Search PubMed⌕ Search

Biomedical subjects

K Oka

Publications and source records attributed to K Oka.

At least 379 records · Page 21Linked to original sources

Structure and polymorphic map of human lipoprotein lipase gene.

Lipoprotein lipase (LPL) catalyzes the key step for the removal of triacylglycerol-rich lipoproteins from the circulation. In this paper, we report the cloning and structure of the normal human LPL gene, which was isolated in three overlapping lambda phage clones that span about 35 kilo bases (kb) of the genetic locus. The peptide coding region of the gene is approx. 23 kb in length and contains nine exons with intron sizes ranging from 0.7 to 8.7 kb. The entire 3' untranslated region is in the tenth exon. Specific sequences in this region support the hypothesis that two mRNA species found for human LPL are generated by differential utilization of polyadenylation signals. The first exon occurs in the 5' untranslated region and the region coding for the signal peptide. The second exon includes the protein domain coding for the N-linked glycosylation site that is required for the expression of enzyme activity. The fourth exon contains the region that was proposed as a lipid binding domain, the sixth for one putative heparin binding domain, and the eighth codes for a domain containing another N-linked glycosylation site. These results suggest that the unique structural and functional domains are confined to specific exons. The PvuII polymorphic site was located within the intron between exon 6 and 7 and the HindIII polymorphic site to the 3' flanking region. The location of these polymorphic sites suggests that the PvuII restriction fragment length polymorphism (RFLP) associated with lipase deficiency in a few Japanese kindred may be a linkage marker for a functional defect of LPL, while the HindIII RFLP associated with hypertriglyceridemia may be important for gene regulation of LPL.

Amino Acid Sequence↗

Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis.

Lipoprotein lipase is the rate determining enzyme for the removal of triglyceride rich lipoproteins from the blood stream. We examined whether genetic variation at the lipoprotein lipase gene locus is related to the occurrence of premature coronary artery disease. Two restriction fragment length polymorphisms, revealed by the enzymes HindIII and PvuII, demonstrated alleles designated H1 (17.5 kb), H2 (8.7 kb), P1 (7.0 kb), P2 (4.4 kb and 2.5 kb) respectively. These were studied in 70 Caucasian subjects with severe coronary atherosclerosis in comparison with 122 Caucasian healthy controls. The allelic frequencies for cases and controls were respectively: H2 0.770, 0.579 (P less than 0.001); P2 0.575, 0.554 (P NS). The allelic frequencies of the HindIII and BglII polymorphic sites at the hepatic lipase gene locus were also studied in the same groups of subjects. These showed no differences between cases and controls. We conclude that DNA variation at or adjacent to the lipoprotein lipase gene may contain genetic determinants for the occurrence of premature coronary artery disease.

Alleles↗

Histological and immunohistochemical prediction for local control of cervical squamous cell carcinoma treated with radiotherapy alone.

Predictability of local control following radiotherapy was evaluated with morphological methods such as histology and immunohistochemistry for 36 cervical squamous cell carcinomas. All these patients showed viable cancer cell predominance on the specimens excised with drill biopsy after radiation therapy. These specimens were stained with routine haematoxylin and eosin staining as well as with antibodies against epithelial membrane antigen (EMA), carcinoembryonic antigen, and S-100 protein. Five histological features, the number of the cancer nests per 22.5mm2 section, stromal reaction, space formation in the cancer nests, foamy cell or foreign body giant cell (FBG) clusters, and epithelial membrane antigen reactivity on the specimens excised after radiation therapy, were significantly related to the local control probability. Namel, less than 20 cancer nests, granulomatous stroma, presence of the space formation, absence of the foamy cell or foreign body giant cell clusters, and epithelial membrane antigen negativity were favorable for local control of the cervical cancer with radiation therapy. These data suggested that radiation sensitivity of cancer and stromal reaction for drainage of the degenerated cancer debris were important for local control of the tumors.

Adult↗

Incidence and properties of renal masses and asymptomatic renal cell carcinoma detected by abdominal ultrasonography.

Renal ultrasonography was performed in 45,905 adults, including 41,364 without any signs suggesting urinary tract malignancies, 1,667 with microscopic hematuria only and 2,874 with some signs of malignancy. Renal lesions were found in 355 adults (0.858%) in the asymptomatic, 39 (2.3%) in the microscopic hematuria and 75 (2.6%) in the symptomatic groups, respectively. Renal cell carcinoma was found in 35 (7.5%) lesions: 19 (5.4%) in the asymptomatic, none in the microscopic hematuria and 16 (21.3%) in the symptomatic groups. A total of 47 patients, including 12 other renal cell carcinoma patients transferred from related hospitals, was grouped into 28 without and 19 with symptoms. Primary tumor size and clinical stages were significantly smaller and lower, respectively, in the asymptomatic group than in the symptomatic group. Radical nephrectomy was performed in all but 2 asymptomatic patients. The 5-year survival rates after nephrectomy were 94.7 and 60.9% for the asymptomatic and symptomatic groups, respectively (p less than 0.01). The results indicate that ultrasonography is a useful tool to detect low stage asymptomatic renal cell carcinoma at low cost.

Carcinoma, Renal Cell↗

Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation.

Intestinal absorption of neocarzinostatin (NCS) and smancs (copolystyrene maleic acid-conjugated NCS), in aqueous and oily formulations, was investigated after oral administration in mice. Blood concentrations of NCS and smancs were determined with a cytotoxicity assay employing the highly sensitive Epstein-Barr (EB) virus-transformed B-lymphoblastoid cell line, TK/B. Smancs was more efficiently absorbed from a medium-chain triglyceride solution (oily smancs) than from an aqueous solution in phosphate-buffered saline (PBS). The maximum blood concentration and the area under the concentration curve versus time course (AUC) of oily smancs were 9 and 11 times greater than those of the aqueous form of smancs, respectively. At 5 hr after administration of oily smancs, 0.044% of the total smancs dose was found in blood, whereas the parent compound NCS was not detectable at any time. When oily smancs was administered orally to sarcoma 180 tumor-bearing mice, a selective accumulation of smancs in tumor tissue was observed. These results indicated that a biologically active protein, which cannot be used orally, may be rendered orally active drug by conjugation with a hydrophobic polymer in combination with an oily formulation.

Administration, Oral↗

T-cell receptor expression in the T-cell malignancies.

Twenty-eight cases with T-cell neoplasms (10 with T-cell acute lymphoblastic leukemia [T-ALL], 10 with T-lymphoblastic lymphoma, and 8 with peripheral T-cell lymphomas) and 2 cases with reactive lymph nodes were immunohistochemically stained with monoclonal antibodies beta F1, delta TCS1, and WT31; beta F1 antibody recognizes the beta-subunit of T-cell receptor (TCR), whereas delta TCS1 and WT31 recognize the delta- and alpha beta-subunits of TCR, respectively. Five cases with T-ALL, four with T-lymphoblastic lymphoma (T-LL), and seven with peripheral T-cell lymphomas were positive for beta F1. None showed positive reactivity for delta TCS1. One case with T-LL and four cases with peripheral T-cell lymphomas were positive for WT31. Of the nine cases positive for beta F1 among T-ALLs and T-LLs, six were also positive for CD1 (OKT6), whereas six of seven positive cases for CD1 were positive for beta F1. The authors therefore suggest that TCR beta is expressed in the immature T-cells just earlier than or around the same stage of differentiation as those expressing CD1. The authors' immuno-electron microscopy study revealed that positive reactivity for beta F1 was localized predominantly in the cytoplasm of the neoplastic cells in the cases with T-ALL, T-LL and peripheral T-cell lymphomas, and in the cytoplasm of the reactive T-cells. However, it was not localized on the surface membrane. In contrast, positive reactivity for WT31 was localized on the surface membrane of the neoplastic and reactive T-cells. Only half of the cases of peripheral T-cell lymphomas showed positive reactivity for WT31. The authors consider that it may not be a very useful antibody for the detection of TCR alpha beta on the T-cell neoplasms using frozen tissue sections.

Antibodies, Monoclonal↗

Crystallographic characterization of wild-type and mutant ribonuclease T1 complexes with several ribonucleotides.

Ribonuclease T1 and the mutant enzymes were cocrystallized with several ribonucleotides, including non-hydrolyzable substrate analogs of di- and triribonucleotides, which have a novel guanylate in which the 2'-hydroxyl group of the ribose is replaced by a fluorine atom. One of the mutant enzymes has a tryptophan residue, instead of Tyr45 of the wild-type enzyme, to enhance the binding of ribonucleotides to the enzyme and the other mutant enzyme has histidine and aspartate residues, instead of Asn43 and Asn44, respectively, to reproduce the natural substitutions found in ribonuclease Ms. Polymorphism of the crystals was observed for wild-type and mutant enzymes. However, orthorhombic crystals, which are virtually all isomorphous to each other, were successfully obtained from wild-type and mutant (Y45W) enzymes by the macroscopic seeding technique using mother crystals of the wild-type ribonuclease T1 complexed with 2'GMP or 3'GMP. The diffraction patterns of these crystals extend beyond 2.5 A resolution and the diffraction data were collected from some of the crystals on a diffractometer up to a range of 2.5 to 1.8 A resolution.

Aspergillus oryzae↗

Cutaneous reactions caused by experimental exposure to jellyfish, Carybdea rastonii.

Dermatitis caused by contact with tentacles of jellyfish was studied on 25 volunteers. Two tentacles cut from a living jellyfish, Carybdea rastonii, were applied on each of the forearms and skin reactions were observed. All volunteers complained of severe pain, which lasted from 10 min to 8 hrs. Erythema and wheal appeared within 3 to 4 min and enlarged for 15 to 20 min. Erythema subsided within 24 hrs to 3 days in all but two individuals. Seven to 13 days after the application, linear erythema and papulo-vesicular lesions with pruritus were observed on the forearms of 15 out of 25 volunteers tested. These flare-up lesions lasted for one week leaving slight pigmentation. Histological findings from the flare-up lesions corresponded to those of allergic contact dermatitis. The lymphocyte response to the jellyfish venom in the subjects who had recurring lesions was greater than that in either the subjects with no recurring lesions or the control group, who was never exposed to jellyfish.

Adult↗

Intraepidermal sebaceous carcinoma: case report.

We report a rare case of intraepidermal sebaceous carcinoma which occurred on the left upper arm of an old woman. Light-microscopic findings revealed that almost all the histopathological lesions were in the epidermis and showed pagetoid spread. The tumor was well differentiated and consisted of germinative, transitional and sebaceous cells. Mitosis and mild and moderate pleomorphism were observed. Ultrastructural findings revealed lipid droplets in the tumor cells although Sudan III staining failed to show any positive materials.

Adenocarcinoma↗

Multiforms of mammalian adenylate kinase and its monoclonal antibody against AK1.

An attempt has been made to determine the intracellular distribution of the multiforms of the adenylate kinase (AK) isoenzymes in mammalian tissues, to shed some light on their physiological roles, especially in energy metabolism. The adenylate kinase zymograms obtained from isoelectric focusing yielded two typical isoform patterns: (1) with a pI greater than or equal to 9 and 8.6, specific for bovine skeletal muscle, heart, aorta and brain, and (2) with a pI = 7.9 and 7.1, specific for liver and kidney. Pattern (1) was attributed to the cytosolic isoenzyme (AK1) as demonstrated by immunostaining with anti-AK1. Pattern (2) was attributed to the mitochondrial isoenzyme (AK2). These results were largely confirmed by chromatofocusing experiments. The AK1 isoenzyme was partially purified from the cytosol fraction of bovine aortic smooth muscle and had an apparent Mr of 23.5 kilodaltons. Its kinetic features are discussed from a comparative standpoint. Finally, the human serum AK1 isoform was also detected by Western blotting with a monoclonal antibody directed against crystalline porcine muscle AK1. These results are to form the basis of further studies on the 'aberrant' adenylate kinase isoenzyme from the serum of Duchenne muscular dystrophics.

Adenylate Kinase↗

Histopathologic and morphometric studies of leptomeningeal vessels in moyamoya disease.

To clarify the morphogenesis of vascular anastomoses in the leptomeninx, we examined the leptomeningeal vessels of six autopsied patients with moyamoya disease who died of cerebral hemorrhage. Sites examined in the brain (the frontal pole, frontoparietal convexity, and lateral occipital region) were selected by the presence of angiographic abnormalities on the convexity of the hemisphere. At all examined sites, neither the vascular density (number of blood vessels per unit length of underlying cortical surface) nor the arterial/venous ratio differed significantly between the patients and 14 controls. All patients showed dilatative changes of both arteries and veins; however, attenuation or disruption of the internal elastic lamina and fibrous intimal thickening were more prominent in those patients who had had moyamoya disease longer. Our results indicate that the leptomeningeal vessels of moyamoya disease are not newly formed but are merely dilated preexisting vessels and that the structural alteration of the vascular walls suggests their adaptability for participation in the collateral circulation at the cerebral surface.

Adolescent↗

A new neurosurgical ventriculoscope--technical note.

A new, flexible fiberoptic ventriculoscope for observation of the ventricles and major cisterns is reported. This device has been safely used to examine patients with obstructive hydrocephalus due to lesions within the lateral and third ventricles or to congenital aqueductal stenosis. With this instrument, a pineal tumor protruding into the third ventricle was successfully observed and photographed in situ.

Adult↗

Antiproliferative activity of mammalian lignan derivatives against the human breast carcinoma cell line, ZR-75-1.

The effect of each of twelve mammalian lignan derivatives on the growth of human mammary tumor ZR-75-1 cells was examined. At a concentration less than 10 micrograms/ml, tumor cell growth was inhibited from 18-68%. The effect of 2,3-dibenzylbutane-1,4-diol(hattalin) was found to be strongest, inhibiting growth by 50% at a concentration (EC50) of 2.1 micrograms/ml. Hattalin inhibited membrane Na+, K(+)-ATPase of canine kidney cortex. It also inhibited the ATPase of the plasma membrane fraction from both cultured cells and a section of human breast cancer tissue at a concentration ranging from 0.5 to 2.0 mM. However, only a few percent of membrane ATPase from either ZR-75-1 cells or breast carcinoma tissue was inhibited by 2.0 mM of ouabain, suggesting that the target ATPase of hattalin was other than ouabain-sensitive ATPase. The relative incorporation of [3H]thymidine per 1 x 10(5) cells into the acid-precipitable fraction of ZR-75-1 cells was not affected by 1-50 micrograms/ml of hattalin, while a marked decrease resulted from 1-10 micrograms/ml of 5-fluorouracil (5-FU). These results suggest that the suppressive effect of hattalin on tumor cell growth may not occur through inhibition of DNA synthesis but rather partly by inhibition of the plasma membrane ATPase other than Na+ and K(+)-dependent ones.

4-Butyrolactone↗

Development of a high-performance electrophoretic light scattering apparatus for mobility determination of particles with their Stokes' radii of several nanometers.

A sophisticated electrophoretic light scattering apparatus was developed. It allows reliable measurements of electrophoretic mobilities of charged macromolecules, such as proteins, nucleic acids and synthetic polyelectrolytes which have been out of the range of the apparatuses of this type aimed at relatively large particles such as microspheres and biological cells. The present apparatus features the monitoring of the electroosmotic flow profile and the determination of the sign of the electrophoretic mobility of an object as well as its high-performance based on the improvement in various facets of acquisition and handling of the signals and data.

Diffusion↗

[The 19mm St. Jude Medical prosthetic aortic valve evaluated by long-term hemodynamic sequelae].

To assess the usefulness of the 19 mm St. Jude Medical (SJM) aortic valve prosthesis for cases of small aortic annulus, post-operative evaluations of pressure gradient of the prosthesis (AVR) and left ventricular (LV) function were performed using bicycle ergometric exercise tests. Seven patients who underwent AVR with 19 mm SJM (19 mm group) and eight control subjects whose SJM was greater than 21 mm in diameter were observed. LV function was assessed by the M-mode echocardiography and the pressure gradients of the prosthesis by the continuous wave Doppler echocardiography. The results were as follows: 1. Mean body surface area (BSA) was 1.35 m2 in the 19 mm group and 1.52 m2 in the control group (p less than 0.01). 2. NYHA functional classes improved equally in both groups after surgery. 3. The post-operative cardiac index at rest measured by cardiac catheterization significantly improved in both groups after surgery. 4. Results of the exercise tests: 1) Left ventricular end-systolic volume index (LVESVI) was decreased on exercise in both groups: from 21.3 to 18.0 ml/m2 in the 19 mm group (p less than 0.01) and from 21.5 to 17.0 ml/m2 in the control group (p less than 0.01). 2) Ejection fraction and fractional shortening significantly increased in both groups on exercise. 3) The pressure gradients significantly increased on exercise in both groups: from 30.4 to 38.3 mmHg in 19 mm group (p less than 0.01) and from 28.8 to 36.6 mmHg in the control group (p less than 0.01). Although the pressure gradients were greater in the 19 mm group, there were no significant differences between the two groups at rest and on exercise. It was concluded that the 19 mm SJM aortic valve prosthesis was acceptable in size for small aortic annulus in elderly women whose body surface area was less than 1.47 m2.

Adult↗

Expression of enolases in T cell tumors and Hodgkin's disease.

Frozen biopsy specimens taken from 30 cases with T cell tumors (8 with T cell acute lymphoblastic leukemia, 8 with T cell lymphoblastic lymphoma, and 14 with peripheral T cell lymphomas), and from 12 with Hodgkin's disease, were investigated using a direct immunohistochemical method to detect alpha-, beta- and gamma-enolases. Normal thymus and lymph node specimens with reactive lymphadenitis were also investigated. Subcortical thymocytes and the majority of deep cortical thymocytes showed reactivity of alpha-/beta-/gamma- approximately +/- -enolases, and medullary thymocytes and small lymphocytes in T zone areas of lymph node showed reactivity of alpha-/beta+/gamma- approximately +/- -enolases. Seven of the 8 cases with T cell acute lymphoblastic leukemia showed reactivity of alpha-/beta-/gamma(-)-enolases or alpha+/beta-/gamma(-)-enolases in leukemic lymphocytes, 7 of the 8 cases with T cell lymphoblastic lymphoma showed reactivity of beta(+)-enolase, and all 14 cases with peripheral T-cell lymphomas showed reactivity of alpha-/beta- approximately +/gamma(+)-enolases in lymphoma cells. All the 12 cases with Hodgkin's disease showed reactivity of alpha-/beta+/gamma(+)-enolases in Reed-Sternberg and Hodgkin's cells. These results indicate the following: (a) The neoplastic cells of T cell acute lymphoblastic leukemia, T cell lymphoblastic lymphoma and peripheral T cell lymphomas present different expressions in each of these three categories. This may imply a difference of maturation and differentiation or activation among neoplastic T lymphocytes. (b) T lymphocytes may switch from alpha- to beta-enolase and from alpha- to gamma-enolase in the course of differentiation and activation. (c) It is worth noting that the Reed-Sternberg and Hodgkin's cells of Hodgkin's disease present an identical expression of enolases.

Antibodies, Monoclonal↗