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Biomedical subjects

T Katayama

Publications and source records attributed to T Katayama.

At least 73 records · Page 4Linked to original sources

Involvement of distinct signaling pathways in activin-induced increases in FSH secretion and enlargement of FSH cell population in the rat pituitary.

Activin-A induces increases in FSH secretion, as well as the number of immunoreactive FSH cells, in cultured rat pituitary cells. In this study, we examined whether mechanisms involved in these two actions of activin-A are identical or not, with respect to the involvement of cellular proliferation and of Ca2+-dependent signaling pathways. Treatment with activin-A (25 ng/ml) for 48 h caused increases in the number of cultured rat anterior pituitary cells that incorporated BrdU, a thymidine analog. The stimulatory effects of activin-A on FSH secretion and on the percentage of immunoreactive FSH cells were, however, not inhibited by the presence of the mitotic inhibitor cytosine arabinoside. On the other hand, the stimulatory effect of activin-A on the percentage of immunoreactive FSH cells was completely blocked in the presence of the Ca2+/calmodulin kinase inhibitor KN-62 or the L-type Ca2+ channel blocker nicardipine. Neither of these inhibitors, however, revealed significant influence on the effect of activin-A on FSH secretion. These results suggest that activin-A exhibits its dual effect on FSH cells without causing cellular proliferation. Furthermore, activin-A appears to induce increases in FSH secretion and enlargement of FSH cell population through distinct intracellular signaling pathways, the former through Ca2+-independent and the latter through Ca2+-dependent mechanisms.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

The fibronectin-derived anti-adhesive peptide III14-2 suppresses adhesion and apoptosis of leukemic cell lines through down-regulation of protein-tyrosine phosphorylation.

We previously found that fibronectin (FN) has a cryptic functional site (YTIYVIAL, #1848-1855) opposing to cell adhesion to extracellular matrix (ECM). The present study demonstrates that the FN peptide containing this anti-adhesive site, termed peptide III14-2, affects programmed cell death (PCD) (apoptosis) as well as cell adhesion by down-regulating protein-tyrosine phosphorylation. Peptide III14-2 suppressed the integrin alpha5beta1-mediated adhesion of leukemic cell lines (K562 and HL60), and protein tyrosine phosphatase inhibitor, 1 microM phenylarsine oxide (PAO) blocked the anti-adhesive effect of peptide III14-2. These leukemic cells underwent PCD when exposed to PAO at the higher concentration (5 microM), as judged by nuclear and DNA fragmentations, and which was reversed by tyrosine kinase inhibitor, genistein. Peptide III14-2 suppressed the PAO-induced PCD, whereas a control peptide in which the anti-adhesive sequence YTIYVIAL is scrambled, was inactive. Western blotting showed that PAO stimulated the tyrosine phosphorylation of cellular proteins including focal adhesion kinase and that peptide III14-2 inhibited them, suggesting that protein-tyrosine phosphorylation represents a common early signal for the adhesion and PCD. The anti-adhesive site of FN molecule may play a crucial role also in a variety of cellular processes other than adhesion and PCD by down-regulating protein-tyrosine phosphorylation.

Apoptosis↗

A case of normotensive scleroderma renal crisis after high-dose methylprednisolone treatment.

A 68-year-old male was admitted for interstitial pneumonia associated with scleroderma. High-dose methylprednisolone was administered for treatment of the pneumonitis. Two weeks later, anemia, thrombocytopenia and progressive increase in BUN, creatinine and LDH were observed. Although the blood pressure remained normotensive, renal biopsy showed thrombosis of the polar arterioles and glomerular capillaries. The affected interlobular artery included concentric intimal thickening and thrombosis in the lumen. Our findings suggested that the antecedent use of high-dose corticosteroids is involved in precipitating normotensive renal crisis. Corticosteroids should be used in low doses and with great caution in scleroderma patients.

Aged↗

[Recovery from pancytopenia and liver dysfunction after administration of thiamazole for hyperthyroidism].

A 45-year-old woman was referred to our hospital because of hyperthyroidism complicated by atrial fibrillation and heart failure. Laboratory data revealed pancytopenia, with a white blood cell count of 2,600/microliter, red blood cell count of 330 x 10(4)/microliter, and platelet count of 6.2 x 10(4)/microliter. The patient had normal transaminase levels, but tests for hepaplastin and cholinesterase showed values of 34% and 1.4 U/ml, respectively, indicating liver dysfunction. There was also decreased excretion of indocyanine green. After initiation of treatment with 30 mg thiamazole and 20 mg propranolol daily, the patient's thyroid function normalized and the other abnormal laboratory findings such as pancytopenia and liver dysfunction also disappeared. Pancytopenia is a rare complication of hyperthyroidism. In this case, various laboratory abnormalities were normalized by antithyroid therapy alone, indicating that the hyperthyroidism itself was closely related to the pathogenesis of pancytopenia and liver dysfunction.

Antithyroid Agents↗

Replication cycle-coordinated change of the adenine nucleotide-bound forms of DnaA protein in Escherichia coli.

The ATP-bound but not the ADP-bound form of DnaA protein is active for replication initiation at the Escherichia coli chromosomal origin. The hydrolysis of ATP bound to DnaA is accelerated by the sliding clamp of DNA polymerase III loaded on DNA. Using a culture of randomly dividing cells, we now have evidence that the cellular level of ATP-DnaA is repressed to only approximately 20% of the total DnaA molecules, in a manner depending on DNA replication. In a synchronized culture, the ATP-DnaA level showed oscillation that has a temporal increase around the time of initiation, and decreases rapidly after initiation. Production of ATP-DnaA depended on concomitant protein synthesis, but not on SOS response, Dam or SeqA. Regeneration of ATP-DnaA from ADP-DnaA was also observed. These results indicate that the nucleotide form shifts of DnaA are tightly linked with an epistatic cell cycle event and with the chromosomal replication system.

Adenine↗

Isolation and characterization of novel cold-sensitive dnaA mutants of Escherichia coli.

We developed an efficient method for isolation of novel dnaA mutations based on PCR mutagenesis in the presence of manganese ion and shuffling of dnaA-carrying plasmids in a dnaA deletion host bacterium. Using this system, we obtained 30 cold-sensitive mutants from 4000 clones carrying plasmids with a mutagenized dnaA gene. All 27 cold-sensitive mutants analyzed were defective in DNA replication; none had a DnaAcos (over-initiation) phenotype. Nucleotide sequencing revealed that novel 15 alleles (mutations in 14 amino acid residues) are responsible for the cold-sensitive phenotype and are all located in the carboxy-terminal half of the DnaA protein.

Adaptation, Physiological↗

The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein.

DP5, which contains a BH3 domain, was cloned as a neuronal apoptosis-inducing gene. To confirm that DP5 interacts with members of the Bcl-2 family, 293T cells were transiently co-transfected with DP5 and Bcl-xl cDNA constructs, and immunoprecipitation was carried out. The 30-kDa Bcl-xl was co-immunoprecipitated with Myc-tagged DP5, suggesting that DP5 physically interacts with Bcl-xl in mammalian cells. Previously, we reported that DP5 is induced during neuronal apoptosis in cultured sympathetic neurons. Here, we analyzed DP5 gene expression and the specific interaction of DP5 with Bcl-xl during neuronal death induced by amyloid-beta protein (A beta). DP5 mRNA was induced 6 h after treatment with A beta in cultured rat cortical neurons. The protein encoded by DP5 mRNA showed a specific interaction with Bcl-xl. Induction of DP5 gene expression was blocked by nifedipine, an inhibitor of L-type voltage-dependent calcium channels, and dantrolene, an inhibitor of calcium release from the endoplasmic reticulum. These results suggested that the induction of DP5 mRNA occurs downstream of the increase in cytosolic calcium concentration caused by A beta. Moreover, DP5 specifically interacts with Bcl-xl during neuronal apoptosis following exposure to A beta, and its binding could impair the survival-promoting activities of Bcl-xl. Thus, the induction of DP5 mRNA and the interaction of DP5 and Bcl-xl could play significant roles in neuronal degeneration following exposure to A beta.

Alzheimer Disease↗

Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats.

The effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y (NPY), on the behavior of rats was investigated. An immediate increase in face washing activity was observed after injection of orexin A or orexin B, but not NPY. Orexin A had a more potent effect on face washing behavior than orexin B. Grooming and burrowing activities also increased significantly after injection of orexin A, whereas, orexin B significantly increased burrowing and searching behavior. Feeding behavior and food consumption increased dramatically within 10 min of injection of NPY. Although the significant increase in feeding behavior was also observed after injection of orexin A, total food intake did not change significantly. These results suggest that orexin may be involved in the regulation of several other behavioral activities in rats, besides feeding.

Animals↗

A case of spinocerebellar ataxia type 6 mimicking olivopontocerebellar atrophy.

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant, slowly progressive cerebellar ataxia without multisystem involvement. We report a 57-year-old woman with genetically confirmed SCA6 who showed clinical features of olivopontocerebellar atrophy. Conventional T2-weighted and FLAIR MRI demonstrated high signal in the middle cerebellar peduncles, in addition to mild atrophy of the pons and cerebellum.

Female↗

Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response.

Missense mutations in the human presenilin-1 (PS1) gene, which is found on chromosome 14, cause early-onset familial Alzheimer's disease (FAD). FAD-linked PS1 variants alter proteolytic processing of the amyloid precursor protein and cause an increase in vulnerability to apoptosis induced by various cell stresses. However, the mechanisms responsible for these phenomena are not clear. Here we report that mutations in PS1 affect the unfolded-protein response (UPR), which responds to the increased amount of unfolded proteins that accumulate in the endoplasmic reticulum (ER) under conditions that cause ER stress. PS1 mutations also lead to decreased expression of GRP78/Bip, a molecular chaperone, present in the ER, that can enable protein folding. Interestingly, GRP78 levels are reduced in the brains of Alzheimer's disease patients. The downregulation of UPR signalling by PS1 mutations is caused by disturbed function of IRE1, which is the proximal sensor of conditions in the ER lumen. Overexpression of GRP78 in neuroblastoma cells bearing PS1 mutants almost completely restores resistance to ER stress to the level of cells expressing wild-type PS1. These results show that mutations in PS1 may increase vulnerability to ER stress by altering the UPR signalling pathway.

Alzheimer Disease↗

Diffuse large B cell lymphoma expressing the natural killer cell marker CD56.

The expression of the natural killer (NK) cell antigen, CD56, in hematological malignancies is rare. However, there are several reports that some hematological malignancies, such as T/NK cell lymphoma, multiple myeloma (MM) and acute myeloid leukemia (AML), express this molecule. In B cell non-Hodgkin's lymphomas (NHL), however, very limited number of cases have been reported to express CD56 molecule. Although one study has recently described that half of microvillous B cell lymphoma (MVL), an uncommon subset of large cell lymphoma, expressed CD56, there have been no reports about most common type of B-NHL, diffuse large B cell lymphoma (DLBL) other than a mention of weak CD56 expression in one of 83 DLBL. We herein presented the first case of diffuse large B cell lymphoma expressing CD56 clearly. The immunophenotype determined by immunostaining and flow cytometric analysis was CD10+, CD19+, CD20+, CD45RO-, CD3- and CD56+. On immunohistochemical study, neither bcl-2 nor TIA-1 was positive for tumor cell. Monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was detected, and the sequence analysis of the variable region of IgH (VH) suggested that this tumor was derived from antigen selected post germinal center B cell. Conventional combination chemotherapy (CHOP) was administered, and the patient has still been in complete remission for 10 months.

Adolescent↗

Video-assisted transsternal radical esophagectomy: three-field lymphadenectomy without thoracotomy for esophageal cancer.

To reduce the invasiveness of radical esophagectomy, we developed a new approach: video-assisted transsternal radical esophagectomy (VATRE). This article presents the operative techniques and our initial results. In our new procedure, cervical U-shaped and longitudinal sternoabdominal incisions are made, and a complete midline sternotomy is carried out. Lymph node clearance from the neck to the upper mediastinum and from the lower mediastinum to the upper abdomen is performed under direct vision. In the middle mediastinum, a video-assisted technique is used to dissect the lymph nodes. After esophageal resection and three-field lymphadenectomy, reconstruction is performed. One-lung ventilation is unnecessary. We have performed this procedure in two cases. These patients had no major complications and recovered more rapidly than patients undergoing conventional transthoracic esophagectomy. Our initial experience shows that VATRE is a technically feasible and less invasive procedure for cancer surgery, and it enables us to easily perform three-field lymphadenectomy.

Aged↗

The influence of the maternal heart rate on the uterine artery pulsatility index in the pregnant ewe.

We investigated the influence of the maternal heart rate on the uterine artery pulsatility index in pregnant ewes. We used an external pacemaker to alter the heart rate of 5 pregnant ewes at 16-17 weeks of pregnancy and examined the effect of changes in the maternal heart rate on the uterine artery flow velocity waveforms and the pulsatility index, as determined by Doppler velocimetry. The uterine artery pulsatility index showed a significant negative correlation with the maternal heart rate. There were no significant changes in other hemodynamic parameters. The maternal heart rate had a significant influence on the uterine artery pulsatility index.

Animals↗

Fetal compromise assessed by Doppler ultrasound of venous flow in pregnancy-induced hypertension.

The purpose of this study was to determine the change of venous flow patterns in the inferior vena cava of fetuses in pregnancy-induced hypertension (PIH). We studied 80 normal pregnant women and 46 pregnant women with PIH and their fetuses. We determined the pulsatility index (PI) for arterial vessels, the ratio of peak flow velocities in early diastole and late diastole (E/A) in atrioventricular valves, and the preload index for the inferior vena cava. Twelve of the 46 PIH women showed an umbilical artery PI higher than the 95th percentile in normal pregnant women. Five of them demonstrated a decreased middle cerebral artery PI. Three of the 5 had an increased mitral E/A. Two of them had a decreased tricuspid E/A, an increased preload index, and a poor prognosis. An increased preload index suggests severe compromise in fetuses with a redistribution of arterial and intracardiac blood flow.

Adult↗

Transcriptional regulation of tyrosine phenol-lyase gene mediated through TyrR and cAMP receptor protein.

Using a lac reporter system in Escherichia coli, we showed that the expression of E. herbicola tpl was regulated through TyrR and cAMP receptor protein. Three TyrR boxes upstream of tpl were essential for full expression. The results suggested that the tyrosine-mediated TyrR hexamerization was an important process. The DNA bending between two TyrR boxes, which is triggered by the binding of cAMP receptor protein, may facilitate the conformational change of TyrRs.

Artificial Gene Fusion↗