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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 325 records · Page 18Linked to original sources
PubMed1996

Evaluation of myocardial viability with iodine-123-BMIPP in a canine model.

UNLABELLED: The tracer 123I-BMIPP was examined for its ability to reflect myocardial lipid metabolism. Studies in mice indicate that myocardial BMIPP uptake correlates with ATP content. Details, however, of myocardial accumulation in the ischemic period with either infarct or ischemia are not well documented. METHODS: Sixteen adult mongrel dogs were investigated. The occluded left anterior descending artery (LAD) alone was reperfused to make the ischemic area, and the first diagonal branch of the LAD was kept occluded to make the infarct area. Regional wall motion was evaluated by echocardiography in the short-axial view from the epicardium. Tissue blood flow was calculated using nonradioactive colored microspheres. Changes in blood glucose levels, lipid levels and lactate extraction were examined in blood collected from the aorta and great cardiac vein (GCV). The ATP concentration and BMIPP count were determined by high-performance liquid chromatography and gamma-counter, respectively. RESULTS: Two hours after reperfusion, blood flow decreased to 20% +/- 5% in the infarct area and 64% +/- 9% in the ischemic area (p < 0.05), despite comparable wall-motion reduction (32% +/- 5% and 42% +/- 12% in the infarct and ischemic areas, respectively). BMIPP content and ATP concentration showed parallel reduction: 40% +/- 7% and 75% +/- 4% (p < 0.05) of BMIPP and 32% +/- 9% and 69% +/- 7% (p < 0.05) of ATP in the infarct and ischemic areas, respectively. The nonesterified fatty acid extraction, defined as flow x ([artery] - [GCV]), decreased to 87% +/- 5.6% during occlusion and 75% +/- 20.1% 2 hr after reperfusion, as compared with the control value. CONCLUSION: BMIPP uptake correlated well with lipid metabolism and tissue ATP levels and may prove useful in differentiating myocardial infarction from ischemia in the acute phase of ischemic episodes.

Adenosine Triphosphate↗
PubMed1996

[Epidemiology of hepatocellular carcinoma].

Hepatocellular carcinoma (HCC), which constitutes the majority of primary liver cancer, is endemic to certain areas of the world. The incidence rate varies considerably from area to area, and the difference between Mozambique, South Africa, and northern Europe in the age group of 25 to 34 years is more than 500-fold in males. It now seems that the area along the Yangtse River to the north of Shanghai, China, has an incidence rate just as high as Mozambique. Such differences are due to the predominant etiologic factors such as aflatoxin B1, and hepatitis B and C virus infections. While the hepatitis B infection rate is decreasing among HCC patients, hepatitis C infection has been increasing in the population and in HCC patients in some countries, such as Japan, Italy and Spain. Regardless of the area, males are more prone to HCC than females, and this ratio is also changing with time in some countries because of the change in the relative proportion of hepatitis B and C among patients. The known etiologic factors, such as hepatitis B, hepatitis C, Budd-Chiari syndrome and chemical carcinogens, are briefly reviewed.

Carcinoma, Hepatocellular↗
PubMed1996

Effects of intracerebroventricular administration of 6-hydroxydopamine on ouabain-like immunoreactivity in plasma and the hypothalamo-pituitary axis in rats.

OBJECTIVE: To examine the role of central mechanisms on the production and release of an ouabain-like factor, the effects of intracerebroventricular injections of 6-hydroxydopamine on the tissue content and on the plasma level of the ouabain-like factor were determined in rats. METHODS: The vehicle (0.1% ascorbic acid in 0.9% saline) and 6- hydroxydopamine (250 micrograms/rat) were injected into the left lateral ventricle in ether-anaesthetized Wistar rats. Hypothalamus, pituitary, adrenal and venous blood was sampled 24h and 7 days later. The procedure was repeated using another rat group 7 days later. Characteristics of immunoreactive ouabain-like factor were determined by a combination of high-performance liquid chromatography and a highly sensitive enzyme-linked immunosorbent assay for ouabain. The level of the ouabain-like factor in these tissues and in plasma extracts measured by the enzyme-linked immunosorbent assay was compared between the two groups receiving 6-hydroxydopamine and the vehicle. RESULTS: Twenty-four hours after the intracerebroventricular injections of 6-hydroxydopamine, the ouabain-like factor level in the pituitary, hypothalamus and plasma had decreased significantly, whereas the ouabain-like factor level in the adrenal had not changed. The content of noradrenaline in the hypothalamus was also decreased markedly 7 days later and the content of ouabain-like factor in the pituitary remained low. On liquid chromatography the elution pattern of the ouabain-like factor in plasma and in tissue extracts coincided with that of authentic ouabain. CONCLUSIONS: Intracerebroventricular treatments with 6-hydroxydopamine elicited decreases in ouabain-like factor contents in the pituitary, the hypothalamus and the plasma. These results suggest that the production and release of ouabain-like factor are closely associated with the brain, particularly the hypothalamus-pituitary axis, and that noradrenergic or dopaminergic neurons, or both, play a key role in this mechanism.

Animals↗
PubMed1996

[Usefulness of continuous arterial infusion chemotherapy for post operative multiple recurrence and residual hepatocellular carcinoma].

Twenty five patients with postoperative multiple recurrence and residual hepatocellular carcinoma received continuous arterial infusion of CDDP and 5-FU via implanted reservoir. For the next five days, 10 mg/body of CDDP and 250 mg/body of 5-FU using arterial infusion were administered. It was discontinued for two days as one course, and 4 courses were basally administered. The efficacy rate was 60%, and there were 7 (28%) CR (complete response) cases. The survival rate was 76.0% for 1 year and 36.5% for 3 years, which is a favorable result considering their advanced stage. Thus, this treatment seemed to be effective for multiple hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Study of hepatic arterial chemoinfusion with continuous CDDP, 5-FU low dose administration for advanced gallbladder cancer].

Eight unresectable cases of gallbladder cancer underwent hepatic-artery infusion (HAI) with a consequent combination of cisplatin (CDDP) and 5-fluorouracil (5-FU) administration at a continuous low dose. Five cases (62.5%) showed a partial response (PR). Median survival time was 481.9 days. Cytoreductive surgery was performed in three patients of PR. One case has been disease free and alive over 52 months postoperatively. Gallbladder cancer is well known as a chemoresistant cancer, whereas the higher response rate and the longer survival were achieved with HAI. These results suggested CDDP, 5-FU HAI is a useful chemotherapy for advanced gallbladder cancer, and it is also worthwhile to introduce the preoperative down-staging for consequent cytoreduction surgery.

Adult↗
PubMed1996

[Evaluation of the factor XIIa assay kit].

The assay for activated coagulation factors has recently been considered to be a useful tool for detecting hypercoagulable state. Measurement of activated factor XI and alpha 1 antitrypsin complex developed by us is the only one measure for detecting contact phase hypercoagulation. The ACTIVATED FACTOR XII kit (Shield Diagnostics) has recently been commercially available, and the reference range was reported in the instruction manual. However, because the recovery rate of purified factor XIIa (XIIa) in normal pooled plasma by this assay kit was strikingly decreased, the effects of inhibitors in plasma, such as low molecular weight serine proteinase inhibitor (diisopropyl fluoro-phosphate, DFP), the specific inhibitor for XIIa (corn trypsin inhibitor, CTI), the main inhibitor for XIIa (C1 inhibitor, C1I) were examined. These three inhibitors and XIIa were incubated for 18 hours, then the XIIa levels of these complexes and the recovery rate in the normal pooled plasma were assayed by this assay kit. The recovery ratios in the normal pooled plasma were; DFP-XIIa 82%, CTI-XIIa 63%, and C1I-XIIa 0%, XIIa without inhibitor 7%. These results suggest that this XIIa kit does not reflect the levels of complexed form of XIIa and inhibitors in plasma samples.

Adult↗
PubMed1996

Metabolic fate of iodine-123-BMIPP in canine myocardium after administration of etomoxir.

UNLABELLED: To clarify the metabolic fate of 123I-(-p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in dysfunctional myocardium, a comparison between normal dogs and those with etomoxir administration was studied using an open-chest canine model. METHODS: Using open-chested dogs under anesthesia, we created a system to release all the blood in the great cardiac vein outside without recirculation, if necessary. Iodine-123-BMIPP was directly injected into the left anterior descending artery, its extraction, retention and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using a high-performance liquid chromatography. Moreover, these factors were compared between normal dogs and those pretreated with etomoxir, that creates a condition similar to ischemia. RESULTS: Although rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, early washout (8 min) of radioactivity significantly increased (49.6% +/- 13.3%-->70.5% +/- 10.7%, p < 0.05) with etomoxir. The levels of the full metabolite formed by complete oxidation of BMIPP decreased significantly with etomoxir (21.4% +/- 10.9%-->5.5% +/- 3.5%, p < 0.01). In addition, back diffusion of BMIPP increased (25.1% +/- 8.0%-->41.9% +/- 12.0%, p < 0.05) in the etomoxir-treated animals without affecting the levels of alpha-oxidation metabolite and the intermediate metabolites. CONCLUSION: BMIPP is very sensitive to etomoxir and is suitable for assessing mitochondrial dysfunction. Iodine-123-BMIPP might be a promising radiopharmaceutical for the evaluation of ischemic heart disease, cardiomyopathy and mitochondrial encephalomyopathy.

Animals↗
PubMed1996

Metabolism and kinetics of iodine-123-BMIPP in canine myocardium.

UNLABELLED: The kinetics and metabolic fate of 123I-15-(p-iodophenyl)-3-(R,S)- methylpentadecanoic acid (BMIPP) in canine myocardium were studied in an open-chest dog model. METHODS: After left anterior descending artery injection of BMIPP, blood samples were collected from the corresponding great coronary vein (V) and femoral artery (A). On the basis of the A-V radioactivity difference as well as the HPLC elution profile at various time points, myocardial extraction, retention and metabolism of BMIPP were evaluated. RESULTS: BMIPP was instantly extracted from the plasma into the myocardium (74% of the injected dose) and was then retained (65.3%). Washout of the retained radioactivity was low (8.7%) and most of the washout was as alpha- and beta-oxidation metabolites (2.3 + 2.9 + 1.4%), with little loss of BMIPP itself (2.1 %). CONCLUSION: BMIPP is suitable for static SPECT imaging of the myocardium, and its slow washout appears to be due to metabolism through alpha- and beta-oxidation.

Animals↗
PubMed1996

Inhibitory effects of funoran on the adherence and colonization of oral bacteria.

Funoran, a sulfated polysaccharide extracted from the seaweed Gloiopeltis furcata, strongly inhibited the adsorption of mutans streptococci to saliva-coated hydroxyapatite (S-HA) used as an experimental pellicle and strongly desorbed cariogenic mutans streptococci pre-adsorbed to S-HA. Colonization inhibition and anticariogenic effects of funoran were also investigated in experimental rats. The colonization of Streptococcus cricetus E49 inoculated on the molar teeth of experimental rats administered funoran was less frequent than that in a funoran-free group. The mean buccal and lingual, sulcal, and total caries scores of rat groups administered funoran were significantly lower than those of the funoran-free group. The inhibitory effect of funoran on periodontopathic bacterial attachment was studied in vitro. Funoran strongly inhibited the adsorption of Porphyromonas gingivalis, Fusobacterium nucleatum, and actinomyces species to S-HA and collagen-coated hydroxyapatite (Co-HA) and apparently inhibited their attachment to the human gingival fibroblast Gin-1 cell line. The present study indicates that funoran inhibits colonization by cariogenic and periodontopathic bacteria and excludes them from human oral cavity.

Actinomyces viscosus↗
PubMed1995

CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells.

The Philadelphia chromosome translocation generates a chimeric oncogene, BCR/ABL, which causes chronic myelogenous leukemia (CML). In primary neutrophils from patients with CML, the major novel tyrosine-phosphorylated protein is CRKL, an SH2-SH3-SH3 linker protein which has an overall homology of 60% to CRK, the human homologue of the v-crk oncogene product. Anti-CRKL immunoprecipitates from CML cells, but not normal cells, were found to contain p210BCR/ABL and c-ABL. Several other phosphoproteins were also detected in anti-CRKL immunoprecipitates, one of which has been identified as paxillin, a 68-kDa focal adhesion protein which we have previously shown to be phosphorylated by p210BCR/ABL. Using GST-CRKL fusion proteins, the SH3 domains of CRKL were found to bind c-ABL and p210BCR/ABL, while the SH2 domain of CRKL bound to paxillin, suggesting that CRKL could physically link p210BCR/ABL to paxillin. Paxillin contains three tyrosines in Tyr-X-X-Pro (Y-X-X-P) motifs consistent with amino acid sequences predicted to be optimal for binding to the CRKL-SH2 domain (at positions Tyr-31, Tyr-118, and Tyr-181). Each of these tyrosine residues was mutated to a phenylalanine residue, and in vitro binding assays indicated that paxillin tyrosines at positions 31 and 118, but not 181, are likely to be involved in CRKL-SH2 binding. These results suggest that the p210BCR/ABL oncogene may be physically linked to the focal adhesion-associated protein paxillin in hematopoietic cells by CRKL. This interaction could contribute to the known adhesive defects of CML cells.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Identification of a chromosomally encoded kanamycin acetylase in Porphyromonas gingivalis.

Sonic extracts from the test strains of Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens were tested for the ability to inactivate kanamycin sulfate in the presence of ATP or acetyl coenzyme A (acetyl-CoA). Residual kanamycin activity was determined by a bio-assay using Escherichia coli JM109 as the assay organism. Sonic extracts of all test strains of P. gingivalis inactivated kanamycin. All strains tested in this study required the presence of acetyl-CoA for inactivation, indicating that inactivation was by acetylation. The gene of a kanamycin-inactivating protein from P. gingivalis 16-1 was cloned into E. coli utilizing the plasmid vector PTZ18R. The resultant kanamycin-resistant clone, harboring plasmid pPG16 with a P. gingivalis insert, expressed a kanamycin-inactivating activity, which was enhanced by the addition of acetyl-CoA, confirming that the kanamycin was inactivated by acetylation. Southern blot analysis indicates that the gene was conserved among all P. gingivalis strains tested.

Acetylation↗
PubMed1995

An antiserum to a synthetic fimbrial peptide of Actinobacillus actinomycetemcomitans blocked adhesion of the microorganism.

The purpose of this study is to certify the importance of the fimbriae as an attachment factor of Actinobacillus actinomycetemcomitans, a human periodontopathic bacterium, and the significance of anti-fimbrial antibody function as an attachment inhibitor. Fimbrial antigen was prepared from the A. actinomycetemcomitans 310-a strain. Oligopeptides were synthesized according to the amino acid sequence of the fimbrial protein. The peptide antigen was conjugated with branched lysine polymer resin beads. The peptide antigen was suspended in PBS emulsified with incomplete Freund's adjuvant and used to immunize rabbits. A rabbit antiserum reacted with an approximately 54 kDa protein of the fimbriae protein from A. actinomycetemcomitans 310-a and with those of other fimbriated strains. This antiserum strongly inhibited the attachment of fimbriated A. actinomycetemcomitans strains to saliva-coated hydroxyapatite beads, buccal epithelial cells, and a fibroblast cell line, Gin-1. Such a synthetic fimbrial peptide antigen may be effective in inducing antibodies which inhibit adhesion and subsequent colonization by A. actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans↗
PubMed1995

Multi-enzyme reference material from established human cell lines and human sources.

A multi-enzyme reference material was prepared from seven enzymes of asparatate aminotransferase (AST, EC 2.6.1.1), alanine aminotransferase (ALT, EC 2.6.1.2), alkaline phosphatase (ALP, EC 3.1.3.1), lactate dehydrogenase (LD, EC 1.1.1.27), creatine kinase (CK, EC 2.7.2.2), gamma-glutamyltranspeptidase (gamma-GT, EC 2.3.2.2) and amylase (AMY, EC 3.2.1.1) which were purified from human sources including established human cell lines. The enzymatic properties of the material closely resembled those of human serum. In lyophilized form the preparation was stable for at least 200 days when stored at 40 degrees C. Intermethod comparisons of the enzyme activities in 80 clinical specimens were done by correcting the mean values with calibration constants for different assay methods resulting from use of a human serum, the multi-enzyme reference and a commercial control serum. The results from the comparison for the six enzymes of AST, ALT, LD, CK, gamma-GT and AMY in use of the multi-enzyme reference were almost the same as those with use of a human serum as a calibrator, but were not satisfactory for ALP. Even though further search for more reliable material for ALP is required the multi-enzyme reference material can be used for standardization in clinical chemistry.

Alanine Transaminase↗
PubMed1995

Augmented production of tumor necrosis factor-alpha in obese mice.

Non-insulin-dependent diabetes mellitus develops in obesity. The insulin resistance of this disease may be mediated by tumor necrosis factor-alpha (TNF-alpha). In particular, the TNF-alpha derived from adipose tissues might be involved in the induction of peripheral insulin resistance in rodent models of obesity. In general, monocytes/macrophages have been considered as the major source of TNF-alpha. This study was designed to examine the potential production of TNF-alpha from monocyte/macrophages in obese mice. In obese (ob/ob) and obese diabetic (db/db) mice, both of which are known to have severe insulin resistance, unstimulated serum bioactivity of TNF-alpha was significantly higher than that in lean control mice. Spontaneous TNF-alpha mRNA expression in splenic macrophages was also enhanced in obese mice, but not in monosodium-L-glutamate (MST)-induced obese mice which have no insulin resistance. In addition, both ob/ob and db/db mice produce more TNF-alpha than lean mice upon in vivo lipopolysaccharide (LPS) stimulation. The LPS-induced increase in serum TNF-alpha activity was not observed in MSG-induced obese mice. Taken together, it is postulated that TNF-alpha produced by monocytes/macrophages may also play an important role in the genesis of insulin resistance in obesity. Further study is needed to reveal the mechanism of enhanced TNF-alpha production in obese states and its possible etiologic relevance to obesity.

Animals↗
PubMed1995

A macromolecular multicomponent peptide vaccine prepared using the glutaraldehyde conjugation method with strong immunogenicity for HIV-1.

The immunogenicity of a newly constructed macromolecular multicomponent peptide vaccine candidate against human immunodeficiency virus type 1 (HIV-1) was compared with that of previously reported vaccine candidates. This vaccine candidate is composed of a macromolecular multicomponent peptide complex consisting of three V3 region peptides, one Gag region peptide, and CD4-binding site peptide and was constructed using the multiple-antigen peptide and glutaraldehyde methods. Sera from rabbits immunized with this newly constructed vaccine showed strong antibody titers against each constituent peptide antigen. Furthermore, these antibodies exhibited strong neutralizing and antifusion activity toward HIV-1IIB, HIV-1MN, and fresh isolates from Japanese HIV-seropositive individuals. These results show that this new vaccine candidate has the capacity to induce strong, polyvalent immunogenicity and therefore may prove to be a powerful peptide vaccine against HIV-1 infection.

AIDS Vaccines↗
PubMed1995

Hypoaminotransferasemia in patients undergoing long-term hemodialysis: clinical and biochemical appraisal.

BACKGROUND & AIMS: It has been reported that patients with chronic renal failure have low serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as a result of vitamin B6 deficiency. Chronic hepatitis C is common among patients undergoing hemodialysis, and low aminotransferase levels cause diagnostic problems. The aim of this study was to determine the cause of hypoaminotransferasemia. METHODS: Serum levels of vitamin B6 and its coenzyme were reassessed in relation to AST and ALT levels in patients undergoing long-term hemodialysis using high-performance liquid chromatography. RESULTS: The mean (+/- SD) serum AST and ALT levels in 304 patients negative for hepatitis B surface antigen and anti-hepatitis C virus were 9.2 +/- 2.4 and 7.4 +/- 1.7 IU/L, respectively. In 556 normal adults, they were 22.7 +/- 5.4 and 18.0 +/- 4.0 IU/L, respectively (P < 0.001). Mean serum vitamin B6 and pyridoxal-5'-phosphate levels in patients undergoing dialysis were not reduced compared with the control, although occasionally patients had low levels. The AST and ALT assay reagents in Japan do not contain added pyridoxal-5'-phosphate; addition of pyridoxal-5'-phosphate (0.1 mmol/L) to the reagent significantly increased measurements to similar extents in both groups. CONCLUSIONS: Serum AST and ALT levels in patients undergoing dialysis are very low, but they are not a result of vitamin B6 deficiency. The upper normal limits of AST and ALT levels in patients undergoing dialysis should be reduced considerably, and these levels should be interpreted with caution in the diagnosis of liver disease.

Adult↗