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Biomedical subjects

K Ochiai

Publications and source records attributed to K Ochiai.

At least 19 recordsLinked to original sources
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

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

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↗
PubMed1998

Bronchiolar-alveolar carcinoma in a cow.

Bronchiolar-alveolar carcinoma was observed in the lung of an 8-year-old Holstein cow. Grossly, the lung contained multiple tumour masses, which were solid, yellowish-white in colour, and firm in consistency. These tumours also occurred in the liver, pancreas, uterus and lymph nodes in the thoracic, abdominal and pelvic cavities. Histologically, the masses were composed of abundant fibrous stroma and proliferating atypical cuboidal epithelial cells, occasionally forming glandular structures. Electron microscopy revealed that the neoplastic cells had microvilli and lamellar bodies in the cytoplasm, suggesting that they originated from immature respiratory epithelial cells differentiating towards either Clara cells or type II pneumocytes.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Characterization and expression of the Mx1 gene in wild mouse species.

The mouse Mx1 gene encodes an interferon (IFN)-inducible nuclear protein and confers resistance to influenza virus infection. The standard laboratory mouse strains all carry the Mx1- allele and are susceptible to influenza virus. In this study, several mouse strains established from wild mice were tested to determine their Mx1+ or Mx1- allele status with polymerase chain reaction-restriction fragment length variation (PCR-RFLV), sequence analysis, reverse transcription (RT)-PCR, and immunofluorescence staining. All of the mouse strains originating from wild mice were found uniformly to carry the Mx1+ allele. Therefore, it is conceivable that the Mx1+ allele in wild populations serves a function against some pathogens related to orthomyxoviruses. The PCR-RFLV and sequence analysis allowed us to classify the Mx1+ alleles of the laboratory and wild-origin mouse strains into distinct classes. RT-PCR and immunofluorescence staining demonstrated that the Mx1 transcripts and proteins were induced by IFN-alpha/beta in macrophages from wild mouse species.

Animals↗
PubMed1998

Purification of immunosuppressive factor from Capnocytophaga ochracea.

Capnocytophaga, one of the genera of oral bacteria, has been implicated in the pathogenesis of several diseases, including endocarditis, septicaemia and disorders of the oral cavity such as abscesses and periodontal disease. This study examined sonic extracts (SE) of Capnocytophaga strains for their ability to alter lymphocyte function. The SE of tested Capnocytophaga caused dose-dependent suppression of spleen cells in response to mitogen. This suppressive effect was heat-labile and sensitive to the proteolytic enzyme pronase E. The suppressive factor (SF) was purified from SE of C. ochrasea by a combination of ultrogel-AcA34, high-pressure liquid DEAE ion-exchange chromatography and hydroxyapatite columns, which revealed a single band of 14 kDa by SDS-PAGE. Rabbit anti-serum against the purified SF inhibited the immunosuppression induced by SE of C. ochracea with the recovery of lymphocyte proliferation.

Animals↗
PubMed1998

Volatile fatty acid, metabolic by-product of periodontopathic bacteria, induces apoptosis in WEHI 231 and RAJI B lymphoma cells and splenic B cells.

The ability of butyric acid, an extracellular metabolite from periodontopathic bacteria, to induce apoptosis in murine WEHI 231 cells, splenic B cells, and human RAJI cells was examined. The culture filtrate of Porphyromonas gingivalis, Prevotella loescheii, and Fusobacterium nucleatum, which contains high a percentage of butyric acid, induced DNA fragmentation in WEHI 231 cells. Volatile fatty acid, especially butyric acid, significantly suppressed B-cell viability in a concentration-dependent fashion. The DNA fragmentation assay indicated that butyric acid rapidly induced apoptosis in WEHI 231 cells (with 1.25 mM butyric acid and 6 h after treatment), splenic B cells (with 1.25 mM butyric acid), and RAJI cells (with 2.5 mM butyric acid). Incubation of WEHI 231 cells with butyric acid for 16 h resulted in the typical ladder pattern of DNA fragmentation and the apoptoic change such as chromatin condensation and hypodiploid nuclei. Cell cycle analysis implied that butyric acid arrested the cells at the G1 phase. The inhibitory assay suggested that butyric acid-induced apoptosis of WEHI 231 and splenic B cells was inhibited by W-7, a calmodulin inhibitor. These results suggest that calmodulin-dependent regulation is involved in the signal transduction pathway of butyric acid.

Animals↗
PubMed1998

Heterogeneous expression of tumor necrosis factor-alpha receptors I and II on human peripheral eosinophils.

BACKGROUND: Expression of the tumor necrosis factor-alpha receptor by human eosinophils has not been determined. We examined the surface expression and mRNA for tumor necrosis factor-alpha receptors I and II (TNF-alphaRI and TNF-alphaRII) on peripheral eosinophils. METHODS: Eosinophils were obtained from 17 asthma patients and 3 healthy volunteers. Flow cytometry was used to examine receptor expression, and the reverse transcriptase-polymerase chain reaction was used to examine receptor mRNA expression. RESULTS: Flow cytometry revealed that 16 out of 20 subjects had eosinophils expressing TNF-alphaRI and 18 subjects had eosinophils expressing TNF-alphaRII. All eosinophils expressed at least one receptor. The mRNA for TNF-alphaRII was detected in all eosinophils examined, but the signals for TNF-alphaRI mRNA were only found in cells expressing this receptor. CONCLUSIONS: Human peripheral eosinophils show heterogeneous expression of TNF-alphaRI and TNF-alphaRII.

Adolescent↗
PubMed1998

Interferon-gamma receptor beta-chain expression and formation of alpha- and beta-chain complexes after receptor conjugation on human peripheral eosinophils.

BACKGROUND: It has been unclear whether or not the interferon-gamma receptor (IFN-gammaR) on human peripheral eosinophils is completely functional. Accordingly, we examined the expression of IFN-gammaR alpha- and beta-chains and the association of the two chains after binding of IFN-gamma to the receptor. METHODS: Peripheral blood eosinophils were obtained from 8 patients (bronchial asthma, n=6, and hypereosinophilic syndrome, n=2), and expression of the alpha- and beta-chain was investigated by flow cytometry with specific antibodies. Expression of mRNA for the alpha- and beta-subunits was also investigated by the reverse transcriptase-polymerase chain reaction. RESULTS: Eosinophils from all the patients were positive for both the alpha- and beta-chains by flow cytometry. In addition, mRNA for both chains was detected by the polymerase chain reaction. Furthermore, coprecipitation of the alpha- and beta-chains was only found after eosinophil stimulation with IFN-gamma. CONCLUSIONS: Human peripheral eosinophils apparently express both the alpha- and beta-chains of the IFN-gammaR, and the two chains may only form the receptor complex after ligand binding.

Adolescent↗
PubMed1998

Expression of cell adhesion molecules in tubulointerstitial nephritis associated with Sjögren's syndrome.

The tissue distribution of cellular adhesion molecules (ICAM-1, ELAM-1, VCAM-1) was studied in specimens from six normal human kidneys and in six biopsies from kidneys with tubulointerstitial nephritis associated with Sjögren's syndrome. In addition, the expression of cellular adhesion molecules was examined both in four renal biopsies from cases of tubulointerstitial nephritis of diverse pathogenesis and in six lip biopsies from cases of Sjögren's syndrome. ICAM-1 was expressed on vascular endothelial cells in normal kidneys, in all specimens of tubulointerstitial nephritis and in salivary glands. On tubular epithelial cells, ICAM-1 appeared slightly in normal kidneys; otherwise tubular epithelial ICAM-1 was observed in and around the foci of cellular infiltration in all cases of tubulointerstitial nephritis. ELAM-1 and VCAM-1 were observed on the newly generated vessels in massive cellular infiltrates in some cases of tubulointerstitial nephritis associated with Sjögren's syndrome; by contrast, they were not seen in normal kidneys and in cases of tubulointerstitial nephritis of diverse pathogenesis. In the lip biopsies from salivary glands, ICAM-1 was observed on ductal epithelial cells in and around the foci of cellular infiltration, and ELAM-1 and VCAM-1 occasionally appeared on the newly generated vessels in massive cellular infiltrates. Chronic and progressive inflammation may be facilitated by such ELAM-1 and VCAM-1 expression on newly generated vessels. The adhesion molecules were thought to play a role in the pathogenesis of tubulointerstitial nephritis and sialoadenitis associated with Sjögren's syndrome. It was thus concluded that the same inflammatory process that took place in the salivary glands to induce the characteristic tissue change of Sjögren's syndrome likely was operative in the renal tubulointerstitial tissue as well.

Adolescent↗
PubMed1998

[Effect of 5'-DFUR used concurrently in radiotherapy and immunotherapy uterine cervical cancer--pilot study. Study of 5'-DFUR for Uterine Cervical Cancer].

We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR and SPG for patients with uterine cervical cancer, which was regarded as suitable for cases of radiotherapy. The patients were randomly allocated into group A (5'-DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or IV a with histologically diagnosed primary squamous cell carcinoma of uterine cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy-evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%-97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety-evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No significant difference in efficacy and safety was observed between the two treatment groups. These results suggested that the combination therapy of radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness must be confirmed for advanced squamous cell carcinoma of uterine cervix. To confirm dose dependency of 5'-DFUR, it seems further consideration with more patients is needed.

Adjuvants, Immunologic↗
PubMed1998

[A clinical phase III trial of MR-20 in gynecologic nephrotoxicity of cisplatin--a comparative study in MR-20-treated and control patients on cyclical intermittent cisplatin treatment].

UNLABELLED: MR-20 was administered to 52 gynecological cancer patients who presented with nephrotoxicity from cisplatin (CDDP) treatment over 3 courses at 33 institutions throughout Japan during the period from July 1992 through March 1994, in order to study its suppressive effect on the nephrotoxicity as well as its safety; and the results are reported in this paper. METHODS: The efficacy and usefulness of MR-20 were studied by a MR-20-untreated-controlled, non-double-blind manner. An efficacy rate of 72.0% was achieved in the MR-20 group, and 37.0% in the untreated group: MR-20 was significantly more effective for nephrotoxicity than the MR-20-untreated group. Ccr was prevented from significant variations in the MR-20 group, compared with the untreated group. It was considered that MR-20 is a safe drug, and that it is useful in suppressing the nephrotoxicity of CDDP treatment.

Adult↗
PubMed1998

[Treatment of gynecologic cancer in elderly patients].

Due to the increasingly elderly population and prolonged life span of women in Japan, population of women older than 75 years of age has become 7.3% of all female population in 1995. According to this change, elderly patients with gynecologic malignancies, such as cervical cancer, endometrial cancer and ovarian cancer have increased markedly. Those patients tend to have progressed disease and therefore treatments should be less invasive and tailored based upon individual conditions to maintain their quality of life.

Aged↗
PubMed1998

[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group].

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.

Administration, Oral↗
PubMed1997

Relationship between progressive microvascular damage and intramyocardial hemorrhage in patients with reperfused anterior myocardial infarction: myocardial contrast echocardiographic study.

BACKGROUND: Recent studies indicated that ischemic microvascular damage may be reversible or progressive after coronary reflow. Intramyocardial hemorrhage is a phenomenon that reflects severe microvascular injury. We examined the relationship between temporal changes in microvascular perfusion patterns detected by myocardial contrast echocardiography (MCE) and intramyocardial hemorrhage detected by magnetic resonance imaging (MRI) in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 24 patients with anterior AMI. All patients underwent MCE shortly after reflow and in the chronic stage (a mean of 31 days after reflow). Wall motion score (WMS) was determined as the sum of 16 segmental scores (dyskinetic/akinetic=3 to normal=0) at days 1 and 31. Gradient-echo acquisition and gadolinium-DTPA-enhanced spin-echo MRI were performed within 10 days after reflow. In MCE shortly after reflow, 16 patients (67%) showed contrast enhancement and the other 8 patients (33%) showed a sizable contrast defect. In the chronic stage, a persistent contrast defect was observed in 7 of 8 patients with a contrast defect shortly after reflow. Consistent contrast enhancement was observed in 12 of 16 patients (75%) with contrast enhancement shortly after reflow, indicating that a contrast defect newly appeared in 4 patients (25%). Intramyocardial hemorrhage was detected in 9 patients (38%): 5 of 7 patients with a persistent contrast defect and in all 4 patients with a new appearance of a contrast defect during the chronic stage. The patients without hemorrhage showed a significant improvement in WMS compared with patients with hemorrhage at day 31 (5+/-5 versus 19+/-6, P<.0005). CONCLUSIONS: These results suggest that irreversible microvascular damage to the ischemic myocardium may cause intramyocardial hemorrhage after reflow, associated with impaired recovery of left ventricular function. Contrast enhancement within the risk area shortly after reflow does not necessarily indicate long-term microvascular salvage.

Aged↗
PubMed1997

Human peripheral eosinophils express functional interferon-gamma receptors (IFN-gammaR).

In order to determine whether or not IFN-gammaR is associated with regulatory mechanisms on human eosinophil function, we examined the expression of functional IFN-gammaR on human peripheral eosinophils. In this study, peripheral blood eosinophils were obtained from seven normal controls and 12 patients (bronchial asthma, n = 9, and hypereosinophilic syndrome (HES), n = 3), and the purity of eosinophils was 97.11 +/- 2.31%, n = 19. We first showed that anti-IFN-gammaR alpha-chain MoAb reacted with all tested eosinophils of both normal controls and patients by flow cytometry analysis. We also showed expression of mRNA for the alpha-chain of IFN-gammaR in all purified eosinophils of six individuals. Further, to characterize IFN-gammaR on eosinophils, we did binding experiments with 125I-IFN-gamma on purified peripheral eosinophils. The linear Scatchard plot indicated a single type of high-affinity binding sites (dissociation constant (Kd) = 3.89-4.95 x 10(-10) M, numbers of binding sites = 183-233/cell, n = 3). To determine whether IFN-gammaR on eosinophils is functional, we examined surface eosinophilic cationic protein (ECP) and CD69 induction after IFN-gammaR ligation with recombinant human IFN-gamma (rhIFN-gamma) on eosinophils by flow cytometry. rhIFN-gamma stimulation significantly induced both ECP and CD69 expression on the 2-18 h-cultured eosinophils in a dose-dependent manner. Further, the effects of rhIFN-gamma stimulation were significantly blocked by both a neutralizing anti-IFN-gamma MoAb and a blocking anti-IFN-gammaR MoAb. These results suggest that human peripheral eosinophils express functional IFN-gammaR.

Adolescent↗
PubMed1997

IL-5 but not interferon-gamma (IFN-gamma) inhibits eosinophil apoptosis by up-regulation of bcl-2 expression.

In order to determine regulatory mechanisms of eosinophil apoptosis, we examined the effect of recombinant IL-5 and interferon-gamma (IFN-gamma) on eosinophil apoptosis and bcl-2 expression. rhIL-5 (2.5 ng/ml) significantly inhibited eosinophil apoptosis in 96 h in vitro culture compared with medium only-cultured eosinophils (89.4 +/- 3.6% versus 31.3 +/- 12.2% (mean +/- s.d.); n = 7, P < 0.05). Further, rhIL-5 significantly increased bcl-2 protein and mRNA expression on cultured eosinophils. A phosphorothioate antisense oligonucleotide targeted at the ATG translation initiation codon of bcl-2 (10(-5) M) could significantly block the supportive effect of rhIL-5 (0.25 ng/ml) for eosinophil survival compared with sense cDNA of bcl-2 on 96 h culture (inhibition rate 28.01 +/- 4.56% versus 0.07 +/- 1.73%; n = 4, P < 0.05). In contrast, rhIFN-gamma (100 U/ml) significantly inhibited eosinophil apoptosis on 96 h in vitro culture (72.7 +/- 10.5%; n = 7, P < 0.05), but did not significantly up-regulate bcl-2 protein and mRNA. These results indicate that IL-5 has inhibitory effects on eosinophil apoptosis by regulation of bcl-2 expression.

Apoptosis↗