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Biomedical subjects

K Ochiai

Publications and source records attributed to K Ochiai.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Relationship between endothelial function and female hormone level in very old females: evaluation from ischemic reactive hyperemic response in forearm vessels].

Recently, the mechanism of longevity in females was proposed to be associated with female hormones. This study examined the effect of aging and sex on vascular endothelial function, and the relationship between female hormone level and endothelial function by ischemic reactive hyperemic response in the forearm using plethysmography. The study population consisted of 246 healthy subjects aged from 20 to 76 years (119 males, 127 females) and 20 healthy females aged 85 years and older (85 to 103 years; mean age 94 years) without distinct cardiovascular disease, hypertension, diabetes mellitus, renal disease, liver dysfunction or anemia. Levels of the female hormones, estradiol and estriol, were measured in females aged more than 85 years. The duration of reactive hyperemia decreased with aging, but the difference between males and females was not significant at any age. In females, the duration was markedly decreased from 110 +/- 36 sec in the fifties to 81 +/- 29 sec in the sixties or older (p < 0.05). Excess flow also showed similar changes to the duration of reactive hyperemia. The duration of reactive hyperemia and excess flow in females aged 85 years and older were similar to those in the fifties, but was significantly longer than those in females 60 years or older. The concentrations of estradiol (44.9 +/- 27.1 pg/ml) and estriol (22.1 +/- 13.4 pg/ml) in females aged 85 years were higher than in the sixties. There was a positive correlation between the duration of reactive hyperemia and the concentration of estradiol (r = 0.56, p < 0.01) or estriol (r = 0.57, p < 0.01). In summary, vascular endothelial function was impaired gradually with aging, but preservation of the function in healthy, very old females was closely associated with levels of female hormone.

Adult↗
PubMed1999

Subendocardial enhancement in gadolinium-diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging in aortic stenosis.

We investigated the usefulness of magnetic resonance imaging (MRI) with gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) in assessing myocardial damage from valvular aortic stenosis (AS). Cardiac catheterization and echocardiography were performed in 17 patients with AS. T1-weighted spin-echo sequence was used to obtain magnetic resonance images of short-axis planes of the left ventricle before and after intravenous Gd-DTPA injection in all patients using a 1.5 Tesla imager. Patients were divided into 2 groups according to the presence or absence of regional myocardial enhancement in the images. The Gd-DTPA-enhanced magnetic resonance images of 7 patients showed circumferential subendocardial enhancement. All patients with enhancement had a history of heart failure and were in New York Heart Association functional class III or IV, whereas patients without enhancement were in New York Heart Association functional class I or II. Patients with enhancement had a smaller aortic valve area (0.28 +/- 0.09 vs 0.38 +/- 0.07 cm2/m2, p <0.05), a higher transvalvular pressure gradient (109 +/- 40 vs 68 +/- 18 mm Hg, p <0.05), greater elevation of left ventricular end-diastolic pressure (22 +/- 11 vs 12 +/- 2 mm Hg, p <0.05), and greater reduction in left ventricular ejection fraction (40 +/- 9 vs 59 +/- 10%, p <0.05). Subendocardial enhancement by Gd-DTPA-enhanced MRI was thus shown to be closely related to the severity of AS. In conclusion, Gd-DTPA-enhanced MRI is a new noninvasive tool that can provide useful information about myocardial damage in AS.

Adult↗
PubMed1999

Allelic imbalance in chromosome band 18q21 and SMAD4 mutations in ovarian cancers.

Recently, three candidate tumor suppressor genes, SMAD2 (MADR2/JV18-1), SMAD4 (DPC4), and DCC, were identified in chromosome band 18q21. We examined allelic imbalance (AI) in 18q21 using six polymorphic microsatellite markers in 38 primary ovarian cancers and four ovarian borderline tumors. AI at one or more loci was detected in 15 of 37 (41%) informative ovarian cancers and in none of the four borderline tumors. Frequent AI was detected at the D18S46 (31%) and D18S474 (36%) loci, which were adjacent to the SMAD4 gene, and at the D18S69 (33%) locus, which was telomeric to the DCC gene. Therefore, we searched for mutations of the SMAD4 gene in 42 primary tumors and eight cell lines by PCR-SSCP and sequencing analyses. Missense mutations were detected in two ovarian tumors and three ovarian cancer cell lines, whereas silent mutation was detected in a primary ovarian cancer. These results suggest that there are at least two tumor suppressor genes on chromosome arm 18q and that SMAD4 is of importance in ovarian tumorigenesis.

Alleles↗
PubMed1999

The contributory role of interstitial water in Gd-DTPA-enhanced MRI in myocardial infarction.

We studied the mechanism underlying regional enhancement of myocardial infarction using T1-weighted MRI with gadolinium (Gd)-DTPA. Anterior myocardial infarction (MI) was produced by left anterior descending coronary artery ligation in three groups of rats as follows: 60 minutes occlusion (occlusion group, N = 6), 60 minutes occlusion plus 120 minutes reperfusion (reperfusion group, N = 8), and sham-operated (control, N = 6). In Gd-DTPA-enhanced MRI, MI was demarcated as a hypoenhanced region in the occlusion group and as a homogeneous hyperenhanced region in the reperfusion group. Both Gd-DTPA tissue concentration and tissue water content in the anterior wall were highest in the reperfusion group (P<0.05), a finding suggestive of microscopically observed interstitial edema. The data suggest that regional accumulation of Gd-DTPA in the reperfused group can be explained by increased interstitial water content, contributing to the delayed washout of the water-soluble contrast medium.

Animals↗
PubMed1999

Two genetically distinct lineages of the sika deer, Cervus nippon, in Japanese islands: comparison of mitochondrial D-loop region sequences.

To investigate genetic diversity among populations of the sika deer, Cervus nippon, nucleotide sequences (705-824 bases) of the mitochondrial D-loop regions were determined in animals from 13 localities in the Japanese islands. Phylogenetic trees constructed by the sequences indicated that the Japanese sika deer is separated into two distinct lineages: the northern Japan group (the Hokkaido island and most of the Honshu mainland) and the southern Japan group (a part of the southern Honshu mainland, the Kyushu island, and small islands around the Kyushu island). All sika deer examined in this study shared four to seven units of repetitive sequences (37 to 40 bases each) within the D-loop sequences. The number of tandem repeats was different among the populations, and it was specific to each population. Six or seven repeats occurred in populations of the northern Japan group, while four or five repeats occurred in populations of the southern Japan group. Each repeat unit included several nucleotide substitutions, compared with others, and 26 types were identified from 31 animals. Sequences of the first, second, and third units in arrays were clearly different between the northern and the southern groups. Based on these D-loop data, colonization and separation of the sika deer populations in the Japanese islands were estimated to have occurred less than 0.5 million years before present. Our results provide an invaluable insight into better understanding the evolutionary history, phylogeny, taxonomy, and population genetics of the sika deer.

Animals↗
PubMed1999

Distal axonopathy does not occur without neurofilament accumulation in gamma-diketone neuropathy: comparative studies of normal and neurofilament-deficient quail.

The neurotoxic effects caused by chronic exposure to 2,5-hexanedione (2,5-HD) were investigated in normal and neurofilament (NF)-deficient quail (Quv strain). These quail were given 175 mg/kg per day of 2,5-HD intraperitoneally for 24 weeks. Five of nine normal quail showed clumsy gait. They had NF-rich axonal swellings in the distal parts of the peripheral nerves, ventral and lateral funiculus of the cervical cord, and cerebellar peduncles. Axonal degeneration consisting of accumulation of mitochondria, vesicles, microtubules and dense bodies was found distal to the axonal swellings. Testicular atrophy appeared in two normal quail. In contrast, four of nine Quv quail showed systemic tonic convulsion, and died of respiratory paralysis within 6 days. No significant changes in the nervous system or testis of these four dead Quv quail. The five other Quv quail survived and did not show any neurological signs. Again, no significant changes were detected in the nervous system or testis of the surviving Quv quail. The present study revealed that distal axonal degeneration did not occur without NF accumulation. These results suggest that NF accumulation is an essential factor in the development of distal axonopathy in gamma-diketone neuropathy.

Animals↗
PubMed1999

Cellular uptake of fluvastatin, an inhibitor of HMG-CoA reductase, by rat cultured hepatocytes and human aortic endothelial cells.

AIMS: To clarify the mechanism for cellular uptake of fluvastatin (FV) into rat primary cultured hepatocytes and human aortic endothelial cells (HAEC). METHODS: Rat primary cultured hepatocytes and Endocell-AO as normal human aortic endothelial cells were used. Effects of incubation time, concentration- and temperature-dependency on cellular FV uptake were investigated after incubation with [14C]-FV and its enantiomers, (+)-FV and (-)-FV. Rat primary cultured hepatocytes were washed with either Na+-containing buffer or Na+-free buffer and incubated with metabolic inhibitors or bile acids. Intracellular radioactivity was measured by liquid scintillation counting. The determination of intracellular unchanged FV and its enantiomers was carried out by stereospecific h.p.l.c. RESULTS: In rat cultured hepatocytes, concentration- and temperature-dependent saturable uptake of [14C]-FV was observed (Km=37.6 microm, V max=869 pmol (mg protein)-1 min-1 ), suggesting a specific uptake mechanism. The uptake of each enantiomer also showed a specific uptake mechanism as observed for the racemate with no difference between enantiomers; (+)-FV, Km=38.5 microm, V max=611 pmol (mg protein)-1 min-1, (-)-FV, Km=41.5 microm, V max=646 pmol (mg protein)-1 min-1. In the presence of cholate and taurocholate, the uptake of FV was inhibited by 39-46%. Pravastatin inhibited FV uptake by 29%. In the absence of Na+, the uptake of FV was markedly inhibited 91-96% by bile acid. The uptake of FV into HAEC at 37 degrees C and 4 degrees C increased with the concentration of FV, but no saturable uptake was observed. CONCLUSIONS: FV transport system may be, at least in part, Na+- and ATP-dependent, and may have some features in common with the bile acid transport system and the organic anion transport system. Since saturable uptake was not observed in HAEC, FV appears to be taken up into these cells mainly via nonspecific simple diffusion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Role of JAK2 signal transductional pathway in activation and survival of human peripheral eosinophils by interferon-gamma (IFN-gamma).

The purpose of this study was to determine whether the JAK pathway is involved in eosinophil activation and survival through IFN-gamma receptor signalling in human peripheral eosinophils. Eosinophils were purified from the blood of six atopic disease patients by anti-CD16 magnetic bead-negative selection. IFN-gamma significantly up-regulated survival and CD69 expression in 24-48 h cultured eosinophils. Further, IFN-gamma induced tyrosine phosphorylation of JAK2 in eosinophils, as indicated by Western blot analysis. Finally, the specific JAK2 inhibitor AG-490 inhibited the tyrosine phosphorylation of JAK2, IFN-gamma-induced survival and CD69 expression in eosinophils. In conclusion, these results indicate that IFN-gamma induces eosinophil survival and CD69 expression through the activation of JAK2 in peripheral eosinophils, suggesting that JAK2 may play a significant role in eosinophil regulation by IFN-gamma-IFN-gammaR interaction.

Adolescent↗
PubMed1999

Arteriovenous malformation of the cervical spinal cord in a dog.

An 8-year-old female German Shepherd dog showed first order Horner's syndrome associated with progressive right-sided hemiplegia and mega-oesophagus. Intramedullary and leptomeningeal arteriovenous malformation (AVM) was identified in the cervical spinal cord. The morphological characteristics were arteriovenous shunting, intramedullary multiple thromboses and haemorrhage, non-inflammatory necrosis of white and grey matter around the shunt, and intervening neural gliosis with neovascularization. These findings suggested that the malformation induced a focal circulatory disturbance within the cervical spinal cord and that fatal thrombosis was responsible for the sudden onset of the nervous signs and progressive neurological deterioration. This is the first report of intramedullary spinal AVM in a dog.

Animals↗
PubMed1999

Hepatic lesions in young rabbits experimentally infected with rabbit haemorrhagic disease virus.

Twenty young rabbits (eleven 2-week-old and nine 4-week-old) were experimentally infected with rabbit haemorrhagic disease virus (RHDV) to clarify susceptibility. They were killed chronologically up to 96 hours post-inoculation (PI) and examined for lesions. All inoculated rabbits were clinically normal, but grossly minute white or grey spots were detected throughout the liver. Histologically, the lesions consisted of aggregates of lymphocytes, macrophages and heterophils, with or without acidophilic bodies and necrotic hepatocytes. Immunohistochemically, RHDV antigens were found in the degenerated hepatocytes and in macrophages. The cellular aggregates were considered to be a reaction to necrotic hepatocytes infected with RHDV. It was concluded that some hepatocytes are susceptible to RHDV in young rabbits.

Animals↗
PubMed1999

Eosinophil activation and in situ interleukin-5 production by mononuclear cells in skin lesions of patients with drug hypersensitivity.

In order to determine the inflammatory mechanisms of skin lesions in patients with drug hypersentivity, we examined eosinophil activation and interleukin-5 (IL-5) production in infiltrating lymphocytes. First, we showed that the number of peripheral eosinophils and the level of serum IL-5 at the eruption-active stage were both significantly higher than those in healed skin eruptions. Histological and immunohistological examination revealed that CD4+ T cells and eosinophils significantly more densely infiltrated drug eruptions than control skin lesions. The infiltrating eosinophils were also shown to be activated by immunostaining using anti-secreted formed eosinophilic cationic protein monoclonal antibody. The expression of mRNA for IL-5 in the infiltrating mononuclear cells at drug eruptions was shown by in situ hybridization. These results suggest that infiltrating CD4+ T cells might regulate both peripheral and tissue eosinophils and facilitate allergic inflammation at drug eruptions by means of IL-5 production.

Adult↗
PubMed1999

Lipopolysaccharide stimulates butyric acid-induced apoptosis in human peripheral blood mononuclear cells.

We previously reported that butyric acid, an extracellular metabolite from periodontopathic bacteria, induced apoptosis in murine thymocytes, splenic T cells, and human Jurkat T cells. In this study, we examined the ability of butyric acid to induce apoptosis in peripheral blood mononuclear cells (PBMC) and the effect of bacterial lipopolysaccharide (LPS) on this apoptosis. Butyric acid significantly inhibited the anti-CD3 monoclonal antibody- and concanavalin A-induced proliferative responses in a dose-dependent fashion. This inhibition of PBMC growth by butyric acid depended on apoptosis in vitro. It was characterized by internucleosomal DNA digestion and revealed by gel electrophoresis followed by a colorimetric DNA fragmentation assay to occur in a concentration-dependent fashion. Butyric acid-induced PBMC apoptosis was accompanied by caspase-3 protease activity but not by caspase-1 protease activity. LPS potentiated butyric acid-induced PBMC apoptosis in a dose-dependent manner. Flow-cytometric analysis revealed that LPS increased the proportion of sub-G1 cells and the number of late-stage apoptotic cells induced by butyric acid. Annexin V binding experiments with fractionated subpopulations of PBMC in flow cytometory revealed that LPS accelerated the butyric acid-induced CD3(+)-T-cell apoptosis followed by similar levels of both CD4(+)- and CD8(+)-T-cell apoptosis. The addition of LPS to PBMC cultures did not cause DNA fragmentation, suggesting that LPS was unable to induce PBMC apoptosis directly. These data suggest that LPS, in combination with butyric acid, potentiates CD3(+) PBMC T-cell apoptosis and plays a role in the apoptotic depletion of CD4(+) and CD8(+) cells.

Adult↗
PubMed1999

Human umbilical vein endothelial cells support interleukin-3- and interleukin-5-induced eosinophil differentiation from cord blood CD34+ cells.

BACKGROUND: Human umbilical vein endothelial cells (HUVEC) are an important source of hematopoietic cytokines, and interleukin-3 (IL-3)- and IL-5-induced eosinophil differentiation from CD34+ cells has been observed. To show the supportive effects of endothelial cells on eosinophil differentiation, we examined the effects of cocultured HUVEC on IL-3 and IL-5-induced eosinophil differentiation from human umbilical cord blood CD34+ cells. METHODS: CD34+ cells were obtained from the heparinized umbilical vein blood of 10 volunteers using a CD34-conjugated magnetic bead positive direct selection procedure. With HUVEC in Transwell, CD34+ cells were then cultured for 14-28 days. In neutralizing experiments on HUVEC-derived cytokines, antibodies to both stem cell factor (SCF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) were added to the cell cultures. RESULTS: Cocultured HUVEC upregulated IL-3 and IL-5-induced eosinophil differentiation from CD34+ cells on day 28 of culture by 75.0%. The eosinophilopoietic effect of HUVEC was significantly only when the cells were present in the culture from day 15 to day 28. Addition of anti-SCF antibody or anti-GM-CSF monoclonal antibody to the culture significantly suppressed HUVEC-combined IL-3- and IL-5-induced eosinophil differentiation on day 28 of culture by 49.2 and 55.0%, respectively. CONCLUSIONS: These results indicate that several cytokines including GM-CSF and SCF from HUVEC promote IL-3- and IL-5-induced eosinophil differentiation from CD34+ cells.

Antigens, CD34↗
PubMed1999

Gadolinium-DTPA-enhanced magnetic resonance imaging and functional outcome in patients with acute myocardial infarction.

This study was designed to test the hypothesis that Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance images (MRI) reflect the severity of ischemic injury during the acute and chronic phases of myocardial infarction (MI). Twenty-nine patients with their first acute MI underwent Gd-DTPA-enhanced MRI in the first week (4.2+/-0.3 days) and at 1 month after onset. Pairs of left ventriculograms were compared with Gd-DTPA-enhanced magnetic resonance images, classified into 3 pattern groups: hyper-enhancement, with and without a central hypo-enhanced region (P1 and P2, respectively), and non-enhancement (P3). In the acute phase of MI, P1 was found in 10, P2 in 11, and P3 in 8 patients. One month later, the image pattern had changed from P1 to P2 in a single patient, from P2 to P3 in 4 patients, and had remained identical in the others. Patients with P3 showed improvement of anterior wall motion in the 1-month follow-up study, and had higher TIMI flow grades and lower peak creatine kinase values than those without recovery. Thus, Gd-DTPA-enhanced magnetic resonance images, closely reflecting the severity of myocardial injury, are useful in predicting myocardial functional recovery after MI.

Adult↗
PubMed1999

5-Hydroxy-4-oxo-L-norvaline depletes intracellular glutathione: a new modulator of drug resistance.

To search for compounds that reverse the drug resistance induced by glutathione (GSH), an original screening system to detect intracellular GSH depleters was established. Among 8843 microbes derived from the soil samples tested, the extracts of two Streptomyces species named KS6701 and KS8846, lowered the intracellular GSH level of Saccharomyces cerevisiae 5 x 47. From both the microbes, 5-hydroxy-4-oxo-L-norvaline (HON) was isolated as the active compound. At a concentration of 50-100 micrograms/ml, HON also decreased the GSH/protein level of the human ovarian tumor cell line, 2008/C13*5.25 and reversed its resistance to cisplatin. We also investigated the mechanism of the depletion. HON had little effect on gamma-glutamylcysteine synthetase (gamma-GCS) or glutathione synthetase, but HON decreased the quantity of thiol substances when it was spontaneously reacted with them. This suggested that the GSH depletion by HON occurred through a mechanism different from that of buthionine sulfoximine, a selective gamma-GCS inhibitor.

Aminolevulinic Acid↗
PubMed1999

Role of T cell subset on the immunosuppression induced by Actinobacillus actinomycetemcomitans.

Purified splenic T cells from C3H/HeN mice primed with sonic extract (SE) from Actinobacillus actinomycetemcomitans were adoptively transferred to syngeneic mice with sheep red blood cell (SRBC). The transfer of splenic T cells from mice, primed with SE for 8 days, resulted in the dose-dependent inhibition of IgM anti-SRBC plaque forming cells (PFC) compared with normal and BSA-primed splenic T cells. Furthermore, the transfer of cells from mice primed with 200 micrograms of SE for 8 days to syngeneic mice caused the highest inhibition. Immunosuppression did not depend on the B cell population in spleen from donor mice primed with SE. Splenic T cells from SE-treated mice could suppress the T cell-dependent proliferative responses of co-cultured normal spleen cells in vitro. Analysis of T cell subsets of spleen cells from mice treated with immunosuppressive factor (ISF) showed that the suppressor cell is susceptible to treatment with anti-CD8 and complement (C). SE-sensitized suppressor T cells also suppressed the secondary IgG anti-SRBC-PFC response after immunization with SRBC in vivo depending on sensitized periods induced by ISF. Treatment of T cells from mice which primed with ISF for 8 days, with goat anti-mouse CD8 antibody and C abrogated their suppressive effects, and secondary IgG response occurred. These results indicate that the adoptive transfer of SE-induced T cells, which increased suppressor function, caused the perfect blocking of the immunoresponse, allowing promotion of secondary infection.

Adoptive Transfer↗