Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 973 records · Page 54Linked to original sources

PubMed1993

Vitamin B6 deficiency causes activation of RNA polymerase and general enhancement of gene expression in rat liver.

The effect of vitamin B6 deficiency on the activity of RNA polymerase and expression of several mRNAs in rat liver was investigated. The activities of RNA polymerase I and II in the liver of vitamin B6-deficient rats were found to be higher than the control rats by 30%. The expression of several mRNAs, including mRNAs for beta-actin and glyceraldehyde-3-phosphate dehydrogenase, and the content of poly(A)+ RNA were also increased in vitamin deficiency. These observations suggest that vitamin B6 influences gene expression in the liver, at least in part, by modulating the activity of RNA polymerase.

Actins↗

PubMed1993

Deletion of the SH3 domain of Src interferes with regulation by the phosphorylated carboxyl-terminal tyrosine.

A current model for the regulation of the Src protein-tyrosine kinase proposes that the COOH-terminal phosphotyrosine, Tyr-527, binds to the Src homology 2 (SH2) region in an intramolecular interaction that represses the kinase domain. This model is consistent with the activation of Src by mutations in the SH2 domain or COOH terminus. Mutations in the SH3 domain also activate Src, although this region is not thought to bind phosphotyrosine. Seidel-Dugan et al. (Seidel-Dugan, C., Meyer, B. E., Thomas, S. M., and Brugge, J. S. (1992) Mol. Cell. Biol. 12, 1835-1845) have shown that Src mutants with deletions in the SH2 or SH3 domain transform chicken embryo fibroblasts and have increased kinase activity. These mutant proteins are underphosphorylated at Tyr-527, a change that could in itself activate the mutants. Therefore, it is not possible to distinguish whether the SH2 and SH3 domains are needed for phosphorylation of Tyr-527 or for Src to adopt or maintain the repressed state. We have artificially increased the level of Tyr-527 phosphorylation of SH2 and SH3 deletion mutants by coexpressing them with the Tyr-527 kinase, Csk, in yeast cells. We find that both the SH2 and SH3 domains are needed for inhibition of Src by Csk. The SH2 domain is needed for efficient phosphorylation by Csk, both in yeast cells and in vitro. The SH3 domain is needed for Src to be inhibited when Tyr-527 is phosphorylated by Csk. This suggests that the SH3 domain cooperates with the SH2 domain and phosphorylated Tyr-527 to inhibit the kinase domain. Dephosphorylation of SH3 domain mutants at Tyr-527 in fibroblasts could be a consequence of a failure of the proposed SH2/phosphotyrosine interaction.

Animals↗

PubMed1993

Constitutive activation of Src family kinases in mouse embryos that lack Csk.

Csk is a novel cytoplasmic protein-tyrosine kinase that has been shown to inactivate members of the Src family of protein-tyrosine kinases in vitro. To examine the function of Csk in vivo, Csk-deficient mouse embryos were generated by gene targeting in embryonic stem cells. These embryos were developmentally arrested at the 10 to 12 somite stage and exhibited growth retardation and necrosis in the neural tissues. The kinase activity of p60c-src, p59fyn, and p53/56lyn in these embryos was greatly enhanced as an apparent consequence of enhanced specific activity. The increase in kinase activity was associated with an increase in tyrosine phosphorylation of several proteins, especially those around 85 and 120 kd. Thus, these results suggest that Csk indeed acts as an indispensable negative regulator of Src family kinases in vivo.

Animals↗

PubMed1993

Presence of mitochondrial large ribosomal RNA outside mitochondria in germ plasm of Drosophila melanogaster.

Mitochondrial large ribosomal RNA (mtlrRNA) has been identified as a cytoplasmic factor that induces pole cell formation in embryos whose ability to form a germ line has been abolished by treatment with ultraviolet light. In situ hybridization analyses reveal that mtlrRNA is enriched in germ plasm and is tightly associated with polar granules, the distinctive organelles of germ plasm, which supports the idea that mtlrRNA functions in pole cell formation. This suggests that a product from the mitochondrial genome, along with nuclear products, participates in a key event in embryonic development: determination of the germ line.

Abdomen↗

PubMed1993

Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit.

All basophils, mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC) are derived from the multipotential hematopoietic stem cell. Mutations at the c-kit locus resulted in deficiency of MMC and CTMC in both mice and rats. To investigate the role of the c-kit receptor tyrosine kinase for production of basophils, we used white spotting/white spotting (Ws/Ws) mutant rats that have a small deletion at the tyrosine kinase domain of the c-kit gene. When Ws/Ws, nude athymic, and normal (+/+) rats were infected with Nippostrongylus brasiliensis (NB), the number of basophils increased greater than 50-fold in the peripheral blood of Ws/Ws and +/+ rats but did not increase in that of nude rats. Blood histamine concentration increased significantly in Ws/Ws and +/+ rats but did not increase in nude rats. Immature basophils increased greater than 10-fold in the bone marrow of Ws/Ws and +/+ rats but did not increase in that of nude rats. Mature and immature basophils that developed after the NB infection were identified by electron microscopy. The present result confirms that T-cell-derived cytokines are indispensable for the augmented production of basophils and suggests that stimulation via the c-kit receptor may not be necessary for the augmented production.

Animals↗

PubMed1993

Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficient Ws/Ws rats.

Ws/Ws rats have a small deletion at the tyrosine kinase domain of the c-kit gene and are deficient in both mucosal mast cells (MMC) and connective tissue-type mast cells (CTMC). The role of the c-kit receptor in the development of MMC and CTMC was investigated by infecting Ws/Ws and control +/+ rats with Nippostrongylus brasiliensis (NB), which induces T-cell-dependent mast cell proliferation. Although mast cells did not develop in the skin of Ws/Ws rats, a significant number of mast cells developed in the jejunum after NB infection. These mast cells had the MMC protease phenotype (rat mast cell protease [RMCP] I-/II+) and lacked heparin because they were not stained with berberine sulfate. Globule leukocytes were also detected in the mucosal epithelium of these rats. However, the number of MMC and the serum concentration of RMCP II in NB-infected Ws/Ws rats were only 13% and 7% of those of NB-infected +/+ rats, respectively. A small number of mast cells also developed in the lung, liver, and mesenteric lymph nodes of Ws/Ws rats after NB infection. Although mast cells in these tissues had the MMC phenotype throughout the observation period, the increased mast cells in the lung and liver of +/+ rats acquired a CTMC-like phenotype and were RMCP I+/II+, berberine sulfate+, and formalin resistant. These results indicate that the need for the stimulus through the c-kit receptor appears to be greater in the development of CTMC in the skin as well as for CTMC-like mast cells in the lung and liver than for the development of MMC.

Animals↗

PubMed1993

Identification of cells expressing a D type G1 cyclin in matured brain: implication for its role in neuronal function.

The multiple cyclins and their catalytic subunit, cdc2-related kinase, play essential roles in the eucaryotic cell cycle. To examine their potential roles in highly differentiated nervous system, we determined their activity and localization in rat brain. p13suc1 associated histone H1 kinase activity was dramatically increased at the onset of brain maturation. The increased kinase activity was coprecipitated with cyclin D1, a type of G1 cyclin, which also increased with brain maturation. Immunohistochemical analysis demonstrated that anti-cyclin D1-like immunoreactivity was exclusively localized to neurons. From these findings, it is suggested that a type of cdc2-related kinase regulated by cyclin D1 might function in neurons independent of cell cycle progression.

Animals↗

PubMed1993

Reduced diameter and conduction velocity of myelinated fibers in the sciatic nerve of a neurofilament-deficient mutant quail.

The diameter and conduction velocity of myelinated fibers in the sciatic nerve isolated from neurofilament-deficient quail ('quiver') were compared with those from wild quail. The diameter was significantly reduced in quiver, however, the frequency distribution formed three peaks as did that observed in the wild. The fibers were categorized in three groups possessing different conduction velocity. The conduction velocity appeared to be proportional to the diameter in each strain, and was significantly reduced in quiver. These results indicate that, although the diameter and conduction velocity are reduced in quiver fiber, the correlation between the parameters observed in wild quail is still preserved.

Animals↗

PubMed1993

Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.

Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen receptors, causes proliferation and differentiation of B cells or inhibition of their growth. The receptor-mediated signaling involves tyrosine phosphorylation of cellular proteins and rapid activation of Src-like kinases. The amino acid sequences of five proteolytic peptides of p75, a major substrate of protein-tyrosine(s) in the signaling, showed that p75 is the human HS1 gene product. The HS1 gene is expressed specifically in hematopoietic cells and encodes p75HS1, which carries both helix-turn-helix and Src homology 3 motifs. p75HS1 showed rapid tyrosine phosphorylation and association with a Src-like kinase, Lyn, after crosslinking of membrane-bound IgM. Thus, p75HS1 may be an important substrate of Lyn and possibly other protein-tyrosine kinases upon B-cell antigen receptor-mediated signaling.

Adaptor Proteins, Signal Transducing↗

PubMed1993

Chemical synthesis of a comb-shaped, branched stereoregular polysaccharide, 4-O-alpha-D-mannopyranosyl-(1-->6)-alpha-D-mannopyranan.

4-O-alpha-D-Mannopyranosyl-(1-->6)-alpha-D-mannopyranan (7) was prepared via ring-opening polymerization of 1,6-anhydro-2,3-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-alpha-D- mannopyranosyl)-beta-D-mannopyranose (5) using phosphorus pentafluoride as initiator in dichloromethane at -60 degrees C, followed by debenzylation. Compound 5 was obtained via glycosidation of 1,6-anhydro-2,3-O- isopropylidene-beta-D-mannopyranose (1) with 2,3,4,6-tetra-O-benzyl-1-O-trichloroacetimidoyl-alpha-D-mannopyran ose (2) using p-toluenesulfonic acid as catalyst and subsequent transformation of the protecting groups of the resulting 1,6-anhydro-4-O-(2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl)-2,3- O-isopropylidene-beta-D-mannopyranose (3).

Carbohydrate Conformation↗

PubMed1993

Porous polyurethane tubes as vascular graft.

A vascular graft with the inner diameter of about 3 mm was prepared from segmented poly (ether urethane) with an extrusion technique. To make the wall of the vascular grafts porous, NaCl salts were added to the polyurethane solution to be extruded and removed with water extraction after evaporating the solvent in the extruded tube. The wall was reinforced with elastic fiber to prevent dilation. The compliance of the vascular graft measured with the method of Hayashi et al. ranged from 0.2 to 0.3% mmHg -1. The initial Young's modulus was close to that of canine carotic artery, to which the porous polyurethane graft 4-cm long was anastomosed. Vascular grafts were occluded within 2 weeks after implantation, when their pore size was 0, 1.7, or 4.4 mum, whereas those with the pore size of 5.5, 7.4, and 30 mum were patent for longer than 4 weeks. When the vascular graft with the pore size of 30 mum was implanted for 6 months, the luminal surface was covered with neointima, but the endothelium-like cells appearing in the middle of the intima of the vascular graft were immature and sometimes had a very big nucleus. In addition, spindle-shaped, modified smooth muscle cells were noticed in the deep layer of the neointima, especially in the tissue where anastomotic intimal hyperplasia occurred.

Animals↗

PubMed1993

Identification of the alpha-subunits of rod and cone transducin in chicken photoreceptor cells.

The chicken retina has several types of cone photoreceptor cells, each of which contains a visual pigment, chicken red (iodopsin), green, blue or violet. Although biochemical and photochemical properties of these cone pigments have been well characterized, no information is available about the chicken photoreceptor G-protein, transducin, which couples with the visual pigment to convert a photon signal into a cellular response. To identify alpha-subunits of chicken rod and cone transducins (Tr alpha and Tc alpha, respectively), we produced two site-directed antibodies which discriminate between bovine Tr alpha and Tc alpha. Immunohistochemical studies on chicken retinas revealed that the antibody against bovine Tr alpha specifically stained the rod outer segments. On the other hand, the antibody against bovine Tc alpha uniformly stained the outer segments of the double cones and all types of single cones, while the single cones were immunohistochemically classified into three types by using a combination of antibodies against bovine rhodopsin and chicken iodopsin. Immuno-blot analyses demonstrated that the antibody against Tc alpha recognized a single band of chicken photoreceptor protein, whose molecular weight (42,000) was in good agreement with that of bovine Tc alpha (41,000). The antibody against Tr alpha recognized a protein having the same molecular weight as that of bovine Tr alpha (39,000). These observations strongly suggested that all types of chicken cone cells have a single common Tc alpha (42 kDa) structurally related to bovine Tc alpha, though each cone cell type has a distinct visual pigment.

Animals↗

PubMed1993

The unusual development of empyema with multiple alveolobronchiolar fistulae 8 years after non-curative resection and radiation for lung cancer: report of a case.

We present herein the case of a man who developed empyema with multiple lung fistulae 8 years after receiving postoperative radiation for a residual tumor on the bronchial stump. The patient was successfully managed with two-stage surgery, involving an open window thoracotomy, followed by omental flap transfer. This case documents how postoperative radiotherapy that was effective following non-curative resection was also responsible for the development of empyema. Furthermore, although the empyema was successfully treated using the omentum, a small free space remained in the thorax, which resolved within 2 months.

Aged↗

PubMed1993

Immunotactoid glomerulopathy in a child with Down syndrome.

A 9-year-old girl with Down (21-trisomy) syndrome was found to have proteinuria and microscopic haematuria at age 6 years. Proteinuria gradually increased during the next 3 years, although blood pressure and renal function remained normal. The patient exhibited no underlying systemic diseases, monoclonal gammopathy, cryoglobulinaemia or histological evidence of plasmacytoma. A percutaneous renal biopsy revealed immunotactoid glomerulopathy (fibrillary glomerulonephritis) characterized by thickening of the glomerular basement membrane, diffuse mesangial expansion and various-sized acid-Schiff-positive nodules that were intensely positive for IgG, light chains (kappa and lambda) and complement components (C3, C4, C1q) along the glomerular capillaries in the mesangium. Congo red dye and amyloid thioflavine T staining were negative. Fibrils (15-17 nm in diameter--larger than amyloid fibrils) were present in the mesangial area and within the glomerular basement membrane. We are not aware of a previous report of immunotactoid glomerulopathy and a patient with chromosomal abnormalities.

Child↗

PubMed1993

Immunohistochemical localization of C3d fragment of complement and S-protein (vitronectin) in normal and diseased human kidneys: association with the C5b-9 complex and vitronectin receptor.

The localization of C3d, a fragment produced by C3 activation and S-protein (vitronectin), a regulatory factor of C5b-9, was studied immunohistochemically in normal human kidney and renal biopsies from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that C3d was present along the glomerular basement membrane (GBM), tubular basement membrane (TBM) and arterioles, and that S-protein was present in the GBM, mesangium, TBM, and arterioles. Immunoelectron microscopy of isolated basement membranes showed that C3d was localized exclusively on the epithelial side of the GBM, and that S-protein was present along both the epithelial and endothelial sides. In nephritic tissues, glomerular staining of C3d, C5b-9, and S-protein was increased when compared with that in normal tissues. S-protein, frequently co-localized with C3d and C5b-9 neoantigen, was intensely positive in the immune deposits of glomerular capillaries and the mesangial area, overlapping the background staining of GBM and mesangial matrix. S-protein and its receptor were occasionally co-localized in the glomeruli. These findings indicate that C3d and S-protein are normally present in the glomeruli. Co-staining of C3d, C5b-9 neoantigen, and S-protein within the immune deposits of nephritic kidneys suggests in situ binding of S-protein to locally-formed C5b-9 complex, or merely co-distribution of S-protein with the complex, rather than trapping of large molecular SC5b-9 complex from the circulation.

Complement C3d↗

PubMed1993

Evaluation of left ventricular mass: comparison of ultrafast computed tomography, magnetic resonance imaging, and contrast left ventriculography.

We measured and compared left ventricular mass in 20 patients by ultrafast computed tomography (UFCT), magnetic resonance imaging (MRI), and contrast left ventriculography (LVG). Left ventricular mass was calculated by UFCT and MRI in two ways: (1) excluding papillary muscles and trabeculae (LV mass), and (2) including papillary muscles and trabeculae (LV mass + PM&T) by Simpson's method. Left ventricular mass excluding papillary muscles and trabeculae (LV mass) in LVG was calculated by Rackley's method by biplane angiocardiography. LV mass was significantly larger in LVG than in MRI and UFCT (p < 0.01). Although LV mass was significantly larger in MRI than in UFCT (p < 0.01), there was no significant difference in LV mass + PM&T between UFCT and MRI. Interobserver and intraobserver variability showed good correlation of coefficient in both UFCT and MRI. We therefore conclude that left ventricular mass is best measured by including papillary muscles and trabeculae by Simpson's method in UFCT or MRI.

Adult↗

PubMed1993

Successful resection of a recurrent leiomyosarcoma of the pulmonary trunk.

We successfully performed a total resection of the pulmonary artery trunk and replaced it with an equine pericardial xenograft roll in a patient with a recurrent leiomyosarcoma. We believe, based on anatomic and embryologic principles, total rather than partial resection of the pulmonary artery trunk should be the treatment of choice for primary leiomyosarcomas of the pulmonary artery.

Aged↗

PubMed1993

Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model.

A newly synthesized ET(A)-selective antagonist, BQ-123, was examined with respect to its anti-endothelin(ET) action in vitro and in vivo and its effect on blood pressure in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP). In isolated porcine coronary arteries, BQ-123 (0.07 microM to 6.0 microM) shifted the concentration-response curve for ET-1 to the right without affecting the maximal response of ET-1, its pA2 value being 7.35. Intravenous infusion of BQ-123 at a rate of 1.2 and 30 mg/kg/hr produced a significant decrease in blood pressure in 20- to 29-week-old SHRSP, but did not alter blood pressure in 13- to 16-week-old WKY or in 18- to 19-week-old and 40-week-old SHR. The hypotensive effect of BQ-123 depended on the pretreatment blood pressure level. These results suggest that ET-1 is involved in part in the maintenance of high blood pressure in malignant hypertension, as exemplified by SHRSP.

Amino Acid Sequence↗