with HBCD 30 min after starting the exercise swam significantly longer (p < 0.05) than the mice who had ingested water, although the enhancement of swimming time was similar to that of the glucose-ingesting mice. The gastric emptying rate of the HBCD solution was significantly faster (p < 0.05) than that of the glucose solution. However, this glucose polymer must have spent more time being absorbed because it has to be hydrolyzed before absorption, reflecting a lower and possibly longer-lasting blood glucose level. We conclude that the prolongation of swimming endurance in mice administered with HBCD depended on its rapid and longer-lasting ability for supplying glucose with a lower postprandial blood insulin response, leading to a delayed onset of fatigue.

Animals↗

Multi-enzymatic glucosylation using Eucalyptus UDP-glucosyltransferase coupled UDPglucose-fermentation by bakers' yeast.

The enzymatic synthesis of glucoside compounds using a membrane-associated UDP-glucosyltransferase fraction from Eucalyptus perriniana cultured cells as a water-insoluble catalyst (N. Nakajima, et. al., J. Ferment. Bioeng., 84 (5), pp. 455-460, 1997) has been effectively done by coupling UDPglucose-fermentation by bakers' yeast. For example, beta-thujaplicin (hinokitiol) and p-aminobenzoic acid were converted respectively to their corresponding beta-D-monoglucosides with the conversion rate of around 24-26% by the multi-enzymatic system with UDPglucose as a glucose donor, which is produced by yeast cells from glucose and 5'-UMP. Addition of either cellobiose, a substrate of beta-glucosidase, or DL-1,2-anhydro-myo-inositol, an inhibitor for the enzyme in the reaction mixture, could increased the yield of these beta-D-monoglucosides. This new enzymatic system could also be used for the synthesis of flavonoid glucosides such as isoquercitrin (quercetin 3-O-beta-D-glucoside).

Eucalyptus↗

[Skin cancer melanoma].

The most common dermal malignancies are basal cell carcinoma, spinous cell carcinoma, and malignant melanoma, of which the latter two carry a poor prognosis. This communication deals with therapies for spinous cell carcinoma and malignant melanoma. Therapies for these malignancies have made huge strides, helping to formulate the policy and strategy for treatment and doing much to improve their prognoses. Chemotherapy, in particular, has become firmly established, contributing a great deal to the improvement of their prognoses. PEP, combination therapy with PEP plus MMC and CPT-11 are used for the treatment of spinous cell carcinoma, while CAV therapy is given to patients with advanced spinous cell carcinoma. In the treatment of malignant melanoma that is considered resistant to chemotherapy, DAV and PAV therapies have been attempted, and CDV and DACTam therapies have been tried on patients with advanced spinous cell carcinoma. Adoptive immunotherapy has also been used in the battle with this malignancy. Furthermore, excellent results have been observed with intratumor administration of IFN-beta. IFN-beta plus DAV has served well adjuvant therapy to improve the prognosis of Stage II or III malignant melanoma.

Antineoplastic Combined Chemotherapy Protocols↗