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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 163 records · Page 9Linked to original sources
PubMed1999

The cytostome of Trypanosoma cruzi epimastigotes is associated with the flagellar complex.

Okuda, K., Esteva, M., Segura, E. L., and Bijovsky, A. T. 1999. The cytostome of Trypanosoma cruzi epimastigotes is associated with the flagellar complex. Experimental Parasitology 92, 223-231. Proliferative forms of Trypanosoma cruzi, amastigotes and epimastigotes, have a cytostome, a specialized structure formed by an invagination of the flagellar pocket's membrane surrounded by microtubules and frequently followed by a row of vesicles. All this assemblage penetrates deeply into the cytoplasm overpassing the nucleus. This structure, together with the flagellar pocket, appears to play an important role in the nutrition of the parasite. We demonstrated that the monoclonal antibody 2C4, made-up against isolated flagellar complex of T. cruzi epimastigotes, recognizes a protein doublet of 76 and 87 kDa in total epimastigotes homogenate. The 76-kDa polypeptide is enriched in the detergent-soluble fraction whereas the 87-kDa polypeptide is highly represented in the insoluble fractions and the purified flagella. Immuno-fluorescence assays show the antigen as a small spot at the flagellar pocket region. Immunogold labeling of ultrathin sections of epimastigote forms reveals gold particles at the opening of flagellar pocket, concentrated in the cytostome region. Immunocytochemistry of epimastigote whole-mount cytoskeletons reveals the labeling on an array of three to four microtubules that appears attached to flagellum, running in the direction of the nucleus. Ultrastructural observations have shown that the posterior region of isolated flagella, corresponding to the level of the flagellar pocket, possesses a microtubular structure compatible with that from the cytostome. The relationship between the cytostome, an endocytic organelle, and the flagellum is here described for the first time.

Animals↗
PubMed1999

Solitary splenic recurrence of ovarian cancer: case report and review of the literature.

We report a rare case of solitary recurrence of ovarian cancer in the spleen which developed 4 years after initial treatment. Only six cases have been reported in the literature and all were serous carcinoma. Our patient had a splenectomy without any complications but developed a liver metastasis 10 months after splenectomy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia.

HMG-CoA reductase inhibitors reduce serum total cholesterol concentrations and the risk of coronary heart disease in patients with hypercholesterolemia. Recently, it has been reported that patients with combined hyperlipidemia are also at risk of coronary heart disease. However, HMG-CoA reductase inhibitor therapy alone does not sufficiently reduce serum triglyceride concentrations. Epidemiological and clinical evidence has shown that fish oil can lower plasma lipid levels, especially triglycerides. Consequently, we investigated the effects of the combination of HMG-CoA reductase inhibitors and eicosapentaenoic acid, a major component of fish oil, on hyperlipidemia. We administered 900-1,800 mg/day of the ethyl ester of eicosapentaenoic acid to patients with hyperlipidemia who had been treated with HMG-CoA reductase inhibitors for 30 +/- 6 months (means +/- SE). Serum total cholesterol and triglyceride concentrations were significantly decreased 3 months after the administration of eicosapentaenoic acid (from 5.63 +/- 0.23 mmol/l to 5.02 +/- 0.20 mmol/l, P < 0.05; from 2.07 +/- 0.41 mmol/l to 1.08 +/- 0.17 mmol/l, P < 0.01, respectively). Serum high-density lipoprotein-cholesterol concentrations were significantly increased after the treatment (from 1.23 +/- 0.12 mmol/l to 1.34 +/- 0.13 mmol/l, P < 0.05). Plasma eicosapentaenoic acid concentrations and the ratio to arachidonic acid in plasma were also significantly increased 3 months after the treatment (from 101.9 +/- 8.1 mg/l to 181.8 +/- 23.9 mg/l, P < 0.001; from 0.640 +/- 0.075 to 1.211 +/- 0.170, P < 0.001, respectively). These results suggested that the combination therapy of HMG-CoA reductase inhibitors and eicosapentaenoic acid was effective for patients with hyperlipidemia.

Aged↗
PubMed1999

Intraosseous neurilemoma of the sternum.

Sternal benign bone tumor is uncommon. We report a very rare case of intraosseous neurilemoma in the sternum. A girl, 10 years of age, was diagnosed as having a sternal tumor. Computed tomographic scan disclosed a mushroom-shape tumor in the region from inside of the sternum to the ventral soft tissues. Surgical resection was performed. Histopathologic findings showed a typical neurilemoma with Antoni type A and B patterns. No recurrence has been found.

Bone Neoplasms↗
PubMed1999

A new direction in automated laboratory testing in Japan: five years of experience with total laboratory automation system management.

The introduction of integrated laboratory systems has proceeded rapidly in Japan in these 15 years, but they require large initial investment for installation and do not always succeed in reducing laboratory cost. We also experienced three major events that taught us that total laboratory systems are not always effective: these were an earthquake, a nerve gas attack, and an outbreak of food poisoning. Political changes in the national health care system in Japan have forced the cutting of expenses for laboratory testing. In this context, cost-effective laboratory testing has been considered, and many hospitals have replaced total laboratory systems with small laboratory systems. Our University Hospital introduced a mini-lab system consisting of compact instruments to increase laboratory efficiency, and we have begun point-of-care testing education for medical students. This combination enables rapid and convenient testing, and is responsive to the political changes in the Japanese health care system.

Automation↗
PubMed1999

Meniscal rasping for repair of meniscal tear in the avascular zone.

We examined experimentally whether a longitudinal tear in the avascular zone of a rabbit meniscus can be healed by meniscal rasping. A full-thickness longitudinal tear 5-mm long was artificially created in the avascular zone of the anterior segment of both medial menisci. Meniscal rasping was then done on the femoral surface of the right meniscus from the parameniscal synovium to the inner segment including the tear. The left meniscus was left without further treatment as control. Two to 4 weeks after surgery, the hypertrophic synovium was observed invading from the parameniscal region to the injured portion. Eight to 16 weeks after surgery, the tear was almost completely healed. In contrast, neither hypertrophy of the synovium covering the tear nor healing was induced in the control meniscus. The mechanical test showed that there was a significant difference in the tensile strength and the stiffness of the injured portion between the rasped meniscus and the control meniscus. Meniscal rasping is easy to do, is effective, and causes few adverse effects with menisci. This procedure may be a treatment option for clinical cases of meniscal tear in the avascular zone for which we have no effective and clinically applicable methods at present, although further investigation is needed before clinical application.

Animals↗
PubMed1999

Basic kinetics of 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in canine myocardium.

BMIPP is a radioiodinated fatty acid analogue used for myocardial single photon emission CT (SPECT) imaging based on high cardiac fatty acid metabolism. In normal dogs, 74% of the injected BMIPP was instantly extracted and was then retained in 65.3%. The washout of the retained radioactivity was low, and most of the washout was alpha- and beta-oxidation metabolites. ATP concentration plays an important role in the myocardial uptake and retention of BMIPP. The ATP-dependent BMIPP uptake at the TG pool was strongly regulated by etomoxir with modifying mitochondrial beta-oxidation and subsequent ATP production. Thus, myocardial viability was reflected on the BMIPP uptake in acute ischemia. In spite of insignificant changes in early extraction and retention. BMIPP back diffusion (r = -0.92) and full-oxidation metabolite (r = 0.78) were correlated with the severity of ischemia. Mismatched region of BMIPP with flow (Tl-201) showed decreased metabolic enzymes such as citrate synthase and 3-hydroxyacyl-CoA dehydrogenase. These data suggest that BMIPP would be feasible for detecting cellular energy state from lipid metabolism.

Animals↗
PubMed1999

Salivary immunoglobulin A production against a synthetic oligopeptide antigen of Actinobacillus actinomycetemcomitans fimbriae.

Actinobacillus actinomycetemcomitans is an important pathogen in human periodontal diseases. We attempted to produce effective antibodies against A. actinomycetemcomitans fimbrial antigen, which was shown to be an attachment factor. An oligopeptide based on the amino acid sequence of A. actinomycetemcomitans fimbriae was synthesized and conjugated with branched lysine polymer resin beads. Mice were immunized with the synthetic antigen together with one or more of Freund's incomplete adjuvant, the Ribi adjuvant system, liposomes, mouse interleukin 4 expression plasmids, and cholera toxin. After immunization, salivary immunoglobulin A (IgA) and serum IgG levels against the synthetic oligopeptide antigen were determined by enzyme-linked immunosorbent assay. The serum IgG responses against the fimbrial antigen were significantly higher in animals immunized intramuscularly with the Ribi adjuvant system. A high salivary IgA response to the fimbriae was induced by intranasal mucosal immunization with cholera toxin and mouse interleukin 4 expression plasmids.

Adjuvants, Immunologic↗
PubMed1999

Macrophage inflammatory protein-1alpha (MIP-1alpha) expression plasmid enhances DNA vaccine-induced immune response against HIV-1.

CD8+ cell-secreted CC-chemokines, MIP-1alpha, and MIP-beta have recently been identified as factors which suppress HIV. In this study we co-inoculated MIP-1alpha expression plasmid with a DNA vaccine constructed from HIV-1 pCMV160IIIB and pcREV, and evaluated the effect of the adjuvant on HIV-specific immune responses following intramuscular and intranasal immunization. The levels of both cytotoxic T lymphocyte (CTL) activity and DTH showed that HIV-specific cell-mediated immunity (CMI) was significantly enhanced by co-inoculation of the MIP-1alpha expression plasmid with the DNA vaccine compared with inoculation of the DNA vaccine alone. The HIV-specific serum IgG1/IgG2a ratio was significantly lowered when the plasmid was co-inoculated in both intramuscular and intranasal routes, suggesting a strong elicitation of the T helper (Th) 1-type response. When the MIP-1alpha expression plasmid was inoculated intramuscularly with the DNA vaccine, an infiltration of mononuclear cells was observed at the injection site. After intranasal administration, the level of mucosal secretory IgA antibody was markedly enhanced. These findings demonstrate that MIP-1alpha expression plasmid inoculated together with DNA vaccine acts as a strong adjuvant for eliciting Th1-derived immunity.

AIDS Vaccines↗
PubMed1999

Serum hyaluronan as a predictor of hepatic regeneration after hepatectomy in humans.

BACKGROUND: The capacity for hepatic regeneration after hepatectomy is important for allowing surgeons to determine the appropriate extent of resection. However, conventional preoperative liver function tests are unsatisfactory for estimating the post-operative regenerative capacity of the remnant liver. The aim of this study was to evaluate the relationship between preoperative serum hyaluronan and hepatic regeneration. METHODS: Preoperative serum hyaluronan levels and the hepatic regeneration rate were estimated in 49 patients using computerized tomographic volumetry. The hepatic fibrotic rate was calculated with non-tumorous tissues stained with Azan-Mallory. Immunolocalization of factor VIII-related antigen (FVIIIAg) was examined as a marker for hepatic sinusoidal capillarization. RESULTS: The serum hyaluronan level was significantly correlated with the hepatic regeneration rate (P < 0. 001). Patients with serum hyaluronan levels below 200 ng mL-1 exhibited a significant correlation between the hepatic regeneration rate and the hepatic fibrotic rate. However, patients with serum hyaluronan levels above 200 ng mL-1 did not demonstrate a distinct correlation. The hepatic regeneration rate of patients with FVIIIAg in the liver and serum hyaluronan levels above 200 ng mL-1 were very low compared with those without FVIIIAg (P < 0.001). Multiple regression analysis revealed that serum hyaluronan was a significant predictor of post-operative hepatic regeneration among several clinical variables (r = 0.857, R2 = 0.735). CONCLUSION: It has been suggested that hepatic regeneration is closely related to both hepatic fibrosis and hepatic sinusoidal capillarization. The serum hyaluronan level is regarded as a useful predictor for hepatic regeneration after hepatectomy.

Adult↗
PubMed1999

Contribution of mast cells to the T helper 2 response induced by simultaneous subcutaneous and oral immunization.

This work examines the contribution of mast cells to the synergistic enhancement of the T helper 2 (Th2) immune response elicited following simultaneous oral and subcutaneous (s.c.) immunization. The s.c. route induced a Th1-biased immune response, characterized by increased interferon-gamma (IFN-gamma) and immunoglobulin G2a (IgG2a) antibody production. In contrast, oral immunization stimulated a primarily Th2-type response in which interleukin-4 (IL-4) and IgG1 antibody production were dominant. Simultaneous immunization also triggered a Th2-biased response, the magnitude of which exceeded the additive effects of s.c. and oral immunization alone by greater than threefold. To analyse whether mast cells in gut-associated lymphoid tissue contributed to this synergistic response, mast cell-deficient mice WBB6F1-w/wv were studied. Whereas the primary response following simultaneously antigen administration was reduced only twofold in these animals compared with wild type controls WBB6F1-+/+ (suggesting that mast cells were not needed to initiate Th2 immunity), reconstitution with bone-marrow-derived mast cells from WBB6F1-+/+ mice resulted in a superoptimal response (suggesting that mast cells contribute to the magnitude and perpetuation of these Th2-biased responses).

Administration, Oral↗
PubMed1999

Immunomodulatory effect of a plasmid expressing CD40 ligand on DNA vaccination against human immunodeficiency virus type-1.

CD40 ligand is a costimulatory molecule which acts a potent immunomodulator. We found the mice inoculated with human CD40 ligand expression plasmid (pMEhCD40L) combined with human immunodeficiency virus type-1 (HIV-1) DNA vaccine exhibited both humoral and cellular antigen-specific immunological enhancement. The expression of hCD40L induced predominantly antigen-specific immunoglobulin G (IgG) antibody response while it failed to induce mucosal IgA response. Delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) activity were induced in a dose-dependent manner. Examination of the relative levels of the two IgG subclasses showed that co-injection of pMEhCD40L enhanced IgG2a response without suppressing IgG1 response. Similarly, the expression of pMEhCD40L enhanced not only T helper 1 (Th1)- but also Th2-type cytokine production. In conclusion, co-inoculation of pMEhCD40L with DNA vaccine was shown to be a useful way to enhance CTL responses without suppressing the humoral immune response in acquired immune deficiency syndrome (AIDS) patients.

AIDS Vaccines↗
PubMed1999

Treatment of chronic hepatitis B virus infection: an Asia-Pacific perspective.

Chronic hepatitis B infection is a serious health threat in the Asia-Pacific area. A consensus meeting on the treatment of chronic hepatitis B infection was conducted in Hong Kong, in August 1997. It was generally agreed that treatment of chronic hepatitis B infection should be based on the understanding of the natural history of chronic hepatitis B infection. To date, interferon alpha is the only Food and Drug Administration (FDA)-approved form of therapy for chronic hepatitis B infection. The overall response in Asian patients is unsatisfactory: approximately 15-20% will clear hepatitis B e antigen, but less than 5% will clear hepatitis B surface antigen. Newer immunomodulatory therapies are under trial. In contrast, nucleoside analogues, such as lamivudine (pending FDA approval) and famciclovir, have been shown to be potent suppressors of hepatitis B viral replication; however, their role as monotherapy in the treatment of chronic hepatitis B infection remains to be defined. Also, the issues of resistance to nucleoside analogues and withdrawal rebound need to be carefully studied. The future direction of therapy in chronic hepatitis B infection is probably a combination of nucleoside analogues or nucleoside analogues with immunomodulatory therapy.

2-Aminopurine↗
PubMed1999

Superinfection of TT virus and hepatitis C virus among chronic haemodialysis patients.

BACKGROUND: The TT virus (TTV), a new DNA virus found in Japan from a patient with post-transfusion hepatitis non-A-non-G, is frequently positive in the sera of patients with liver disease. It is not established whether this virus causes liver damage. We studied the frequency of superinfection of this virus and hepatitis C virus (HCV) known to be endemic among haemodialysis patients, and the possible deleterious effect of TTV on HCV-induced chronic liver disease. METHODS: We used primers from a conservative region in the TTV genome (Okamoto, 1998) to detect TTV. Sera from 163 dialysis patients positive for anti-HCV and 77 dialysis patients negative for anti-HCV (control) were tested. RESULTS: TT Virus positivity was 35% among HCV antibody (anti-HCV)-positive patients and 45.4% among anti-HCV-negative patients. TT Virus positivity was unrelated to the length of haemodialysis or amounts of blood the patients had received in the past. More anti-HCV-positive patients had a history of transfusion, but TTV positivity was not as closely associated with transfusion as anti-HCV positivity. The severity of chronic liver disease was estimated from peak serum alanine aminotransferase levels in the preceding 6 months. Among anti-HCV positives, TTV-positive patients tended to have less active disease; at least there was no indication that TTV superinfection aggravated chronic hepatitic C in long-term dialysis patients. Four of 35 anti-HCV-negative, TTV-positive patients had chronic active liver disease, while none of the anti-HCV-negative and TTV-negative patients did. CONCLUSIONS: TT Virus infection is prevalent among haemodialysis patients. Its transmission occurs not only by blood transfusion, but also by non-parenteral infection. Superinfection of TTV does not exert deleterious effects on the liver disease induced by HCV. However, it may cause chronic hepatitis in a limited number of patients, but remains dormant most of the time. Triple infection, HCV and TTV plus HBV or HGV (one case each), did not cause severe liver disease.

Antibodies, Viral↗