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M Noda

Publications and source records attributed to M Noda.

At least 577 records · Page 32Linked to original sources

High lateral mobility of endogenous and transfected alkaline phosphatase: a phosphatidylinositol-anchored membrane protein.

The lateral mobility of alkaline phosphatase (AP) in the plasma membrane of osteoblastic and nonosteoblastic cells was estimated by fluorescence redistribution after photobleaching in embryonic and in tumor cells, in cells that express AP naturally, and in cells transfected with an expression vector containing AP cDNA. The diffusion coefficient (D) and the mobile fraction, estimated from the percent recovery (%R), were found to be cell-type dependent ranging from (0.58 +/- 0.16) X 10(-9) cm2s-1 and 73.3 +/- 10.5 in rat osteosarcoma cells ROS 17/2.8 to (1.77 +/- 0.51) X 10(-9) cm2s-1 and 82.8 +/- 2.5 in rat osteosarcoma cells UMR106. Similar values of D greater than or equal to 10(-9) cm2s-1 with approximately 80% recovery were also found in fetal rat calvaria cells, transfected skin fibroblasts, and transfected AP-negative osteosarcoma cells ROS 25/1. These values of D are many times greater than "typical" values for membrane proteins, coming close to those of membrane lipid in fetal rat calvaria and ROS 17/2.8 cells (D = [4(-5)] X 10(-9) cm2s-1 with 75-80% recovery), estimated with the hexadecanoyl aminofluorescein probe. In all cell types, phosphatidylinositol (PI)-specific phospholipase C released 60-90% of native and transfection-expressed AP, demonstrating that, as in other tissue types, AP in these cells is anchored in the membrane via a linkage to PI. These results indicate that the transfected cells used in this study possess the machinery for AP insertion into the membrane and its binding to PI. The fast AP mobility appears to be an intrinsic property of the way the protein is anchored in the membrane, a conclusion with general implications for the understanding of the slow diffusion of other membrane proteins.

Alkaline Phosphatase↗

Effects of nicorandil on electromechanical activity of frog atrial muscle.

The effects of the antianginal drug nicorandil on electrical and mechanical activity of bullfrog atria were examined. The application of nicorandil at concentrations from 0.3 to 10 mM caused a negative inotropic effect without any appreciable change in the resting membrane potential. The amplitude of action potentials was attenuated. In the voltage clamp experiments, the slow inward current was slightly inhibited, but the background inward current and delayed outward current were not affected in the presence of nicorandil. The inward rectifying properties of time-independent outward current were slightly inhibited by 10 mM nicorandil. Nicorandil inhibited the caffeine-induced contractures elicited in the depolarized preparation, but had no effect on the contracture mediated through the Na-Ca exchange mechanism. These results suggest that the negative inotropic action of nicorandil is caused by inhibition of Ca influx and intracellular mobilization of Ca. Nicorandil had little effect on the potassium conductance in this preparation.

Animals↗

Lack of effects of carbachol on the Na-Ca exchange mechanism in frog atrial muscle treated with goniopora toxin.

Carbachol (CCh) at a concentration of 10(-7) M completely inhibited the twitch contraction of frog atrial muscle. However, when the preparation was treated with goniopora toxin (GPT), a selective inhibitor of Na channel inactivation, and the twitch contraction was augmented through the activation of Na-Ca exchange by this toxin, the reduction in contractile amplitude by CCh was only about 30% even at higher concentrations. The maximum rate of rise of the twitch contraction was not affected by CCh in GPT-treated preparations. The time course of configuration change of the twitch contraction after application of CCh in GPT-treated muscle indicated that the attenuation of amplitude preceded the shortening of duration. The residual contraction under the combined treatments with GPT and CCh was abolished by removal of external Ca++ or addition of TTX. CCh only moderately shortened the action potential which was prolonged by GPT, and further addition of TTX abolished the action potential. From these results, we suggest that CCh does not influence the twitch contraction which is augmented via the activation of the Na-Ca exchange mechanism in frog atrial muscle.

Action Potentials↗

Structure and function of sodium channel.

The primary structures of the Electrophorus electroplax sodium channel and two distinct sodium channel large polypeptides from rat brain have been deduced by cloning and sequencing the cDNAs. The sodium channel molecule contains four internal repeats with homologous amino acid sequences, which are oriented presumably in a pseudosymmetric fashion across the membrane, thus forming the channel. The mRNAs generated by transcription of the cloned cDNAs encoding the rat brain sodium channel large polypeptides, when injected into Xenopus oocytes, direct the formation of functional sodium channels. The transmembrane topology of the sodium channel molecule and the structure that may be involved in the voltage-dependent gating of the channel are discussed.

Amino Acid Sequence↗

Mechanism of sodium channel block in crayfish giant axons by 711389-S, a new antiarrhythmic drug.

The effects of 711389-S, a new antiarrhythmic drug, on the sodium channel of crayfish giant axon were studied using micro-electrode and sucrose-gap voltage-clamp techniques. When applied externally, 711389-S suppressed the action potential and the rate of rise without affecting the resting membrane potential. Voltage-clamp experiments revealed that 711389-S inhibits the sodium current more selectively than the potassium current and that the inhibition is more evident with internal rather than external application. The inhibitory effect of internally applied 711389-S on sodium current was enhanced at less negative holding potentials. 711389-S also shifted the steady-state inactivation curve in the direction of hyperpolarization. Use-dependent block became evident in the 711389-S-treated axons; this block resulted from an increase in the slow inactivating state during repetitive depolarization and from a slow recovery from the inactivated state during the pulse interval. 711389-S produced an additional inhibition when sodium channels were open at large depolarizations. This additional inhibition could be reversed by small depolarizations that opened the sodium channels. These observations suggest that 711389-S binds the resting, inactivated and open states of the sodium channel, resulting in a reduction of sodium channel availability. 711389-S also shifted the voltage dependence of peak sodium conductance toward a less negative potential.

Action Potentials↗

[Small-cell carcinoma of the lung relapsing at the primary site three years after radiation therapy with chemotherapy].

A 55-year-old man was diagnosed as having limited disease (T2N2M0, stage III) of small-cell carcinoma of the lung. He underwent radiation therapy (60 Gy in 30 fractions) in addition to combination chemotherapy, resulting in complete response with advantage for irradiation. Relapse in the primary site was seen three years after completion of the initial treatment. As a result, retreatment was started using radiation therapy (50 Gy in 25 fractions) with chemotherapy. The tumor almost disappeared again. Subsequently, cerebral metastasis was observed in the fourth year, indicating clinical and prognostic significance. Thoracic irradiation contributed to prolonged survival in this case. The most effective manner of combining irradiation and chemotherapy and the most efficacious doses were discussed.

Carcinoma, Small Cell↗

[A case of hepatocellular carcinoma associated with multiple pulmonary tumor thrombi and rupture of its right adrenal metastasis].

A 54-year-old man, who had the history of a blood transfusion 29 years ago, was admitted to our hospital because of dyspnea and abdominal fullness. Physical examination revealed jaundice and massive ascites and laboratory data suggested liver cirrhosis. The high level of AFP and a CT scan indicated the association of hepatocellular carcinoma and its metastasis to the right adrenal gland. On the 21st hospital day, he suddenly complained of severe pain in the right upper quadrant and the right flank, and fell into hemorrhagic shock. Blood transfusion was given, but he died on the 24th hospital day. Autopsy revealed liver cirrhosis, accompanied by hepatocellular carcinoma with the metastasis to the right adrenal gland and multiple pulmonary tumor thrombi. Massive hemorrhaging due to rupture of the right adrenal metastasis was seen in the retroperitoneal space.

Adrenal Gland Neoplasms↗

Autologous bone marrow transplantation in acute lymphoblastic leukemia following in vitro treatment with monoclonal antibodies and with complement: analyses for two cases of failure.

Two children with acute lymphoblastic leukemia (ALL) received autologous bone marrow transplantation (BMT) using remission bone marrow treated in vitro with the monoclonal antibodies, CD24 (BA-1), CD9 (BA-2) and CD10 (BA-3), and with rabbit complement. In one child with second remission ALL, hematopoietic recovery after BMT was prompt but, 81 days after BMT, isolated central nervous system (CNS) relapse occurred. Bone marrow relapse developed three months later, and she died 11 months after BMT. In patients with CNS leukemia prior to BMT, as in the present case, more intensive pretransplant CNS treatment and/or a conditioning regimen may reduce the risk of relapse. In the other patient, with primary refractory ALL in first remission, marrow reconstitution was slower. The patient developed interstitial pneumonitis with pleural effusion, and died 54 days after BMT. No infectious causes could be detected by culture or from serological studies of the pleural effusion. The rationale for applying autologous BMT to children with second remission ALL and first remission refractory ALL is discussed.

Antibodies, Monoclonal↗

[Experience with cefuzonam in the field of obstetrics and gynecology].

Cefuzonam (CZON, L-105) was studied clinically in the field of obstetrics and gynecology, and the results obtained are summarized below: 1. The concentration of the drug in blood decreased rapidly after drip infusion was completed, and the concentration diminished after 1 hour to one tenth of the level detected at 5-9 minutes, and to an almost undetectable level after 3 hours. The rapid decrease of blood concentrations appears to indicate that the excretion of CZON was much faster than other antibiotics. No conclusive data were obtained on changes of concentrations with time in tissues due to the small number of cases analyzed and scattering of the data obtained. 2. The concentration in the pelvic dead space exudate reached a peak of 18.5 micrograms/ml at 30 minutes after the end of infusion and decreased to 0.092 microgram/ml after 10 hours. 3. CZON was administered to 5 cases of obstetric and gynecological infections. The efficacy was good in 4 cases and poor in 1 case. No side effects or laboratory test abnormalities were observed.

Adult↗

Type-beta transforming growth factor inhibits proliferation and expression of alkaline phosphatase in murine osteoblast-like cells.

TGF-beta modulates growth and differentiation in many cell types. MC3T3E1 is a clonal non-transformed murine bone cell line which differentiates in culture. We tested the effect of porcine TGF-beta on the proliferation and differentiation of MC3T3E1 cells in monolayer cultures by following cell number, and alkaline phosphatase activity. TGF-beta treatment (2 ng/ml) altered the shape of MC3T3E1 cells from cuboidal to elongated/spindle-shape. TGF-beta inhibited the growth of MC3T3E1 by up to 40% (P less than 0.02) in a dose-dependent manner with half maximal inhibition at 1 ng/ml. Growth inhibition depended on serum concentration, maximal inhibition occurring at 2% serum. Expression of alkaline phosphatase, which peaks in vitro when the cells reach confluence, was strongly inhibited by TGF-beta, in a dose-dependent manner with half maximal inhibition at around 0.05 ng/ml and complete inhibition at 2 ng/ml. Alkaline phosphatase inhibition was irreversible after 24 hours exposure to TGF-beta.

Alkaline Phosphatase↗

Ouabain sensitivity is linked to ras -transformation in human HOS cells.

Mouse cells transformed by the retroviral oncogene v-Ki- ras are significantly more sensitive to the toxic effects of 1mM ouabain than are their nontransformed counterparts. We have extended these findings to a human cell line (HOS). HOS cells (ATCC CRL 1543) are relatively resistant to treatment with 1 microM ouabain while KHOS cells (transformed by Kirsten murine sarcoma virus) are extremely sensitive. Two flat revertant cell lines isolated from the KHOS line and lacking the v- ras gene sequences are resistant to ouabain. This effect may be observed morphologically and can also be demonstrated by dye exclusion and plating efficiency tests. In addition, the toxic effects of ouabain may be rapidly and efficiently quantitated in a 51Cr-release assay. This differential lethality may be used to enrich the proportion of non-transformed revertants in populations of mutagen-treated transformed cells.

Animals↗

Primary structure of the alpha-subunit of bovine adenylate cyclase-inhibiting G-protein deduced from the cDNA sequence.

The primary structure of the alpha-subunit of the adenylate cyclase-inhibiting G-protein (Gi) has been deduced from the nucleotide sequence of cloned DNA complementary to the bovine cerebral mRNA encoding the polypeptide. A much higher degree of amino acid sequence homology is observed between the alpha-subunits of Gi and transducin (68%) than between those of Gi and the adenylate cyclase-stimulating G-protein (Gs) (43%) or between those of transducin and Gs (42%).

Adenylyl Cyclase Inhibitors↗

Primary structure of the beta-subunit of Torpedo californica (Na+ + K+)-ATPase deduced from the cDNA sequence.

DNA complementary to the Torpedo californica electroplax mRNA coding for the beta-subunit of (Na+ + K+)-ATPase has been cloned by screening a cDNA library with an oligodeoxyribonucleotide probe. Nucleotide sequence analysis of the cloned cDNA has revealed that this polypeptide consists of 305 amino acid residues (including the initiating methionine). The transmembrane topology and the potential N-glycosylation sites of this polypeptide are discussed.

Amino Acid Sequence↗