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Biomedical subjects

Y Nishida

Publications and source records attributed to Y Nishida.

At least 235 records · Page 13Linked to original sources
PubMed1994

Abnormal occurrence of a large chondroitin sulfate proteoglycan, PG-M/versican in osteoarthritic cartilage.

The expression of PG-M in osteoarthritic cartilage was investigated. Cartilage from five hip joints with osteoarthritis (OA) and control cartilage from five knee joints with post-traumatic injury were obtained and analyzed with anti-PG-M antibodies. Control cartilage showed no staining, but in osteoarthritic cartilage there was strong staining of the cytoplasm of chondrocytes with abnormal morphology. The cytoplasm of inflammatory cells invading the osteoarthritic cartilage matrix was also strongly stained which led to determining the sequence of PG-M core protein. The deduced amino acid sequence and homology analysis indicated that PG-M had a complement regulatory protein-like domain, a lectin-like domain, two EGF-like domains from the carboxyl-terminal with an extremely high homology to the respective domains of versican, a large proteoglycan expressed by human fibroblasts. The anti-PG-M antibodies cross-reacted with Ver-27b fusion protein which was expressed by a cDNA clone coding the N-terminal portion of versican core protein. Thus, the immunological and sequencing data suggest that PG-M is a molecule similar to or identical with human versican, and that the material in cartilage reactive to the anti-PG-M antibodies is versican. These findings suggest the PG-M/versican is expressed in osteoarthritic cartilage.

Base Sequence↗
PubMed1994

Myelodysplastic syndrome with t(9;11)(p22;q23) after treatment for B-cell acute lymphoblastic leukemia without epipodophyllotoxins.

Secondary myelodysplastic syndrome (MDS) with t(9;11)(p22;q23) developed in a child after intensive treatment for B-cell acute lymphoblastic leukemia diagnosed 12 months earlier. His chemotherapy had consisted mainly of cyclophosphamide and methotrexate, but no epipodophyllotoxins. The combination of MDS, the cytogenetic anomaly involving bands at 11q23 and no previous exposure to epipodophyllotoxins represents a unique case of therapy-related leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Alternative cell fate choice induced by low-level expression of a regulator of protein phosphatase 2A in the Drosophila peripheral nervous system.

The Drosophila gene twins encodes the regulatory B subunit of type 2A protein phosphatase. Here we report that its partial loss-of-function mutations caused abnormal morphogenesis in the adult peripheral nervous system. In wild-type flies, the mechanoreceptor, one major class of sensory organs, is composed of four specialized cells (one neuron and three accessory cells) that are derived from a single precursor cell. The hypomorphic twins mutations did not block division of this precursor, but most likely altered cell fate in this lineage to produce only accessory cells that form sensory structures. Stepwise reductions of twins protein enhanced this transformation. In these mutants, another regulatory subunit, A, and the catalytic subunit, C, of the phosphatase were expressed at normal levels. Therefore, the modulation of the phosphatase activity by the B subunit appears to be crucial for specification of neural cell identity.

Alleles↗
PubMed1994

Effects of DNA polymerase beta gene over-expressed in transgenic Drosophila on DNA repair and recombination.

DNA polymerase beta (pol beta) cDNA of rat fused to an enhancer-promoter region plus a poly(A) signal sequence of actin 5C gene of Drosophila (abbreviated pol beta) was transferred to the Drosophila genome. Three of four constructed transgenic strains possessing transgene pol beta on different chromosomes were studied. Levels of the pol beta transcript and those of the polymerization activity of pol beta were markedly elevated in cultured cells transfected with pol beta-bearing vectors as well as in embryos of the transgenic strains. The popular idea that DNA polymerase beta participates in DNA repair was not supported by the observation that a pair of a normal and a pol beta strain, and the other pair of a mei-9 mei-41 (DNA-repair deficient double mutations) strain and a pol beta mei-9 mei-41 strain, showed no difference in survival within each pair after treatment with ultraviolet light, methylmethane sulfonate and mitomycin C. The other idea that DNA polymerase beta participates in recombination was supported by the findings that spontaneous frequency of recombination, either meiotic or mitotic, is significantly higher in a transgenic pol beta strain than in a non-transgenic strain. The enhanced recombination frequency in the pol beta strain may, however, reflect an indirect effect of over-produced pol beta proteins on chromosomal stability. Whatever the direct effect of rat pol beta is, the transgenic pol beta flies will be useful for study of the physiological role of pol beta and the mechanism of recombination.

Animals↗
PubMed1994

Changes of calmodulin concentration and cyclic 3',5'-nucleotide phosphodiesterase activities in cardiac muscle of hyper- and hypothyroid rats.

To investigate the effect of thyroid hormone on cardiac muscle dysfunction in hyper- and hypothyroid states, we evaluated cyclic 3',5'-nucleotide metabolism by measuring cyclic 3',5'-nucleotide phosphodiesterase activity and calmodulin concentrations in the cardiac muscles of hyper- and hypothyroid rats. Cyclic AMP (cAMP) concentration was significantly high in the cardiac muscle of hyperthyroid rats and low in that from hypothyroid rats compared with control rats. Cyclic AMP and cyclic GMP phosphodiesterase activities were significantly decreased in the soluble fraction of cardiac muscle from hyperthyroid rats and markedly increased in this fraction in hypothyroid rats compared with normal animals. Calmodulin concentration was high in hyperthyroid and low in hypothyroid rats. It was concluded from these findings that low cAMP-phosphodiesterase activity might, in part, bring about the high concentration of cAMP. Calmodulin was significantly high in the cardiac muscle of hyperthyroid rats and the reverse was the case in hypothyroid rats compared with normal rats. The implication is that, in hyper- and hypothyroid states, these changes may play an important role in cardiac function via their effect on cyclic nucleotide and Ca2+ metabolism.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

[A study on predicting factors of the effect of intra-arterial infusion chemotherapy in patients with bladder cancers: the usefulness of in-vitro chemisensitivity test measuring intracellular ATP contents (ATP assay)].

We studied a relationship between in vitro sensitivity of the tumors to anti-cancerous drugs and histopathological effectiveness of an intra-arterial infusion chemotherapy in 15 patients with bladder cancers. The in vitro sensitivity test was performed by measuring intra-cellular ATP contents (ATP assay). The intra-arterial chemotherapy were performed by injecting methotrexate (MTX), adriamycin (ADM) and eisplatin (CDDP) from the internal iliac artery. When the intra-cellular ATP contents of the tumor cells treated with an anti-cancerous drug decreased to less than 50% of the untreated tumor cells, the tumor was evaluated as sensitive to the drug. The effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. When the histopathological responses of higher than grade 2 were observed in the tumor, the chemotherapy was evaluated as effective. In 8 of 9 tumors sensitive to ADM, chemotherapy were effective histopathologically and in all 6 tumors resistant to ADM, histopathological response of the chemotherapies were poor. The overall coincidence ratio between sensitivity to ADM and the histopathological effectiveness of the chemotherapy was 93%, showing statistically significant correlation. In 7 of 12 tumors sensitive to CDDP, the chemotherapies were effective and in 2 of 3 tumors resistant to CDDP, the chemotherapies were ineffective. Although the overall coincidence ratio between the sensitivities to CDDP and chemotherapeutic effectiveness was 60%, there was no significant correlation between them. In 7 of 8 tumors sensitive to both of ADM and CDDP, the chemotherapies were effective and in 6 of 7 tumors resistant to at least one of them, the chemotherapies were ineffective. (ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Bilateral ptosis with ophthalmoplegia in a 72-year-old woman with diabetes.

Ophthalmoplegia is common cranial neuropathy of Diabetes. In case of 3rd nerve involvement, usually unilateral extra ocular muscles are affected. However, ptosis is very rare in patients with diabetic neuropathy. In this report, we describe bilateral ptosis with ophthalmoplegia in diabetes. In ophthalmoplegia associated with diabetes, ischemic nerve infarction was reported. We treated this patient with Lipo prostaglandin (PG) E1. Since then, increased platelet aggregation activity was found in this patient. After two months, the symptoms of this patient were improved.

Aged↗
PubMed1994

Multiple functions of raf proto-oncogene during development from analysis of a temperature-sensitive mutation of Drosophila.

A temperature-sensitive (ts) mutation of Drosophila melanogaster for D-raf, encoding a serine/threonine protein kinase, was newly induced by EMS-treatment. Temperature-shift experiments on the ts mutant revealed that D-raf is required during most of the developmental stages, and confirmed the previously reported roles of D-raf in the regulation of cell proliferation and in the determination of cell fates at terminal regions of the embryo (Nishida et al., EMBO J. 7:775-781, 1988; Ambrosio et al., Nature 342:288-291, 1989a). Detailed analysis of cell proliferation demonstrated the role of D-raf at other than M-phase in cell cycle. TSP analysis during pupal stages revealed yet another role of D-raf in eclosion. Mosaic analysis of an eclosion-defective hypomorphic mutation revealed the tissue responsible for this defect to be the muscle and/or nervous system in the thorax. Molecular lesion associated with the ts mutation was found to be an alteration of an amino acid residue in a highly conserved region that defines the kinase subdomain VIII. Molecular analysis of null mutations also suggested the importance of the kinase domain for the biological functions of D-raf. Elucidation of the multi-functional nature of signal transducers is of great importance for our understanding of the molecular mechanisms of development, and the ts mutation for pleiotropic D-raf obtained in this study promises to be useful for dissecting signal transduction pathways during development.

Animals↗
PubMed1994

[Clinical evaluation of dynamic MRI in the re-diagnosis of therapeutic effect and recurrence after transcatheter arterial embolization for hepatocellular carcinoma].

We evaluated re-diagnostic ability of dynamic MRI as compared with T2 weighted image in the diagnosis of primary therapeutic effect and tumor recurrence after transcatheter arterial embolization (TAE) for hepatocellular carcinoma. Thirty-four nodules in 30 patients with hepatocellular carcinoma were estimated based on operative and angiographic findings. According to the time when dynamic MRI was taken, nodules were classified as a short-term observation group consisting of 15 nodules obtained within a month after TAE, or as a long-term observation group consisting of 19 nodules obtained over a month after TAE. In the short-term observation group, sensitivity, specificity, accuracy was 89%, 100%, 93% on dynamic MRI and 78%, 67%, 73% on T2WI, respectively. In the long-term observation group, these were 94%, 100%, 95% on dynamic MRI and 100%, 33%, 89% on T2WI and 94%, 67%, 89% on Lipiodol-CT, respectively. In both groups, dynamic MRI was superior in accuracy. Conclusively, we consider that dynamic MRI is a most accurate diagnostic method that should be added to routine MRI after TAE. Especially in the case diagnosed positive on T2WI, the usefulness of dynamic MRI should be emphasized to determine the schedule of the therapy, because the cases that were false positive on T2WI were accurately diagnosed on dynamic MRI.

Aged↗
PubMed1993

Survival of syngeneic and allogeneic grafted bone in transgenic mice.

The viability of syngeneic, allogeneic and xenogeneic bone grafts was investigated in mice and rats by the polymerase chain reaction method using carcinoembryonic antigen transgenic mice as donors. DNA of syngeneic grafts was detected more than 24 weeks after bone grafting. In contrast, the DNA of allogeneic thymic grafts and xenogeneic bone grafts disappeared by 3 weeks after transplantation. However, DNA of allogeneic bone grafts was detected until 20 weeks after transplantation. Histological examination at 12 weeks after surgery detected some donor nuclei in both syngeneic and allogeneic bone grafts.

Animals↗
PubMed1993

cDNA cloning of PG-M, a large chondroitin sulfate proteoglycan expressed during chondrogenesis in chick limb buds. Alternative spliced multiforms of PG-M and their relationships to versican.

We have isolated cDNA clones encoding the core protein of PG-M, a large chondroitin sulfate proteoglycan that has been shown to be expressed in the prechondrogenic condensation area of the developing chick limb buds (Shinomura T., Jensen, K. L., Yamagata, M., Kimata, K., and Solursh, M. (1990) Anat. Embryol. 181, 227-233). The amino acid sequence deduced from the cDNA analysis revealed the presence of a hyaluronic acid binding domain at the amino-terminal side and two epidermal growth factor-like domains, a lectin-like domain, and a complement regulatory protein-like domain at the carboxyl-terminal side. These domains show an extremely high homology to corresponding domains of a human fibroblast large chondroitin sulfate proteoglycan, versican. Such evolutionally conserved structures in the PG-M core protein might be involved in important biological functions of this molecule. On the other hand, the chondroitin sulfate attachment domain at the middle region of the PG-M core protein shows no significant amino acid sequence homology to the corresponding domain of the versican core protein. Further, the chondroitin sulfate attachment domain of PG-M core protein is about 100 kDa larger than that of versican core protein. The finding of alternatively spliced forms of the PG-M core protein suggests that versican might be one of the multiple forms of PG-M.

Alternative Splicing↗
PubMed1993

Determination of the lipase stereoselectivities using circular dichroism (CD); lipases produce chiral di-O-acylglycerols from achiral tri-O-acylglycerols.

A general method was described to determine the optical purity of 1,2 (or 2,3)-di-O-acylglycerols via a key compound, 3 (or dibenzoyl-sn-glycerol (3 or 3'). The chiral di-O-acylglycerols were first silylated and the acyl groups were removed by the Grignard degradation to 3 (or 1) O-tert-butyldimethylsilyl-sn-glycerol and subsequent benzoylation lead to the key compound 3 or 3' without racemization. The optical purity was determined from the strong exciton Cotton effect of 3 (+) or 3' (-) at 238 nm in the concentration of ca. 1 mM. The method was successfully applied to determine the stereoselectivities of lipases (EC 3.1.1.3) from three origins, bacteria, mammal and fungus such as Pseudomonas (AP, 89% optical purity, sn-1 preference), porcine pancreatin (PPL, 9.3% optical purity, sn-3 preference) and Candida (CC, sn-2 preference) using tripalmitin. The similar studies were extended to tri-O-benzoylglycerol (6) and tri-O-(cyclohexanecarbonyl)glycerol (5). All the enzymes showed high stereoselectivities with tri-O-benzoylglycerol. PPL and AP showed high and low stereoselectivities with tri-O-(cyclohexanecarbonyl)glycerol, while low and high stereoselectivities with tri-O-palmitoylglycerol, respectively. The results show that the stereoselectivities are ruled by the origins of lipases and acyl groups. The structures of the recognition site might be associated with enantioselectivities of the enzymes.

Animals↗
PubMed1993

A protein kinase similar to MAP kinase activator acts downstream of the raf kinase in Drosophila.

D-raf, a Drosophila homolog of Raf-1, plays key roles in multiple signal transduction pathways. Dsor1, a putative factor downstream of D-raf, was genetically identified by screening of dominant suppressors of D-raf. Dsor1Su1 mapped on X chromosome significantly suppressed the D-raf mutant phenotypes, and the loss-of-function mutations of Dsor1 showed phenotypes similar to those of the D-raf null mutations. Dsor1Su1 also significantly suppressed the mutations of other terminal class genes acting further upstream of D-raf. Molecular cloning of Dsor1 revealed its product with striking similarity to the microtubule-associated protein (MAP) kinase activator and yeast PBS2, STE7, and byr1. Our genetic results demonstrate the connection between raf and the highly conserved protein kinase cascade involving MAP kinase in vivo.

Amino Acid Sequence↗
PubMed1993

Molecular characterization and expression of the Drosophila Ca2+/calmodulin-dependent protein kinase II gene. Identification of four forms of the enzyme generated from a single gene by alternative splicing.

Four cDNA sequences encoding Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) were isolated from a Drosophila adult head cDNA library using rat CaM kinase II alpha and beta cDNA sequences under low stringency hybridization conditions. These cDNA clones encoded polypeptides of 490, 509, 516, and 530 amino acids, which are identical to one another except for amino acid insertions or deletions near the carboxyl-terminal of the putative "link" segment. These polypeptides showed considerable similarity to rat brain CaM kinase II with more than 70% of the amino acids being identical. The Drosophila adult head contains three major species of CaM kinase II with molecular masses of 55, 58, and 60 kDa. These cross-react with anti-rat CaM kinase II antibody. An expression study of the four cDNA sequences in mammalian cells revealed that the polypeptides of 490, 509, and 530 amino acids that had been predicted from the cDNA sequences correspond to the 55-, 58-, and 60-kDa polypeptides found in the head, respectively, and all exhibited enzymatic properties similar to those of rat brain CaM kinase II, including self-regulation. The Drosophila CaM kinase II gene was located in segment 102E-F on the fourth chromosome and consisted of at least 16 exons spanning approximately 20 kilobase pairs. Four forms of the enzyme are generated from a single gene by alternative splicing. Transcripts of CaM kinase II are expressed in great quantities in the central nervous system in the late embryonic stage of development and are more abundant in the head than in the body of the adult fly.

Amino Acid Sequence↗
PubMed1993

The usefulness of postoperative continuous epidural morphine in abdominal surgery.

The influence of continuous epidural morphine on the recovery course of intestinal activity, urinary function, and ambulation after surgery was studied in 40 patients who underwent either gastrectomy for gastric cancer or cholecystectomy for cholelithiasis. Compared with a control group of patients whose postoperative pain was managed by pentazocine or hydroxyzine as before, the length of time before passing flatus or faeces was significantly shortened in the morphine groups (P < 0.05). Following gastrectomy, the urinary catheter was able to be removed significantly earlier in the morphine group (P < 0.05) although there was no statistical difference between both cholecystectomy groups. The morphine group experienced no difficulty with postoperative ambulation and exercise, although the difference in time before ambulation between the two groups was not considered significant. The results of this study led us to conclude that the postoperative continuous epidural infusion of morphine would be more beneficial following major abdominal surgery than the conventionally used methods of administering postoperative analgesia.

Abdomen↗