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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 199 records · Page 11Linked to original sources

A case of lymphoepithelial cyst of the pancreas.

We report a relatively rare case of lymphoepithelial cyst of the pancreas. The patient, a 43-year-old man with no subjective symptoms, was found to have a pancreatic tumor during a physical examination. Based on the ultrasonographic and abdominal computed tomographic findings, a pancreatic cystic tumor was diagnosed. Endoscopic retrograde pancreatography showed a normal duct system. Enucleation was easily performed. Macroscopically, the cyst resembled an atheroma. Histopathologic examination disclosed lymphoepithelial cyst of the pancreas.

Adult↗

Evaluation of curability and prediction of prognosis after surgical treatment for hepatocellular carcinoma by lens culinaris agglutinin-reactive alpha-fetoprotein.

The clinical significance of serum lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), which can distinguish between hepatocellular carcinoma and hepatitis by detecting a sugar chain micro heterogeneity, was evaluated for its possible ability to recognize previously undetectable residual tumors, and for increasing the accuracy of prognosis after surgical treatment for hepatocellular carcinoma. Serum lens culinaris agglutinin-reactive alpha-fetoprotein was measured pre- and post-operatively in 130 patients who underwent curative surgical treatment for hepatocellular carcinoma. The preoperative AFP-L3 positive rate was 35.4%. AFP-L3 remained positive postoperatively in 28 of the 46 preoperative AFP-L3 positive patients, and converted to positive in 4 of the 84 preoperative AFP-L3 negative patients. Regardless to preoperative AFP-L3, the postoperative AFP-L3 positive patients had a poorer recurrence-free rate (p<0.0001). The postoperative L3 positive patients had a high incidence of recurrence due to metastasis, but did not have recurrence due to multicentric origin. Multivariate analysis revealed that AFP-L3 (p<0.0001) was the most independently significant factor for predicting survival after surgery among several conventional prognostic factors. Thus, AFP-L3 is a valuable marker for evaluation of curability of surgical treatment and for improving the accuracy of prognosis.

Aged↗

Prognostic benefit in cytoreductive surgery for curatively unresectable hepatocellular carcinoma - comparison to transcatheter arterial chemoembolization.

As a strategy for treating advanced hepatocellular carcinoma (HCC), cytoreductive surgery was studied comparing to transcatheter arterial chemoembolization (TACE). Patients who had curatively unresectable intrahepatic multiple HCC with the main tumor 30 mm or more in size were selected for this study. The patients were classified into two groups; i) cytoreductive surgery group (CRS group): 28 patients in whom the main tumor was resected but other cancer nodules remained in the remnant liver, ii) TACE group: 25 patients at Child A grade who underwent TACE, and in whom it was also evaluated retrospectively that the main tumor had been resectable. The cumulative 5-year survival rate was significantly higher in CRS (48.7%) than TACE (17.1%) group. Multivariate analysis revealed that performing cytoreductive surgery was a significant and independent factor to prolong survival. However, 6 of 28 patients died within one year of surgery. Residual tumor thrombus, and the absence or non-effectiveness of adjuvant therapy were significant high risk factors for postoperative death within one year. Conclusively, cytoreductive surgery contributes to a significant lengthening of survival in patients with advanced HCC. To reduce the risk of early postoperative death, the importance of postoperative adjuvant therapy is also recognized.

Aged↗

Myocardial metabolism of 123I-BMIPP in a canine model with ischemia: implications of perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease.

UNLABELLED: 123I-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) is a fatty acid analog for SPECT imaging. This radiopharmaceutical possesses the unique property, that is, perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease. However, the reason of this mechanism remains unclear. METHODS: Using open-chest dogs under anesthesia, we made a system to release all the blood of the great cardiac vein outside without recirculation, if necessary. Left anterior descending artery (LAD) was occluded for 30 min after reperfusion. After the injection of BMIPP into LAD, blood samplings from the cardiac vein and abdominal aorta (6 dogs) or serial biopsy specimens from the LAD region (5 dogs) were performed, and then compared with the normal control. The catabolites of BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated with high-performance liquid chromatography (HPLC) in the efflux study. Thin-layer chromatography (TLC) technique was introduced in the tissue analytical study. RESULTS: Although the rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, the early washout (8 min) of radioactivity significantly increased (51% +/- 12% to 65% +/- 7%; P < 0.05) with ischemia. The metabolites from the myocardium consisted of backdiffusion of nonmetabolized BMIPP, alpha, intermediate, and full oxidation metabolites. Among these metabolites, backdiffusion of nonmetabolized BMIPP in blood significantly increased (27.9% +/- 7.7% to 42.3% +/- 8.1%; P < 0.05), especially in the early phase with ischemia. In tissue, the radioactivity was concentrated in the triglyceride pool even in the early phase, and in addition, BMIPP and alpha-oxidized metabolite significantly decreased in the early phase with ischemia (t = 1 min after BMIPP injection, 25.9% +/- 8.6% to 14.5% +/- 2.1%, P < 0.01; t = 2 min, 8.9% +/- 5.0% to 4.5% +/- 1.7%, P < 0.05). CONCLUSION: These results show that backdiffusion of nonmetabolized BMIPP from the myocardium increased and BMIPP (long-chain fatty acids) in tissue decreased with ischemia, suggesting backdiffusion of nonmetabolized BMIPP might play an important role in myocardial perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease.

Animals↗

Discovery of vitamin B12 in the liver and its absorption factor in the stomach: a historical review.

This review describes the early chronological events in the pursuit of a treatment for pernicious anaemia, and the subsequent discovery of vitamin B12 and the intrinsic factor. It details Castle's experiments which established the theory of extrinsic and intrinsic factors as hemopoietic principles, and describes the studies on purification of the anti-pernicious anaemia principle from liver tissue that terminated in the crystallization of vitamin B12 and identification of its coenzyme forms. Biochemical purification and characterization of the intrinsic factor secreted by the gastric parietal cells, and two other vitamin B12 proteins, R-binder (transcobalamin I, haptocorrin), and transcobalamin II, are discussed in detail. The biochemical reactions in micro-organisms and humans in which vitamin B12 is involved are then briefly reviewed, and finally and briefly the immunological basis of pernicious anaemia is discussed.

Anemia, Pernicious↗

[Successful treatment of pleuritis carcinomatosa using combination therapy of 5'-DFUR, MPA and CPA as maintenance therapy].

A 44-year-old female patient with inoperable, local advanced left breast cancer was treated with 3 cycles of high dose CAF therapy followed by combination therapy of 5'-DFUR, MPA and CPA. The patient was discharged after receiving 3 cycles of high-dose CAF therapy and continued to receive daily oral doses of 5'-DFUR (800 mg), MPA (800 mg), and CPA (100 mg) for 15 months. After 3 cycles of high-dose CAF therapy, tumor marker (CEA, CA 15-3) levels were reduced. Six months later, after 3 cycles of high-dose CAF therapy, the tumor marker levels were within the normal range. No serious side effects were observed during chemotherapy. The patient enjoyed a good quality of life. We thus confirmed that this combination regimen was effective as a maintenance therapy for local advanced breast cancer.

Adenocarcinoma↗

The C-terminus of c-ABL is required for proliferation and viability signaling in a c-ABL/erythropoietin receptor fusion protein.

Activated ABL oncogenes cause B-cell leukemias in mice and chronic myelogenous leukemia in humans. However, the mechanism of transformation is complex and not well understood. A method to rapidly and reversibly activate c-ABL was created by fusing the extra-cytoplasmic and transmembrane domain of the erythropoietin (EPO) receptor with c-ABL (EPO R/ABL). When this chimeric receptor was expressed in Ba/F3 cells, the addition of EPO resulted in a dose-dependent activation of c-ABL tyrosine kinase and was strongly antiapoptotic and weakly mitogenic. To evaluate the contributions of various ABL domains to biochemical signaling and biological effects, chimeric receptors were constructed in which the ABL SH3 domain was deleted (triangle upSH3), the SH2 domain was deleted (triangle upSH2), the C-terminal actin-binding domain was deleted (triangle upABD), or kinase activity was eliminated by a point mutation, K290M (KD). The mutant receptors were stably expressed in Ba/F3 cells and analyzed for signaling defects, proliferation, viability, and EPO-induced leukemia in nude mice. When compared with the ability of the full-length EPO R/ABL receptor to induce proliferation and support viability in vitro, the triangle upSH3 mutant was equivalent, the triangle upSH2 mutant was moderately impaired, and the triangle upABD and KD mutants were profoundly impaired. None of these cell lines caused leukemia in mice in the absence of pharmacological doses of EPO. However, in mice treated with EPO (10 U/d), death from leukemia occurred rapidly with wild-type and triangle upSH3. However, time to death was prolonged by at least twofold for triangle upSH2 and greater than threefold for triangle upABD. This inducible model of ABL transformation provides a method to link specific signaling defects with specific biological defects and has shown an important role for the C-terminal actin-binding domain in proliferation and transformation in the context of this receptor/oncogene.

Amino Acid Substitution↗

Immune responses but no protection against SHIV by gene-gun delivery of HIV-1 DNA followed by recombinant subunit protein boosts.

The efficacy of combining immunization with human immunodeficiency vitus type 1 (HIV-1) DNA and HIV-1 recombinant proteins to obtain protection from chimeric simian/human immunodeficiency virus (SHIV) was determined. Four cynomolgus monkeys received four gene-gun immunizations intraepidermally of plasmid DNA encoding HIV-1lai env (gp160), gag, tat, nef, and rev proteins. Ten micrograms of DNA was used per immunization. The animals were boosted twice intramuscularly with 50 microgram of HIV-1lai Env (MicroGeneSys), Gag, Tat, Nef, and Rev recombinant proteins mixed in Ribi adjuvant. The antibody responses were amplified following the administration of the recombinant subunit boosts. One month after the final subunit immunization, the vaccinated animals together with four control animals were challenged intravenously with 10 monkey infectious doses of SHIV that expresses the env, tat and rev genes of HIV-1 and gag and nef from SIV. However, only low titers of neutralizing antibodies were present at the day of challenge. The consecutive HIV-1 DNA and recombinant protein immunizations induced B- and T-cell responses but not protection against SHIV replication nor reduction of the viral load.

AIDS Vaccines↗

Induction of entry into the stationary growth phase in Pseudomonas aeruginosa by N-acylhomoserine lactone.

N-acylhomoserine lactone (AHSL, autoinducer) is capable of regulating a set of genes by sensing cell density and developing an intercellular communication in Pseudomonas aeruginosa. Addition of AHSL in the exponential growth phase, regardless of cell density, induces a repression of cell growth of P. aeruginosa, an expression of stationary phase specific factor sigma 8 in vivo and a morphological change into smaller spherical shape indistinguishable from that in the stationary phase. It is demonstrated that AHSL can trigger an entry of bacteria into stationary phase as a growth controlling signal.

4-Butyrolactone↗

Assay of 25-hydroxyvitamin D3 1 alpha-hydroxylase in rat kidney mitochondria.

An assay method for 25-hydroxyvitamin D3 1alpha-hydroxylase [calcidiol, NADPH: oxygen oxidoreductase (1-hydroxylating), EC 1.14. 13.13] in rat kidney is described. The mitochondrial and nuclear fraction was solubilized effectively with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate(Chaps). By subsequent ultracentrifugation of the solubilized suspension the effect of inhibitory factor(s) in mammals was removed. The enzyme was then assayed by the reconstitution method using saturated amounts of adrenodoxin and NADPH-adrenodoxin reductase. Products were analyzed by HPLC, monitoring absorbance at 265 nm. The enzyme activity depended on not only pH of the medium but also the kind of buffers. N,N-Bis(2-hydroxyethyl)glycine was the best buffer. At 30 degrees C, the reaction velocity was linear at least up to 10 min, by which time enough amounts of the product needed for analysis were formed. The enzyme activity was linear to a protein concentration up to 0.8 mg of protein/ml. Under the best assay conditions established, the maximal velocity of enzyme in the rachitic rat was 12.9 pmol of product/min/mg of protein, which was 30- to 1000-fold higher than those reported by other authors with the enzyme of rachitic rat. Michaelis constant was 1.8 microM. Specific activity with the enzyme of normal rat was 0.25 pmol of product/min/mg.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗