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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 685 records · Page 38Linked to original sources
PubMed1994

Free oxygen radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries.

OBJECTIVES: The purpose of this study was to test the hypothesis that free oxygen radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured coronary arteries. BACKGROUND: Although free oxygen radicals, such as superoxide anion and hydrogen peroxide, have been shown to alter platelet function in vitro, the potential role of free oxygen radicals has not been fully described in an in vivo model of coronary artery thrombosis. METHODS: Cyclic flow variations were produced in dogs by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery was monitored by a pulsed Doppler flow probe. If cyclic flow variations were observed during postoperative days, dogs intravenously received superoxide dismutase plus catalase. In anesthetized dogs that did not develop an episode of cyclic flow variations, the effect of intracoronary infusion of xanthine plus xanthine oxidase or hydrogen peroxide on arterial blood flow velocity was studied. In platelet studies, the effect of free oxygen radicals and radical scavengers on platelet aggregation was examined. RESULTS: In conscious dogs with cyclic flow variations, superoxide dismutase plus catalase significantly reduced cyclic flow variations (n = 7), whereas saline infusion had no effect (n = 7). The infusion of xanthine plus xanthine oxidase or hydrogen peroxide significantly induced cyclic flow variations in four of six dogs or in five of seven dogs, respectively. In vitro platelet studies showed that xanthine plus xanthine oxidase or hydrogen peroxide significantly enhanced platelet aggregation, and superoxide dismutase or catalase significantly inhibited such aggregation. CONCLUSIONS: Reduction of free radical formation decreases platelet aggregation and may eliminate cyclic flow variations, whereas promotion of free radical generation enhances platelet aggregation and may induce cyclic flow variations. Thus, free oxygen radicals are an important mediator in this model.

Animals↗
PubMed1994

Tumour destruction and proliferation kinetics following periodic, low power light, haematoporphyrin oligomers mediated photodynamic therapy in the mouse tongue.

Photodynamic therapy (PDT) is an experimental modality in the treatment of cancer. It involves photochemical reactions that require the interaction of a photosensitising drug, light and oxygen. The development of an efficient protocol based on assuring oxygen availability through modulation of the incident light power density and its mode of delivery was addressed in this study. An estimated energy dose of 180 J/cm2 of 630 nm light from pulsed Nd:YAG dye laser was delivered 24 h after injection of 10 mg/kg haematoporphyrin oligomers in C3H/HeNCrj mice bearing the transplantable squamous cell carcinoma NR-S1, by either of these light regimens: (1) 5 mJ/cm2/pulse for 30 min, 1 h dark interval, followed by another 30 min exposure to the same power (low power, periodic light regimen) or (2) 15 mJ/cm2/pulse for 20 min (high power, continuous light regimen). Results showed a higher mean percentage area of tumour destruction with the low power, periodic light regimen at 54.34% in contrast to 12.44% of the high power, continuous light regimen 2 days after PDT. Furthermore, the mean bromodeoxyuridine labelling indices of the remaining viable-appearing cancer cells were 27.90 and 42.41, respectively, indicating a smaller tumour growth fraction with the former regimen. These results suggest that use of low power, periodically delivered light increases the antitumour efficacy of PDT.

Animals↗
PubMed1994

Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice.

When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is replaced by the Y of certain strains of Mus musculus domesticus, testis determination fails and all XY fetuses develop either as hermaphrodites or XY females (XY sex reversal). This suggests the presence of at least two alleles of Sry, the male-determining gene on the Y:M. m. domesticus and B6. The B6 Y chromosome is derived from the Japanese house mouse, M. m. molossinus and therefore carries a molossinus Sry allele. As a first step to determine how the molossinus Sry allele evolved, its distribution pattern was determined in wild mice. The cumulative data of 96 M. musculus samples obtained from 58 geographical locations in Europe, North Africa, and Asia show the molossinus Sry allele is restricted to Japan and the neighboring Asian mainland and confirm that Japanese M. m. molossinus mice were derived in part from a race of M. m. musculus from Korea or Manchuria. Sry polymorphisms, as illustrated by the molossinus Sry allele, can serve as molecular markers for studies on the evolution of wild M. musculus populations and can help determine the role sex determination plays in speciation.

Alleles↗
PubMed1994

The protein kinase C inhibitor, H-7, induces acute lung injury in guinea pigs.

OBJECTIVES: To determine if the protein kinase C inhibitor, H-7, alone can cause acute lung injury. In cell studies, H-7 inhibited phorbol myristate acetate-induced neutrophil oxygen radical release. Additionally, one animal study demonstrated that H-7 inhibited phorbol myristate acetate-induced lung injury. There have been no studies on the effect of H-7 alone on lung function or on neutrophil release of oxygen radicals. DESIGN: Prospective, randomized, laboratory study along with in vitro studies using flow cytometry and lucigenin-dependent chemiluminescence. SETTING: Experimental laboratory. SUBJECTS: Specific, pathogen-free guinea pigs and isolated human peripheral neutrophils. INTERVENTIONS: Guinea pigs were randomized into three experimental groups: saline control, H-7 low dose (2 mg/kg bolus + 0.2 mg/kg/hr), and H-7 high dose (6 mg/kg bolus + 0.5 mg/kg/hr). Human neutrophils were randomized into control and experimental groups. The effects of H-7 on pulmonary permeability in guinea pigs were examined over an 8-hr period. MEASUREMENTS AND MAIN RESULTS: We measured the wet/dry weight ratio as an index of pulmonary edema and we measured the concentration ratios of 125I-labeled albumin in lung tissue and in bronchoalveolar lavage fluid and compared the ratios with those values in plasma as indices of pulmonary permeability. We also studied the in vitro effect of H-7 on human neutrophil oxygen radical production, using flow cytometry and lucigenin-dependent chemiluminescence. By flow cytometry, we measured oxygen radical production using the 2',7'-dichlorofluorescin and hydroethidine assays. The 2',7'-dichlorofluorescin assay mainly measures hydrogen peroxide, while the hydroethidine assay measures either superoxide anion alone or in combination with other oxygen intermediaries like hydrogen peroxide. Neutrophils (5 x 10(5)) were obtained by Ficoll-Hypaque gradient centrifugation and were incubated with H-7 (5, 25, 100 microM). In the H-7 high-dose group, wet/dry weight ratio, and 125I-labeled albumin ratios in lung/plasma, and bronchoalveolar lavage/plasma were significantly increased (p < .05 for each ratio). Pulmonary endothelial gap and subendothelial bleb formation were demonstrated in the high-dose group by electron microscopy. One hundred micromols of H-7 caused a small, significant decrease (23.3%, p < .05) in neutrophil oxygen radical production assessed by 2',7'-dichlorofluorescin. H-7 had no other effects on neutrophil oxygen radical production. H-7 did not stimulate neutrophil chemiluminescence; it decreased chemiluminescence. CONCLUSIONS: a) Protein kinase C inhibition with high-dose H-7 increased wet/dry weight and albumin in lung/plasma and bronchoalveolar lavage/plasma ratios in guinea pigs; b) the H-7 high-dose group demonstrated damaged pulmonary endothelium by electron microscopy; and c) since neutrophil oxygen radical production was not increased by H-7 as assessed by flow cytometry and chemiluminescence, it appears that H-7-induced acute lung injury and endothelial damage are not mediated by increased neutrophil oxygen radical production.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Restriction map of the genomic DNA of Lactobacillus casei bacteriophage PL-1 and nucleotide sequence of its cohesive single-stranded ends.

A restriction map of the genomic DNA of Lactobacillus casei phage PL-1 was constructed using the restriction endonucleases BamHI, EcoRI, HindIII, KpnI, NruI and XhoI. The PL-1 genome was 42.2 kb in size and had complementary cohesive ends forming a ring-like monomer. The cohesive ends, analysed with exonuclease III and S1 nuclease, were 3'-terminated single strands protruding from both ends. The nucleotide sequence of the cohesive ends, determined by the dideoxynucleotide method, comprised four A + T and 10 G + C pairs: 5' GAGGCCGACCGTTC 3'/3' CTCCGGCTGGCAAG 5'. Thus, the cohesive ends of PL-1 DNA were higher in G + C content than those of other known bacteriophage DNAs.

Amino Acid Sequence↗
PubMed1994

Opsonic activity of sera and blister fluid from severely burned patients evaluated by a chemiluminescence method.

Burn wound sepsis is the most common and severe complication in the patients with severe burn. To know the systemic and local defect in immunity of burned patients, we measured the luminol-enhanced chemiluminescence (CL) response of normal polymorphonuclear leukocytes (PMNs) upon exposure to zymosan particles, bacteria or Candida albicans that were opsonized with any of patient's serum, blister fluid of burn wound or pooled normal serum (blood type AB). Sera from patients exhibited lower opsonic activities than those of pooled normal serum in the early postburn days. The levels of serum immunoglobulins, complement components and plasma fibronectin were found to correlate well with opsonin-index (OI), which was determined based on the CL response data obtained during the course of infusion therapy with fresh frozen plasma. Furthermore, patient's blister fluid showed much lower opsonic activity against bacteria such as Pseudomonas aeruginosa than patient's own serum. These results indicate that blister fluid is also not effective to opsonize bacteria because of the marked depression of the levels of immunoglobulins and complement components. Destruction of the skin barrier by thermal injury and impairment of systemic or local humoral immunity may predispose these patients to burn wound sepsis.

Adolescent↗
PubMed1994

IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease.

IL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC), 18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found to contain significantly more IL-8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P < 0.001; CD, P < 0.001), in patients with other types of colitis (UC, P < 0.05; CD, P < 0.01), or in normal control subjects (UC, P < 0.001; CD, P < 0.001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P < 0.001). Colonic IL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0.950, P < 0.001; CD, r = 0.940, P < 0.001), and with colonic IL-1 beta (r = 0.911, P < 0.001) and tumour necrosis factor-alpha (TNF-alpha) levels (r = 0.604, P < 0.001) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-1 and TNF-alpha in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease.

Adolescent↗
PubMed1994

A human monoclonal antibody to high-frequency red cell antigen Jra.

A human-mouse heterohybridoma (HMR0921) secreting human monoclonal IgG3, lambda antibody was produced from peripheral blood lymphocytes of a healthy blood donor with serum antibody to Jra, by EBV transformation and hybridization with mouse myeloma cell line P3X63Ag8.653. The reactivity of HMR0921 antibody was assessed by antiglobulin test with a panel of red cells including 14 different rare blood types. Only Jr(a-) red cells were negative. The strict specificity of this antibody to Jra antigen was further confirmed by absorption test with fluorescence flow cytometry. On screening of 28,744 blood donor samples by HMR0921 antibody, we detected 19 agglutination-negative samples, which were confirmed as Jr(a-) by conventional anti-Jra antisera. Therefore, our HMR0921 antibody is extremely useful for detecting rare Jr(a-) blood.

Animals↗
PubMed1994

Comparison of inhibition of Escherichia coli topoisomerase IV by quinolones with DNA gyrase inhibition.

In order to examine the inhibitory activities of quinolones against topoisomerase IV, both subunits of this enzyme, ParC and ParE, were purified from Escherichia coli. The specific activity of topoisomerase IV decatenation was found to be more than five times greater than that of topoisomerase IV relaxation. Thus, the decatenation activity of topoisomerase IV seems the most relevant activity for use in studies of drug inhibition of this enzyme. Although topoisomerase IV was less sensitive to quinolones than DNA gyrase, the 50% inhibitory concentrations for decatenation were significantly lower than those for type I topoisomerases. Moreover, there was a positive correlation between the inhibitory activity against topoisomerase IV decatenation and that for DNA gyrase supercoiling. These results imply that topoisomerase IV could be a target for the quinolones in intact bacteria and that quinolones could inhibit not only supercoiling of DNA gyrase but also decatenation of topoisomerase IV when high concentrations of drug exist in bacterial cells.

4-Quinolones↗
PubMed1994

Homologous recombination of monkey alpha-satellite repeats in an in vitro simian virus 40 replication system: possible association of recombination with DNA replication.

To study homologous recombination between repeated sequences in an in vitro simian virus 40 (SV40) replication system, we constructed a series of substrate DNAs that contain two identical fragments of monkey alpha-satellite repeats. Together with the SV40-pBR322 composite vector encoding Apr and Kmr, the DNAs also contain the Escherichia coli galactokinase gene (galK) positioned between two alpha-satellite fragments. The alpha-satellite sequence used consists of multiple units of tandem 172-bp sequences which differ by microheterogeneity. The substrate DNAs were incubated in an in vitro SV40 DNA replication system and used to transform the E. coli galK strain DH10B after digestion with DpnI. The number of E. coli galK Apr Kmr colonies which contain recombinant DNAs were determined, and their structures were analyzed. Products of equal and unequal crossovers between identical 172-bp sequences and between similar but not identical (homeologous) 172-bp sequences, respectively, were detected, although those of the equal crossover were predominant among all of the galK mutant recombinants. Similar products were also observed in the in vivo experiments with COS1 cells. The in vitro experiments showed that these recombinations were dependent on the presence of both the SV40 origin of DNA replication and SV40 large T antigen. Most of the recombinant DNAs were generated from newly synthesized DpnI-resistant DNAs. These results suggest that the homologous recombination observed in this SV40 system is associated with DNA replication and is suppressed by mismatches in heteroduplexes formed between similar but not identical sequences.

Animals↗
PubMed1994

Relation of principal components of ECG maps to loci of wall motion abnormality in old myocardial infarction.

The purpose of this study was to examine the correlation between body surface potential distribution and the extent of abnormally contracting segments (ACS) of the left ventricle in patients with old myocardial infarction (MI). Body surface potential distribution was quantitatively analyzed using principal component analysis. The first six principal components were extracted from data set obtained from both 25 normal subjects and 100 patients. The z scores (principal component weights) were calculated in a time domain at every 4 or 8 ms in another 81 patients with previous MI. In anterior MI, the second z scores on T wave and the fourth z scores on QRS complex were significantly lower in the presence than in the absence of ACS at the lateral wall. In inferior MI, the first z scores on QRS complex, the second on T wave, and the third on both Q and T represented significant differences between the presence and the absence of ACS at the posterior wall. Minute differences in the extent of ACS were sensitively and noninvasively detected on z scores of principal components.

Adolescent↗
PubMed1994

Electrophysiological studies on light damage in the mouse retina after sodium iodate injection.

Acute experimental retinal degeneration was induced in 3-month-old mice with sodium iodate (NaIO3) injection to investigate the effect of bright light with electroretinography (ERG). Eight C 57 black male mice were anesthetized. The ERG was recorded before and 24 h after the injection of NaIO3. Next, only one eye of each mouse was exposed to a bright light of 3.0 x 10(4) lx white light for 30 min. Ten hours later, ERGs of both the light-exposed and the unexposed eye were recorded. The amplitudes and peak latencies of the a wave and b wave were measured. The ERG was recorded as both eyes were exposed to stimulating flashes that were given in an increasing order of 0.6 log unit steps from the dimmest flash to produce a detectable ERG. The ERG from the light-exposed eye showed a distinctly elevated threshold (approx 2.0 log), while the contralateral unexposed eye did not. The peak latencies of both waves were significantly prolonged by exposure to light. In conclusion, light exposure affected ERG thresholds in mice with experimentally induced acute retinal degeneration.

Animals↗
PubMed1994

Capsaicin reduces ozone-induced airway inflammation in guinea pigs.

We investigated whether neural pathways are involved in mediating ozone (O3)-induced airway inflammation. To determine this, we studied the contribution of adrenergic and cholinergic pathways to the O3-induced increase in airway vascular permeability, an indicator of airway inflammation, by measuring vascular permeability after giving guinea pigs propranolol or atropine to block these pathways. We also studied the contribution to O3-induced airway inflammation of neuropeptides localized in unmyelinated airway sensory nerves, by measuring vascular permeability after giving capsaicin to deplete neuropeptides from these nerves. We found that capsaicin reduced but did not abolish the increase in airway vascular permeability induced by 3 ppm O3 for 30 min. Propranolol and atropine had no effect on airway vascular permeability. These results indicate that neuropeptides released from sensory nerves, presumably by acting through the axon reflex, partly mediate O3-induced airway inflammation, and that adrenergic and cholinergic pathways are not involved.

Analysis of Variance↗
PubMed1994

Clonal expansion of CD8+ cytotoxic T lymphocytes against human T cell lymphotropic virus type I (HTLV-I) genome products in HTLV-I-associated myelopathy/tropical spastic paraparesis patients.

Short-term culture of peripheral blood mononuclear cells (PBMC) derived from patients with human T cell lymphotropic virus type I-associated myelopathy (HAM)/tropical spastic paraparesis resulted in dominance by DR+ activated CD8+ T cells. Variations in the T cell receptor (TCR) V alpha and V beta chains in these cells were analyzed, and in all 10 patients examined, 2-3 V gene families were dominant in both TCR V alpha and V beta. In five patients we examined, cultured lymphocytes contained cytotoxic lymphocytes for p40tax (patients HAM2, 3, 7, and 8) or env protein (patient HAM4) of human T lymphotropic virus type I. In patients HAM2 and HAM8, cultured lymphocytes contained a large proportion of V beta 8+ CD8+ and/or V beta 12+ CD8+ cells. The sequence of V beta 8+ and V beta 12+ cDNA revealed that they were oligoclonal with identical or similar sequences in each patient. Elimination experiments with monoclonal antibodies for TCR V beta 8 and V beta 12 showed that they were CD8+ cytotoxic T lymphocytes (CTL) for p40tax. In addition, flow cytometry and sequencing analysis of uncultured PBMC revealed that in HAM2, V beta 8+ CTL and their precursors account for 7% and V beta 12+ CTL and their precursors account for 18% of total CD8+ cells. This indicates the presence of two markedly expanded clones in vivo. No common dominant TCR V alpha or V beta were observed among 10 HAM patients analyzed.

Amino Acid Sequence↗
PubMed1994

A protease inhibitor, NCO-700, improves the contractile function in stunned canine myocardium.

To explore the role of calcium-dependent protease in the stunned myocardium, open-chest dogs underwent 15 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Dogs received a single bolus intravenous injection of either the protease inhibitor NCO-700 (n = 6) or saline (n = 6) 1 min before reperfusion followed by a 30-min infusion at the same dose. Regional myocardial function was assessed in terms of systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during occlusion. After reperfusion, recovery of contractile function, expressed as a percentage of the baseline value, was significantly greater in NCO-700-treated dogs as than in control dogs: -14.3 +/- 10.6 vs -48.9 +/- 7.2 (p < 0.05) at 15 min, 10.8 +/- 10.3 vs -31.1 +/- 9.0 (p < 0.05) at 30 min, 42.5 +/- 10.1 vs -16.4 +/- 9.1 (p < 0.005) at 1 h, and 47.5 +/- 8.3 vs -14.9 +/- 9.4 (p < 0.001) at 2 h. The data suggest that the protease inhibitor markedly improved contractile function in stunned myocardium by inhibiting intracellular protease activity.

Animals↗