PubMed Health⌕ Search

Biomedical subjects

K Shimbo

Publications and source records attributed to K Shimbo.

13 recordsLinked to original sources

Celogentins A-C, new antimitotic bicyclic peptides from the seeds of Celosia argentea.

Three new bicyclic peptides, celogentins A (1), B (2), and C (3), have been isolated together with a known-related peptide, moroidin (4), from the seeds of Celosia argentea, and their structures including absolute stereochemistry were determined by using extensive NMR methods and chemical means. Celogentins A (1), B (2), and C (3) inhibited the polymerization of tubulin, and celogentin C (3) was four times more potent than moroidin (4) in the inhibitory activity. Structure-activity relationship study using moroidin derivatives 5-7 and analogue 8 as well as celogentins A-C (1-3) and moroidin (4) indicates that the bicyclic ring system including unusual non-peptide connections among beta(s)-Leu, Trp, and His residues characteristic of celogentins and moroidin, with ring size and conformations suitable for interaction with tubulin would be important for their biological activity.

Animals↗

Absolute stereochemistry of amphidinolides G and H.

[structure: see text] Absolute stereochemistry of amphidinolides G (1) and H (2), potent cytotoxic 27- and 26-membered macrolides, respectively, isolated from a marine dinoflagellate Amphidinium sp., was determined by X-ray diffraction analysis, synthesis of a degradation product (3) of 2, and interconversion between 1 and 2.

Animals↗

Ion selectivity and activation of the M2 ion channel of influenza virus.

The influenza A virus-associated M2 ion channel is generally believed to function during uncoating of virions in infected cells. On endocytosis of a virion into the lumen of endosomes, the M2 ion channel is thought to cause acidification of the virion interior. In addition, the influenza virus M2 ion channel is thought to function in the exocytic pathway by equilibrating the pH gradient between the acidic lumen of the trans-Golgi network and the neutral cytoplasm. A necessary test of the proposed roles of the influenza virus M2 ion channel in the virus life cycle is to show directly that the M2 ion channel conducts protons. We have measured the ionic selectivity and activation of three subtypes (Udorn, Weybridge, and Rostock) of the M2 ion channel in oocytes of Xenopus laevis by measurement of 1) the intracellular pH (pHin) of voltage-clamped oocytes, 2) the current-voltage relationship in solutions of various pH and ionic composition, and 3) the flux of 86Rb. We took advantage of the low pHin achieved during incubation in low pH medium to study the effects of low pHin on M2 activation. Oocytes expressing each of the three subtypes of the M2 protein a) underwent a slow acidification when incubated in medium of low pH (acidification was blocked by the M2 ion channel inhibitor, amantadine); b) had current-voltage relationships that shifted to more positive values and had greater conductance when the pHout was lowered (this relationship was modified when Na- was replaced by NH4+ or Li+); c) had an amantadine-sensitive influx of Rb+. The effects on the current-voltage relationship of reduced pHin were opposed to the increased conductance found with reduced pHout. We interpret these results to indicate that the M2 ion channel is capable of conducting H+ and that other ions may also be conducted. Moreover, the channel conductance is reduced by decreased pHin. These findings are consistent with the proposed roles of the M2 protein in the life cycle of influenza A virus.

Animals↗

Viral and cellular small integral membrane proteins can modify ion channels endogenous to Xenopus oocytes.

A slowly activated, inward current could be evoked from Xenopus oocytes in response to application of a strong (approximately -190 mV) hyperpolarizing pulse. However, a much lesser hyperpolarization (approximately -130 mV) was able to evoke a similar current from oocytes that expressed the cellular proteins IsK and phospholemman, the synthetic protein SYN-C, and the NB protein of influenza B virus. All of these currents were carried principally by Cl-, and they had similar blocker profiles. The time course (the function of time that described the current increase during a hyperpolarizing voltage-clamp pulse, i.e., activation kinetics) varied from one batch of oocytes to another, but did not vary within each batch with the type of protein expressed. This slowly activated, inward current evoked by hyperpolarization to approximately -130 mV required the expression of a characteristic, minimum level of each of the proteins IsK, SYN-C, and NB. However, not every integral membrane protein expressed in oocytes allowed substantial inward currents to be generated at -130 mV. Oocytes that expressed large amounts of the M2 protein of influenza A virus, which is known to possess an intrinsic cation channel activity, did not display a Cl- current when hyperpolarized to -130 mV. These results suggest that expression of any of the four proteins-IsK, phospholemman, SYN-C, or NB- acts as an activator of an endogenous Cl- conductance.

Animals↗

The expression of rat GAP-43 cDNA in transgenic carp.

To understand more about growth-associated protein-43 (GAP-43), we produced transgenic carp by introduction of a rat GAP-43 cDNA linked to the Rous sarcoma virus-long terminal repeat into fertilized eggs. Of 180 eggs microinjected with exogenous gene, 59 embryos hatched and 4 fish were found to contain the exogenous gene sequences in the genomic DNA. From a mature female transgenic carp, parthenogenetically, 126 progeny were derived and 52 of them survived for more than 90 days. The exogenous gene sequences were detected in 22 F1 progeny, and its messenger RNA was detected in all of 10 transgenic F1 carp examined. In serum-free medium, cultured retinal ganglion cells isolated from transgenic carp elongated their axons, while non-transgenic cells did not elongate axons.

Animals↗

Push-pull modulation of ganglion cell responses of carp retina by amacrine cells.

The responses of a ganglion and an amacrine cell were recorded simultaneously in the carp retina. Sinusoidal current injected into amacrine cells modulated ganglion cell discharges either in phase (excitation) or in opposite phase (inhibition). ON-center ganglion cells received excitatory inputs and OFF-center ganglion cells received inhibitory inputs from ON-center amacrine cells. They received inputs of opposite polarity from OFF-center amacrine cells. Namely, inputs from ON-center and OFF-center amacrine cells augment the responses of ON-center and OFF-center ganglion cells in a push-pull manner.

Animals↗

[Efficacy of magnetic resonance imaging in treatment of neuroblastoma].

Magnetic resonance imaging (MRI) was performed in 36 children with neuroblastoma at Chiba University from 1984 through 1989, and 29 patients of them were discussed about efficacy of MRI in treatment of neuroblastoma in this paper and the results were as follows. 1) MRI was difficult to differentiate tumor from normal kidney in the image intensity and was more efficient in determining the relationship of tumor to liver and to vascular structures. 2) MRI was better than CT in detecting the size and extent of tumor mass and in identifying lymph node spread using multiple planes. 3) MRI was more efficient than CT in defining displacement and encasement of renal vessels by tumor. It was useful to predict to reserve kidney before surgery. 4) MRI was useful to monitor tumor response to combined modalities of therapy. A favorable response was seen as a change in the image intensity in bone marrow metastases of neuroblastoma.

Adrenal Gland Neoplasms↗

A test of K(+)-sensitive electrode responses to changes in K+ concentration.

Tests of K(+)-sensitive microelectrodes were made using a plastic chamber, which consisted of upper and lower compartments separated by a partition with a small opening in the center. After the upper and lower compartments were filled with 25 and 100 mM KCl respectively, the tip of a K(+)-sensitive electrode was moved up and down through the partition opening, while recording potential changes. Some hydrodynamic events associated with electrode movement and effects of gravity upon spherical diffusion are discussed.

Diffusion↗

Involvement of protein kinase in the regulation of beta-adrenergic receptors by antidepressants.

The role of serotonin (5-HT) and protein kinases in the regulation of the beta-receptor induced by typical and atypical antidepressants was investigated. Treatment with either mianserin or maprotiline for seven days produced a significant decrease in the beta-receptor density measured 6h after the last dose. The reduction in beta-receptors disappeared within 24h. However, combined treatment of mianserin or maprotiline with either fluoxetine or 5-hydroxytryptophan significantly decreased beta-receptors even 24h after the last dose. Following treatment with p-chlorophenylalanine the reduction in beta-receptors induced by desipramine was reversible within 24h. These results demonstrate that an increase in the synaptic 5-HT availability may contribute to the prolongation of the beta-receptor down-regulation by antidepressants. The intraventricular infusion of 12-0-tetradecanoyl-phorbol-13-acetate (TPA), a potent protein kinase C (PK-C) activator for seven days caused a significant decrease in beta-receptors, while forskolin or dibutyryl cyclic adenosine monophosphate had no influence on the receptor. The TPA-induced and desipramine-induced decreases in beta-receptors were not additive, suggesting that a similar mechanism is involved. The infusion of the PK-C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) caused an inhibition of the desipramine-induced decrease in beta-receptors. It is suggested that the beta-receptor down-regulation by antidepressants might be also regulated by PK-C through 5-HT-Ca2+-inositol-phospholipid systems.

5,7-Dihydroxytryptamine↗

Color-opponent responses of small and giant bipolar cells in the carp retina.

The physiological and morphological properties of color-opponent bipolar cells in the carp retina were studied. Fifty nine OFF-center bipolar cells and 63 ON-center bipolar cells out of about 500 total bipolar cells recorded showed color-opponent responses. The OFF-center color-opponent bipolar cells were classified into three subgroups according to their spectral and spatial responses. Fifty OFF-center color-opponent cells responded with depolarization to a blue light spot and with hyperpolarization to a red spot in the receptive-field center. The polarity of the surround response was opposite to that of center response at each wavelength. Therefore these cells were classified as OFF double-opponent cells (OFF-DO). Eight cells responded with hyperpolarization to a blue and green spot and with depolarization to a red spot. The surround responses of those cells were depolarizing at any wavelength (R+G- cell). One responded with hyperpolarization to a blue and red spot and with depolarization to a green spot. The surround response showed a different spectral characteristic from that of the center response. It responded with depolarization to a blue and green annulus and with hyperpolarization to a red annulus (R-G+B- cell). The ON-center color-opponent bipolar cells were similarly classified into three subgroups. Sixty of ON-center color-opponent cells were the double color-opponent type (ON-DO cell), showing the responses of opposite polarity to the OFF-DO cells. Two cells were classified as R- G+ cell, and one cell as R+G-B+ cell. Both OFF- and ON-DO cells were identified by their morphology as Cajal's giant bipolar cells, and R+G-, R-G+, R-G+B-, and R+G-B+ cells as Cajal's small bipolar cells. The analysis of the latency and the ionic mechanisms of their responses suggest that DO cells under light-adapted conditions receive direct inputs from long-wavelength (red) cones, RG cells from middle-wavelength (green) cones, and RGB cells from short-wavelength (blue) cones. Possible mechanisms of the opponent inputs to these bipolar cells are discussed.

Animals↗