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Biomedical subjects

H Ishida

Publications and source records attributed to H Ishida.

At least 343 records · Page 19Linked to original sources
PubMed1998

Dissection of the effects of tumor necrosis factor-alpha and class II gene polymorphisms within the MHC on murine systemic lupus erythematosus (SLE).

Gene(s) in the MHC of the NZW strain (H-2z) up-regulate(s) systemic lupus erythematosus (SLE) in (NZB x NZW) F1 mice. So far, two plausible mechanisms have been implicated: (i) unique mixed haplotype class II molecules formed in the F1 mice act as a restriction element for self-reactive T cells and (ii) a unique polymorphism in the H-2-linked NZW tumor necrosis factor (TNF)-alpha allele which down-regulates TNF-alpha is contributory. Because of the difficulty in dissecting these alleles within the H-2 complex, it has not been determined which is indeed the case. We addressed this issue by establishing three different H-2-congenic (NZB x NZW) F1 mice bearing distinct haplotypes at class II and TNF-alpha regions, i.e. (NZB x NZW) F1 (H-2d/z:A(d/u)E(d/u)TNF(d/z)), (NZB x NZW.PL) F1 (H-2(d/u):A(d/u)E(d/u)TNF(d/d)) and (NZB x NZW.H-2d) F1 (H-2(d/d):A(d/d)E(d/d)TNF(d/d)). Among these, only (NZB x NZW) F1 produced a markedly lower level of TNF-alpha, due to the unique NZW TNF-alpha allele (TNF(z)). Studies of anti-DNA antibodies and lupus nephritis revealed that, compared to (NZB x NZW) F1, the disease of (NZB x NZW.H-2d) F1 was markedly reduced. In (NZB x NZW.PL) F1, the onset of renal disease was significantly delayed, while the extent of proteinuria and renal histopathology in individuals that had developed the disease was comparable to that seen in (NZB x NZW) F1. It seems likely that both class II and TNF-alpha gene polymorphisms are functioning as H-2-linked predisposing genetic elements, and that the TNF-alpha polymorphism acts to modulate an initial process of the renal disease.

Animals↗
PubMed1998

Fluorescence resonance energy transfer between points on tropomyosin and actin in skeletal muscle thin filaments: does tropomyosin move?

Fluorescence resonance energy transfer (FRET) spectroscopy has been used to determine spatial relationships between residues on tropomyosin and actin in reconstituted muscle thin filament, and to detect a positional change of tropomyosin relative to actin on the thin filament in the presence and absence of Ca2+ ions. In addition to Cys-190 which is a single cysteine residue in rabbit skeletal muscle alpha-tropomyosin, a new site, Cys-87 which is a unique cysteine residue in a mutant alpha-tropomyosin, was labeled with a resonance energy donor molecule, 5-(2-iodoacetylaminoethyl)aminonaphthalene 1-sulfonic acid (IAEDANS). On the other hand, Gln-41, Lys-61, Cys-374, and the ATP-binding site of actin were selectively labeled with acceptor probes: fluorescein cadaverine, fluorescein 5-isothiocyanate, 4-dimethyl-aminophenylazophenyl 4'-maleimide, and TNP-ATP (or TNP-ADP), respectively. The distances between probes attached to position 87 of the mutant tropomyosin and Gln-41, Lys-61, Cys-374, or the nucleotide-binding site of actin on the reconstituted thin filament in the presence of Ca2+ ion were measured to be 43.2, 49.7, 45.4, and 35.2 A, respectively, and the distance between probes attached to position 190 of tropomyosin and Gln-41 or the nucleotide-binding site of actin were 51.6 and 43.1 A, respectively. The transfer efficiencies between these donor and acceptor molecules were large, so that the efficiency should be very sensitive to changes in distance between probes attached to tropomyosin and actin. However, the transfer efficiency did not change appreciably upon removal of Ca2+ ions, suggesting that tropomyosin does not change its position on the reconstituted thin filament in response to a change in Ca2+ ion concentration. The present results do not support the notion of tropomyosin movement on skeletal muscle thin filaments as proposed in the steric blocking theory.

Actins↗
PubMed1998

Peroxynitrite formation in focal cerebral ischemia-reperfusion in rats occurs predominantly in the peri-infarct region.

Peroxynitrite (ONOO-) exhibits potent neurotoxicity and plays an important role in neuronal death, but no evidence shows that it is formed in the brain during ischemia or subsequent reperfusion. To detect the formation of ONOO-, we used a hydrolysis/HPLC procedure to measure the formation of 3-nitro-L-tyrosine (NO2-Tyr), which is considered to reflect attack of ONOO- on L-tyrosine residues of cellular components in the brain. Focal ischemia was produced by occluding the right common carotid and right middle cerebral arteries for 2 hours, and the ischemic area was reperfused by reopening the middle cerebral artery. After 2 hours of ischemia, the values of the ratio of NO2-Tyr to L-tyrosine were 0% +/- 0%, 0.42% +/- 0.13% and 0.29% +/- 0.10% in the noninfarct, periinfarct, and core-of-infarct regions, respectively. After 3 hours of reperfusion following 2 hours of ischemia, the ratio in the periinfarct region reached 0.89 +/- 0.22%, which was significantly higher than that in the core-of-infarct region (0.35 +/- 0.09%). The NO2-Tyr was not detected in 50 mg/kg of N-monomethyl-L-arginine-treated or sham-operated rats. Regional CBF in the periinfarct region decreased to 30.8 +/- 15.9 mL/100 g/min during occlusion, but recovered more rapidly than did that in the core-of-infarct region.

Animals↗
PubMed1998

Changes in endothelin-1, 6-keto-PG-F1 alpha, and TX-B2 in random pattern flaps.

In this study we investigated kinetic changes in the ratio of endothelin-1 (ET-1) and eicosanoids (6-keto-PG-F1 alpha TX-B2) in 20 x 60 mm random pattern flaps from rats. The ET-1 content of regions A (20 mm from the peripheral end) and B (20-40 mm) 6 h after surgery tended to decrease slightly compared to the ET-1 content immediately after surgery. The ET-1 content of region C (20 mm from the flap base) 6 h postoperatively increased significantly compared to that immediately after surgery. The ET-1 content of region C 6 h after surgery was significantly higher compared to that of regions A and B, which were obtained simultaneously. The ratios of eicosanoids in the three regions 6 h after surgery were significantly lower than those immediately after operation. However, the ratio in region A was higher than that in region C, showing that there was a difference in distribution in the flap between ET-1 and eicosanoids. The administration of an ETA receptor antagonist, FR-139317, extended the survival length of the flap. These results suggest that ET-1 can regulate the microcirculation in a flap directly and/or indirectly.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Treatment of insomnia by concomitant therapy with Zopiclone and Aniracetam in patients with cerebral infarction, cerebroatrophy, Alzheimer's disease and Parkinson's disease.

For insomniac patients, sleeping drugs are used: in addition, concomitant therapy with other drugs has been tried in an effort to prevent a decrease in the effects due to long-term continuous use. This report presents the results of a study on the sleeping effects in nine aged patients with insomnia associated with cerebrovascular and noncerebrovascular disorders who received concomitant therapy with Zopiclone and Aniracetam. The treatment in 7/9 cases (78%) was found to be effective, showing more than 50% prolongation of sleeping time, and in two cases (22%) was found to be ineffective. We discuss the mechanism of action referring to the literature.

Aged↗
PubMed1998

Spontaneous rupture of an intrahepatic bile duct with biloma treated by percutaneous drainage and endoscopic sphincterotomy.

A case of spontaneous rupture of an intrahepatic bile duct with biloma formation treated by percutaneous drainage and endoscopic sphincterotomy is reported. A 73-yr-old woman was admitted with fever and abdominal pain. There was no past history of abdominal surgery, instrumentation, or trauma. Ultrasound and computed tomography revealed a massive fluid collection in the abdominal cavity. Endoscopic retrograde cholangiography demonstrated extravasation of contrast medium from a distal biliary radicle in the left lobe of the liver. After successful treatment by percutaneous drainage and endoscopic sphincterotomy, the patient did well. Ultrasound and computed tomography showed resolution of the biloma. Nontraumatic bilomas are very rare: in fact, only 24 cases of spontaneous biloma have been reported. Endoscopic treatment for patients with spontaneous bilomas can be safe and effective, and should be considered.

Aged↗
PubMed1998

In vitro and in vivo activities of levofloxacin against biofilm-producing Pseudomonas aeruginosa.

Interactions between biofilm cells of Pseudomonas aeruginosa and levofloxacin were studied. P. aeruginosa incubated for 6 days with Teflon sheets formed a biofilm on its surface. Against the biofilm bacteria, levofloxacin at an MIC determined by the standard method for the strain was highly bactericidal whereas gentamicin, ceftazidime, and ciprofloxacin showed no significant killing activity. Levofloxacin, ciprofloxacin, and gentamicin, but not ceftazidime, exhibited killing activity against nongrowing cells of the strain incubated in phosphate buffer. In addition, levofloxacin, ciprofloxacin, and ceftazidime, but not gentamicin, showed the ability to penetrate an agar containing alginate. These findings may explain the efficacy of levofloxacin and the ineffectiveness of gentamicin and ceftazidime against biofilm bacteria; however, the cause of the ineffectiveness of ciprofloxacin still remains to be determined. In experimental pneumonia in guinea pigs, in which the biofilm mode of growth of the strain was observed in the lung, only levofloxacin exhibited substantial therapeutic efficacy. These findings suggest the significant role of levofloxacin in therapy of biofilm bacterium-associated infectious diseases.

Alginates↗
PubMed1998

Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic beta-cells.

The effect of metabolic inhibition on the blocking of beta-cell ATP-sensitive K+ channels (KATP channels) by glibenclamide was investigated using a patch-clamp technique. Inhibition of KATP channels by glibenclamide was attenuated in the cell-attached mode under metabolic inhibition induced by 2,4-dinitrophenol. Under a low concentration (0.1 microM) of ATP applied in the inside-out mode, KATP channel activity was not fully abolished, even when a high dose of glibenclamide was applied, in contrast to the dose-dependent and complete KATP channel inhibition under 10 microM ATP. On the other hand, cibenzoline, a class Ia antiarrhythmic agent, inhibits KATP channel activity in a dose-dependent manner and completely blocks it, even under metabolic inhibition. In sulfonylurea receptor (SUR1)- and inward rectifier K+ channel (Kir6.2)-expressed proteins, cibenzoline binds directly to Kir6.2, unlike glibenclamide. Thus, KATP channel inhibition by glibenclamide is impaired under the condition of decreased intracellular ATP in pancreatic beta-cells, probably because of a defect in signal transmission between SUR1 and Kir6.2 downstream of the site of sulfonylurea binding to SUR1.

2,4-Dinitrophenol↗
PubMed1998

The novel insulinotropic mechanism of pimobendan: direct enhancement of the exocytotic process of insulin secretory granules by increased Ca2+ sensitivity in beta-cells.

Pimobendan is a new class of inotropic drug that augments Ca2+ sensitivity and inhibits phosphodiesterase (PDE) activity in cardiomyocytes. To examine the insulinotropic effect of pimobendan in pancreatic beta-cells, which have an intracellular signaling mechanism similar to that of cardiomyocytes, we measured insulin release from rat isolated islets of Langerhans. Pimobendan augmented glucose-induced insulin release in a dose-dependent manner, but did not increase cAMP content in pancreatic islets, indicating that the PDE inhibitory effects may not be important in beta-cells. This agent increased the intracellular Ca2+ concentration ([Ca2+]i) in the presence of 30 mM K+, 16.7 mM glucose, and 200 microM diazoxide, but failed to enhance the 30 mM K+-evoked [Ca2+]i rise in the presence of 3.3 mM glucose. Insulin release evoked by 30 mM K+ in 3.3 mM glucose was augmented. Then, the direct effects of pimobendan on the Ca2+-sensitive exocytotic apparatus were examined using electrically permeabilized islets in which [Ca2+]i can be manipulated. Pimobendan (50 microM) significantly augmented insulin release at 0.32 microM Ca2+, and a lower threshold for Ca2+-induced insulin release was apparent in pimobendan-treated islets. Moreover, 1 microM KN93 (Ca2+/calmodulin-dependent protein kinase II inhibitor) significantly suppressed this augmentation. Pimobendan, therefore, enhances insulin release by directly sensitizing the intracellular Ca2+-sensitive exocytotic mechanism distal to the [Ca2+]i rise. In addition, Ca2+/calmodulin-dependent protein kinase II activation may at least in part be involved in this Ca2+ sensitization for exocytosis of insulin secretory granules.

Androstadienes↗
PubMed1998

Altered bcl-2 and bax expression and intracellular Ca2+ signaling in apoptosis of pancreatic cells and the impairment of glucose-induced insulin secretion.

Apoptosis is the process of cellular self-destruction, and genes such as bcl-2 and bax are known to inhibit and promote apoptosis, respectively. In this study, we show that apoptosis can be induced in pancreatic beta-cell lines, and we investigate the apoptotic pathways through the bcl-2 and bax genes and intracellular Ca2+. Serum deprivation induces apoptosis in the MIN6 and RINm5F pancreatic beta-cell lines, and alters the bcl-2 messenger RNA (mRNA) and protein. KCl, BayK, A23187, and ionomycin elicit an elevation of cytosolic/nuclear Ca2+, which, however, is insufficient to evoke apoptosis or to alter bcl-2 or bax mRNA expression in MIN6 cells. The extracellular Ca2+ chelators, EGTA and 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetrapotassium salt, hydrate, evoke apoptosis and also alter the ratio of bcl-2 to bax mRNA and protein concomitantly with the depletion of cytosolic/nuclear Ca2+. This indicates that there are at least two apoptotic pathways in pancreatic beta-cells: through serum deprivation and through a decrease in cytosolic/nuclear Ca2+. MIN6 cells exhibit reduced insulin secretion induced by glucose regardless of the molecular pathway of apoptosis. Apoptosis in pancreatic beta-cells, therefore, may be closely related to the impairment of insulin secretion in certain pathological conditions such as diabetes mellitus.

Animals↗
PubMed1998

Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages.

We demonstrated endothelial production of C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and its regulation by cytokines, including tumor necrosis factor-alpha (TNF alpha). We thus proposed that CNP can control vascular tone and growth as an endothelium-derived relaxing peptide. We also revealed the marked elevation of plasma CNP concentration in patients with septic shock, in which TNF alpha plays a significant part. As the interaction between endothelial cells (EC) and monocytes-macrophages plays a pivotal role in the pathogenesis of atherosclerosis, we investigated the effect of coculture of EC and macrophages on endothelial production of CNP. We used a human monocytic leukemia cell line, THP-1, which differentiates into macrophages when treated with phorbol 12-myristate 13-acetate. The coculture of EC and THP-1-derived macrophages enhanced CNP secretion by more than 10-fold compared with the single culture of EC or the coculture of EC and THP-1 without phorbol 12-myristate 13-acetate treatment. Prevention of direct contact between EC and THP-1-derived macrophages did not attenuate the increase in CNP secretion. Northern blotting revealed the augmentation of CNP messenger RNA expression in EC in the coculture. We detected TNF alpha in the conditioned medium from the coculture of EC and THP-1-derived macrophages. Furthermore, anti-TNF alpha antibody inhibited the stimulation of CNP secretion in the coculture. CNP at a concentration of 1 nM did not stimulate cGMP production in EC or THP-1-derived macrophages, but it elevated cGMP production significantly in vascular smooth muscle cells. These results indicate that endothelial production of CNP is stimulated mainly by TNF alpha released from THP-1-derived macrophages in the coculture. Endothelial CNP at the enhanced level may be one of the vascular mediators to regulate local vascular tone and growth through cGMP production by vascular smooth muscle cells, suggesting the potential significance of endothelial CNP in atherosclerosis.

Animals↗
PubMed1998

Study of the pharmacological effect of the bile salt, sodium scymnol sulfate, from Rhizoprionodon acutus. II. Prophylactic effect of scymnol on lesion development in a rat peripheral arterial occlusion model.

The effect of scymnol on the development of lesions in a rat peripheral arterial occlusion model, involving injection of 5% lactic acid into the femoral artery, was investigated. In this model oral administration of scymnol significantly prevented edematous swelling and development of lower limb lesions, including gangrene, and also reduced changes in blood coagulation parameters, platelet aggregation and retention rate at a dose of 10 or 30 mg/kg. However, it had no effect on these clotting system functions in sham-operated rats at a dose of 10 mg/kg. The effects of scymnol were also compared with those of ticlopidine and argatroban. The findings suggest that scymnol may be clinically useful for preventing thrombotic peripheral arterial occlusive disorders. Its prophylactic action appears to be mainly due to its potent ability to protect against endothelial cell damage due to lactic acidosis.

Animals↗
PubMed1998

Preventive effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized rats fed a calcium-deficient diet.

The effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized (ovx) rats fed a calcium-deficient diet were investigated. Daidzin and genistin were orally administered to ovx rats for 4 weeks. The femurs of these rats showed significantly lower density, strength (breaking forces), ash weight and calcium and phosphorus content (p<0.01) in comparison with those of sham-operated rats. These changes were largely prevented in animals receiving oral daidzin or genistin for 4 weeks at a dose of 50 mg/kg/d and in animals receiving subcutaneous estrone (7.5 microg/kg/d) as a positive control. Ovariectomy caused atrophy of the uterus and increased the ratio of the urinary excretion of pyridinoline and deoxypyridinoline to endogenous creatinine excretion. This was prevented by administration of daidzin or estrone, but, interestingly, not genistin. The preventive effect of daidzin treatment on bone loss in ovariectomized rats appears to be due to suppression of bone turnover. Genistin has a different mechanism of action from daidzin.

Adipose Tissue↗
PubMed1998

Synthetic studies on selectin ligands/inhibitors. Synthesis and biological evaluation of sulfated and phosphorylated beta-D-galacto- and lactopyranosides containing fatty-alkyl residues of different carbon chain lengths.

To investigate the biological selectin-ligand interactions, fourteen sulfated and eight phosphorylated beta-D-galacto- and lactopyranosides containing branched fatty-alkyl residues in place of the ceramide have been synthesized. Regioselective sulfation of the parent glycolipids through the dibutylstannylene acetal with a certain amount of sulfur trioxide-trimethylamine complex produced the target sulfated glycolipids, while stepwise phosphorylation by treatment of the properly protected diol with dibenzyloxy(diisopropylamino)phosphine gave the phosphorylated glycolipids. The synthetic glycolipids showed an interesting mode of inhibition of the binding of HL-60 cells to immobilized P-, L- and E-selectins during in vitro experiments. In addition, using computer modeling techniques, we examined the molecular basis for the ligand-selectin complex formation. These glycolipids may be useful as therapeutic agents against selectin-dependent inflammation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

A convenient and efficient synthesis of sialyl Lewis X.

A convenient synthesis of the sialyl Lewis X (sLe(x)) tetrasaccharide, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc (8), as a carbohydrate ligand for selectins is described. The key step is the reaction between NeuAc alpha 2-3GalSMe (5) as a glycosyl donor and the suitably protected Fuc alpha 1-3GlcNAc derivative (4) as the glycosyl acceptor by using dimethyl(methylthio)sulfonium triflate (DMTST) as the promoter.

Carbohydrate Sequence↗
PubMed1998

Normalization of reproductive function in germfree mice following bacterial contamination.

The capacity for reproduction in germfree mice remain inferior to their conventional counterparts even after improvement of feed and other such rearing conditions. The authors provide evidence of increased reproductive capacity in germfree mice following association with bacteria. Estrous cycles were normalized in female mice accidentally contaminated with bacteria, and in mice given fecal suspensions of the accidentally contaminated mice per os. Significant rises were seen in their copulation and implantation rates, reaching levels comparable to values in conventional mice. In male mice, bacterial contamination induced significant increase in sperm motility. Bacteria were identified in the feces of the contaminated mice, and reproductive capacity was examined in mice associated with the identified bacteria. As a result, normalization of the estrous cycle, and rises in copulation and implantation rates were noted in B. distasonis and C. perfringens di-associated mice. Values from B. subtilis mono-associated mice were comparable to those in germfree mice. These results from our accidental contamination indicate that B. distasonis and C. perfringens are capable of normalizing estrous cycles in female germfree mice, and in increasing their reproductive capacity by raising their rates of copulation and implantation.

Animals↗
PubMed1998

A new reduction technique for a patellar fracture.

We report 4 cases of patellar fracture with skin injury over the patella which were treated operatively immediately after onset with a new reduction technique using Ilizarov pins. This technique made it possible to perform early operative treatment even in the cases with skin injury over the patella which prevents conventional surgical approach.

Adult↗