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Biomedical subjects

Y Terada

Publications and source records attributed to Y Terada.

At least 127 records · Page 7Linked to original sources

Serum leptin levels do not rise during pregnancy in age-matched rats.

The serum leptin profile and its production in adipose tissue during pregnancy and lactation were investigated along with changes in appetite and factors reflecting nutritional status in 11-week-old rats. Serum leptin levels in pregnant rats were stable except on day 20 of pregnancy and significantly reduced during lactation compared to nonpregnant rats (P < 0.001). Circulating leptin levels corresponded with changes in appetite during pregnancy and postparturition. Leptin mRNA in parametrial adipose tissue reflected the circulating levels, also being significantly reduced during late pregnancy and during lactation (P < 0.05). Leptin mRNA expression was observed in placenta, but the amount suggested little influence on circulating leptin levels. These results indicate that reduction in leptin mRNA in parametrial adipose tissue and circulating leptin levels may increase appetite during late pregnancy and lactation and may play a role in regulating metabolic homeostasis around parturition in rats.

Adipose Tissue↗

Human AIM-1: cDNA cloning and reduced expression during endomitosis in megakaryocyte-lineage cells.

The rat AIM-1 gene encoding an Aurora- and Ipl1-like midbody-associated protein serine/threonine kinase has a mitotic regulator function playing a key role in the onset of cytokinesis during mitosis. This report presents a cDNA sequence and megakaryocytic differentiation-dependent expression profile of the human AIM-1 gene. The nucleotide sequences of the human AIM-1 were identified from cDNAs of three cell lines, including cervical carcinoma HeLa cells, colorectal tumor SW480 cells, and normal human diploid skin fibroblast NHDF cells, and no mutation was found. The expression levels of AIM-1 transcript were markedly reduced during differentiation into megakaryocytic cell lineage in human leukemia cells induced by 12-o-tetradecanoyl-phorbol-13-acetate (TPA), suggesting that the downregulation of AIM-1 contributes to the differentiation by repeated duplication of DNA without cytokinesis (endomitosis).

Amino Acid Sequence↗

Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells.

Aurora- and Ipl1-like midbody-associated protein (AIM-1) is a serine/ threonine kinase that is structurally related to Drosophila aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. A kinase-negative form of AIM-1 inhibits the formation of cleavage furrow without affecting nuclear division, indicating that the gene controls entry into cytokinesis during M phase in mammalian cells. A human gene that encodes the protein AIM-1 was overexpressed in colorectal and other tumor cell lines. The regulation of AIM-1 expression was cell cycle dependent in normal and tumor cells, and the maximum accumulation was observed at G2-M. Exogenous overexpression of wild-type AIM-1 produced multinuclearity in human cells, suggesting that the excess amount of AIM-1 had a dominant-negative effect on the overexpressing cells. In long-term culture of AIM-1-overexpressing cells, multiple nuclei in a cell were occasionally fused, and then an increased ploidy and aneuploidy were induced. Thus, the overexpression of AIM-1 in colorectal tumor cell lines is thought to have a causal relationship with multinuclearity and increased ploidy. Cytokinesis error caused by AIM-1 overexpression is a major factor in the predisposition of tumor cells to the perturbation of chromosomal integrity that is commonly observed in human neoplasia. Thus, defects of pathways essential for mitotic regulation are important during human cancer development.

Amino Acid Sequence↗

Specific detection of phosphatidylinositol 3,4,5-trisphosphate binding proteins by the PIP3 analogue beads: an application for rapid purification of the PIP3 binding proteins.

Phosphatidylinositol (PI) 3-kinase is known as one of the key molecules involved in the various biological events such as vesicle trafficking, cytoskeletal rearrangements and cell survival. T clarify the molecular basis underlying these events, we have tried to identify the proteins that can interact with phosphatidylinositol 3,4,5-trisphosphate (PIP3), the lipid product of PI3-kinase. Using a new PIP3 analogue, PIP3-APB, we synthesized an affinity column for PIP3 binding proteins. This enabled us to purify and identify several PIP3 binding proteins such as Tec tyrosine kinase, Gap1m, and Akt, as the candidates for the downstream molecules of PI3-kinase. All of these proteins contain PH domains, possible binding sites for phospholipids. Studies with various deletion mutants of Tec or Gap1m revealed that their PH domains are indeed the binding sites for PIP3. These results demonstrate that this PIP3-analogue binds various PIP3 binding proteins with high specificity and may be useful to elucidate the downstream mechanisms of PI3-kinases-mediated signaling pathways.

Adaptor Proteins, Signal Transducing↗

Differential contribution of Na+-K+ pump and K+ conductance to the post-tetanic hyperpolarization of the subtypes of tetrodotoxin-resistant C-fibers in the isolated bullfrog sciatic nerve.

The post-tetanic hyperpolarizations (PTHPs) of the fast and slow tetrodotoxin-resistant (TTX-R) C-fibers were recorded from isolated bullfrog sciatic nerves using a modified vaseline gap method. Under control solutions, the monophasic fast and slow TTX-R C-fibers compound action potentials (C-CAPs) increased in amplitude up to 133.9+/-17.9% (mean+/-SD; n = 9) and 167.0+/-41.5% (n = 7), respectively, shortly after tetanic stimulation. The recovery time constants of the fast and slow ones were 66.5 and 101.2 s, respectively. Significant differences between the rates of amplitude augmentation of the fast and slow TTX-R C-CAPs were found for the most pairs of measured points (P < 0.05 or P < 0.01). After application of ouabain solutions, the augmentation of the fast TTX-R C-CAP was inhibited to an insignificant level, while that of the slow TTX-R C-CAP remained significant with the recovery time constant being 90.9 s. After additional application of TEA, the post-tetanic augmentation of the slow TTX-R C-CAP was blocked. These results suggest that Na+-K+ pump contributes to the PTHPs of the fast and slow TTX-R C-fibers and that K+ conductance contributes only to the PTHP of the slow TTX-R C-fibers, indicating differential modulation of the firing rate of each TTX-R C-fibers group.

Action Potentials↗

AIM-1: a mammalian midbody-associated protein required for cytokinesis.

Mitosis is a highly coordinated process that assures the fidelity of chromosome segregation. Errors in this process result in aneuploidy which can lead to cell death or oncogenesis. In this paper we describe a putative mammalian protein kinase, AIM-1 (Aurora and Ipl1-like midbody-associated protein), related to Drosophila Aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. AIM-1 message and protein accumulate at G2/M phase. The protein localizes at the equator of central spindles during late anaphase and at the midbody during telophase and cytokinesis. Overexpression of kinase-inactive AIM-1 disrupts cleavage furrow formation without affecting nuclear division. Furthermore, cytokinesis frequently fails, resulting in cell polyploidy and subsequent cell death. These results strongly suggest that AIM-1 is required for proper progression of cytokinesis in mammalian cells.

Amino Acid Sequence↗

Adsorption of human lysozyme onto hydroxyapatite. Identification of its adsorbing site using site-directed mutagenesis.

To elucidate hydroxyapatite-protein interaction, mutant human lysozymes in which the surface charge was modified by site-directed mutagenesis were used. Five mutant human lysozymes (K1A, K13A, K33A, R10A, R14A) were expressed in yeast. The chromatographic behavior of these lysozymes was studied with a HPLC hydroxyapatite column. Elution molarities of K1A and R14A mutants were greatly lowered. While Lys-13 and Arg-10 are located around Lys-1 and Arg-14, K13A and R10A mutants bound onto hydroxyapatite stronger than K1A and R14A mutants. In combination with an X-ray crystal structure of human lysozyme, it is concluded that the adsorbing site of human lysozyme is at the back of the active site and that Arg-14, Lys-1, Arg-10 and Lys-13 play important roles in binding.

Adsorption↗

Mitral reoperation via right thoracotomy in a patient with pulmonary hypertension.

A 62-year-old woman with pulmonary hypertension underwent mitral valve re-replacement through right thoracotomy. Severe adhesion occurred to the right lung. During pleural dissection the lung collapsed under single-lung ventilation, rapidly elevated pulmonary vascular resistance caused hemodynamic instability. When pulmonary hypertension is preoperatively present, this approach under single-lung ventilation is not recommended.

Female↗

Cell cycle regulation and differentiation in the human podocyte lineage.

Mature podocytes are regarded as growth-arrested cells with characteristic phenotypic features that underlie their function. To determine the relationship between cell cycle regulation and differentiation, the spatiotemporal expression of cyclin A, cyclin B1, cyclin D1, the cyclin-dependent kinase inhibitors (CKIs) p27 and p57, and markers of differentiating podocytes in developing human kidneys was investigated by immunohistochemistry. In S-shaped body stage, Ki-67, a cell proliferation marker that labels the G1/S/G2/M phase, was expressed in the majority (more than 80%) of presumptive podocytes, along with cyclin A (approximately 20% of the Ki-67-positive cells) and cyclin B1 (less than 5% of Ki-67-positive cells) expression. Among these cells), cyclin D1 and CKIs were markedly down-regulated. At the capillary-loop stage, by contrast, CKIs and cyclin D1 were intensely positive in podocytes, whereas no Ki-67, cyclin B1, or cyclin A expression was seen. Moreover, double-immunolabeling and serial-section analysis provided evidence that CKIs and markers specific for differentiating podocytes, namely PHM-5 (podocalyxin-like protein in humans), synaptopodin (a foot process-related protein), and C3b receptor, were co-expressed at the capillary-loop stage. Podocytes were the only cells within the glomeruli that expressed CKIs at immunohistochemically detectable levels. Furthermore, bcl-2 (an apoptosis inhibitory protein) showed a reciprocal expression pattern to that of CKI. These results suggest that 1) the cell cycle of podocytes is regulated by cyclin and CKIs, 2) CKIs may act to arrest the cell cycle in podocytes at the capillary-loop stage, and 3) the specific cell cycle system in podocytes may be closely correlated with their terminal differentiation in humans.

Biomarkers↗

Cyclin D1, p16, and retinoblastoma gene regulate mitogenic signaling of endothelin in rat mesangial cells.

To elucidate the mechanisms by which endothelin (ET)-1 induces proliferation of mesangial cells, we investigated the involvement of the first gap phase of the cell cycle (G1) cyclin, cyclin-dependent kinase 4 (CDK4) activity, and the retinoblastoma gene product (pRb) in ET-1-stimulated cell cycle progression. In the present study, ET-1 stimulated CDK4 activity and cell cycle progression via ET A-type receptors and induced cyclin D1 mRNA and protein expression in rat mesangial cells. We also found that ET-1 stimulation of mesangial cell proliferation was inhibited by antisense oligonucleotides directed against cyclin D1 and by overexpression of a nonphosphorylatable form of pRb. To investigate the functional roles of p16INK4 and p21cip1 in ET-1-stimulated mesangial cell proliferation, we used adenovirus-mediated gene transfer. Endothelin-1-stimulated [3H]-thymidine incorporation, CDK4 kinase activity, and the percent of cells in S phase were found to be significantly inhibited by overexpression of p16INK4 and slightly inhibited by overexpression of p21cip1. Thus, ET-1 induced cyclin D1 expression and stimulated CDK4 activity and cell cycle progression via the A-type receptor in rat mesangial cells. These effects were regulated by the expression of cyclin D1, p16INK4, p21cip1, and phosphorylatable form of pRb. The results of the present study provide the basis for further investigation of basic and therapeutic approaches towards mesangial proliferative diseases.

Animals↗

Changes in nasal responsiveness to histamine and to specific antigen after laser surgery.

An initial treatment with several kinds of anti-allergic medicines is useful for reducing nasal allergy symptoms in patients suffering from Japanese cedar pollinosis during the pollen season. Since laser surgery before the pollen season seems to have a preventive effect as well, it would be of interest to know the time course of changes in the nasal reactivity to specific and non-specific stimuli after laser surgery. In this study, we investigated the changes in the nasal reactivities to specific antigen and histamine after CO2 laser surgery. The nasal reactivities to both specific antigen and histamine were enhanced 2 weeks after the laser surgery. On the other hand, they were significantly reduced after 4 weeks. Our data strongly suggest. therefore. that laser surgery must be done more than 4 weeks before the start of the pollen season to avoid temporary enhancement of nasal allergy symptoms.

Adolescent↗

Cyclins and the cyclin-kinase system--their potential roles in nephrology.

Our understanding of the cell-cycle mechanisms has progressively advanced in the past few years. Cyclins and cyclin-dependent kinases play major roles as positive cell-cycle regulatory proteins and CDK inhibitors; while the Kip family and INK4 family are negative regulatory proteins in mesangial cells and renal tubular cells. An understanding of the cell cycle is essential for the rational design of novel pharmacotherapeutic approaches to suppress the excessive proliferation of mesangial cells in glomerular disease and hypertrophic tubular disease.

Animals↗

Endoscopic harvesting of radial artery graft for coronary artery bypass.

The radial artery is used frequently in cardiac revascularization and requires an average 23-cm forearm incision. With proper instrumentation (Tsukuba-West Virginia Endoscopic Radial Artery: TW-ERA series, Takumi Cardio Co., Chiba, Japan), the radial artery can be harvested utilizing two small transverse incisions. The authors report six cases of endoscopic harvest of a radial artery graft. Length of the endoscopic incision is 2 cm proximally and 3 cm distally. Operation time and tourniquet times were approximately 80 to 120 minutes. No complications such as hematomas, nerve damage, or delay in healing were observed at the donor sites. Plastic surgeons, with their expertise in radial forearm flaps, hand surgery, and subcutaneous endoscopic techniques, can contribute greatly to the minimally invasive harvesting of the radial artery, preventing associated morbidity and improving the aesthetic and functional outcome of the donor site.

Adult↗

A water channel of the nematode C. elegans and its implications for channel selectivity of MIP proteins.

A genome project focusing on the nematode Caenorhabditis elegans has demonstrated the presence of eight cDNAs belonging to the major intrinsic protein superfamily. We functionally characterized one of these cDNAs named C01G6.1. Injection of C01G6.1 cRNA increased the osmotic water permeability (Pf) of Xenopus oocytes 11-fold and the urea permeability 4.5-fold but failed to increase the glycerol permeability. It has been speculated that the MIP family may be separated into two large subfamilies based on the presence or absence of two segments of extra amino acid residues ( approximately 15 amino acids) at the second and third extracellular loops. Because C01G6.1 (designated AQP-CE1), AQP3, and glycerol facilitator (GlpF) all have these two segments, we replaced the segments of AQP-CE1 with those of AQP3 and GlpF to identify their roles. The functional characteristics of these mutants were principally similar to that of wild-type AQP-CE1, although the values of Pf and urea permeability were decreased by 39-74% and 28-65%, respectively. These results suggest that the two segments of extra amino acid residues may not contribute to channel selectivity or formation of the route for small solutes.

Amino Acid Sequence↗

Essential roles for G1 cyclin-dependent kinase activity in development of cardiomyocyte hypertrophy.

Although cardiomyocytes undergo terminal differentiation soon after birth, irreversibly withdrawing from the cell cycle, growth stimulation induces cell hypertrophy. Such growth stimulation is also responsible for the upregulation of G1 cyclins and cyclin-dependent kinase (CDK) activity in proliferating cells. We sought to determine whether G1 CDK activity is involved in the hypertrophy of rat neonatal cardiomyocytes in culture. We show that serum stimulation promoted the G1 CDK activity without induction of DNA synthesis in cardiomyocytes. Furthermore, overexpression of CDK inhibitors p16(INK4a) and p21(CIP1/WAF1) by use of the adenovirus vector effectively prevented cell enlargement and depressed serum-induced protein synthesis and expression of skeletal alpha-actin and atrial natriuretic factor, genetic markers of cardiac hypertrophy. These results suggest that the G1 CDK activity promoted by serum stimulation is required for the induction of cardiomyocyte hypertrophy and provide novel evidence for understanding the regulation of cardiac hypertrophy by cell cycle regulators.

Animals↗