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Biomedical subjects

H Kitayama

Publications and source records attributed to H Kitayama.

At least 37 records · Page 2Linked to original sources
PubMed1999

Long-term treatment with antipsychotic drugs in conventional doses prolonged QTc dispersion, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease.

OBJECTIVE: The aim of this study was to examine the hypothesis that long-term treatment with antipsychotic drugs in conventional doses prolongs QTc dispersion and increases ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease. METHODS: We measured QTc and QTc dispersion and ventricular tachyarrhythmias in 64 patients with schizophrenia, including 59 patients who received psychiatric medications, and five patients who did not receive psychiatric medications, and 45 healthy volunteers. None of the subjects had a history of cardiac disease or showed any abnormality in chest radiograph and transthoracic echocardiographic studies. None of the subjects had electrolyte abnormality. None of the subjects were taking drugs known to influence the QT interval, other than psychiatric medications. RESULTS: QTc and QTc dispersion were significantly (P < 0.017) increased in patients who received psychiatric medications compared with patients who did not receive psychiatric medications, or with healthy volunteers [QTc: 0.442 (0.029), 0.418 (0.029), 0.417 (0.028) s, QTc dispersion: 0.054 (0.013), 0.038 (0.017), 0.038 (0.009) s]. Daily ventricular premature beats were 183 (689), 77 (23), and 86 (149), respectively. No ventricular tachycardia was observed. There were no correlation between QTc and QTc dispersion and ventricular premature beats. CONCLUSION: Long-term treatment with antipsychotic drugs in conventional doses prolonged both QTc and QTc dispersion in patients with schizophrenia, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease. However, despite the negative findings, ventricular tachyarrhythmias may occur as a rare side-effect of antipsychotic drugs, particularly if a patient has additional risk factors.

Adult↗
PubMed1999

Experimental orthotopic heart and bilateral lung transplantation completed without cardiopulmonary bypass.

INTRODUCTION: Most experimental studies of orthotopic heart and lung graft failure are complicated by an inability to eliminate the rejection-specific inflammatory mediator from the cardiopulmonary bypass. METHODS: The following model was developed in our laboratory to investigate the feasibility of performing an orthotopic heart and bilateral lung transplantation without performing a cardiopulmonary bypass. Nineteen transplants were attempted using 19 pairs of mongrel dogs. The recipient dog (mean weight, 23 kg) was anesthetized, and the ascending aorta, the superior vena cava (SVC), the inferior vena cava (IVC), and the main bronchus were dissected. Then, the donor dog (mean weight, 20 kg) was anesthetized, and the heart and lung block was prepared and explanted from the chest under cardioplegic arrest. A Gore-tex shunt (W. L. Gore; Flagstaff, AZ) was placed side-to-side between the recipient IVC and SVC, and then the donor right atrium was anastomosed to the Gore-tex shunt. The donor ascending aorta was anastomosed to the recipient ascending aorta with a partial clamp. On completion of these anastomoses, the donor heart was reperfused by the recipient heart and allowed to beat. When hemodynamic conditions were stable with double hearts, the recipient SVC and IVC were ligated just proximal to the venous anastomosis and the recipient aorta was ligated proximal to the anastomotic site. The recipient trachea was anastomosed to the donor trachea with an end-to-end anastomosis. Finally, the recipient heart and lungs were removed from the chest and the sternum was closed. RESULTS: Four of the 19 transplants failed. Three died due to left ventricular dysfunction, and one died due to bleeding. Mean (+/- SD) ischemic time was 67 +/- 11 min with a mean (+/- SD) anastomotic time of 54 +/- 12 min. The 15 survivors were hemodynamically stable with or without the minimal use of inotropic support (dopamine, 2 to 3 microg/kg/min) 6 h after grafting, with normal cardiac output, satisfactory oxygenation, and normal wall motion. The sternotomy was repaired without loss of cardiopulmonary function. CONCLUSIONS: On the basis of our experiences, the experimental model of orthotopic heart and bilateral lung transplantation completed "off pump" can be technically feasible without the loss of cardiac and pulmonary functions.

Anastomosis, Surgical↗
PubMed1999

Extracardiac total cavopulmonary connection via an atrial and pericardial tunnel.

We performed extracardiac total cavopulmonary connection using only native tissue in two patients with complex heart disease. The extracardiac lateral tunnel was constructed from pedicled autologous pericardium and atrial wall During follow-up both patients remained in the New York Heart Association functional class I and demonstrated normal sinus rhythm. These modifications not only avoid the risk of potential postoperative complications due to artificial materials, but also allow growth of the conduit.

Angiography↗
PubMed1998

Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK.

A human fibroblast cDNA expression library was screened for cDNA clones giving rise to flat colonies when transfected into v-Ki-ras-transformed NIH 3T3 cells. One such gene, RECK, encodes a membrane-anchored glycoprotein of about 110 kDa with multiple epidermal growth factor-like repeats and serine-protease inhibitor-like domains. While RECK mRNA is expressed in various human tissues and untransformed cells, it is undetectable in tumor-derived cell lines and oncogenically transformed cells. Restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis. Moreover, purified RECK protein was found to bind to, and inhibit the proteolytic activity of, MMP-9. Thus, RECK may link oncogenic signals to tumor invasion and metastasis.

3T3 Cells↗
PubMed1998

Monitoring of response to radiotherapy with fluorine-18 deoxyglucose PET of head and neck squamous cell carcinomas.

We examined the usefulness of positron emission tomography (PET) using fluorine-18 deoxyglucose (FDG) in determining the therapeutic effects of irradiation and chemotherapy on head and neck malignant tumors. Twenty-two patients with head and neck lesions who underwent histological examinations were studied. Squamous cell carcinoma was histologically diagnosed in all cases. Sixteen of them underwent radiotherapy with approximately 40 Gy in combination with carboplatin therapy. The remaining 6 patients underwent radiotherapy alone. After these treatments, 11 underwent surgery. For PET study, each patient was injected with intravenous FDG 185-370 MBq. We evaluated the degree of FDG accumulation using scanned images taken 40-55 min after the injection. We measured the standardized uptake value (SUV), a semiquantative evaluation, ROI activity divided by the dosage per weight of each patient. FDG-PET, CT and MRI were performed twice for each patient, before and after treatment. FDG uptake, but not the tumor size in CT or MRI, was significantly reduced in each patient after the treatment. Therefore, our findings have clearly demonstrated that FDG-PET provides for more valuable therapeutic outcomes than conventional imaging such as CT and MRI. FDG-PET should thus provide a new dimension in the management of head and neck malignant tumors.

Carcinoma, Squamous Cell↗
PubMed1997

Value of cardiac ultrafast computed tomography for detecting right atrial thrombi in chronic atrial fibrillation.

We evaluated the accuracy of cardiac ultrafast computed tomography in diagnosing atrial thrombi in 70 patients with chronic atrial fibrillation, and identified the predictors of atrial thrombi from among clinical, echocardiographic, and ultrafast computed tomographic features. Ultrafast computed tomography identified 11 atrial thrombi in 9 patients: 4 patients had thrombi in the left atrium, 3 in the right, and 2 in both. Transthoracic echocardiography detected only 4 left atrial thrombi, and enlargement of the left or right atrium was associated with atrial thrombi (p <0.05).

Aged↗
PubMed1997

Two-directional aortic annular enlargement for aortic valve replacement in the small aortic annulus.

We have encountered 3 patients with a small aortic annulus for whom the conventional posterior enlargement alone was not extensive enough to implant an artificial valve of acceptable size. Therefore, we performed two-directional enlargement, which is a combination of posterior and anterior enlargement. First, the posterior enlargement was done, and then an additional aortotomy was made anteriorly and extended to the ventricular septum. The aortic annulus was enlarged by 68% after the two-directional enlargement. At a follow-up of 31 months, the patients' functional status was New York Heart Association class I.

Adult↗
PubMed1997

Reconstruction of right ventricular outflow tract by pedicled pericardial valved conduit.

A modification of the Rastelli technique using a pedicled autologous pericardial valved conduit was performed on 3 patients aged 10 months to 3 years. Two patients in whom a prosthetic gusset was not used or was partially used showed good recovery during the follow-up period (3 months to 3 years). The pedicled autologous pericardial conduit may be expected to increase its diameter with physical growth.

Child, Preschool↗
PubMed1997

Single lead atrial synchronous ventricular pacing in Japanese patients with complete atrioventricular block.

The purpose of this study was to review our experience with atrial synchronous ventricular pacing devices (THERA VDD pacing systems, Medtronic, Inc., U.S.A.) using single atrioventricular leads in Japanese patients with complete atrioventricular block and normal sinus function. Twenty patients with a mean age of 55 +/- 13 years underwent implantation of VDD pacemakers. At implantation the amplitude of atrial signals in the supine position during normal breathing, which was measured directly using an external pacing system analyzer, ranged from 1.8 to 5.8 mV with a mean amplitude of 3.4 +/- 1.4 mV. Atrial amplitudes did not change during deep breathing (3.3 +/- 1.1 mV) or in the semi-Fowler position (3.4 +/- 1.6 mV). Atrial oversensing or undersensing was not observed in any of the patients. During a follow-up period, the percentage of atrial synchronization was >95% in 19 patients, and none of the patients had pacemaker related tachycardia or pacemaker related complications. These results were promising enough to warrant the extension of the clinical use of the VDD pacemaker.

Adult↗
PubMed1997

Possible involvement of MSX-2 homeoprotein in v-ras-induced transformation.

A truncated MSX-2 homeoprotein was found to induce flat reversion when expressed in v-Ki-ras-transformed NIH3T3 cells. Although the expression of endogenous MSX-2 gene is low in most of the normal adult tissues examined, it is frequently activated in carcinoma-derived cell lines. Likewise, the gene is inactive in untransformed cells but is transcriptionally activated after transformation by v-Ki-ras oncogene, suggesting that the intact MSX-2 may play a positive, rather than suppressive, role in cell transformation. To test this possibility, we isolated a full-length human MSX-2 cDNA and tested its activities in two cell systems: fibroblast and myoblast. In NIH3T3 fibroblasts, although the gene by itself failed to confer a transformed phenotype, antisense MSX-2 cDNA as well as truncated MSX-2 cDNA interfered with the transforming activities of both v-Ki-ras and v-raf oncogene. In C2C12 myoblasts, MSX-2 was found to suppress MyoD gene expression, as do activated ras oncogenes, under certain culture conditions, and truncated MSX-2 cDNA was found to inhibit the activities of both MSX-2 and ras in this system as well. Our findings not only suggest that the truncated version MSX-2 may act as a dominant suppressor of intact MSX-2 but also raise the possibility that MSX-2 gene may be an important downstream target for the Ras signaling pathways.

3T3 Cells↗
PubMed1996

A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants.

Caenorhabditis elegans UNC-18 protein, homologous to yeast Sec1p, is important in neurotransmitter release, because the unc-18 mutation leads to severe paralysis and presynaptic acetylcholine (ACh) accumulation. To examine the functional conservation in mammals, we tried to isolate unc-18 isoforms from mouse and human brain cDNA libraries and obtained two classes of isoforms-neural genes and ubiquitous genes. Neural genes were identical to Munc-18 (also known as n-Sec1 or rbSec1), identified in rat and bovine brains as a syntaxin-binding protein. According to "Munc-18" terminology, we call the neural genes Munc-18-1 and the ubiquitous genes Munc-18-3. These mammalian isoforms exhibit 58% (Munc-18-1) and 42-43% (Munc-18-3) amino acid sequence identity with UNC-18. Next, we constructed transgenic unc-18 mutants to test biological activity of mouse Munc-18-1 and Munc-18-3 under the control of C. elegans unc-18 promoter. Munc-18-1 compensates for severe locomotion disability and cholinergic defects, e.g., abnormal sensitivities to cholinesterase inhibitors and cholinergic receptor agonists in unc-18 mutants, but Munc-18-3 fails. These data suggest that Munc-18-1 and C. elegans unc-18 may play positive roles in ACh release and that the molecular mechanism of neuronal regulated secretion has been partially conserved from nematodes to mammals.

Animals↗
PubMed1996

The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells.

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.

Acute Disease↗
PubMed1996

Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is crucial to hematopoiesis, melanogenesis, and gametogeneis. Although the enzymatic activity of the c-kit product (KIT) is regulated by its ligand, both the Val559-->Gly (G559) mutation in the juxtamembrane domain and the Asp814-->Val (V814) mutation in the phosphotransferase domain lead to constitutive activation of KIT. By retroviral infection of hematopoietic progenitor cells with KIT(G559) or KIT(V814), KIT(G559) induced development of granulocyte/macrophage and mast-cell colonies in vitro without the addition of exogenous growth factors. KIT(V814) induced factor-independent growth of various types of hematopoietic progenitor cells, resulting in the development of mixed erythroid/myeloid colonies in addition to granulocyte/macrophage and mast-cell colonies. Furthermore, transplantation of KIT(G559) and KIT(V814)-infected bone marrow cells led to development of acute leukemia in one of 10 and six of 10 transplanted mice, respectively. No mice developed hematologic malignancies after transplantation of wild-type KIT-infected cells. Furthermore, transgenic mice expressing KIT(V814) developed acute leukemia or malignant lymphoma. These results demonstrate a direct role of the mutant KITs, particularly KIT(V814), in tumorigenesis of hematopoietic cells and suggest that similar mutations may contribute to the development of human hematologic malignancies.

Animals↗
PubMed1996

Characterization of a human MSX-2 cDNA and its fragment isolated as a transformation suppressor gene against v-Ki-ras oncogene.

A cDNA (termed CT124) encoding a carboxyl-terminal fragment of the human homeobox protein MSX-2 was found to induce flat reversion when expressed in v-Ki-ras-transformed NIH3T3 cells. Although the expression of endogenous MSX-2 gene is low in most of the normal adult tissues examined, it is frequently activated in carcinoma-derived cell lines. Likewise, the gene is inactive in NIH3T3 cells but is transcriptionally activated after transformation by v-Ki-ras oncogene, suggesting that the intact MSX-2 may play a positive, rather than suppressive, role in cell transformation. To test this possibility, we isolated a near full-length human MSX-2 cDNA and tested its activities in two cell systems, i.e. fibroblast and myoblast. In NIH3T3 fibroblasts, although the gene by itself failed to confer a transformed phenotype, antisense MSX-2 cDNA as well as truncated CT124 cDNA interfered with the transforming activities of v-Ki-ras oncogene. In C2C12 myoblasts, MSX-2 was found to suppress MyoD gene expression, as do activated ras oncogenes, under certain culture conditions, and CT124 was found to inhibit the activities of both MSX-2 and ras in this system as well. Our findings not only suggest that CT124 may act as a dominant suppressor of MSX-2 but also raise the possibility that MSX-2 gene may be an important downstream target for the Ras signaling pathways.

3T3 Cells↗
PubMed1996

Role of aspartic acid 814 in the function and expression of c-kit receptor tyrosine kinase.

The c-kit receptor tyrosine kinase (KIT) is constitutively activated in three different types of neoplastic mast cell lines by naturally occurring mutations that result in substitutions of Val or Tyr for Asp814 in the phosphotransferase domain. In an effort to characterize the role of the Asp814 residue, we have investigated the properties of mutant KITs in which the Asp814 residue was deleted or mutated to a series of other amino acids. With the exception of rare instances, mutant KITs with substitutions of Asp814 were found to be constitutively phosphorylated on tyrosine and activated in the absence of the ligand, stem cell factor (SCF), whereas a deletion mutant lacking Asp814 (KITDel-Asp-814) did not exhibit tyrosine phosphorylation and activation even after treatment with SCF. In addition to constitutive activation, furthermore, both highly activated substitution mutants (KITVal-814 and KITTyr-814) and modestly activated substitution mutants (KITGly-814 and KITHis-814) were continuously degraded in the absence of SCF, whereas wild-type KIT (KITWild) required SCF stimulation to undergo degradation. These results suggested that the Asp814 residue may play a crucial role in regulating enzymatic activity and expression of KIT and that various types of mutations at the Asp814 residue may generate oncogenic protein with constitutive activation and degradation.

Amino Acid Sequence↗
PubMed1996

Constitutive activation of c-kit in FMA3 murine mastocytoma cells caused by deletion of seven amino acids at the juxtamembrane domain.

A peculiar point mutation results in constitutive activation of c-kit receptor tyrosine kinase (KIT) in three different tumor mast cell lines; ie, the HMC-1, P-815, and RBL-2H3. Because constitutive activation of KIT was also observed in the FMA3 mouse mastocytoma cell line, we investigated the molecular mechanism. Sequencing of the whole coding region of the c-kit showed that the point mutation found in HMC-1, P-815, and RBL-2H3 cells was absent in FMA3 cells and that the c-kit cDNA of FMA3 cells carried an in-frame deletion of 21 base pairs (bp) encoding Thr-Gln-Leu-Pro-Tyr-Asp-His at codons 573 to 579 at the juxtamembrane domain. The FMA3-type c-kit cDNA with 21 bp deletion was introduced into the IC-2 cell line, which was derived from murine cultured mast cells. IC-2 cells were dependent on interleukin (IL)-3 and did not express KIT on the surface. In IC-2 cells introduced with the FMA3-type c-kit cDNA, KIT was constitutively phosphorylated on tyrosines and activated. Moreover, the FMA3-type KIT was dimerized without the stimulation by stem cell factor (SCF), a ligand for KIT. The spontaneously dimerized FMA3-type KIT without SCF binding was not internalized even after the activation. IC-2 cells expressing the FMA3-type KIT grew in suspension culture without IL-3 and SCF and became leukemic in nude athymic mice. The deletion of seven amino acids at the juxtamembrane domain appeared to be a new activating mutation of KIT that might be involved in neoplastic growth of mast cells.

Amino Acid Sequence↗
PubMed1996

Avoiding hypoxemia during unifocalization.

An 11-month-old child underwent unifocalization of the major aortopulmonary collateral arteries, but did not tolerate occlusion of both vessels simultaneously. Using a Y-shaped homograft tube, we translocated the vessels sequentially and avoided severe hypoxemia.

Abnormalities, Multiple↗