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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 451 records · Page 25Linked to original sources

New trends in hepatocellular carcinoma.

This review discusses the etiological association of hepatitis C virus with hepatocellular carcinoma and recent progress in the understanding of early histopathological changes that occur in cirrhotic livers leading to hepatocarcinogenesis. In some parts of the world (for example Japan) hepatitis C virus infection is becoming a more important etiological factor in the pathogenesis of hepatocellular carcinoma than infection with hepatitis B virus. Biopsy-proven adenomatous hyperplasia often progresses to hepatocellular carcinoma and adenomatous hyperplasia should be treated as a potentially malignant lesion.

Carcinoma, Hepatocellular↗

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and diabetes mellitus: molecular genetic analysis and family study.

Two MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) patients with diabetes mellitus (DM), and their family members are described clinically and genetically. The probands have the following features in common; normal early development, short stature, deterioration of intellectual ability, convulsions, cardiac conduction defect, sensorineural hearing loss, cortical blindness, and hemiparesis. Biochemical tests showed high levels of lactate and pyruvate in the blood and cerebrospinal fluid. Muscle biopsy showed ragged-red fibers. Molecular genetic analysis of both patients revealed that they had an A-to-G substitution at nucleotide position 3243 of the mitochondrial DNA in a heteroplasmic fashion. From these clinical and molecular genetic data they were diagnosed as having MELAS. In addition, fasting blood glucose levels were also high and they were diagnosed as having insulin-dependent DM. Some of the maternal family members in both cases also had insulin-dependent DM and several clinical symptoms of MELAS. DM and clinical features of MELAS were transmitted exclusively in the maternal line. In these cases, DM and MELAS might be a clinical manifestation of the same metabolic defect.

Adolescent↗

Histological changes in bovine endometrium during the estrous cycle.

Endometrial biopsy specimens were obtained from 46 normally cyclic heifers at known stages of their estrous period to show precise characteristic changes. These tissues were embedded in paraffin, sectioned, and stained with hematoxylin and eosin. The following histological changes were observed during the estrous cycle. Metrorrhagia was observed on Days 0 to 1 (estrus = Day 0). Mitoses in glandular epithelium occurred on Day 5. Basal vacuolation in the surface epithelium occurred on Days 5 to 6. Leukocyte invaded the functional layer on Day 7. Stromal mitoses were observed on Days 9 to 12. The results indicate that clincians need to be aware that histological evaluation is important for the diagnosis of endometrial function and that biopsy is useful for this purpose.

Journal Article↗

Glucose requirement at different developmental stages of in vitro fertilized bovine embryos cultured in semi-defined medium.

Three experiments were conducted in which 2-cell bovine embryos were prepared from oocytes, obtained from abattoir ovaries, by in-vitro maturation for 22 to 24 hours, followed by exposure to spermatozoa for 8 hours and culture for 40 hours within the cumulus. The cumulus cells were then removed, and the cleaved embryos were cultured for a further 120 hours or longer, in the presence or absence of glucose, pyruvate and lactate. Very few embryos developed in the complete absence of energy substrates. Lactate and pyruvate, alone or combined, supported development to the 8-cell stage, but pyruvate was required to support development to the morula stage (Experiment 1). When present throughout culture or when added at 48 or 96 hours postinsemination, 5.56 mM glucose was detrimental to development (Experiments 1 and 2). However, when added at 120 hours postinsemination, 5.56 mM glucose improved development to the blastocyst and expanded blastocyst stages, compared with no glucose or 11.12 mM glucose (Experiment 3).

Journal Article↗

Autoimmune T-cell recognition sites of human thyrotropin receptor in Graves' disease.

Five overlapping synthetic peptides representing two regions of thyrotropin (TSH) binding sites of human thyrotropin receptor (TSHR) (peptides 12-30, 24-44, 308-328, 324-344 and 339-364) were investigated for their ability to cause proliferation of peripheral blood lymphocytes (PBL) from eight patients with Graves' disease. The same experiment was done using PBL from four cases with Hashimoto's thyroiditis, two cases with subacute thyroiditis, two cases with rheumatoid arthritis (RA) and eight normal volunteers. PBL obtained from each patient with Graves' disease responded to one or more of peptides 12-30, 24-44, 308-328 and 324-344, while peptide 339-364 had no stimulating activity. The level of stimulating activity of each of the four aforementioned TSHR peptides varied from patient to patient. None of the five TSHR peptides caused the proliferation of PBL from patients with Hashimoto's thyroiditis, subacute thyroiditis, or RA and from normal volunteers. The results indicate that the proliferation of PBL by TSHR peptides is specific in patients with Graves' disease and that the regions of TSHR which are involved in the binding to TSH are also the target of autoimmune T-cell recognition in Graves' disease. The difference in T-cell response from patient to patient could be explained by genetic regulation toward each autodeterminant.

Adolescent↗

Effects of phosphate, energy substrates, and amino acids on development of in vitro-matured, in vitro-fertilized bovine oocytes in a chemically defined, protein-free culture medium.

Bovine oocytes that had been matured and fertilized in vitro were cultured in a simple, chemically defined, protein-free medium (mTLP-PVA). When the medium was supplemented with 19 amino acids, development to the 8-cell (14-20% vs. 38-46%), morula (0-6% vs. 27-32%), and blastocyst (0-1% vs. 9-13%) stages 96, 144, and 192 h after insemination, respectively, was significantly greater in the absence than in the presence of glucose (5.56 mM) regardless of the presence of phosphate (1.05 mM). However, blastocyst development was difficult in medium with any combination of glucose and phosphate without amino acids. In mTLP-PVA with amino acids and different concentrations of phosphate, the highest proportions of embryos reaching the > or = 8-cell (56%), morula (44%), and blastocyst (24%) stages were obtained at a 0.35 mM concentration. When lactate and pyruvate were omitted from mTLP-PVA (mT-PVA) supplemented with amino acids and 0.35 mM phosphate, the first cleavage was completely inhibited. Although lactate or pyruvate alone could support blastocyst development to a limited extent (10-15%), a significantly higher proportion (22%) of blastocysts was obtained in medium with both lactate (10 mM) and pyruvate (0.5 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Adherence and hydrophobicity of invasive and noninvasive strains of Porphyromonas gingivalis.

The adherence of Porphyromonas gingivalis to cell surfaces of periodontal tissues may play an important role in its pathogenicity. In this study, 12 strains of P. gingivalis, including both invasive and noninvasive strains, were investigated for adherence to gingival ligament components. The test strains of P. gingivalis adhered to collagen, fibronectin, and laminin to significantly different degrees. An overall positive correlation was noted between hydrophobicity and the number of cells that attached to collagen coated on hydroxyapatite beads. Invasive strains had low hydrophobicity and bound less to collagen than did noninvasive strains that possessed strong hydrophobic properties. 3H-fimbriae extracted from P. gingivalis were found to attach to collagen-coated hydroxyapatite. The fimbriae extracted from noninvasive strains bound strongly to collagen, whereas invasive strains' fimbriae with low hydrophobicity bound weakly to collagen or saliva-coated hydroxyapatite. These data suggest that 1) fimbriae play an important role in colonization through their hydrophobic activity; 2) fimbriae of noninvasive strains are associated with the major adhesin for attachment to gingival tissue, whereas fimbriae of invasive strains are weakly involved in adherence; and 3) there is no correlation between colonization and the invasiveness of P. gingivalis.

Bacterial Adhesion↗

Significance of serum antibody against surface antigens of Actinobacillus actinomycetemcomitans in patients with adult periodontitis.

This study was undertaken to examine the prevalence of Actinobacillus actinomycetemcomitans, its serotype distribution and the serum immune responses against its surface antigens in 41 Japanese patients with adult periodontitis. The dominant A. actinomycetemcomitans serotype isolated was serotype c. Immunoblot analysis of 3 serotypes of A. actinomycetemcomitans-sonicated antigens and the patient sera revealed that the reactivities with serotype c were the most frequent and that heat-stable surface serotype-specific antigen appeared to be immunodominant. Elevated serum immunoglobulin G titers to extracted lipopolysaccharide and fimbriae antigen of A. actinomycetemcomitans were noted for the patient sera by enzyme-linked immunosorbent assay. High serum immunoglobulin G titers to the fimbriae antigen detected in patients without cultivable A. actinomycetemcomitans suggested the possibility that the elicited antibody to the antigen played a role in eliminating A. actinomycetemcomitans from the periodontal lesions.

Adult↗

Relative avidity of serum immunoglobulin G antibody for the fimbria antigen of Actinobacillus actinomycetemcomitans in patients with adult periodontitis.

The relative avidity of serum immunoglobulin G antibody for the fimbria antigen of Actinobacillus actinomycetemcomitans was assessed by diethylamine dissociation enzyme-linked immunosorbent assay in patients with adult periodontitis. High-titer sera from patients not harboring A. actinomycetemcomitans had significantly higher avidities for the fimbria antigen than did high-titer sera from patients with A. actinomycetemcomitans in their periodontal pockets. The elicited antibodies against the fimbria antigen may afford protection against A. actinomycetemcomitans infection.

Actinobacillus Infections↗

Site-directed mutagenesis of Glu-141 and His-223 in Pseudomonas aeruginosa elastase: catalytic activity, processing, and protective activity of the elastase against Pseudomonas infection.

Both Pseudomonas aeruginosa elastase and Bacillus thermoproteolyticus thermolysin are zinc metalloproteases. On the basis of the high homology of the P. aeruginosa elastase with the Bacillus thermolysin, we hypothesized that Glu-141 and His-223 are the key residues for catalytic activity of the Pseudomonas elastase. To test this possibility, we replaced Glu-141 with Asp, Gln, and Gly and His-223 with Gly, Glu, and Leu by site-directed mutagenesis. These substitutions dramatically diminished the proteolytic activities of the mutant elastases when they were expressed in Escherichia coli cells. Although these mutant elastase precursors (proelastases) were produced, no appreciable processing was observed with these mutants. The possibility that autocatalysis is involved in both the processing and activation of elastase is discussed. Furthermore, by immunizing mice with vaccines made from these mutant elastase, we were able to obtain good protection against an intraperitoneal P. aeruginosa challenge.

Animals↗

[Effects of quinapril on the development of hypertension, cardiac hypertrophy and stroke in salt-sensitive Dahl rats and stroke-prone spontaneously hypertensive rats].

The effects of repeated administration of quinapril (10 mg/kg/day) on the development of hypertension, cardiac hypertrophy and survival rate were examined, and compared with those of enalapril (10 mg/kg) in salt-sensitive Dahl (Dahl S) rats and 1% saline-loaded stroke-prone spontaneously hypertensive rats (SHRSP). The Dahl S rats were treated with the drugs at 10 to 20 weeks of age and the SHRSP, at 8-19 weeks of age. (1) In the Dahl S rats, salt loading rapidly raised systolic blood pressure, which was around 220 mmHg at 10 weeks of age. Both quinapril and enalapril significantly prevented the development of hypertension (below 160 mmHg) and cardiac hypertrophy. Age-associated histopathological alterations in the kidney and mesenteric artery in Dahl S rats were suppressed by the drug treatment. (2) Salt-loaded SHRSP rapidly developed severe hypertension (270 mmHg at 12 weeks of age) accompanied with stroke signs, and 19 animals out of 20 died by the end of the experiment. Both quinapril and enalapril significantly inhibited the age-associated development of hypertension and markedly improved the survival rate (only two animals out of 16 died in both groups). These results suggest that quinapril has protective actions against age-associated development of hypertension and cardiac hypertrophy, and as a result, it prolongs the life span.

Animals↗

Immune recognition of hormonogenic sites of human thyroglobulin: studies of Graves' sera and a murine monoclonal antibody with thyroid hormone antibody activity.

We synthesized four peptides (HTg-1, 1-10; HTg-2, 2547-2558; HTg-4, 2592-2603 and HTg-6, 2737-2748) and two peptides (HTg-3, 2582-2591 and HTg-5, 2687-2694) with or without hormonogenic acceptor tyrosine of human thyroglobulin (hTg). They were iodinated with 127I or 125I. 127I-labeled peptides were tested for their ability to displace 125I-T4 binding to thyroid hormone autoantibodies (THAA) in two cases of Graves' disease and to a murine anti-hTg monoclonal antibody with anti-T4 activity (mAb). 125I-labeled peptides were tested for the direct binding to the aforementioned antibodies. None of the peptides displaced 125I-T4 binding to THAA or to a mAb, or exhibited increased binding to THAA and to a mAb. 125I-T4 binding to a mAb was equally displaced by hTgs obtained from a normal thyroid gland (NTg) and a case of Hürthle cell adenoma with undetectable iodine content (CTg). 125I-T4 binding to serum gamma globulin in each patient's serum was completely displaced by NTg, but CTg displaced 125I-T4 binding 2% and 5% in Case 1 and Case 2, respectively. It was speculated that the mAb recognizes a topological epitope around the hormonogenic site of hTg, while that of THAA in our two cases recognizes only T4 or an iodine dependent topological epitope(s) of hTg.

Animals↗

Maturation-promoting factor (MPF) is responsible for the transformation of sperm nuclei to metaphase chromosomes in maturing bovine oocytes in vitro.

Bovine oocytes at the germinal vesicle stage were inseminated in Brackett and Oliphant's medium in the presence of BSA (10 mg ml-1), caffeine (5 mmol l-1) and heparin (10 micrograms ml-1). When oocytes were transferred into tissue culture medium (TCM)-199 containing 10% fetal calf serum (FCS) with or without 6-dimethylaminopurine (6-DMAP; 2 mmol l-1) 8 h after insemination and cultured for 15-40 h at 39 degrees C in 5% CO2 in air, 74-83% of oocytes were penetrated and polyspermy (67-80%) was common. At 40 h after culture in 6-DMAP-free medium, 65% and 63% of unpenetrated and penetrated oocytes, respectively, reached metaphase II or beyond. A few (6%) oocytes were activated and contained both male and female pronuclei. Sperm metaphase chromosomes were observed in 90% of the penetrated oocytes. Penetration by more than four spermatozoa greatly retarded the meiotic maturation of the oocyte. However, sperm chromosomes were never observed in oocytes cultured in 6-DMAP supplemented medium and oocyte maturation did not proceed beyond the stage of prometaphase I. These results demonstrate the possible participation of maturation-promoting factor in metaphase chromosome formation in spermatozoa.

Adenine↗

Transfusion-associated graft versus host disease following hepatectomy for hepatocellular carcinoma--a case report.

A case of transfusion-associated graft versus host disease (TA-GVHD) following hepatectomy for hepatocellular carcinoma is described in a 53 year-old male patient. The intraoperative bleeding was estimated to be 1220 ml, and he was transfused with 4 units of fresh whole blood. On postoperative day (POD) 12, a fever of 38 degrees C developed, followed by a systemic erythema on POD 14, and a marked progressive leukopenia starting from POD 19. The patient died of multiple organ failure (MOF) on POD 29. Just before death, the results of skin, bone marrow, and liver biopsies had no physical evidence of GVHD. TA-GVHD was found in the HLA typing of the patient's family. This TA-GVHD case was considered to be a reduced immunity due to severe surgical stress or preoperative transcatheter arterial embolization (TAE), in view of the fact that he was transfused with fresh whole blood during the operation. TA-GVHD has frequently been reported in patients after open heart surgery, but also after hepatectomy. It is therefore necessary to take all available means to prevent it by restricting the use of blood preparations as much as possible, and if hetero blood transfusions are performed, blood should be irradiated prior to transfusion.

Carcinoma, Hepatocellular↗

A polymerase chain reaction system for rapid diagnosis of scrub typhus within six hours.

A rapid diagnostic system for scrub typhus (tsutsugamushi disease) was established using the polymerase chain reaction (PCR) combined with microplate hybridization. With this system, diagnosis can be made within six hours without the need for radioisotopes, electrophoresis, or membrane hybridization. The use of a PCR processor and DNA-precoated enzyme-linked immunosorbent assay plates allows a rapid and precise diagnosis to be easily made even in primary medical care clinics.

Aged↗

Cell kinetic effects of granulocyte colony-stimulating factor on the sensitivity of nonlymphocytic leukemia cells to cytosine arabinoside.

We measured the percentage of proliferating cells in peripheral blood and bone marrow of patients with nonlymphocytic leukemia by flow cytometry and immunostaining with antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67. We evaluated the effects of granulocyte colony-stimulating factor (G-CSF) on nonlymphocytic leukemia cells. The S phase cell ratio, PCNA positive cell ratio, and Ki-67 positive cell ratio were higher after culture with G-CSF than culture without G-CSF. The ratio of viable cells was lower after culture with G-CSF followed by cytosine arabinoside (Ara-C) than culture with Ara-C alone. The number of clonogenic leukemic cells in methylcellulose was also smaller after culture with G-CSF followed by Ara-C than Ara-C alone. Our results suggest that the administration of G-CSF before induction chemotherapy enhances the sensitivity of antitumor agents against leukemic cells.

Adolescent↗