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Biomedical subjects

M Hamaguchi

Publications and source records attributed to M Hamaguchi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Efficacy of inhaled nitric oxide in children with ARDS.

STUDY OBJECTIVE: Data concerning inhaled nitric oxide (iNO) on pediatric ARDS is rare. We investigated the effects of iNO on pediatric ARDS in order to examine the ability to predict a response to iNO, the optimal concentration of iNO, the effects of < or = 1 ppm nitric oxide (NO), and the effect of iNO on PaCO2. SETTING: ICU at Kumamoto (Japan) University Hospital. PATIENTS AND INTERVENTIONS: Seven children with ARDS. The initial responses to 16 ppm NO and the dose-response effects of 0.13 to 16 ppm NO were assessed. MEASUREMENTS AND RESULTS: Sixteen ppm of iNO improved oxygenation in all seven children. The use of iNO significantly increased the ratio of arterial oxygen tension to the fraction of inspired oxygen (PaO2/FIO2). A correlation between the NO-induced increase in PaO2/FIO2 and the baseline PaO2/FIO2 was observed (r=0.93, p<0.01). Dose-response tests showed that the optimal concentration of iNO was < or = 4 ppm, improvements in PaO2/FIO2 could be observed with concentrations of < or = 1 ppm NO, and iNO induced a slight decrease in PaCO2. CONCLUSIONS: In children with ARDS, iNO frequently improves oxygenation and induces a slight decrease in PaCO2, with the baseline PaO2/FIO2 functioning as a predictor of all NO response. Improvements of PaO2 and PaCO2 were observed with concentrations of iNO of < or = 1 ppm, a level in which the risk of a toxic reaction in children is minimal. Effects on outcome need verification in larger controlled trials.

Administration, Inhalation↗
PubMed1998

Contraction properties of the superior pharyngeal constrictor muscle.

OBJECTIVE: The mechanical contraction property of the superior pharyngeal constrictor (PC) muscle was analyzed and compared with the levator veli palatini (LVP) muscle. DESIGN: Twenty adult dogs anesthetized with sodium pentobarbital were used. RESULTS: The isometric contraction curves of LVP and PC were recorded after direct electric stimulation to each muscle. The contraction time of isometric twitch contraction of the superior PC muscles was 30.3+/-5.25 msec, and the half relaxation time was 22.97+/-5.44 msec. The summation curve was observed at a stimulus frequency above 20 Hz of a repetitive pulse stimulus frequency of 85 Hz. CONCLUSIONS: The mechanical contraction properties of the PC muscle are similar to those of the LVP, but with more aspects that are characteristic of a fast twitch muscle.

Animals↗
PubMed1998

Suppression of cell growth by ectopic expression of N-cadherin.

We found that ectopic expression of N-cadherin in 3Y1 caused tight association of cells and, thereby, substantially suppressed cell growth. N-cadherin expression inhibited neither tyrosine phosphorylation of cellular proteins, GTP uptake onto Ras, nor activation of MAP kinase, suggesting that it does not directly interfere the Ras-MAP kinase pathway. However, co-expression of N-cadherin with dominant negative Ras, S17N Ras, showed synergestic growth inhibitory effect, suggesting that N-cadherin signaling antagonizes the Ras-MAP kinase signaling. In addition, we found that N-cadherin yielded cell-cycle arrest at G0/G1 phase. These results strongly suggest that N-cadherin cell adhesion machinery works as a negative controller of cell cycle in 3Y1 and this growth suppressive function of cadherin is distinct from the epithelial morphogenetic function.

Actins↗
PubMed1998

[FK506 for the prophylaxis of graft-versus-host-disease after bone marrow transplantation from HLA-genotypically mismatched unrelated donor].

Eleven leukemia patients who had undergone bone marrow transplants from HLA-A, B, DR genotypically mismatched unrelated donors received FK506 and short-term methotrexate as prophylaxis for graft-versus-host disease (GVHD). Grade III-IV acute GVHD developed in 2 of the patients, and chronic GVHD developed in 4 of the other patients. Adverse drug reaction included reversible nephrotoxicity, hyperglycemia (all patients) and hypertension (9 patients). Hyperglycemia and hypertension of grade 3 or higher occurred mostly in the patients who were on supplemental steroids. However, severe nephrotoxicity was not observed. Complications included cystitis (4 patients), cytomegalovirus colitis (3 patients), Interstitial Pneumonitis (IP) (3 patients), tuberculosis (1 patient), and thrombotic microangiopathy (1 patient). None of patients relapsed. Although close monitoring of FK506 blood concentration and patient clinical signs are required, we concluded that FK506 is effective for GVHD prophylaxis after bone marrow transplantation from HLA-A, B, DR genotypically mismatched unrelated donors, and that adverse reactions due to FK506 are controllable. To determine the long-term effectiveness of this drug, it will be necessary to conduct prospective randomized studies that compare it wiht cycloporin A as a preventive treatment against GVHD in patients who receive bone marrow transplants from HLA genotypically mismatched unrelated donors.

Adolescent↗
PubMed1998

Analysis of bax protein in sphingosine-induced apoptosis in the human leukemic cell line TF1 and its bcl-2 transfectants.

Sphingosine, a sphingolipid breakdown product, has been proposed as an apoptosis-inducing agent. In this study, we examined the effect of sphingosine in bcl-2-overexpressing cells compared with cells that do not express the bcl-2 gene. The human erythroleukemic cell line TF1, which lacks bcl-2 expression, was easily induced to undergo apoptotic cell death by a variety of stimuli, including depletion of granulocyte-macrophage colony-stimulating factor (GM-CSF) or exposure to methylmethane sulfonate (MMS) (100 microg/mL), ultraviolet light (15 J/m2), X-ray irradiation (20 Gy), or sphingosine, a sphingolipid breakdown product (5 microM). In contrast, bcl-2 transfectants of TF1 (TF1-bcl2), which we established, were resistant to most of these treatments but remained sensitive to sphingosine. Neither C2- nor C6-ceramide (short-chain ceramide) induced apoptosis in TF1-mock and TF1-bcl2 cells. Sphingosine-induced apoptosis could not be inhibited by fumonisin B1, which can prevent conversion of sphingosine to ceramide, suggesting that sphingosine itself, not ceramide, possesses apoptosis-inducing capability. Western blotting, which revealed a 21-kDa bax protein in untreated cells, revealed the presence of an additional 18-kDa protein in GM-CSF-depleted and MMS- or sphingosine-treated TF1-mock cells. In TF1-bcl2 cells, this protein was not detected after GM-CSF depletion or MMS treatment, but was observed after sphingosine treatment. Immunoprecipitation with anti-bcl2 antibody, followed by immunoblotting with anti-bax antibody, showed that both the 21-kDa bax protein and the 18-kDa protein heterodimerized with bcl-2 protein. These results suggest that sphingosine is a unique reagent for apoptosis and that it can overcome bcl-2 gene expression. Furthermore, induction of 18-kDa bax-related protein may play an important role in apoptosis. Sphingosine, but not ceramide, may prove applicable as a reagent for future cytotoxic drugs used to treat intractable tumors overexpressing bcl-2.

Apoptosis↗
PubMed1997

Fibronectin secretion from human peritoneal tissue induces Mr 92,000 type IV collagenase expression and invasion in ovarian cancer cell lines.

Our previous study showed that human peritoneal conditioned medium (CM) increased the matrix metalloproteinase-9 (MMP-9) secretion and invasiveness of ovarian cancer cells (NOM1). In an effort to identify this MMP-9-stimulating factor, we examined the effects of extracellular matrix components, such as type IV collagen, laminin, and fibronectin, on ovarian cancer cells. We found that fibronectin increased the MMP-9 activity of NOM1 cell CM in a concentration-dependent manner and that the peritoneal CM contained high level of fibronectin. An increase of MMP-9 activity in NOM1 cell CM by the peritoneal CM was almost completely blocked by 20 microg/ml of anti-integrin alpha5/FnR antibody and RGD polypeptides. Furthermore, after immunoprecipitation by antifibronectin antibody supernatant of the peritoneal CM did not increase MMP-9 activity in NOM1 cells. Fibronectin and the peritoneal CM also increased MMP-9 activity and expression in NOM1 cell lysate, and these effects were blocked by anti-integrin alpha5/FnR antibody. Invasiveness of NOM1 cells was enhanced by fibronectin and the peritoneal CM in a concentration-dependent manner, and anti-integrin alpha5/FnR antibody blocked these effects. These results suggested that fibronectin secreted from peritoneum increased MMP-9 activity and expression, and, in turn, invasiveness of ovarian cancer cells.

Antibodies, Monoclonal↗
PubMed1997

Cell to substratum adhesion is involved in v-Src-induced cellular protein tyrosine phosphorylation: implication for the adhesion-regulated protein tyrosine phosphatase activity.

Protein tyrosine phosphorylation accompanies the integrin-mediated cell to substratum adhesion, and is essential for the progression of G1/S phase of the cell-cycle in normal fibroblasts. To examine how cellular protein tyrosine phosphatase (PTPase) activity is involved in regulating the adhesion-dependent protein tyrosine phosphorylation, we employed fibroblast cells bearing an active form of a protein tyrosine kinase (PTK), v-Src. We found that the v-Src induced tyrosine phosphorylation in certain proteins such as tensin, talin, p120, p80/85 (cortactin) and paxillin was greatly reduced when the cell to substratum adhesion was lost. Readhesion of the cells onto fibronectin restored these phosphorylation events, while this was inhibited by the addition of RGD peptide. The kinase activity of the v-Src was unchanged by the loss of cell to substratum adhesion. On the other hand, treatment with a protein tyrosine phosphatase inhibitor vanadate caused much the same increase in the v-Src-mediated cellular tyrosine phosphorylation between cells adhered to the culture environments and cells kept in suspension. These data suggest that PTPase(s) appears to be more critical than the v-Src PTK in determining the cell adhesion-dependent protein tyrosine phosphorylation. Moreover, most of the protein tyrosine phosphorylations that are mediated by the v-Src but still dependent on the cell adhesion were indeed greatly reduced during an anchorage-independent growth of v-Src cells. Thus our data collectively indicate that the v-Src induced high level of tyrosine phosphorylation in certain types of proteins are still under the control of the integrin(s) or the cell adhesion to culture substratum, and most of these adhesion-regulated high levels of tyrosine phosphorylations are not essential for the transformed phenotype.

Actins↗
PubMed1997

c-Ras is required for the activation of the matrix metalloproteinases by concanavalin A in 3Y1 cells.

Concanavalin A (Con A) is known to trigger augmented secretion and proteolytic activation of the matrix metalloproteinases (MMPs) in fibroblasts. To study the signaling pathway critical for the activation of MMPs in fibroblasts, we examined the effects of dominant negative ras (S17N ras) expression under the control of conditionally inducible promoter in Con A-activated 3Y1 cells. We found that augmented secretion and proteolytic activation of MMP-2 and MMP-9 together with expression of MT1-MMP in Con A-activated 3Y1 were dramatically suppressed by S17N ras expression. These results strongly suggest that c-Ras plays a critical role in the augmented expression and proteolytic activation of MMPs in fibroblasts.

Animals↗
PubMed1997

Magnitude of protein tyrosine phosphorylation-linked signals determines growth versus death of thymic T lymphocytes.

Using concanavalin A (Con A) as a multireceptor-reactive agonist, we studied the relationship between the growth or death of thymic T lymphocytes and the agonist concentration-dependent magnitude of the intracellularly delivered signal. Both immature and mature thymic T lymphocytes were subjected to a high concentration of Con A-mediated signal for apoptotic cell death. In this model, a number of cellular proteins including mitogen activated protein kinases were phosphorylated at tyrosine depending on the concentration of Con A. This effect was followed by corresponding increase in serine 73 phosphorylation of c-jun and transcription of c-fos. DNA fragmentation and cell membrane disruption developed concomitantly after stimulation with high concentrations of Con A. The addition of inhibitors of protein kinases which completely inhibited the growth of cells stimulated with low concentrations of Con A only partially prevented death, and even promoted DNA fragmentation of cells stimulated with high concentrations of Con A. The dissociated sensitivities of Con A-mediated cell growth and cell death to the inhibitors were, however, shown to be due to the different efficiency of inhibition of high and low levels of intracellularly delivered signals. The results indicate that the magnitude of signaling could be the principal element that determines the growth versus death of thymic T lymphocytes.

Animals↗
PubMed1997

Induction of matrix metalloproteinases following brain injury in rats.

Matrix metalloproteinases (MMPs) are important in various pathophysiological processes related with the tissue remodeling. We planned the experiments to determine whether MMPs participate in disruption and repair of the tissue following brain injury. We have studied induction of MMP-9, a 92 kilodalton (kDa) gelatinase, in traumatic brain tissue, which may be produced by brain residual cells. We speculate that MMP-9 plays a role in post-traumatic brain edema formation.

Animals↗
PubMed1997

Role of tyrosine specific phosphorylation of cellular proteins, especially EGF receptor and p125FAK in human lung cancer cells.

To clarify the role of tyrosine phosphorylation of cellular proteins in human lung cancer cells, phosphotyrosine (PTYR)-containing proteins in lung cancer cell lines and in paired tissues resected from cancerous and normal lungs were studied by immunoblotting with an anti-PTYR antibody. We found that the profiles of protein phosphorylation were very similar among those cell lines which had different histological features. The major PTYR-containing proteins (180-190 KDa, 120-130 KD, and 95-100 KDa) were detected in lung cancer cell lines. The expression of EGF receptor (EGF-r) (p185) and o-erb B2 protein, and tyrosine phosphorylation of p125FAK were examined in cancerous lung tissues and normal lung tissues. In surgical specimens, approximately half of the samples of lung cancer tissues showed clear elevation of tyrosine phosphorylation. In these cancerous tissues, no clear amplification of EGF-r and c-erb B2 protein expression was observed. However, elevation of tyrosine phosphorylation of p125FAK was observed in cancerous lung tissues but not in normal lung tissues, and its phosphorylation was closely correlated with the nodal involvement of cancer and disease-free survival time. These results suggested that the intracellular signaling pathway via tyrosine phosphorylation plays a role in the generation and immortalization of lung cancer, and assessment of tyrosine phosphorylation of cellular proteins. especially p125FAK, may be available clinically as a prognostic factor.

Adult↗
PubMed1997

Unrelated bone marrow transplantation from the National Marrow Donor Program.

Between November 1992 and December 1996, we carried out bone marrow transplantation through the National Marrow Donor Program (NMDP) for 11 patients who lacked an appropriate donor among their family members and the Japan Marrow Donor Program (JMDP). They accounted for 11% of 101 patients who had registrated to the NMDP Transplant Center Office in Japan. The median time required from the initiation of preliminary search to transplant for these 11 patients was 198 days. The 11 donors included four Caucasians, one Native American and the others were Asian/Pacific islanders. A median of 17 h was required to transport bone marrow from harvest institutes to our hospital and their viability determined in our laboratory had a median of 96%. Engraftment was observed in all recipients and the incidence of grade III-IV acute graft-versus host disease was 27%. Of four patients three (75%) with chronic myelogenous leukemia in chronic phase (standard-risk) and two (29%) of seven patients in progressive state of the disease (high-risk), are alive at present. Cooperation between the JMDP and the NMDP, which began in April 1997, could shorten the time for donor search and allow transplantation to more patients with more appropriate timing.

Adolescent↗
PubMed1997

Hepatic injury localized to the field of total lymphoid irradiation.

A 37-year-old woman with severe aplastic anemia underwent allogeneic bone marrow transplantation following cyclophosphamide (CY) and total lymphoid irradiation (TLI). On day +30, a CT scan was carried out because of a mild elevation in liver enzymes, and it revealed a low density area with a sharp border in the left lobe corresponding to the irradiated area. MRI showed a hypersignal intensity on both T1 and T2-weighted images and suggested that hepatic damage was mainly severe fatty change. These abnormalities resolved with no treatment. CY with TLI for adult patients with severe aplastic anemia may induce hepatic injury.

Adult↗
PubMed1997

Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells.

Mitogen-activated protein (MAP) kinase appears to be one of the key regulators of cell proliferation and differentiation. Very little, however, has been revealed as to how MAP kinase is involved in leukemogenesis. We have studied the activation of the MAP kinase pathway in 100 human primary leukemia cells including 73 acute myelogenous leukemias (AMLs). Forty acute leukemia samples (40% of the total), including 37 AML samples (51% of AML), showed activation of MAP kinase as revealed by the mobility shift of the phosphorylated form of the protein and by in vitro kinase assay. This activation was correlated with MAP kinase kinase activity in these cells. In contrast, none of 14 chronic myelogenous leukemia samples showed the activation of MAP kinase. These results suggest that the MAP kinase pathway is constitutively activated in a subset of primary acute leukemias, and thus indicate the possible role of the constitutively activated MAP kinase in leukemogenesis.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Nitrogen dioxide production in a nitric oxide inhalation system using the Servo Ventilator 900C.

During nitric oxide (NO) inhalation therapy, toxicity may be produced by the reactive metabolite nitrogen dioxide (NO2). The purpose of the present study was to determine the NO2 concentration in a NO inhalation system used for respiratory failure in children at relatively low concentrations of NO (< 20 ppm). The production of NO2 in the NO inhalation system using the Servo Ventilator 900C connected to the test lung under each of 30 combinations of NO concentrations (0, 4, 8, 12, 16, and 19 ppm) and inspired oxygen (O2) concentrations (21, 40, 60, 80, and 100%). Pressure controlled ventilation was used with a respiratory rate of 20 breaths/min. NO and NO2 measurements were obtained on the inspiratory side of the Y-piece connected to the test lung. At a given NO level, increases in the concentration of inspired O2 resulted in increases in the concentration of NO2 produced, as did increases in the amount of NO at a given concentration of O2. The mean NO concentration at the inspiratory site of the Y-piece did not exceed 0.05 ppm (the limit of NO2 as an outdoor air pollutant in the United States) when the NO concentration did not exceed 8 ppm, regardless of the O2 concentration. NO inhalation therapy for children with severe respiratory failure using the Servo Ventilator 900C can be performed safely when the concentration of NO does not exceed 8 ppm.

Nitric Oxide↗
PubMed1997

Measurement of velopharyngeal movements induced by isolated stimulation of levator veli palatini and pharyngeal constrictor muscles.

The levator veli palatini (LVP) and superior pharyngeal constrictor muscles (PC) close the velopharynx. However, for the velopharyngeal movements to be understood in detail, each muscle contraction must be analyzed precisely. This study was performed to clarify the velopharyngeal movement which was induced by a single muscle contraction, LVP or PC. Using a nasopharyngeal fiberscope, we analyzed the velopharyngeal movement associated with the contraction of the LVP and PC muscles in mongrel dogs. To elicit the maximal contraction of each muscle, we applied repetitive electrical stimulation to each peripheral nerve efferent to the LVP or PC muscle. Stimulation with a frequency of 77 Hz and 83 Hz induced maximal tension in the LVP and PC muscles, respectively, in isometric contraction. In a second series of experiments, fiberscopic views of the velopharyngeal movements associated with each muscle's maximal contraction were recorded. The degree of closure was calculated at several sections. The LVP muscle pulled the caudal fourth of the soft palate, while the PC projected the posterior wall at the level of the caudal end of the soft palate. The PC muscle also projected the lateral wall of the velopharynx. The effect of LVP contraction on the lateral wall was very small. These results show that the velopharyngeal movement associated with LVP contraction is very different from that with PC contraction.

Animals↗
PubMed1997

Activities of superior pharyngeal constrictor and levator veli palatini muscles related to respiration in dogs.

OBJECTIVE: This study, using mongrel dogs, attempted to delineate the respiratory activity of two closure muscles of the velopharynx, the levator veli palatini (LVP) and superior pharyngeal constrictor (PC) muscles. METHOD: Fifteen mongrel dogs were given tracheotomies, with intratracheal tubes being connected to their respiratory circuits. Activities of the PC and LVP muscles were recorded electromyographically, and the effects of PaO2 and PaCO2 were analyzed along with the effects of lung inflation intratracheally with O2 and N2. RESULTS: Under hypoxic conditions, expiratory LVP activity was observed while PC activity diminished. The effects of lung inflation on both LVP and PC activities were also studied. The activities of both muscles were enhanced by lung inflation. CONCLUSION: It was thus suggested that the roles of both muscles during velopharyngeal closing movements are not the same.

Administration, Inhalation↗