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Biomedical subjects

K Oka

Publications and source records attributed to K Oka.

At least 253 records · Page 14Linked to original sources

Benign renal tumors detected among healthy adults by abdominal ultrasonography.

Renal ultrasonography was performed on 17,941 healthy adults without any signs suggestive of urinary tract malignancies. Diffusely hyperechoic renal masses indicative of angiomyolipoma were found in 41 (0.23%) of them and those with echogenic image suggestive of renal cell carcinoma in 45 (0.25%). Final diagnosis of the former group included 24 angiomyolipoma, 1 renal cell carcinoma, 9 calculus and 7 normal variants. The latter group included 19 renal cell carcinomas, 1 leiomyoma, 1 cavernous hemangioma and 24 normal variants or cysts. In total, 24 (0.13%) angiomyolipomas, 20 (0.11%) renal cell carcinomas, 1 leiomyoma, and 1 cavernous hemangioma were discovered. The results indicate that asymptomatic benign renal tumors mainly consisting of angiomyolipoma are not uncommon.

Adult↗

A novel 16,23-epoxy-5 beta-cholestane glycoside with potent inhibitory activity on proliferation of human peripheral blood lymphocytes from Ornithogalum saundersiae bulbs.

A novel 16,23-epoxy-5 beta-cholestane triglycoside (1) was isolated from the bulbs of Ornithogalum saundersiae (Liliaceae). The structure was determined by extensive spectroscopic analysis. The conformation of the E-ring part of 1 was studied through molecular mechanics and molecular dynamics calculation methods. Compound 1 potently inhibited proliferation of peripheral blood lymphocytes provided from a chronic renal failure patient without causing any cytotoxicity in the lymphocytes and HL-60 human leukemia cells.

Carbohydrate Conformation↗

Frequent expression of shared idiotypes in mantle cell lymphoma and extranodal small lymphocytic/non-mantle cell diffuse small cleaved lymphoma.

A panel of 14 anti-shared idiotype (Sid) monoclonal antibodies selected according to their high cross-reactivity to various lymphomas was immunohistologically tested for reactivity with seven reactive lymphoid tissue specimens and 227 B cell lymphoma specimens obtained from Japanese patients. In the reactive lymphoid tissues, the anti-Sld antibodies each reacted with a subpopulation of cells in the mantle zone and interfollicular areas; they rarely reacted with cells in the germinal center. In the B cell lymphomas, 13 anti-Sld antibodies reacted with a total of 78 of 186 (42%) specimens bearing immunoglobulin; none of the antibodies reacted with 41 specimens not bearing immunoglobulin. In mantle cell lymphomas (15/19, 79%) and extranodal small lymphocytic/non-mantle cell diffuse small cleaved lymphomas (11/15, 73%), the reactivity of the antibodies was high compared with that in the other lymphomas (52/152, 34%; P = 0.0002 and 0.004, respectively), including follicular lymphomas (11/42, 27%; P = 0.002 and 0.002, respectively). Since idiotypes are associated with the hypervariable regions and antigen-binding sites of immunoglobulin, these findings may reflect the differences in the regions/sites in each of these diseases.

Antibodies, Monoclonal↗

Gramicidin as a potential immunosuppressant for organ transplantation: suppression of human lymphocyte blastogenesis in vitro and prolongation of heart allograft survival in the rat.

Linear polypeptide antibiotic gramicidin is known to interact with the cell membrane and deregulate cation exchange. Because perturbation of cell membrane function may suppress the immune cell network, the authors investigated the effects of gramicidin on lymphocyte blastogenesis in vitro and allograft survival in vivo. Gramicidin blocked blastogenesis of human peripheral blood lymphocytes that responded to mitogens (IC50 = 0.2-10.1 ng/ml) or allogeneic lymphocytes (IC50 = 4.9 ng/ml). The extent of these suppressive effects was equal to or superior to that of cyclosporine or prednisolone. The antibiotic caused no apparent cytotoxicity at a dose of 10,000 ng/ml. The suppression of lymphocyte blastogenesis in vitro by cyclosporine or prednisolone was restored by addition of interleukin (IL)-1, IL-2, IL-4, IL-5 or IL-6. In contrast, none of these cytokines affected the suppressive activity of gramicidin on lymphocyte blastogenesis. The immunosuppressive efficacy of gramicidin was further examined in vivo in heterotopically heart-transplanted rats. A heart graft from (Lewis x BN) F1 donor was implanted in the neck of allogeneic Lewis rats. In this model, beating of the graft in control recipients (placebo group) stopped as a result of acute allograft rejection at 5.4 +/- 0.4 days after transplantation (n = 38), whereas beating of the graft in recipients that received 2.0 or 4.0 mg kg-1 day-1 of gramicidin i.p. for 6 days was significantly prolonged to 15.4 +/- 4.3 (n = 5) or 18.4 +/- 3.9 (n = 5) days after transplantation, respectively (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Fatal Epstein-Barr virus-associated lymphoproliferative disorder in childhood.

OBJECTIVE: We report five childhood cases of fatal Epstein-Barr virus-associated lymphoproliferative disorder to determine their immunopathologic and immunogenotypic features. DESIGN: Clinicopathologic features are described, using clinical, histologic, immunophenotypic, and genotypic examinations. SETTING: Autopsy cases were performed at Nagoya and Tsukuba university hospitals, Japan. RESULTS: Infiltrating lymphocytes, which were positive for the EBV genome by in situ hybridization, were polymorphic and showed polyclonal immunoglobulin staining in all five cases. Two cases, however, showed genetic clonality of EBV termini. In one case, the clonality was observed only in the spleen, and in the other case, clonal rearrangement of the JH gene was also found. The former case showed none of the morphologic features of neoplasia and presented a morphology similar to virus-associated hemophagocytic syndrome. In the latter case, infiltrating lymphoid cells were much less polymorphous, and nodular masses of the lymphoid cells in colon and lung specimens were observed. CONCLUSION: We suggest that some polyclonal EBV-associated lymphoproliferative disorders develop into polymorphic, but genotypically monoclonal, lymphoproliferative disorders.

Adolescent↗

Frequent expression of CD3 epsilon in CD3 (Leu 4)-negative nasal T-cell lymphomas.

Adult natural killer (NK) cells had not generally been thought to express CD3 proteins other than zeta; however they were recently demonstrated to express CD3 epsilon in an activated condition. This prompted us to investigate the tumor tissues from 17 patients with Leu4-negative peripheral T-cell lymphoma, including eight with nasal T-cell lymphoma (NTCL), for the expression of CD3 epsilon. The tissues were immunohistologically stained with rabbit anti-human CD3 epsilon antibody. The expression of CD3 epsilon was more frequent in the tissues of nasal lymphoma than in the non-nasal lymphoma tissues: specimens from six of eight of the NTCL patients expressed CD3 epsilon, while only one of nine of the non-NTCL patients did so. The NTCL patients presented clinically with lethal midline granuloma, had histologic findings of tumor necrosis and angioinvasion, and had a peculiar CD2+, Leu4-, CD3 epsilon+, CD5-, CD7+, CD45RO+, CD4-, CD8-, beta F1-, T-cell receptor (TRC) delta 1-, CD56+ phenotype. This peculiar phenotype seems to be closely associated with NTCL. No clonal rearrangement of the TCR genes was detected in three NTCL patients examined. The NK cell origin of NTCL has been suggested by previous investigators. The phenotypic correspondence of our nasal tumors to adult activated NK cells supports this possibility, together with their lack of clonal rearrangement of the TCR genes.

Adult↗

Physical activity and immune senescence in men.

A cross-sectional survey examined whether habitual endurance exercisers retained a higher level of T cell function than sedentary individuals in old age. Subjects, all male, comprised 17 elderly runners, 16 young, and 19 elderly controls (mean ages +/- SD: 63.8 +/- 3.3, 23.6 +/- 1.6, and 65.8 +/- 3.5 yr, respectively), whose resting blood samples served for the immunological tests. Compared with the young subjects, both elderly groups had lower circulating CD3+ and CD8+ cell-counts (P = 0.029, P = 0.001, respectively), with a trend to a higher CD4/CD8 ratio, but higher percentages of activated CD3+, and "memory" CD4+ and CD8+ cells (all, P < 0.0001). Proliferative responses to phytohemagglutinin, pokeweed mitogen, and alloantigens were markedly reduced in the elderly (P < 0.001, and P = 0.024, respectively). IL-2 production tended to be decreased in the elderly sedentary subjects. However, natural killer cell activity and other cytokine production remained unchanged in the elderly sedentary subjects. Comparison between the active and sedentary elderly groups showed no differences in circulating counts of immunocompetent cells. However, the active elderly subjects demonstrated significantly greater proliferative responses to phytohemagglutinin ( P = 0.016) and to pokeweed mitogen (P = 0.011), and higher rates of IL-2 (P = 0.021), IFN-gamma (P = 0.015) and IL-4 production (P = 0.012). These results suggest that endurance training in later life is associated with a lesser age-related decline in certain aspects of circulating T cell function and related cytokine production.

Age Factors↗

Glutamate-induced deporalization in earthworm ventral nerve cord.

We investigated glutamate-induced neuron response in the ventral nerve cord of the earthworm (Eisenia foetida) using a voltage-sensitive dye-imaging technique. Isolated earthworm ganglia were stained by fluorescence voltage-sensitive dye, RH414, and voltage image was acquired by a conventional charge-coupled device (CCD) technique or a confocal laser scanning microscope. The fluorescence images before and during the glutamate stimulation was acquired and the relative fluorescence change was imaged as pseudo-color. Bath-applied glutamate (1 mM) depolarized many neurons on the ventral side, and in the three giant fibers on the dorsal side.

Animals↗

Calcium wave propagation in the giant axon of the earthworm.

We examined a spatio-temporal pattern of intracellular free Ca2+ concentration in the giant axons of the earthworm, Eisenia foetida, with a fluorescent imaging technique using conforcal laser-scanning microscope and calcium indicator. 'Calcium Green 1'. Electrical tetanic stimulation applied to the nerve cord induced calcium waves along the giant axon. The calcium waves propagated both anteriorly and posteriorly with various speeds, and sometimes were split into several waves with different velocities. The results suggest that some types of calcium-releasing mechanisms may be associated with the calcium wave propagation.

Animals↗

Mouse very-low-density-lipoprotein receptor (VLDLR) cDNA cloning, tissue-specific expression and evolutionary relationship with the low-density-lipoprotein receptor.

The very-low-density-lipoprotein receptor (VLDLR) is a recently described lipoprotein receptor that shows considerable similarity to the low-density-lipoprotein receptor (LDLR). This receptor has been suggested to be important for the metabolism of apoprotein-E-containing triacylglycerol-rich lipoproteins, such as very-low-density-lipoprotein (VLDL), beta-migrating VLDL and intermediate-density lipoprotein. cDNA clones that code for the VLDLR were isolated from a mouse heart cDNA library. The deduced amino acid sequence predicts a mature protein of 846 amino acids preceded by a 27-residue signal peptide. Three mRNA species for the VLDLR with sizes of 3.9, 4.5 and 7.9 kilobases were present in high concentration in heart and muscle, which utilize triacylglycerols as an energy source. VLDLR mRNA is also detected in decreasing amounts in kidney, brain, ovary, testis, lung and adipose tissue. It is essentially absent in liver and small intestine. The amino acid sequence of the VLDLR is highly conserved among rabbit, human and mouse. VLDLR contains five structural domains very similar to those in LDLR, except that the ligand-binding domain in VLDLR has an eightfold repeat instead of a sevenfold repeat in LDLR. Sequence conservation among animal species is much higher for the VLDLR than the LDLR. Sequences of the VLDLR from three vertebrate species and the LDLR from five vertebrate species were aligned and a phylogenetic tree was reconstructed. Although both receptors contain five domains and share amino acid sequence similarity, our computations showed that they diverged before the divergence between mammals and amphibians. In addition, sequence comparison of both receptor sequences suggests that the rabbit is evolutionarily closer to man than to the mouse. These results are consistent with the hypothesis that the VLDLR and the LDLR have evolved from a common ancestral gene to play distinct roles in lipoprotein metabolism and that the metabolic handling of triacylglycerol by the body via the VLDLR is a highly conserved mechanism.

Amino Acid Sequence↗

Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo.

Plasminogen activators regulate a variety of processes involved in tissue morphogenesis, as well as cell differentiation, migration, and invasion. We examined the relative amounts of mRNA and protein and localization of urokinase-type plasminogen activator (uPA) in human astrocytomas in vivo. Using fibrin zymography and densitometric quantitation, we found that uPA activity was significantly higher in malignant astrocytomas, especially in glioblastomas, than it was in normal brain tissues or low-grade gliomas. The amounts of uPA mRNA, as determined by Northern blot analysis, were higher in anaplastic astrocytomas and glioblastomas than in normal brain tissues and low-grade gliomas, consistent with the amount of uPA activity. To investigate the cellular source of uPA in various tissues, we performed immunocytochemical localization of uPA protein and in situ hybridization of uPA mRNA with astrocytomas and normal brain tissues. Immunocytochemical staining for uPA showed strong immunoreactivity in the tumor cells and vasculature of glioblastomas and anaplastic astrocytomas but undetectable or very low immunoreactivity for uPA in low-grade gliomas and normal brain tissues. uPA mRNA was located in astrocytoma and endothelial cells and was heterogeneously distributed within glioblastoma, with preferential localization near vascular proliferation and at the leading edge of the tumor. uPA expression was dramatically higher in highly malignant astrocytomas, especially glioblastomas, and was correlated with malignant progression of astrocytomas.

Astrocytoma↗

Crystal structure of RNase T1 complexed with the product nucleotide 3'-GMP. Structural evidence for direct interaction of histidine 40 and glutamic acid 58 with the 2'-hydroxyl group of the ribose.

The crystal structure of RNase T1 complexed with 3'-GMP has been determined. The glycosyl conformation of 3'-GMP is in the syn conformation, and the ribose adopts the O4'-endo pucker. This observed pucker is different from that in any complex structures of RNase T1. In the present complex, this energetically unfavorable conformation is stabilized by the water molecule with the bridged hydrogen bonds between the O2' and the O3' atoms of the ribose. The guanine base is recognized in the same manner as observed in the complex of 2'-GMP. The 2'-hydroxyl group of the ribose shows a tight hydrogen bond to both His-40 and Glu-58 with the suitable geometry for the proton transfer. These hydrogen bonds suggest that the two residues can participate directly in the proton transfer. His-92 is hydrogen bonded to two the proton transfer. His-92 is hydrogen bonded to two oxygen atoms of the phosphate group. Based on the geometry in the active site, the O1P atom may correspond to the O5' atom of the leaving nucleotide in the phosphoryl transfer or a water molecule as a nucleophile in the hydrolysis reaction. In the present complex, the conformations of the 3'-GMP molecule and the side chains of the catalytic residues would be represented as the conformation before the phosphoryl transfer reaction and/or after the hydrolysis reaction.

Binding Sites↗

Expression and cellular localization of messenger RNA for plasminogen activator inhibitor type 1 in human astrocytomas in vivo.

We investigated the expression and cellular localization of plasminogen activator inhibitor type 1 (PAI-1) in human astrocytoma in vivo. Northern blot and densitometric quantitation of PAI-1 mRNA indicated that PAI-1 transcripts were significantly higher in human malignant astrocytomas and especially in glioblastomas than in low-grade gliomas and normal brain tissues in vivo. Using in situ hybridization with paraffin-embedded surgical specimens of human gliomas and normal brain tissues, PAI-1 mRNA was abundantly expressed in glioblastomas. PAI-1 mRNA was localized mainly in tumor cells and endothelial cells. The distribution of PAI-1 mRNA expression was particularly abundant around areas of vascular proliferation and in remnant tumor cells surrounding necrotic foci. PAI-1 mRNA was also expressed in both the tumor and endothelial cells of anaplastic astrocytomas, whereas it was not expressed or only weakly expressed in low-grade astrocytomas or normal brain tissues. These results suggest that high expression of PAI-1 is associated with the malignant progression of astrocytic tumors and that excessive PAI-1 expression might be associated with intratumoral necrosis in glioblastomas.

Astrocytoma↗

Clinical significance of glucocorticoid pharmacodynamics assessed by antilymphocyte action in kidney transplantation. Marked difference between prednisolone and methylprednisolone.

A number of studies have demonstrated the impact of glucocorticoid response of peripheral lymphocytes on kidney allograft survival, suggesting that the better the glucocorticoid selection, the better the clinical outcome. However, individual differences in pharmacodynamics of clinically important glucocorticoids have not been taken into account. Four glucocorticoids (hydrocortisone, prednisolone, methylprednisolone, and dexamethasone) were examined for their ability to suppress in vitro blastogenesis of mitogen-stimulated PBL obtained from 122 chronic renal failure (CRF) patients waiting for renal transplantation and 98 healthy volunteers. Concentrations of steroids that gave 50% inhibition of lymphocyte blastogenesis (IC50) were determined individually in order to compare steroids and subject groups. Graft outcomes in 36 kidney transplant recipients treated with prednisolone were compared retrospectively with the prednisolone pretransplant IC50 values. Lymphocyte response to each glucocorticoid showed wide deviations among the subjects. Prednisolone IC50 values of the CRF patients showed the largest deviation, ranging from 1.0 to 10,000 micrograms/L. Thus, a significantly large population of the CRF patients (26.2%), when compared with the healthy subjects (4.1%) showed a marked decrease in lymphocyte response to prednisolone (P < 0.01). The binding capacity and affinity of lymphocyte glucocorticoid receptors did not differ significantly between the responders and nonresponders, suggesting that steroid resistance is a post-receptor event. The antilymphocyte potency of prednisolone assessed by IC50 of the steroid was less than that of hydrocortisone, whereas methylprednisolone was > 12-fold superior to prednisolone. After kidney transplantation, CRF patients who showed impaired preoperative lymphocyte response to prednisolone had a significantly high incidence of acute allograft rejection under prednisolone/CsA therapy (P < 0.01). It is concluded from these results that methylprednisolone could be of benefit to prednisolone-resistant recipients, who can be identified by the preoperative lymphocyte culture.

Adolescent↗

Structure of the mouse cholesterol 7 alpha-hydroxylase gene.

Three overlapping cholesterol 7 alpha-hydroxylasecDNAs were cloned from total mouse liver RNA by a combination of the polymerase chain reaction and mouse liver cDNA library screening. One of the cDNA clones was used to screen a mouse genomic library; three genomic clones were isolated and one of them was fully characterized. The mouse cholesterol 7 alpha-hydroxylase gene spans approximately 10 kb. The gene contains six exons including a 1509-bp open reading frame encoding 503 amino acid residues. The predicted amino acid sequence of mouse cholesterol 7 alpha-hydroxylase showed 93 and 82% identity to the rat and human enzymes, respectively. The transcription initiation site is mapped to 64 bases 5' of the translation initiation codon. Several transcription factor binding sequences are identified in the 5' flanking region of the mouse cholesterol 7 alpha-hydroxylase gene.

Amino Acid Sequence↗

Human very-low-density lipoprotein receptor complementary DNA and deduced amino acid sequence and localization of its gene (VLDLR) to chromosome band 9p24 by fluorescence in situ hybridization.

A complementary DNA for the very-low-density lipoprotein receptor (VLDLR) that codes for a protein of 873 amino acids was cloned from a human heart cDNA library. The mature protein of 846 amino acids, preceded by a 27-residue signal peptide, shares 97% amino acid sequence identity with the rabbit VLDLR. Like the low-density lipoprotein receptor, the VLDLR contains five different domains, all of which are highly conserved between human and rabbit. A tetrapeptide NPVY that potentially serves as a signal for clustering of the VLDLR on coated pits is present in the cytoplasmic domain, which is 100% conserved between human and rabbit. We localized the VLDLR gene to chromosome 9p24 by fluorescence in situ hybridization using the cloned cDNA as hybridization probe. The high amino acid sequence homology of the VLDLR between two mammalian species suggests that the receptor plays a fundamental role in lipoprotein metabolism and that energy metabolism mediated by triglyceride utilization may be an evolutionarily highly conserved mechanism.

Amino Acid Sequence↗

c-erbB-2 Oncoprotein expression is associated with poor prognosis in squamous cell carcinoma of the cervix.

BACKGROUND: A polyclonal antihuman c-erbB-2 oncoprotein antibody recognized c-erbB-2 oncoprotein in routinely formaldehyde-fixed, paraffin-embedded specimens. METHODS: Specimens taken from 192 patients with Stage III squamous cell carcinoma of the cervix treated with radiation therapy alone were investigated for c-erbB-2 oncoprotein expression using an immunohistochemical method. RESULTS: Cancer cells that were positive for c-erbB-2 oncoprotein showed a surface membrane staining pattern. Of the 192 patients, 143 were negative for c-erbB-2 oncoprotein, 12 were weakly positive or ambiguous, 31 were positive, and 6 were strongly positive. The 5-year survival rate of the 155 patients who tested c-erbB-2 negative or weakly positive was significantly better than that of the 37 patients whose results were positive or strongly positive (61% versus 41%, P = 0.022). CONCLUSION: c-erbB-2 Oncoprotein expression in cancer cells may imply a poor prognosis for patients with Stage III squamous cell carcinoma of the cervix treated with radiation therapy alone.

Adult↗