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Biomedical subjects

K Adachi

Publications and source records attributed to K Adachi.

At least 343 records · Page 19Linked to original sources
PubMed1994

[Clinical feature and mechanism of cardiac failure in patients with Becker muscular dystrophy].

Patients with Becker muscular dystrophy (BMD) have milder muscular impairment and better prognosis than patients with Duchenne muscular dystrophy (DMD). Another difference is that while cardiac failure due to myocardial involvement is a frequent cause of death in BMD, respiratory failure is the most common cause of death in DMD. We examined cardiac function and the mechanism of cardiac failure in 21 BMD patients aged 3 to 63 years (mean, 40.4) by electrocardiography, mechanocardiography, echocardiography, and post-mortem examination. Diagnosis of BMD was made by characteristic symptoms, dystrophic change in muscle histology, and the followings: 1) a deletion in the dystrophin gene, 2) "patchy" staining of dystrophin on immunocytochemical analysis, 3) abnormal dystrophin size on Western blotting, and 4) presence of a definite carrier in the family. To be diagnosed as BMD, patients exhibited one or more of 1)-3). Patients who were diagnosed only by 4) had a relative who had been diagnosed as BMD by one of 1)-3). The control group included 43 DMD patients (age 4-26 years, mean 16.2) and 20 healthy males (age 15-60 years, mean 33.3). Electrocardiogram showed prominent Q waves in leads II, III, aVF and V6, and tall R in V1, suggesting myocardial injury in the posteroinferior and lateral walls. The ratio of ejection time to pre-ejection period (ET/PEP) decreased to 2.0-3.3 in BMD, and was significantly lower than that in DMD patients with comparable muscle weakness. Left ventricular dilatation became more prominent with age, and end-diastolic left ventricular dimension (EDLVD) averaged 52.3 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of beta 6 aromatic amino acids on polymerization and solubility of recombinant hemoglobins made in yeast.

Valine, leucine, tryptophan, and phenylalanine substitutions at the beta 6 position of hemoglobin (Hb) were made using a yeast expression system coupled with a polymerase chain reaction-based mutagenesis strategy. The oxygen affinity and absorption spectra of these mutants were similar to recombinant Hb A except for Hb beta E6W which had a higher absorbance at approximately 280 nm. The deoxy forms of Hb beta E6L and Hb S showed characteristic delay times prior to polymerization. Tetrameric deoxy-Hbs containing tryptophan or phenylalanine at the beta 6 position had higher solubilities and polymerized less readily compared with deoxy-Hb S. However, when oversaturated, these Hbs polymerized without a delay time. These results suggest that Hb beta E6W and Hb beta E6F form polymers upon deoxygenation by a linear polymerization mechanism without nuclei formation. During polymerization, bulky hydrophobic amino acids, like phenylalanine and tryptophan at the beta 6 position, might interact with the acceptor pocket on the surface of an adjacent Hb molecule but may not be able to form stable hydrophobic interactions like beta 6 valine and leucine. Difficulty in insertion of the bulky side chains of these aromatic amino acids into the hydrophobic acceptor pocket on an adjacent tetramer may inhibit nuclei formation prior to polymerization.

Amino Acids↗
PubMed1993

A deletion of mitochondrial DNA in murine doxorubicin-induced cardiotoxicity.

A deletion of about 4 kb has been determined in the mutated mitochondrial DNA (mtDNA) in cardiomyocytes with chronic doxorubicin (DOX)-induced cardiotoxicity in mouse. The incidence of the mtDNA deletion increased with the dosage and with the duration of the DOX administration. Coenzyme Q10 administration prevented the mtDNA deletion and decreased the thiobarbituric acid reactive substance content in the heart mitochondria, suggesting some free radical involvement in this mtDNA deletion. This mtDNA deletion may be involved in cardiomyopathy, which is known to be dosage-dependently induced by DOX administration.

Animals↗
PubMed1993

Cyclic flow variations in a conscious dog model of coronary artery stenosis and endothelial injury correlate with acute ischemic heart disease syndromes in humans.

OBJECTIVES: The purpose of this study was to test the hypothesis that episodes of cyclic flow variations (CFVs) in conscious dogs with coronary stenoses and endothelial injury correlate with acute ischemic heart disease syndromes in humans. BACKGROUND: Although the canine model with CFVs has proved to be a useful model of coronary thrombosis, whether CFVs progress to these syndromes has not been clearly described. METHODS: Cyclic flow variations were produced by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery and 24-h Holter electrocardiogram (ECG) were recorded during the 1st 5 postoperative days. RESULTS: Of 41 dogs that underwent the initial operative procedure successfully, 29 developed an episode of CFVs. In five dogs in which CFVs persisted throughout the monitoring period, the left anterior descending coronary artery flow decreased until day 3 and thereafter increased through day 5. Transient coronary occlusion during CFVs induced ST segment changes that returned to baseline after reflow. In 12 dogs, CFVs progressed to persistent coronary occlusion, and histologic examination revealed thrombus formation at the stenotic site and evidence of myocardial infarction. Four of these 12 dogs died suddenly of ventricular arrhythmias during persistent coronary occlusion; another 5 dogs died of reperfusion arrhythmias during CFVs with no evidence of myocardial infarction. CONCLUSIONS: Conscious dogs with CFVs closely correlated with clinical acute ischemic heart disease syndromes, suggesting them to be a useful model for investigating the complex mechanisms of cellular interactions in the pathogenesis of these syndromes.

Animals↗
PubMed1993

Effects of beta 6 amino acid hydrophobicity on stability and solubility of hemoglobin tetramers.

The relationship between different amino acids at the beta 6 position of hemoglobin and tetramer stability was addressed by a site-directed mutagenesis approach. Precipitation rates during mechanical agitation of oxyhemoglobins with Gln, Ala, Val, Leu and Trp at the beta 6 position increased 2, 5, 13, 21 and 53 times, respectively, compared with that for Hb A. There was a linear relationship between the log of the precipitation rate constant and amino acid hydrophobicity at the beta 6 position, suggesting that enhanced precipitation of oxy Hb S during mechanical agitation results in part from increased hydrophobicity of beta 6 Val. Deoxyhemoglobin solubility increased in the order of beta 6 Ile, Leu, Val, Trp, Gln, Ala and Glu suggesting that hydrophobic interactions between beta 6 Val and the acceptor site of another hemoglobin molecule during deoxy-Hb S polymerization not only depend on hydrophobicity but also on stereospecificity of the amino acid side chain at the beta 6 position. Furthermore, our results indicate that hydrophobic amino acids at the beta 6 position which promote tetramer instability in the oxy form do not necessarily promote polymerization in the deoxy form.

Hemoglobins↗
PubMed1993

Changes in erythrocyte membrane phospholipid composition induced by physical training and physical exercise.

The effects were investigated of physical training and exercise on lipids of the erythrocyte membrane of healthy students. Membrane cholesterol and phospholipids were analysed simultaneously by thin-layer chromatography with a flame ionization detector and the fatty acid composition was determined by gas chromatography. Physically trained students had similar physical characteristics to control students but a significantly higher aerobic capacity, estimated as the maximal oxygen uptake and anaerobic threshold. Of the phospholipids examined, only the content of membrane phosphatidylserine was significantly lower in the trained group. Fatty acid analysis showed that the amount of docosahexaenoic acid in membrane phosphatidylserine was lower in the trained group. There was no significant difference between the fatty acid compositions of membrane phosphatidylcholine in the two groups. Maximal exercise decreased membrane phosphatidylserine in the control group but not in the trained group. It also significantly decreased the relative amounts of unsaturated fatty acids in both phosphatidylcholine and phosphatidylserine in the untrained group. Maximal oxygen uptake was negatively correlated with the amount of erythrocyte membrane phosphatidylserine. These results would indicate that both physical training and acute exercise decrease phosphatidylserine and polyunsaturated fatty acids in erythrocyte membranes, possibly due to lipid peroxidation, suggesting limited enhancement of erythrocyte defense mechanisms in adaptation to chronic oxidative stress.

Adult↗
PubMed1993

Decrease in urinary excretion of 3-methylhistidine by patients with Duchenne muscular dystrophy during glucocorticoid treatment.

Seven patients, aged 10-17 years, with Duchenne muscular dystrophy were treated orally with prednisolone (PSL) at a dose of 0.8-1.0 mg/kg per day for 8 weeks. During the treatment their muscle strength, serum creatine kinase (CK) activity, serum levels of myoglobin (Mb), and urinary excretion of 3-methylhistidine (3-MeH) and glycine (Gly) were measured serially. In all the patients, the motor function or muscle strength improved, and the serum CK activity and Mb level decreased during PSL treatment. Urinary excretion of 3-MeH, a unique constituent of muscle contractile proteins, decreased to 51-63% of the baseline value in weeks 6-9 after the start of PSL administration, and returned to the baseline level in week 12. The ratios of 3-MeH to creatinine and to Gly also decreased during the treatment. Urinary excretion of Gly, which is ubiquitous in all tissues including muscle, did not decrease during the treatment. These findings suggest that PSL inhibits proteolysis of muscle contractile protein.

Adolescent↗
PubMed1993

A novel mechanism for disposing of effete epithelial cells in the small intestine of guinea pigs.

BACKGROUND: We previously showed that at the villus tips in the small intestine of guinea pigs effete enterocytes are not simply exfoliated into the lumen but phagocytosed by subepithelial macrophages, leaving only a thin apical cell portion in the epithelial lining. The aim of the present study is to investigate the fate of these apical pieces of enterocytes. METHODS: The ileum of guinea pigs was perfusion-fixed and processed for transmission and scanning electron microscopic observation. RESULTS: The apical cytoplasmic plates were found to be pushed by neighboring enterocytes and protruded from the epithelial surface, finally being pinched off into the lumen. In this process observed at the villus tips, the junctional complexes between the apical cytoplasmic plate and the adjacent enterocytes were preserved until the pinching-off of the plate. Luminal cell elements revealed a rich existence of cup-shaped or spherical cell fragments covered with microvilli; nuclei were never observed in the luminal fragments. CONCLUSIONS: The findings in the small intestine of the guinea pig are the first to account for the mechanism of the epithelial barriers being preserved while apoptotic enterocytes drop out at the tips of the villi.

Animals↗
PubMed1993

Levels of somatostatin and cholecystokinin in the brain of ataxic mutant mice.

Changes in immunoreactive somatostatin (SOM) and cholecystokinin (CCK-8) levels in the cerebellum and cerebrum were investigated in three types of genetically-determined ataxic mutant mice: rolling mouse Nagoya (RMN), weaver, and Purkinje cell degeneration (PCD) mice. The cerebellar pathology in each of these types differs. The concentration of both SOM and CCK-8 (ng/mg weight) was significantly higher in the cerebellum and the cerebrum of the three types of ataxic mutant mice than in these regions in the respective controls. SOM and CCK-8 content (ng/organ) was significantly higher in PCD and RMN than in controls but this was not in the weaver mice. The possible involvement of both peptides in manifestations of ataxia is discussed.

Animals↗
PubMed1993

Structure-dependent antitumor activities of novel anthracyclines YM1, YM3, YM4 and YM6: drug transport properties and effects on biomacromolecule synthesis in drug sensitive and resistant leukemia cells.

The antitumor activities of four novel doxorubicin (DOX) analogues, YM1, YM3, YM4 and YM6 in relation to their structure and drug transport properties, have been investigated in U937 monocytic and CCRF-CEM lymphoid drug sensitive leukemia cell lines, as well as in CEM/VLB100, a drug resistant subline displaying high levels of P-glycoprotein. Treatment of all cell lines with YM1, 3, 4 and 6 produced a dose-dependent decrease in DNA, RNA and protein synthesis as measured by [3H]-thymidine, [3H]-uridine and [3H]-leucine uptake respectively. YM1 was more effective than YM3, YM4 or YM6 against the drug sensitive cells. The antitumor effects of all these DOX-analogues on macromolecule synthesis in U937 and CCRF-CEM cells were lower than that of DOX and epirubicin (EDR). A rapid accumulation of the novel anthracyclines was found in all cell lines compared with DOX or EDR. However, the maximal accumulation of the DOX-analogues was lower than that of EDR. There is a greater efflux from CCRF-CEM sensitive cells and less from CEM/VLB100 resistant cells of the DOX-derivatives when compared with EDR and DOX. Drug-induced cytotoxicity significantly correlated (P < 0.05) with drug retention levels in CCRF-CEM and U937 drug sensitive cells as indicated by an inverse correlation curve between anthracycline retention and drug-induced IC50 value. It was demonstrated that an increased level of drug retained within the sensitive cells would therefore produce a more cytotoxic effect of the drug. However, no such correlation was observed in CEM/VLB100 resistant cells. YM3 was shown to have an increased antitumor activity against CEM/VLB100 resistant cells compared with DOX with a lower resistance factor. These results showed that the antitumor effects of four novel DOX-analogues, like DOX or EDR, were associated with inhibition of DNA replication, transcription and translation. The finding that resistant leukemic cells are more susceptible to the cytotoxic effect of YM3 than DOX warrants further investigation to identify the intrinsic mechanism of resistance.

Biological Transport↗
PubMed1993

Effect of physical exercise on the content of 8-hydroxydeoxyguanosine in nuclear DNA prepared from human lymphocytes.

Effects of exercise on the formation of 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of oxidative DNA damage, and other purine metabolites such as hypoxanthine, xanthine and uric acid were examined. Venous blood and urine were collected from swimmers and distance runners before and after the usual training. The amount of 8-OH-dG obtained from nuclear DNA of lymphocytes decreased remarkably after intermittent swimming. The amount of nuclear 8-OH-dG also declined after distance running, but this difference is statistically not significant. After each exercise, plasma concentrations of hypoxanthine, xanthine and uric acid rose significantly. Urinary excretion of hypoxanthine increased, and xanthine and uric acid decreased after exercise. The 8-OH-dG-to-creatinine ratio in urine increased slightly after swimming or running. It is supposed that the repair of oxidative DNA damage is augmented by exercise. As far as we know, this is the first report concerning the effect of exercise on oxidative damage in nuclear DNA.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1993

Image analysis studies of the degree of irreversible deformation of sickle cells in relation to cell density and Hb F level.

We analyzed, quantitatively by image analysis, the degree of irreversible deformation of red cells (SS cells) from patients with homozygous sickle cell disease, and studied the relationships among the degree of irreversible cell deformation, cell density, and Hb F level. SS cells from 25 patients (aged 1-36 years) whose Hb F levels ranged from 2.5% to 40.0%, were fully oxygenated and then were separated into four fractions by density centrifugation. Every fraction was studied for morphology and Hb F content. We found that the irreversible deformation of SS cells from the circulation occurred mainly by elongation and that the degree of elongation was extremely variable. We also found that in the cells of patients with Hb F levels < 20% the degree of irreversible elongation increases as cell density increases, suggesting that dehydration occurs concomitantly with irreversible elongation. Statistical analysis (Student t test) indicated that there were significant differences (P = 0.008 or < 0.001) in the degree of elongation among density-fractionated SS cells from patients with Hb F < 20%, although there was no significant difference (P > 0.1) among those from patients with Hb F > or = 20%. We also found that cell density increased as Hb F level of the density fraction decreased in all patients with Hb F < 20% but not always in those with Hb F > or = 20%. This suggests that cells with lower Hb F levels are selectively susceptible to dehydration. Furthermore, we found that the mean degree of irreversible elongation decreases linearly with increasing levels of Hb F and reaches the normal range at 21-24%. Since the degree of irreversible deformation of SS cells quantified by image analysis is directly related to cell density, and inversely to Hb F levels, mechanical stress or membrane damage caused by Hb S polymerization may be an important factor in the formation of dense cells in vivo.

Adolescent↗
PubMed1993

Menstrual stage-specific expression of epidermal growth factor and transforming growth factor-alpha in human oviduct epithelium and their role in early embryogenesis.

We studied the expression of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha in human oviduct epithelium at various menstrual stages. Immunohistochemical stainings using anti-EGF and anti-TGF alpha antibodies showed a specific staining in ampullary oviduct epithelium at late follicular and luteal stages, but the stainings were very weak at early follicular stage. Quantitative reverse transcription and polymerase chain reaction, using beta-actin messenger RNA as an internal standard, revealed the menstrual stage-specific expression of EGF and TGF alpha gene transcripts: relative amounts of EGF and TGF alpha messenger RNA to those of beta-actin were 1.5 +/- 1.9% (mean +/- SD) and 1.4 +/- 0.6% (n = 3) at early follicular, 16.5 +/- 4.9% and 12.6 +/- 2.6% (n = 3) at late follicular, and 18.9 +/- 2.2% and 13.8 +/- 3.2% (n = 3) at luteal stages, respectively. The expression of these growth factors was in proportion to the increase in serum estradiol but not to progesterone levels. To clarify the biological significance of these growth factors, mouse two-cell embryos were cocultured with human oviduct epithelial cells with or without blocking the action of these growth factors. Cocultures significantly promoted blastocyst formation, but this promotive effect of the oviduct epithelial cells was completely abolished by the addition of anti-EGF and/or anti-TGF alpha monoclonal neutralizing antibodies to the coculture system. All these results showed that EGF and TGF alpha were synthesized and expressed in human oviduct epithelium specifically to menstrual stages, and that these growth factors may be involved in early embryonic development.

Actins↗
PubMed1993

Failure of killed Corynebacterium parvum in induction of protection in C57BL/6 mice against Babesia rodhaini challenge infection.

We examined the survival rate of C57BL/6 mice challenged with Babesia rodhaini 21 days post-killed Corynebacterium parvum (KCP) inoculation in comparison with ICR mice. All KCP-inoculated ICR mice survived the challenge infection, while all KCP-inoculated C57BL/6 mice died. To account in part for the difference in protective effects of KCP, stimulatory effects of KCP on splenic phagocyte chemiluminescence (CL) response were investigated in C57BL/6 and ICR mice. The KCP-inoculated ICR mice exhibited significantly higher CL values than ICR mice without KCP inoculation. No significant difference in CL value was observed between C57BL/6 mice with and without KCP inoculation. These results taken together, the lack of resistance of the KCP-inoculated C57BL/6 mice to B. rodhaini infection may be attributed in part to small stimulatory effect of KCP on splenic phagocytes.

Animals↗
PubMed1993

Suppressed antibody response to sheep erythrocytes in experimentally Babesia rodhaini-infected mice.

Mice experimentally infected with Babesia rodhaini were immunized with sheep red blood cells (SRBC), and the splenic plaque forming cell (PFC) response to SRBC was investigated. Suppressed splenic antibody response to SRBC accompanied with the elevated parasitemia was recognized. This evidence suggests that an immunosuppression in B. rodhaini infection may be involved in the multiplication of parasites contributing to high mortality of mice infected with B. rodhaini.

Animals↗
PubMed1993

Isolation of Babesia gibsoni piroplasms from infected erythrocytes of dogs.

To eliminate the influence of anti-dog erythrocyte membrane antibodies in Babesia gibsoni-infected dogs on the immunological investigations of parasites, an attempt was made to purify B. gibsoni piroplasms from infected erythrocytes by N2 cavitation and centrifugation in a Percoll discontinuous density gradient. Although electron microscopic examination revealed that the concentrated piroplasms visible as a band at the interface between 30% and 40% Percoll solutions were contaminated with a small amount of erythrocyte membrane debris, little contamination was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblots. Hence, the isolated parasites may be usable for immunological examinations of parasites.

Animals↗
PubMed1993

Immunosuppression in dogs naturally infected with Babesia gibsoni.

We examined lymphoproliferative response to phytohemagglutinin and anti-parasite antibody level in dogs naturally infected with Babesia gibsoni. The dogs with subclinical B. gibsoni infection exhibited suppressed lymphocyte blastogenesis. Prominent depression of lymphocyte blastogenesis and anti-parasite antibody production was observed in dogs suffering from relapses of clinical B. gibsoni infection.

Animals↗