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Biomedical subjects

H Kitayama

Publications and source records attributed to H Kitayama.

At least 19 recordsLinked to original sources
PubMed2006

Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model.

Peritoneal sclerosis is a major and serious complication in patients on long-term continuous ambulatory peritoneal dialysis (PD). The involvement of angiogenesis and proangiogenic factors such as vascular endothelial growth factor (VEGF)-A in progressing peritoneal sclerosis has been reported. We previously reported the therapeutic efficacy of endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen, in a mouse diabetic nephropathy model. Here, we examined the therapeutic effect of endostatin peptide in preventing progression in a mouse peritoneal sclerosis model. Male ICR mice received intraperitoneal injections of chlorhexidine gluconate (CG) every other day to induce peritoneal sclerosis. Endostatin peptide (1 or 4 mg/kg/day) was administered via subcutaneously implanted osmotic minipumps. Peritoneal sclerosis (day 24) was significantly suppressed by endostatin peptide in a dose-dependent manner. Peritoneal accumulation of type III collagen was significantly suppressed by endostatin peptide. Increase in the number of CD31(+) blood vessels, F4/80(+) monocyte/macrophage accumulation, and 5-bromodeoxyuridine(+) proliferating cells was significantly inhibited by endostatin peptide. Increase in peritoneal expression of VEGF-A, profibrotic transforming growth factor-beta1, and alpha-smooth muscle actin was suppressed by endostatin peptide. Immunoreactivity for endogenous endostatin (whole molecule) and endostatin receptor alpha5beta1-integrin was increased and colocalized to CD31(+) blood vessels in the thickened peritonea of CG-injected mice. These results demonstrate the potential use of antiangiogenic endostatin peptide as a novel therapeutic agent in preventing peritoneal sclerosis, a severe complication in patients undergoing long-term PD.

Actins↗
PubMed2006

Histone deacetylase inhibitor FK228 suppresses the Ras-MAP kinase signaling pathway by upregulating Rap1 and induces apoptosis in malignant melanoma.

Histone deacetylase (HDAC) inhibitors are expected to be effective for refractory cancer because their mechanism of action differs from that of conventional antineoplastic agents. In this study, we examined the effect of the HDAC inhibitor FK228 on malignant melanoma, as well as its molecular mechanisms. FK228 was highly effective against melanoma compared with other commonly used drugs. By comparing the gene expression profiles of melanoma cells and normal melanocytes, we defined a subset of genes specifically upregulated in melanoma cells by FK228, which included Rap1, a small GTP-binding protein of the Ras family. The expression of Rap1 mRNA and protein increased in FK228-treated melanoma cells in both a dose- and a time-dependent manner. A decrease in the phosphorylation of c-Raf, MEK1/2, and ERK1/2 was accompanied by an increase in Rap1 expression in both FK228-treated and Rap1-overexpressing cells. Inhibition of Rap1 upregulation by small interfering RNA (siRNA) abrogated the induction of apoptosis and suppression of ERK1/2 phosphorylation in FK228-treated melanoma cells. These results indicate that the cytotoxic effects of FK228 are mediated via the upregulation of Rap1. Furthermore, we found that Rap1 was overexpressed and formed a complex with B-Raf in melanoma cell lines with a V599E mutation of B-Raf. The siRNA-mediated abrogation of Rap1 overexpression increased the viability of these cells, suggesting that Rap1 is also an endogenous regulator of Ras-MAP kinase signaling in melanomas.

Animals↗
PubMed2004

Effects of ras and Rap1 on electrical excitability of differentiated NG108-15 cells.

Effects of two small G-proteins, Rap1 and Ras, on the sodium channel activity in NG108-15 cells were studied using sindbis virus-mediated gene transfer. When an activated Rap1A mutant (Rap1-12V, the activated mutant of Rap1 carrying glycine to valine substitution at codon 12) or a dominant-negative H-Ras mutant (Ras-17N, carrying serine to asparagine substitution at codon 17) was expressed in differentiated NG108-15 cells, the proportion of cells generating action potential decreased and the amplitudes of sodium current diminished. This effect was sensitive to an inhibitor of protein kinase A. The effects of a cyclic AMP (cAMP) analog (dibutyl cAMP) on sodium current in these cells were biphasic: inhibitory at lower concentrations (<100 microM) and enhancing at higher concentrations (200-500 microM). The inhibitory phase of cAMP effect was suppressed by an activated Ras mutant (Ras-12V) while the enhancing phase was suppressed by Rap1-12V. These data are consistent with the model that Rap1 and Ras function as counteracting regulators of voltage-gated sodium current through cAMP-dependent mechanisms.

Action Potentials↗
PubMed2003

Possible involvement of Rap1 and Ras in glutamatergic synaptic transmission.

Rap1A, first identified as a suppressor of transformed phenotype induced by an activated ras oncogene, is abundantly expressed in the brain. Its neurophysiological function, however, is poorly understood. When an activated Rap1A mutant (Rap1-12V) or a dominant negative H-Ras mutant (Ras-17N) was expressed in CA1 neurons in cultured hippocampal slices using the sindbis virus-mediated gene transfer technique, NMDA receptor current in response to Schaffer collateral stimulation was suppressed. Expression of activated H-Ras mutant (Ras-12V) resulted in the elevation of both NMDA receptor current and AMPA receptor current. These results implicate counteracting functions of Ras and Rap1 in the regulation of NMDA receptor-mediated synaptic transmission and a positive regulatory role of Ras in AMPA receptor-mediated synaptic transmission.

Animals↗
PubMed2003

Isolation of a set of genes expressed in the choroid plexus of the mouse using suppression subtractive hybridization.

The choroid plexus produces cerebrospinal fluid, providing a specialized environment for the CNS. We previously demonstrated that choroid plexus ependymal cells can enhance nerve regeneration in vivo and promote neurite outgrowth in vitro. To understand the molecular mechanisms of choroid plexus functions, we isolated genes predominantly expressed in the mouse choroid plexus using suppression subtractive hybridization. Out of the 49 complementary DNA (cDNA) fragments isolated in two types of screening, 43 matched known sequences in the database and six were novel. In one type of screening where choroid plexus cDNAs were subtracted with cerebral cortex cDNAs, transthyretin and phosphodiesterase I alpha were predominant. This is consistent with previous reports and supports the authenticity of our approach. In the other type of screening, cDNAs derived from the choroid plexus of neonatal (postnatal day 5) mice were subtracted with cDNAs from the choroid plexus of adult mice. RNA blot and/or in situ hybridization confirmed abundant expression, in the mouse choroid plexus, of the mRNA encoding gelsolin, phospholipid transfer protein, ATP-binding cassette transporter A8 (ABCA8), androgen-inducible aldehyde reductase, and Na(+)/sulfate cotransporter SUT-1. Also, one novel gene (FS88) was found to be expressed in the choroid plexus from neonatal mice. Our data suggest that the choroid plexus cells produce molecules involved in processes such as prevention of fibrillization of amyloid beta-protein (transthyretin and gelsolin), lipid metabolism (phospholipid transfer protein and ABCA8), and detoxification (androgen-inducible aldehyde reductase).

Animals↗
PubMed2003

Obstructed coarctation in a right aortic arch in an adult female.

Coarctation of a right aortic arch is rare congenital anomaly. We report a rare case of a 24-year-old female with coarctation of the right aortic arch with aberrant left subclavian artery between the right common carotid and right subclavian arteries. The coarctation progressed into complete obstruction as the interruption of the aorta in adulthood. To prevent cerebral complications and progression to heart failure, surgical procedure was selected. Extraanatomical bypass grafting between the ascending and descending aorta was successfully performed using cardiopulmonary bypass. Some patients diagnosed with interruption of the aortic arch in adulthood might be displaying progression of undiagnosed coarctation, as our in case. Three-dimensional computed tomography was useful to detect the obstructive lesion and to determine the surgical approach and methods.

Aortic Coarctation↗
PubMed2002

[Pitfall of modified ultrafiltration in pediatric cardiac surgery].

Since June, 1998, modified ultrafiltration (MUF) was performed for 92 consecutive children who underwent cardiac surgery using cardiopulmonary bypass, except those with atrial septal defect. Among 92 cases, MUF could not be completed in two cases because of the accident that many air bubbles were found in the arterial line of the CPB circuit. The causes of such trouble were discussed.

Cardiopulmonary Bypass↗
PubMed2001

The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis.

Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with defects in collagen fibrils, the basal lamina, and vascular development, and that this phenotype is partially suppressed by MMP-2 null mutation. Also, vascular sprouting is dramatically suppressed in tumors derived from RECK-expressing fibrosarcoma cells grown in nude mice. These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis.

Animals↗
PubMed2001

Modified ultrafiltration may improve postoperative pulmonary function in children with a ventricular septal defect.

To evaluate the effectiveness of modified ultrafiltration (MUF) on ventricular septal defect (VSD) repair in children, we retrospectively examined 10 patients who underwent VSD repair with MUF at the Kinki University School of Medicine hospital between June 1998, and December 1998 (MUF group). These patients were compared with 14 patients who underwent the same procedure without MUF (control group) between January 1997 and June 1998. Systolic blood pressure and hematocrit values increased significantly during MUF. By the time of postoperative transfer to the intensive care unit, PaO2 was higher in the MUF group than in the control group (503.3 +/- 112.2mmHg vs 376.3 +/- 149.2mmHg; P = 0.0491), whereas A-aDO2 was lower in the MUF group than in the control group (171.9 +/- 109.2mmHg vs 301.1 x 150.4mmHg; P = 0.0449). These findings demonstrate that MUF had a beneficial effect on pulmonary function in children who underwent surgery to repair a VSD.

Cardiopulmonary Bypass↗
PubMed2001

Surgical strategy for left ventricular free wall rupture after acute myocardial infarction.

BACKGROUND: Left ventricular free wall rupture is usually fatal without surgical intervention. However, the most appropriate surgical procedure remains controversial. METHODS: Seventeen patients (14 men, 3 women) who developed left ventricular free wall rupture after acute myocardial infarction were treated surgically. Their mean age was 65.4 years (range, 55 to 79 years). The following surgical procedures were performed: infarctectomy and patch reconstruction in 1 patient, direct closure with or without patch covering in 4 patients, simple patch covering anchored by running suture in 4 patients, and a sutureless technique in 7 patients. Endventricular patch closure was performed in 1 patient with ventricular septal perforation. RESULTS: One of 3 patients with a blow-out type rupture and 1 of 13 patients with an oozing type rupture died shortly after operation. The overall surgical mortality rate was 11.8%. CONCLUSIONS: Selection of the optimal procedure for each cardiac condition is important for obtaining good results. For patients with ongoing squirting bleeding, patch covering is the technique of choice. For oozing, the sutureless technique is preferable.

Aged↗
PubMed2001

Total cavopulmonary connection using a pedicled pericardial conduit for a patient with apicocaval juxtaposition.

A 5-year-old boy, with a double inlet solitary ventricle, pulmonary atresia, and apicocaval juxtaposition underwent an extracardiac total cavopulmonary connection. A pedicled pericardial conduit was placed behind the ventricle to make a straight pathway between the inferior vena cava and pulmonary artery. This report presents a solution for managing patients with complicated heart defects with apicocaval juxtaposition during the completion of a total cavopulmonary connection.

Angiography↗
PubMed2001

A case of Standford type B aortic dissection involving a right-sided aortic arch with mirror-image branching and right-sided descending aorta.

Isolated right aortic arch with mirror-image branching is a rare congenital anomaly. To date, no case has been reported for aortic dissection involving a right aortic arch with mirror-image branching. We report here on a case involving a 58-year-old man in whom expanding type B aortic dissection was demonstrated in the right aortic arch with mirror-image branching and a right descending aorta. The patient was successfully treated by interposition of a prosthetic graft via a right posterolateral thoracotomy approach. We also reviewed the literature.

Aortic Dissection↗
PubMed2001

Whole-body hybrid PET with 18F-FDG in the staging of non-Hodgkin's lymphoma.

UNLABELLED: PET with a double-head gamma camera (hybrid PET) is a new approach to tumor imaging with 18F-FDG. This study was conducted to clarify the feasibility of whole-body FDG hybrid PET in the staging of non-Hodgkin's lymphoma (NHL) in comparison with PET with a dedicated camera (dedicated PET) and to compare the results of both FDG studies with those of CT and 67Ga scanning as conventional imaging studies (CIS). METHODS: Thirty patients with NHL were prospectively evaluated. The results of the imaging studies regarding detection of the sites involved and staging were compared with each other and with those of the reference standard based on the final overall clinical evaluation. RESULTS: Of the total of 206 sites, whole-body FDG hybrid PET and dedicated PET detected 159 sites (77.2%) and 179 sites (86.9%), respectively. Eighteen of the 20 sites missed by hybrid PET alone consisted of lesions < 1.5 cm. Both FDG studies provided concordant staging results in all but 2 patients. CIS, on the other hand, detected 164 (79.6%) of the 206 sites, 137 of which were also detected by hybrid PET. Hybrid PET detected an additional 22 sites not found by CIS, whereas CIS detected 27 additional sites. Hybrid PET and CIS provided concordant staging results in 19 patients. Hybrid PET correctly staged NHL in 5 additional patients, whereas CIS correctly staged NHL in only 1 additional patient. CONCLUSION: Whole-body FDG hybrid PET appeared to be an accurate method of staging NHL. Despite its poorer image quality compared with dedicated PET, hybrid PET provided NHL staging results comparable with those of dedicated PET. Hybrid PET also yielded results comparable with those of CIS. However, whole-body FDG hybrid PET is currently inadequate as a single modality for staging NHL and is complementary to CT.

Adolescent↗
PubMed2001

[Two-cusp plasty using a pedicled auto pericardial patch for the right ventricular outflow tract in complete repair of tetralogy of Fallot].

BACKGROUND: Pulmonary stenosis (PS) and regurgitation (PR) are major concerns late after transannular patching for tetralogy of Fallot (TOF). In this study, we reviewed the TOF patients undergoing transannular patching to reveal whether the valvuloplasty technique (two cusp plasty) improved long-term results. We also reviewed potential for grow of the pedicled autopericardial patch. METHODS AND RESULTS: Since 1977, 151 patients underwent corrective surgery for TOF. Transannular patching was required in 58 (38.4%). PS and PR in the postoperative long-term period of these 59 cases were reviewed. 25 patients had the standard transannular patching (S-TAP), and 33 had two-cusp plasty (TCP). Pedicled autologous pericardial patch were used in 9 patients of TCP. Actuarial freedom from PS at 7 years was 70.8 +/- 9.2% in S-TAP and 79.2 +/- 8.3% in TCP, and there was no significant difference. Incidence of severe PR was significantly higher in S-TAP (7/24) than TCP (1/24) (p < 0.05). Actuarial freedom from PR at 7 year was 69.6 +/- 9.6% in the former and 95.8 +/- 4.2% in the later, respectively. The diameter of the pulmonary arterial annuals was augmented with the somatic growth in 6 patients with the pedicled pericardial patch. CONCLUSIONS: Two cusp plasty was more effective to prevent PR in the postoperative long-term period, comparing to S-TAP. As the material of the patch, pedicled autologous pericardium showed satisfactory outcome.

Blood Vessel Prosthesis Implantation↗
PubMed2001

[Efficacy and toxicity of lenograstim (glycosylated recombinant human granulocyte-colony stimulating factor) on peripheral blood stem cell harvest in healthy donors].

Peripheral blood stem cell harvest with lenograstim (glycosylated rhG-CSF) was performed 12 times from 10 normal donors. Five micrograms/kg of lenograstim was administered subcutaneously twice a day (10 micrograms/kg/day) for 4 to 6 days, and apheresis was performed on day 5 to 7 depending on the collected CD 34+ cell counts. We collected a sufficient number of CD 34+ cells in 9 mobilizations from 7 donors less than 50 years of age, with a total number of collected CD 34+ cells in each mobilization of 22.1 +/- 6.5 x 10(7). In contrast, we could not obtain a sufficient number of CD 34+ cells in 2 mobilizations from 3 donors above 50 years of age, with a total number of collected CD 34+ cells of 9.8 +/- 3.3 x 10(7). Although all donors had adverse events in response to lenograstim administration, all of them were grade 2 or less toxicity. These results indicate that peripheral blood stem cell mobilization and apheresis by lenograstim is safe and well tolerated, but the risk of poor mobilization may become higher in donors more than 50 years of age.

Adjuvants, Immunologic↗
PubMed2000

Expanded polytetrafluoroethylene monocuspid valve for right ventricular outflow tract reconstruction.

BACKGROUND: Numerous materials have been used for reconstruction of the right ventricular outflow tract (RVOT) in patients with complex congenital heart defects. METHODS: Between January 1982 and March 1999, 19 patients (10 boys and 9 girls; mean age, 8.5 years) with severe RVOT obstruction underwent reconstruction using a transannular patch and expanded polytetrafluoroethylene (ePTFE) monocuspid valve. RESULTS: There were no perioperative deaths. Postoperatively, the mean +/- standard deviation RVOT gradient was 12 +/- 9 mm Hg. Echocardiography showed good motion of all cusps, and most had no or trivial pulmonary regurgitation. The difference between the preoperative and postoperative mean ratio of right-to-left ventricular peak systolic pressure was significant (p = 0.0001). In the 8 patients followed for 3 years or longer, pulmonary regurgitation was mild or better in 5 and moderate in 2, and the mean peak systolic RVOT gradient was 16.3 +/- 5.9 mm Hg. Five patients had good mobility of the monocusps. Two patients needed reoperation because of stenosis at the distal anastomosis of the transannular patch; 1 patient died. CONCLUSIONS: The ePTFE monocuspid valve may be useful in reconstruction of the RVOT.

Adolescent↗