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Biomedical subjects

Ken Watanabe

Publications and source records attributed to Ken Watanabe.

At least 37 records · Page 2Linked to original sources
PubMed2005

A RANKL-inducible gene Znf216 in osteoclast differentiation.

Osteoclasts possess catabolic activity in mineralized tissues and are involved in bone remodeling coordinating with osteoblasts. Although the pathway using receptor and activator of NF-kappa B (RANK) and its ligand, RANKL, is known to be essential for osteoclast differentiation, their precise mechanisms are not fully understood. Using DNA microarray technology, we searched for genes that were up-regulated after RANKL stimulation in the macrophage cell line, RAW264.7 cells. A gene, Znf216, which encodes a zinc-finger protein, was detected among those genes up-regulated after RANKL stimulation. Expression of Znf216 was also induced by other cytokines such as TNFalpha and IL-1beta. Although ectopic expression of full-length ZNF216 abrogated osteoclast differentiation, its truncated forms accelerated it. No significant inhibitory effect on the NF-kappa B pathway was observed, however. These results suggest that ZNF216 is a potent inhibitory factor for osteoclast differentiation and that the mechanism is unlikely due to direct attenuation of the NF-kappa B pathway.

Animals↗
PubMed2005

Biological and biochemical characteristics of prion strains conserved in persistently infected cell cultures.

Abnormal prion protein (PrP(Sc)) plays a central role in the transmission of prion diseases, but the molecular basis of prion strains with distinct biological characteristics remains to be elucidated. We analyzed the characteristics of prion disease by using mice inoculated with the Chandler and Fukuoka-1 strains propagated in a cultured mouse neuronal cell line, GT1-7, which is highly permissive to replication of the infectious agents. Strain-specific biological characteristics, including clinical manifestations, incubation period as related to the infectious unit, and pathological profiles, remained unchanged after passages in the cell cultures. We noted some differences in the biochemical aspects of PrP(Sc) between brain tissues and GT1-7 cells which were unlikely to affect the strain phenotypes. On the other hand, the proteinase K-resistant PrP core fragments derived from Fukuoka-1-infected tissues and cells were slightly larger than those from Chandler-infected versions. Moreover, Fukuoka-1 infection, but not Chandler infection, gave an extra fragment with a low molecular weight, approximately 13 kDa, in both brain tissues and GT1-7 cells. This cell culture model persistently infected with different strains will provide a new insight into the understanding of the molecular basis of prion diversity.

Animals↗
PubMed2005

[Association between laryngeal findings and vocal qualities in muscle tension dysphonia with supraglottic contraction].

Muscle tension dysphonia (MTD) is a voice disorder associated with abnormal laryngeal posture or glottic configuration induced by excessive contraction of the laryngeal muscles, and supraglottic contraction is one of the characteristic findings in MTD. In recent study we investigated the changes in laryngeal findings and voice quality and the association between them in the course of voice therapy for MTD with supraglottic contraction. The effects of voice therapy on the laryngeal and the vocal findings were assessed by two rating methods: the MTD score and the conventional GRBAS scores and both scores were gradually improved. Of the two components of supraglottic contraction, false vocal cord compression was more curable than anterior-posterior compression at the aryepiglottic level. Little correlation was found between the scores at the first examination, but significant associations (p < 0.05) were found between the differences of MTD score and G/R/S scores but not B/A scores before and after the series of voice therapy. These results suggest that supraglottic contraction is a crucial factor worsening voice quality and that MTD score is useful to assess the efficacy of voice therapy for MTD.

Glottis↗
PubMed2004

Abnormalities of neurohormonal and cardiac autonomic nervous activities relate poorly to functional status in fontan patients.

BACKGROUND: Impaired cardiac autonomic nervous activities and increased neurohumoral activities (CANA, NHA) characterize Fontan patients. However, the clinical significance of these changes is not clearly understood. Our purpose was to clarify the clinical significance of the CANA and NHA in stable Fontan patients. METHODS AND RESULTS: We divided 22 atriopulmonary connection (APC) and 75 total cavopulmonary connection (TCPC) patients into 4 subgroups according to New York Heart Association (NYHA) class (1.8+/-0.6) and measured various CANA and NHA indices. All NHA indices were elevated in the symptomatic patients (P<0.001). Natriuretic peptides were higher in the APC than in the TCPC patients, and the hemodynamics showed no correlation with brain natriuretic peptide in the APC patients. Low arterial oxygen saturation and impaired hemodynamics greatly influenced all elevated NHA indices (P<0.01), except for plasma renin activity, in the TCPC patients. Impaired CANA indices did not relate to NYHA class, although surgeries were associated with lower heart rate variability. In addition to poor correlation between NHA and CANA, age and ventricular morphology had no impact on all CANA and NHA indices, except for high norepinephrine in right ventricular Fontan patients. CONCLUSIONS: Although symptomatic Fontan patients exhibit higher NHA, CANA is not related to either NYHA class or NHA. APC itself is responsible for higher natriuretic peptides, and arterial oxygen desaturation has a great impact on elevated NHA in the TCPC patients. These characteristics of the NHA and CANA differ from those of heart failure patients with biventricular physiology.

Adolescent↗
PubMed2004

Blood pressure dynamics during simulated ventricular tachycardia in patients after right ventricular outflow tract reconstruction mainly for tetralogy of Fallot compared with patients after ventricular septal defect closure.

We studied hemodynamic changes during simulated ventricular tachycardia using ventricular pacing. Hemodynamic deterioration during pacing is more significant in patients after right ventricular outflow tract reconstruction, especially in adults, than after closure of a ventricular septal defect. The cardiac autonomic nervous system has a significant impact on hemodynamics during simulated ventricular tachycardia.

Adult↗
PubMed2004

Progeroid syndrome as a model for impaired bone formation in senile osteoporosis.

Senile or age-related/dependent osteoporosis is caused by reduced bone formation, rather than increased bone resorption as in postmenopausal osteoporosis. Here we review genetically engineered mouse models with defects in osteoblastic proliferation or differentiation with focus on IGF signaling and stem cells. Model mice for human progeroid syndromes may provide useful tools for studying the pathogenesis of senile osteoporosis.

Aging↗
PubMed2004

Proventricular adenocarcinoma in a Humboldt penguin (Spheniscus humboldti) and a great horned owl (Bubo virginianus); identification of origin by mucin histochemistry.

Cases of proventricular neoplasm in a Humboldt penguin (Spheniscus humboldti) and a great horned owl (Bubo virginianus) were observed. Microscopically, the neoplastic cells formed branching tubules or acini in both cases. Galactose oxidase-Schiff (GOS) staining revealed that the cytoplasm of the normal surface epithelium and surface mucosubstances of the proventriculus adjacent to the neoplasm were positive in both cases. The neoplastic cells in both cases were also classified as GOS-positive. Therefore, the two proventricular neoplasms in this report were diagnosed as proventricular adenocarcinoma that arose from the proventricular surface epithelium. This study suggests that the mucosubstances, which the neoplastic cells produced, were a useful index for identifying the origin of the neoplastic cells in the birds.

Adenocarcinoma↗
PubMed2004

Progressive and nonprogressive rheumatoid arthritis over a 10-year period in Japan.

We followed 207 patients with rheumatoid arthritis who were registered at our hospital over a 10-year period from between 1989 and 1990. The number of patients who were still treated at our hospital in 2001 was 87. Sixty patients had died, 39 had changed hospitals, 11 had interrupted treatment, and 10 had not had further followup. The patients at our hospital in 2001 were divided into 2 groups: progressive and nonprogressive disease. We compared clinical and laboratory data obtained for the 2 groups from the initial examination against data obtained from the final examination. The progressive group had a greater number of operations, used a greater variety of disease modifying antirheumatic drugs, and received higher dosages of steroids than the nonprogressive group. In the progressive group the levels of C-reactive protein, erythrocyte sedimentation rate, and IgG were significantly higher, while the levels of hemoglobin were lower at final laboratory examination. However, the initial laboratory examination revealed no significant differences between these groups that could be used to predict the likely progression of disease.

Arthritis, Rheumatoid↗
PubMed2003

MIP-T3 associates with IL-13Ralpha1 and suppresses STAT6 activation in response to IL-13 stimulation.

To unravel the mechanism of interleukin-13 (IL-13)-specific functions, we sought to identify IL-13 receptor (IL-13R) binding molecules. A novel human IL-13Ralpha1 binding protein (IL13RBP1) has been identified using yeast tri-hybrid system, which was found to encode the same protein as MIP-T3 (microtubule interacting protein that associates with tumor necrosis factor (TNF) receptor associating factor-3 (TRAF3)). It constitutively associates with IL-13Ralpha1 and suppresses IL-4/13-induced signal transducer and activator of transcription-6 (STAT6) phosphorylation. IL-13-induced STAT6 activation was also inhibited as determined by dual luciferase assay and electrophoretic mobility shift assay (EMSA). These results suggest that MIP-T3 is a novel inhibitor of IL-13 signaling and may be a useful molecule in ameliorating various conditions in which IL-13 plays a central role.

Animals↗
PubMed2003

The receptor tyrosine kinase Ror2 associates with the melanoma-associated antigen (MAGE) family protein Dlxin-1 and regulates its intracellular distribution.

The mammalian Ror family receptor tyrosine kinases, Ror1 and Ror2, play crucial roles in developmental morphogenesis. Although the functions of Ror1 and Ror2 are redundant, Ror2 exhibits more specific functions during development. We show that when expressed in mammalian cells, Ror2, but not Ror1, associates with the melanoma-associated antigen (MAGE) family protein, Dlxin-1, which is known to bind to the homeodomain proteins Msx2 and Dlx5 and regulate their transcriptional functions. This association requires the cytoplasmic C-terminal region of Ror2, containing proline-rich and serine/threonine-rich domains, and the C-terminal necdin homology domain of Dlxin-1. Interestingly, the cytoplasmic C-terminal region of Ror2 is missing in patients with brachydactyly type B. Interestingly, transient expression and immunohistochemical analyses reveal that both Dlxin-1 and Msx2 are co-localized in the nuclei in the absence of Ror2. In the presence of Ror2, Dlxin-1 is co-localized with Ror2 at the membranous compartments and Msx2 is retained in the nuclei. It was also found that the majority of cellular Dlxin-1 is retained in the membrane fractions of wild-type but not Ror2-/- mouse embryonic fibroblasts. Furthermore, we show that transcriptional activity of Msx2, irrespective of Ror2 kinase activity, is regulated by ectopic expression of Ror2 using a reporter plasmid containing the WIP element. Thus, Ror2 sequesters Dlxin-1 in membranous compartments, thereby affecting the transcriptional function of Msx2.

Amino Acid Sequence↗
PubMed2003

UNC5H1 induces apoptosis via its juxtamembrane region through an interaction with NRAGE.

The UNC5Hs are axon guidance receptors that mediate netrin-1-dependent chemorepulsion, and dependence receptors that mediate netrin-1-independent apoptosis. Here, we report an interaction between UNC5H1 and NRAGE. Our experiments show that this interaction is responsible for apoptosis induced by UNC5H1, and this level of apoptosis is greater than the amount induced by either UNC5H2 or UNC5H3. We mapped the NRAGE binding domain of UNC5H1 to its ZU-5 domain and show that this region, in addition to an adjacent PEST sequence, is required for UNC5H1-mediated apoptosis. Chimeric UNC5H2 and UNC5H3 receptors, containing the NRAGE binding domain and PEST sequence of UNC5H1, bind NRAGE and cause increased levels of apoptosis. UNC5H1 expression does not induce apoptosis in differentiated PC12 cells, which down-regulate NRAGE, but induces apoptosis in native PC12 cells that endogenously express high levels of NRAGE and in differentiated PC12 cells when NRAGE is overexpressed. Together, these results demonstrate a mechanism for UNC5H1-mediated apoptosis that requires an interaction with the MAGE protein NRAGE.

Animals↗
PubMed2003

Balloon angioplasty of postoperative coarctation in the transverse arch in infants: protecting the common carotid artery.

We performed balloon angioplasty in three patients with postoperative coarctation in the transverse arch adjacent to the left common carotid artery. The age at arch reconstruction was 5, 6, and 2 days, while the interval between operation and balloon dilatation was 59 days, 87 days, and 12 months, respectively. Two balloons, one in the stenosis and the other in the left common carotid artery, were introduced over a wire sequentially and inflated simultaneously until the waist of the balloon in the arch disappeared. After balloon dilatation, a significant reduction in the peak-to-peak pressure gradient and an increase in vessel diameters were observed in all patients. Further growth of the transverse arch was documented at follow-up in two patients. No aneurysm has been detected in any patients. We believe that placing a protective balloon in the neck vessel increases safety during balloon dilatation of coarctation in the transverse arch.

Angioplasty, Balloon↗
PubMed2003

Inhibition of the protease activity of influenza virus RNA polymerase PA subunit by viral matrix protein.

Influenza virus PA is a subunit of RNA-dependent RNA polymerase. We demonstrated that PA has a unique chymotrypsin-like serine protease activity with Ser624 as an active site. To obtain further insight into the role of the protease activity of PA in viral proliferation, we examined the interaction between PA and matrix protein (M1). Both M1 purified from virion and hexa-histidine-tagged M1 expressed in Escherichia coli bound to PA. Hexa-histidine-tagged M1 pulled down PA. The interaction of PA with M1 was sensitive to ionic strength, suggesting that the interaction is formed by electrostatic force. Using Suc-Leu-Leu-Val-Tyr-MCA, a specific substrate for PA protease, M1 was demonstrated to inhibit the amidolytic activity of PA, whereas M1 did not inhibit that of chymotrypsin or trypsin at all. These results suggest that M1 binds to and inhibits the amidolytic activity of PA.

Animals↗
PubMed2003

Stent implantation and subsequent dilatation for pulmonary vein stenosis in pediatric patients: maximizing effectiveness.

The outcome of stent implantation and redilatation was investigated in 4 pediatric patients with 7 stenotic lesions of the pulmonary vein (PV), paying particular attention to late neointimal proliferation. The minimal diameter of the lesions increased from 0.8-3.6 (2.3+/-1.1) mm to 3.6-8.4 (5.1+/-1.6) mm immediately after stent implantation. Although the pressure gradient across the lesion was not measured in patient 4, in patients 1-3, it decreased from 4-34 (18+/-13) mmHg to 3-15 (7+/-4) mmHg. Except for case 4, who achieved a lesion diameter of 8.4 mm after initial stent dilatation, the other 6 lesions all restenosed within a few months, with an increasing pressure gradient. One patient with multiple PV stenoses associated with persistent severe pulmonary hypertension died suddenly. However, repeat dilatations were effective in all other lesions. Furthermore, in one lesion in patient 1, no serious restenosis developed for 20 months after the lesion was dilated up to 5.6 mm. Although further follow-up is mandatory, the final stent diameter within a vessel may determine long-term patency, and aggressive redilatation may be crucial for successful therapy of such a difficult disease.

Angiography↗
PubMed2003

Intravenous indomethacin therapy in infants with a patent ductus arteriosus complicating other congenital heart defects.

In the present study, 0.2-0.6 mg/kg (0.4+/-0.2, mean +/- standard deviation) indomethacin was administered intravenously to close a patent ductus arteriosus in 13 infants with co-existing congenital heart defects whose ages ranged from 3 to 48 (14+/-14) days. All of them were hemodynamically ductus-independent and symptomatic. Echocardiography demonstrated that the ductus had closed in 8 infants, aged 3-33 (12+/-10) days (responders), but had not closed in 5 infants aged 6-48 (19 +/-19) days (non-responders). There was no significant difference between the responders and non-responders in their age, body weight, minimal diameter of the duct, dose of indomethacin, gestational age, birthweight, or Apgar score. One possible major complication might be associated with indomethacin. However, intravenous indomethacin should be considered prior to surgical ligation as one option for infants with a symptomatic patent ductus arteriosus complicated by other congenital heart defects.

Cardiovascular Agents↗
PubMed2003

Acute recoil of stents used for the relief of stenotic great vessels in the setting of congenital cardiac disease.

We implanted either large or medium Palmaz stents, or a Palmaz Corinthian stent, in various stenotic vessels, such as the pulmonary arteries, pulmonary veins, aorta, or superior caval vein. Using angiograms, we measured the diameter of the stenotic vessel before or after the implantation, the minimal diameter of the lumen, the minimal diameter of the largest fully expanded balloon used to expand the stent, and the diameter immediately after withdrawal of the balloon. The minimal diameter of the fully expanded balloon, and the minimal diameter of the lumen subsequent to expansion, were 8.2 +/- 2.4, and 7.7 +/- 2.3 mm, giving an absolute recoil of 0.5 +/- 0.4 mm, and a proportional recoil of 7 +/- 4%. There was no significant difference in either the absolute or proportional recoil for any of the stents, or for any of the different stenotic vessels. The proportional recoil correlated linearly with the minimal diameter of the lumen prior to the procedure, and with the ratio of the stenosis to the balloon, while the diameter of the stenotic vessels, the minimal diameter of the largest fully expanded balloon, the proportional stenosis prior to the procedure, and the ratio of the balloon to the diameter of the stenotic vessel, had no significant correlation with proportional recoil. The proportional recoil exceeded more than one-tenth when the minimal diameter of the lumen prior to the dilation was less than 3 mm, or the ratio of the balloon to the stenosis was greater than 3.0. An absolute recoil of around 1 mm is common when a large or medium Palmaz, or a Palmaz Corinthian stent, is implanted in great vessels. Balloons with a diameter of approximately one-tenth greater than that of the adjacent vessel may be needed if the minimal diameter of the lumen is small prior to the procedure.

Acute Disease↗