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M Noda

Publications and source records attributed to M Noda.

At least 631 records · Page 35Linked to original sources

Structural homology of Torpedo californica acetylcholine receptor subunits.

The nicotinic acetylcholine receptor (AChR) from the electroplax of the ray Torpedo californica is composed of five subunits present in a molar stoichiometry of alpha 2 beta gamma delta (refs 1-3) and contains both the binding site for the neurotransmitter and the cation gating unit (reviewed in refs 4-6). We have recently elucidated the complete primary structures of the alpha-, beta- and delta-subunit precursors of the T. californica AChR by cloning and sequencing cDNAs for these polypeptides. Here, we report the whole primary structure of the gamma-subunit precursor of the AChR deduced from the nucleotide sequence of the cloned cDNA. Comparison of the amino acid sequences of the four subunits reveals marked homology among them. The close resemblance among the hydrophilicity profiles and predicted secondary structures of all the subunits suggests that these polypeptides are oriented in a pseudosymmetric fashion across the membrane. Each subunit contains four putative transmembrane segments that may be involved in the ionic channel. The transmembrane topology of the subunit molecules has also been inferred.

Amino Acid Sequence↗

Cloning and sequence analysis of cDNA for ovine corticotropin-releasing factor precursor.

Previously, Guillemin and Rosenberg and Saffran and Schally demonstrated the presence of hypothalamic factors that stimulated the secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland. Recently, Vale et al. have isolated and sequenced an ovine hypothalamic peptide of 41 amino acids, which is believed to represent the major physiological corticotropin-releasing factor (CRF) (reviewed in refs 5, 6). Available data suggest that hypothalamic CRF enhances both the synthesis and secretion of ACTH and related peptides such as beta-endorphin and beta-lipotropin (beta-LPH) (reviewed in ref. 6), which are all derived from the common precursor, termed ACTH-beta-LPH precursor or preproopiomelanocortin (reviewed in ref. 7). Because CRF mediates the neural control of the pituitary-adrenocortical system, the characterization of its biosynthetic precursor and the gene encoding it is essential for understanding the molecular mechanism underlying the endocrine response to stress. We have now cloned DNA sequences complementary to the ovine hypothalamic mRNA encoding the CRF precursor (referred to hereafter as prepro-CRF). The nucleotide sequence of the cloned cDNA, reported here, has revealed the primary structure of prepro-CRF. The carboxyl end represents the CRF sequence preceded by the tetrapeptide, Arg-Lys-Arg-Arg, and followed by the dipeptide, Gly-Lys. Comparison of the amino acid sequence of prepro-CRF with those of the ACTH-beta-LPH precursor and the arginine vasopressin-neurophysin II precursor suggests that these precursor proteins may be evolutionarily related.

Amino Acid Sequence↗

Primary structures of beta- and delta-subunit precursors of Torpedo californica acetylcholine receptor deduced from cDNA sequences.

The nicotinic acetylcholine receptor (AChR) from fish electric organ and mammalian skeletal muscle is the best characterized neurotransmitter receptor (reviewed in refs 1-3). The AChR from the electroplax of the ray Torpedo californica consists of five subunits present in a molar stoichiometry of alpha 2 beta gamma delta (refs 4-6); the apparent molecular weights of the alpha-, beta-, gamma- and delta-subunits are 40,000 (40K), 50K, 60K and 65K, respectively. Knowledge of the primary structures of these constituent polypeptides would facilitate the understanding of the molecular mechanism underlying the function of the neurotransmitter receptor. Recently, we have cloned cDNA for the alpha-subunit precursor of the T. californica AChR and have deduced the primary structure of this polypeptide from the nucleotide sequence of the cloned cDNA. Here we report the cloning and nucleotide analysis of cDNAs for the AChR beta- and delta-subunit precursors. The primary structures of the two polypeptides deduced from the cDNA sequences reveal conspicuous amino acid sequence homology among these and the alpha-subunits. The three subunits contain several highly conserved regions which may be essential for the receptor function or inter-subunit interaction.

Amino Acid Sequence↗

Flat revertants isolated from Kirsten sarcoma virus-transformed cells are resistant to the action of specific oncogenes.

Two flat revertants have been isolated from mutagen-treated populations of Kirsten murine sarcoma virus (Ki-MuSV)-transformed NIH/3T3 cells. These revertants, which appear to be cellular variants resistant to transformation by the Ki-MuSV oncogene v-Ki-ras, contain Ki-MuSV-specific DNA, elevated levels of the v-Ki-ras gene product p21, and rescuable transforming virus. Cell hybridization studies indicated that the revertant phenotype is dominant in hybrids between revertant cells and cells transformed by Ki-MuSV or the closely related Harvey MuSV and BALB MuSV. Analysis of hybrid cells resulting from the fusion of these revertants to cell lines transformed by other retroviruses showed that the action of certain oncogenes structurally unrelated to v-Ki-ras also could be suppressed. Thus, there appear to be functional relationships and diversities among transforming genes (oncogenes) not readily apparent from their structural characteristics.

Animals↗

Crystallization and some properties of leukocidin from Pseudomonas aeruginosa.

A leukocidin was isolated and purified from autolysates of Pseudomonas aeruginosa strain 158 by a combination of procedures such as column chromatography on DEAE-Sephadex A-50, gel filtration on Sephadex G-100, and zone electrophoresis on pevikon. The purified preparation showed a single band in each experiment using electrophoreses in the presence or absence of sodium dodecyl sulfate (SDS), and the agar-gel Ouchterlony immunodiffusion test. The purified pseudomonal leukocidin was crystallized by salting out with saturated ammonium sulfate at pH 7.0 in a needle-leaf like form. The molecular weight of the leukocidin was estimated to be 42,500 by SDS-polyacrylamide gel electrophoresis, 40,000 by gel filtration, and 44,700 (3.3 S20,W) by sucrose density gradient centrifugation. The isoelectric point of the leukocidin was estimated to be at pH 6.3 by isoelectrofocusing. Morphological studies of a leukocidin-treated leukocyte showed that the formation of vacuoles of cytosolic granules and the swelling of the lobulated nuclei occurred prior to leukocyte enlargement. In a slide adhesion test with rabbit polymorphonuclear leukocytes (1 X 10(6], the minimum cytotoxic dose for the destruction of all leukocytes was 13-20 ng of the crystallized toxin. Rabbit lymphocytes were one-thirtieth as sensitive as rabbit leukocytes. Leukocidin did not act on rabbit erythrocytes or on platelets.

Amino Acids↗

[Clinical experience with cefotiam in otorhinolaryngologic infections].

Clinical studies of cefotiam (CTM), a new cephalosporin derivative, in otorhinolaryngological field were performed, and the results were summarized as follows. CTM was intravenously injected to 31 cases of otorhinolaryngological infections in daily dose of 1--4 g. Clinical efficacy was 33.3% in acute otitis media and chronic otitis media (acute exacerbation) (6 cases), 90% in acute tonsillitis (including peritonsillitis, peritonsillar abscess) (20 cases), 50% in acute pharyngitis (2 cases), 100% in acute sinusitis (2 cases) and 100% in epiglottis abscess (1 case), respectively. Bacteriological efficacy was 80% for beta-Streptococcus, 100% for K. pneumoniae, 50% for P. aeruginosa, and 85.7% for Peptococcus and Peptostreptococcus, respectively. No difference was observed in various daily doses for clinical efficacy. As for side effects and laboratory findings, eruption in 1 case, elevation of GOT in 1 case and elevation of GOT, GPT in 2 cases were observed. But, all of the cases were normalized after stoppage of administration or postadministration.

Adult↗

Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence.

DNA sequences complementary to the Torpedo californica electroplax mRNA coding for the alpha-subunit precursor of the acetylcholine receptor were cloned. The nucleotide sequence of the cloned cDNA indicates that the precursor consists of 461 amino acids including a prepeptide of 24 amino acids. Possible sites for acetylcholine binding and antigenic determinants on the alpha-subunit molecule are discussed.

Amino Acid Sequence↗

Cloning and sequence analysis of cDNA for porcine beta-neo-endorphin/dynorphin precursor.

The primary structure of a precursor protein that contains beta-neo-endorphin, dynorphin and a third leucine-enkephalin sequence with a carboxyl extension has been deduced from the nucleotide sequence of cloned DNA complementary to the porcine hypothalamic mRNA encoding it. The three peptides are each bounded by Lys-Arg. This precursor protein, like adrenal preproenkephalin and the corticotropin/beta-lipotropin precursor, comprises multiple repetitive units and a cysteine-containing amino-terminal sequence preceded by a signal peptide.

Amino Acid Sequence↗

Retrovirus-related sequences in human DNA: detection and cloning of sequences which hybridize with the long terminal repeat of baboon endogenous virus.

Human DNA sequences which hybridized with the long terminal repeats (LTR) of baboon type C virus M7 were detected by non-stringent blot hybridization. About 7 to 10 discrete bands of the LTR-related sequences were commonly observed in the DNAs from four independent human cell lines after digestion with either Eco RI, Hind III or Bam HI. The amounts of these sequences were more abundant in tumor cell lines than in a non-malignant cell line. The human sequences related to the M7 LTR seemed to be located at relatively specific sites on the cell DNA. The human DNA clones which hybridized with M7 LTR were detected in the human DNA library described by Lawn et al. (Cell 15, 1157-1174, 1978), at a frequency of about 300 per haploid genome. Five clones were isolated which shared different extent of homology with M7 LTR and whose restriction maps were totally different one another. The DNA structures of two of them resembled the genome of retroviruses. These results suggest the presence of various types of the LTR-related sequences in human DNA: some of them might represent endogenous virus genomes of human cells.

Animals↗

Cloning and sequence analysis of cDNA for bovine adrenal preproenkephalin.

The nucleotide sequence of cloned cDNA for preproenkephalin from bovine adrenal medulla indicates that the precursor protein contains four copies of Met-enkephalin and one copy each of Leu-enkephalin, Met-enkephalin-Arg6-Phe7 and Met-enkephalin-Arg6-Gly7-Leu8, a previously undetected opioid peptide. The enkephalin and extended enkephalin sequences are each bounded by paired basic amino acid residues. Preproenkephalin may represent a multi-hormone precursor, like the corticotropin-beta-lipotropin precursor.

Adrenal Glands↗

Mode of action of staphylococcal leukocidin: effects of the S and F components on the activities of membrane-associated enzymes of rabbit polymorphonuclear leukocytes.

The cytotoxic action of the S component of leukocidin from Staphylococcus aureus on rabbit polymorphonuclear leukocytes was supported by the following observations, (i) Leukocytes displayed a large chemotactic response to the S component (10(-10) M) as well as to the chemotactic factor N-formylmethionylleucylphenylalanine (10(-11) M). (ii) The S component stimulated high levels of phospholipase A2 activity in the cell membranes, with concomitant synthesis and release of prostaglandins. (iii) Uptake of 45Ca into leukocytes exposed to the S component was about double the rate of uptake into untreated cells. The increased 45Ca uptake into the cells was not inhibited by trifluoperazine and ruthenium red. (iv) Indomethacin and alloxazine, which had no effects on the binding of the S component to the cells, attenuated markedly the stimulation of phospholipase A2 activity, the syntheses of prostaglandins, and the increased uptake of 45Ca caused by the S component. The F component of leukocidin, bound to rabbit leukocytes with the aid of the S component, rapidly induced complete release of 86Rb from preloaded leukocytes. This release resulted from stimulation of ouabain-insensitive (Na+ + K+)-adenosine triphosphatase activity and inhibition of cyclic AMP-dependent protein kinase.

Animals↗

[Pharmacokinetics and clinical studies of cefmetazole in the otorhinolaryngological field].

Cefmetazole (CMZ), a new cephamycin preparation, has been investigated to give following results. 1) Pharmacokinetics: Serum and tonsil concentration of CMZ were determined by micropore method in humans. The mean concentrations in 5 cases about 30 minutes after administration of 0.5--1.0 g intravenously were 55.4 micrograms/ml in serum, 21.7 micrograms/g in tonsil. 2) CLINICAL STUDIES: Seventy-one patients with ear, nose and throat infections were treated with CMZ receiving 1 to 6 g per day intravenously (one shot and drip infusion). Thirty-eight of 70 patients were cured excellent, 19 were good, 8 were fair and 6 were failure and effective rate was 80.3%. Adverse reaction was observed in 4 cases. Three cases showed exanthema and 1 case showed fever elevation.

Adolescent↗

[Comparative study on cefmetazole and cefazolin in the treatment of suppurative otitis media].

Cefmetazole (CMZ) was compared to cefazolin (CEZ) for efficacy and safety in the treatment of suppurative otitis media (including acute otitis media and chronic otitis media in acute aggravating stage) under well controlled clinical trials. The therapeutic effects were analyzed statistically in 172 patients (82 administered CMZ, 90 administered CEZ). The adverse reactions were also analyzed statistically in 199 patients (CMZ 99, CEZ 100) in whom the judgement was possible. 1. The efficacy rate of CMZ (72.3% for good to excellent response) was assessed by physicians in charge to be similar to that of CEZ (59.3%). This was the same being assessed by the committee, too (CMZ 64.6%, CEZ 56.7%). 2. When patients were classified into 2 groups (acute otitis media, chronic otitis media in acute aggravating stage) with respect to diagnosis, statistically significant difference in clinical efficacy assessed by physicians in charge was observed in the cases with chronic otitis media (CMZ, CEZ). In addition, the improvements of flares on the drum membrane and the mucous membrane of eardrum were significantly better in the CMZ group than in the CEZ group. 3. Bacteriologically, 16 cases (19.8%) of S. aureus were resistant to CEZ, while only 1 case (1.2%) to CMZ. CMZ was judged to be effective in 5 of the 6 cases in which CEZ-resistant strains were detected. 4. Side effects were found in 2 cases (2.0%) treated with CMZ: one complained of retching and abdominal pain and the other developed skin eruption. On the other hand, only 1 case (1.0%) developed skin eruption in the CEZ group. These results suggest that CMZ is a new antibiotic agent which is highly valuable in the treatment of suppurative otitis media.

Adolescent↗