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Biomedical subjects

K Oda

Publications and source records attributed to K Oda.

At least 487 records · Page 27Linked to original sources

[A case of orthostatic tremor in parkinsonism].

A 79-year-old woman presenting with orthostatic tremor (OT) was reported. In addition to OT, neurological examination showed mild dementia, bradykinesia, rigidity of the neck and the upper limbs and positive Babinski reflex on the left. These clinical signs and CT as well as MRI findings suggested vascular parkinsonism as its pathological background. Upon standing with her feet together, she rapidly developed rhythmic repetitive contraction of all leg muscles. The shaking disappeared by walking, sitting, or lying down. The EMG recording revealed 4-Hz tremor which consisted of alternating contraction of anti-gravity muscles and their antagonists. The EMG bursts associated with the tremor were synchronous in corresponding muscles of both legs. OT could be bilaterally reset by unilateral voluntary or passive movement of leg. In the supine position, the tremor was not evoked by voluntary contraction of leg muscles against resistance. As the tremor was aggravated by the administration of haloperidol was suppressed by L-DOPA, it was thought to have the pharmacological basis common to the resting tremor of parkinsonism. Furthermore, we postulated that the postural tonus-regulating system, which is thought to set and maintain the tonus of antigravity muscles for standing upright, might be involved in the generation of the rhythmic discharge pattern (reciprocal bursts in a given leg and synchronized bursts in both legs) of OT.

Aged↗

[Pharmacokinetic and clinical studies of cefteram pivoxil granule in the pediatric field].

Cefteram pivoxil (CFTM-PI), the pivaloyloxymethyl ester of cefteram (CFTM) in which aminothiazol was also introduced into the 7 position of cephem nucleus, is a new oral cephem antibiotic. CFTM-PI was absorbed through the intestines and hydrolyzed to CFTM by esterases in the intestinal wall and existed in the body fluids as CFTM. A tablet form of this drug has been released in Japan and now a granular form for pediatric patients has been developed. We have determined MICs of 5 drugs (CFTM, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), erythromycin (EM], against stock strains and MICs of 6 drugs (CFTM, CEX, CCL, ABPC, methicillin, cloxacillin) against fresh strains from patients received to CFTM-PI, with an inoculum size of 10(6) cfu/ml. A total of 149 strains included Gram-positive cocci i.e. Staphylococcus aureus (11), Streptococcus pyogenes (85), Streptococcus agalactiae (16) and Streptococcus pneumoniae (4), and Gram-negative rods i.e. Haemophilus influenzae (11), Bordetella pertussis (11), Escherichia coli (9), Proteus mirabilis (1) and Morganella morganii (1). The granular form of CFTM-PI was administered to 9 boys (age: 8 years 3 months approximately 10 years 10 months) to determine serum and urinary concentrations of the drug and its urinary recovery rates using bioassay. Doses of 1.5, 3.0 and 6.0 mg/kg were given orally 30 minutes after meal to 3 boys, respectively. Urinary concentrations and its urinary recovery rates of T-2525A, a main metabolite of CFTM, were determined using high performance liquid chromatography (HPLC). To study clinical and bacteriological effects of this drug, a mean daily dose of 3.3 mg/kg divided 3-4 times a day (3 times: 133 cases, 4 times: 9 cases) was administered for 8 days on the average to a total of 142 cases with pharyngitis (22), tonsillitis (12), acute bronchitis (3), pneumonia (11), pleurisy (1), scarlet fever (28), acute purulent otitis media (16), impetigo (13), abscess (2), purulent lymphadenitis (1) and urinary tract infection (33). Adverse reactions and abnormal effects on laboratory test values attributable to this drug were studied in patients. The results obtained are summarized as follows. 1. With regard to Gram-positive cocci, MICs of CFTM against 11 fresh strains of S. aureus ranged from 3.13 to 6.25 micrograms/ml except for 1 strain, thus CFTM was equally effective to CEX, but less active than the other drugs tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

Brefeldin A causes disassembly of the Golgi complex and accumulation of secretory proteins in the endoplasmic reticulum.

The antiviral antibiotic brefeldin A (BFA) strongly inhibits the protein secretion in cultured rat hepatocytes (Misumi, Y., Misumi, Y., Miki, K., Takatsuki, A., Tamura, G., and Ikehara, Y. (1986) J. Biol. Chem. 261, 11398-11403). We have further examined the inhibitory effect of the drug on intracellular transport of albumin by an immunocytochemical technique with peroxidase-conjugated Fab fragments of anti-rat albumin IgG. In hepatocytes treated with BFA (2.5 micrograms/ml) for 1 h at 37 degrees C, no characteristic structures of the Golgi complex could be observed, and albumin was diffusely distributed in the endoplasmic reticulum (ER), nuclear envelope, and small vesicles around, in contrast to its condensed localization in the Golgi complex in the control cells. Such an unusual distribution of the secretory protein, however, was rearranged to the normal localization in the Golgi complex after 4 h even in the presence of the drug, possibly due to a metabolism of the drug to an inert form. Exposure of the cells to BFA with constant renewals (2.5 micrograms/ml at 1-h intervals) or at a higher concentration (10 micrograms/ml) caused a prolonged accumulation of albumin in the ER, resulting in its dilation. These results indicate that BFA primarily blocks the protein transport from the ER to the Golgi complex, consistent with the biochemical data previously reported.

Animals↗

Molecular cloning and characterization of cellular genes whose expression is repressed by the adenovirus E1a gene products and growth factors in quiescent rat cells.

Several cDNA clones of cellular genes, whose expression is repressed by the adenovirus type-12 E1a gene products, were isolated from a rat 3Y1 cell cDNA library by differential plaque hybridization with labeled cDNA probes prepared from 3Y1 and the derivative cell line expressing the E1a gene constitutively. The changes in the levels of these gene transcripts during cell-cycle progression from G0 to G1 to S phase were analyzed with 3Y1 cells and gMA cell lines, derived from 3Y1 cells, in which the expression of the E1a gene or its 13S, 12S cDNA can be switched on by the addition of dexamethasone. Quantitation of the transcripts by Northern-blot hybridizations and by nuclear run-on experiments revealed the following. (i) The level of clone-53 mRNA (which turned out to be the fibronectin (FN)-coding mRNA) is very high in resting gMA cells and decreased rapidly after switching on of the E1a gene or its 13S, or 12S cDNA. (ii) The addition of serum or platelet-derived growth factor to resting 3Y1 cells also resulted in a rapid decrease in the FN mRNA level, but the addition of epidermal growth factor (EGF) had little or no effect. (iii) The level of clone-56 mRNA in gMA cells was not affected by the induction of the E1a gene expression; however, the addition of EGF to resting gMA or 3Y1 cells resulted in a decrease of this mRNA after a 12- to 16-h lag period. Induction of the E1a gene expression in gMA cells treated with EGF shortened the lag period. The addition of serum to resting 3Y1 cells decreased the clone-56 mRNA level without a significant lag period.

Adenoviridae↗

Tris inhibits both proteolytic and oligosaccharide processing occurring in the Golgi complex in primary cultured rat hepatocytes.

Tris caused the distention of the Golgi cisternae in primary cultured rat hepatocytes and perturbed the functions occurring there. Proteolytic cleavage of precursors of both albumin and complement C3 was inhibited, whereas that of prohaptoglobin was not affected by Tris. These effects on the proteolytic cleavages resemble those of acidotropic amines (Oda, K., and Ikehara, Y. (1985) Eur. J. Biochem. 152, 605-609; Oda, K., Koriyama, Y., Yamada, E., and Ikehara, Y. (1986) Biochem. J. 240, 739-745). However, the effects of Tris significantly differed from acidotropic amines on the basis of its effects on the processing of N-linked oligosaccharides of glycoproteins. Both alpha 1-protease inhibitor and haptoglobin secreted from the Tris-treated cells were found to contain almost equal amounts of endo-beta-N-acetylglucosaminidase H-sensitive and -resistant oligosaccharides, whereas the glycoproteins from both the control and methylamine-treated cells were resistant to the enzyme. The endo-beta-N-acetylglucosaminidase-sensitive oligosaccharides were analyzed to be Man8-5GlcNAc by high resolution gel permeation chromatography, suggesting that trimming of alpha-mannose residues from the precursor Man9GlcNAc2 is incomplete in the Tris-treated cells. On the other hand, Tris did not significantly inhibit incorporation of radioactive monosaccharides (N-acetylglucosamine, galactose, and fucose) into the glycoproteins. However, two-dimensional gel electrophoresis in combination with neuraminidase digestion demonstrated that sialylation was markedly inhibited by Tris. Taken together, our results reveal that Tris inhibits not only the sialic acid addition which takes place in the trans Golgi region, but also the trimming step of high mannose-type oligosaccharides, which is thought to occur before glycoproteins reach the trans Golgi region.

Animals↗

Cloning and expression of the metallo-proteinase inhibitor (S-MPI) gene from Streptomyces nigrescens.

The coding and regulatory regions of a proteinaceous metallo-proteinase inhibitor (S-MPI) gene have been cloned from the genomic DNA of Streptomyces nigrescens using a deoxyinosine-containing synthetic probe designed from the amino acid sequence of the S-MPI protein. The S-MPI gene was located to the DNA region of about 1.2 kilobase pairs, which was verified to be sufficient for the gene expression in S. lividans.

Amino Acid Sequence↗

Tyrosine O-sulfation of the fibrinogen gamma B chain in primary cultures of rat hepatocytes.

Sulfation of fibrinogen was studied in a primary culture of rat hepatocytes. After cells were incubated with [35S]sulfate, 35S-labeled fibrinogen was obtained from the medium by immunoprecipitation and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/fluorography. It was demonstrated that [35S]sulfate is exclusively incorporated into the gamma B chain, which is a minor variant form found in rat fibrinogen, in addition to a major gamma A chain. When the purified 35S-gamma B chain was digested with carboxypeptidase Y, the radioactivity was almost completely released from the protein, and the labeled product released was identified as tyrosine O-sulfate. Based on the available primary structure of the gamma B chain, the results suggest that sulfation occurs on the tyrosine residue at the second position from its COOH terminus. Pulse-chase experiments using both [3H]leucine and [35S]sulfate showed that 35S-labeled fibrinogen is secreted into the medium much faster than the 3H-labeled molecule. Incubation of cells with monensin, an inhibitor of Golgi function, strongly inhibited the sulfation of fibrinogen. In addition, in vitro sulfation experiments demonstrated that sulfotransferase activity is localized in the Golgi fraction. These results indicate that the sulfation of fibrinogen takes place in the Golgi complex, especially in the trans Golgi region, just before its secretion.

Animals↗

Antigenic difference of acetylcholine receptor between single and multiple form endplates of human extraocular muscle.

The acetylcholine receptor (AChR) of human extraocular muscle (EOM) has been studied by the immunological method using anti-AChR antibodies obtained from the sera of patients with myasthenia gravis (MG) of ocular type, whose symptoms have been restricted to EOM. Those antibodies could distinguish the AChR of multiple (en grappe) form endplates from that of single (en plaque) form endplates. This result indicates the antigenic difference of AChR between those two forms of endplates of human EOM.

Autoantibodies↗

Biosynthesis, assembly and secretion of fibrinogen in cultured rat hepatocytes.

The biosynthesis, assembly and secretion of fibrinogen were investigated in cultured rat hepatocytes which were incubated with [35S]methionine. When initial rates of the synthesis of three fibrinogen subunits were compared, the A alpha-subunit was found to be synthesized significantly slower than the B beta- and gamma-subunits. Pulse-chase experiments revealed that the secreted fibrinogen contained different proportions of the newly synthesized subunits, depending upon the chase times. Radioactivity in the A alpha subunit, which initially had the highest level of the three, was rapidly decreased in parallel with the chase time. The gamma-subunit had an increasing amount of the radioactivity in the secreted molecule during the chase periods, whereas that in the B beta-subunit was gradually decreased at the later stages of chase. Analysis of intracellular components of fibrinogen confirmed that the nascent A alpha-subunit was most rapidly exhausted, and the gamma-subunit occupied the largest proportion among the non-assembled subunits at later stages of chase. Taken together, these results suggest that the synthesis of A alpha-subunit, which has the lowest rate, could be the rate-limiting step in the production and secretion of fibrinogen in cultured rat hepatocytes, in contrast with what has been proposed for human and rabbit fibrinogen, namely that the synthesis of B beta-subunit is the rate-limiting step. The results also indicate that there is a large intracellular pool of gamma-subunit.

Animals↗

Biosynthesis of placental alkaline phosphatase and its post-translational modification by glycophospholipid for membrane-anchoring.

The biosynthesis and post-translational modification of placental alkaline phosphatase were studied in human choriocarcinoma cells, JEG-3. Pulse-chase experiments with [35S]methionine demonstrated that placental alkaline phosphatase was synthesized as a major precursor form with Mr 63,000, which was then converted to a mature form with Mr 66,000, by processing of its N-linked oligosaccharides from the high-mannose type to the complex type. In addition, the two forms of the protein were found to be modified by a glycophospholipid, components of which were characterized by metabolic incorporation into placental alkaline phosphatase of 3H-labeled compounds such as myo-inositol, palmitic acid, stearic acid, mannose, glucosamine, and ethanolamine. When placental alkaline phosphatase labeled with these compounds was treated with phosphatidylinositol-specific phospholipase C or papain, the phospholipase C removed only the 3H-labeled fatty acids, whereas papain, that is known to cleave the C-terminal region, released all the radioactive glycolipid components including [3H]ethanolamine. More detailed analysis with shorter pulse-chase experiments demonstrated that placental alkaline phosphatase was primarily synthesized as a form with Mr 64,500 which was not yet labeled with [3H]palmitic acid. This form was converted by papain digestion to the above-mentioned major precursor with Mr 63,000. Taken together, these results suggest that placental alkaline phosphatase is initially synthesized as the precursor with Mr 64,500, which is immediately converted to the intermediate form with Mr 63,000 by simultaneously occurring proteolysis of the C terminus and replacement by the glycophospholipid, and finally to the mature form with Mr 66,000 by terminal glycosylation of its N-linked oligosaccharides. The glycophospholipid thus attached is considered to function as the membrane-anchoring domain of placental alkaline phosphatase.

Alkaline Phosphatase↗

Central vs peripheral nerve conduction. Before and after treatment of subacute combined degeneration.

Central and peripheral nerve conduction was studied in two patients with subacute combined degeneration by using the short-latency somatosensory evoked potentials and the peripheral nerve conduction study during treatment with cyanocobalamin. Before the treatment, somatosensory evoked potentials with median nerve stimulation were normal, but those with peroneal nerve stimulation revealed prolonged central conduction indicating dysfunction within the posterior column. Peripheral sensory and motor nerve action potentials were reduced with normal or slightly reduced conduction velocity. After treatment, marked shortening of the central conduction time (by 24% and 31%, respectively) was observed with mild or no recovery of peripheral nerve action potentials. These physiologic findings suggest that the main pathologic changes in the central nervous system may be demyelination in the posterior column in addition to axonal degeneration in the peripheral nerve. The former was responsive to treatment but the latter was poorly responsive to treatment. Sensory symptom in subacute combined degeneration appears to be, at least partially, attributed to the spinal cord lesion.

Adolescent↗

Clinical picture of HTLV-I associated myelopathy.

Clinical and electrophysiological findings in 16 consecutive cases of HTLV-I associated myelopathy are reported. Symmetric spastic paraparesis associated with only mild hyperreflexia in the arms, clinical and electrophysiological evidence of moderate posterior column involvement at the thoracic level, urinary frequency and urgency associated with the detrusor-urethral sphincter dyssynergia but without systemic autonomic involvement, and absence of the segmental grey matter involvement, all suggest the presence of diffuse lesions of the white matter predominantly involving the thoracic cord. We conclude that HTLV-I associated myelopathy is a chronic diffuse leukomyelitis predominantly involving the thoracic cord.

Adolescent↗

Putative convertase involved in the proteolytic conversion of rat proalbumin to serum albumin.

We have found a proteolytic activity in Golgi membranes which efficiently converts [35S]methionine-labeled proalbumin, isolated from pulse-labeled rat hepatocytes in culture, to serum albumin in an in vitro assay system. The proalbumin-converting activity was dependent on Ca2+ and the maximum activity was observed at pH 5.5-6.0. Since the enzyme activity was found to be resistant not only to both leupeptin and E-64 but also to thiol-blocking reagents, it is unlikely that cathepsin B is involved in the proteolytic conversion of proalbumin occurring in the Golgi complex.

Animals↗

Somatosensory and acoustic brain stem reflex myoclonus.

A patient with brain stem reflex myoclonus due to a massive midbrain infarct was studied electrophysiologically. Myoclonic jerks were elicited at variable latencies by tapping anywhere on the body or by acoustic stimuli, and mainly involved flexor muscles of upper extremities. The existence of convergence of somatosensory and acoustic inputs in the brain stem was suggested. This myoclonus seemed to be mediated by a mechanism similar to the spino-bulbo-spinal reflex.

Aged↗

Multimodality evoked potentials in HTLV-I associated myelopathy.

Multimodality evoked potentials (EPs) consisting of somatosensory EPs (SEPs), visual EPs (VEPs) and brainstem auditory EPs (BAEPs) were studied in 16 cases with HTLV-I associated myelopathy (HAM). Median nerve SEPs were normal in all cases. In posterior tibial nerve SEPs, the potential recorded at the 12th thoracic spinal process was normal in every case but cortical components were significantly prolonged in 10 cases, although five of these showed no sensory impairment. BAEPs were normal in every case whose hearing was intact, but VEPs were abnormal in two cases whose visual acuities were normal. The present results in HAM indicate predominant lesion in the thoracic cord, and might also suggest some subclinical lesion in the visual pathway.

Adult↗