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Biomedical subjects

D Yamamoto

Publications and source records attributed to D Yamamoto.

At least 91 records · Page 5Linked to original sources
PubMed1992

pokkuri, a Drosophila gene encoding an E-26-specific (Ets) domain protein, prevents overproduction of the R7 photoreceptor.

Studies on sevenless and bride of sevenless genes have revealed that the R8 cell plays a key role in the fate of the R7 photoreceptor cell, presenting on its surface an inductive cue to which R7 responds. sev-independent induction of R7 cells has been reported in the seven-up mutation, which appears to transform R1 and R6 cells to R7 cells. We have induced recessive mutations in a gene pokkuri (pok; pokkuri is a Japanese word that means "dropping dead") that lead to overproduction of R7 cells with rather minor effects on outer photoreceptors and R8 cells. Pok protein may function as a transcription factor, as the predicted amino acid sequence contains a region similar to the consensus established for the E-26-specific (Ets) domain.

Amino Acid Sequence↗
PubMed1992

Radiotherapy resolves leukemic involvement of the optic nerves.

A 40-year-old woman with acute lymphoblastic leukemia had a visual disturbance OD. The optic disc was slightly swollen in the right fundus, and blast cells in the cerebrospinal fluid were found. Radiotherapy to the brain and orbit resolved these findings. Five months later, visual acuity decreased OS. Radiotherapy also was effective in treating the leukemic involvement of the optic nerve.

Adult↗
PubMed1991

Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution.

E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex.

Binding Sites↗
PubMed1991

[A case of adult T-cell leukemia (ATL) complicated with multiple nocardial abscesses].

A 45-year-old woman was admitted to our hospital with complaints of fever and lumbago. She was treated for adult T-cell leukemia and thrombocytopenia with 20 mg/day of prednisolone. CT scan showed multiple abscesses in right peri-kidney, right iliopsoas muscle, left subcutaneous region in the abdominal wall and the brain. Left subcutaneous abscess was drained. Gram-positive organisms consisting of filaments were found, and Nocardia farcinica was grown in cultures. After two months of chemotherapy (FMOX, MINO and AMK), all abscesses except one in the brain disappeared. Cerebral abscess was cured fifty days after the start of the treatment with oral administration of Sulfamethoxazole-trimethoprim (SMX/TMP). The mortality of Nocardial cerebral abscess is high. This patient is a very rare case in which multiple Nocardial abscesses including brain abscess was cured by chemotherapy.

Abscess↗
PubMed1990

A comparison between the binding modes of a substrate and inhibitor to papain as observed in complex crystal structures.

On the basis of the crystal structures of papain complexed with the substrate analogue benzyloxycarbonyl-L-phenylalanyl-L-alanine chloromethyl-ketone (Drenth, J., Kalk, K.H., and Swen, H.M. (1976) Biochemistry 15, 3731-3738) and with the inhibitor E-64-c, the binding modes were compared at the atomic level to clarify the functional difference between the substrate and inhibitor. Irrespective of the reverse chemical bonding in the peptide bonds, both the molecules are located at the S subsites of papain with similar interactions. However, the inhibitory activity of E-64-c is characterized by the stereochemical function of a carboxyoxirane ring and the tight binding of the isopentylaminoleucyl side chain to the S subsites.

Amino Acid Chloromethyl Ketones↗
PubMed1990

The importance of Val-157 hydrophobic interaction for papain inhibitory activity of an epoxysuccinyl amino acid derivative. A structure-activity relationship based on the crystal structure of the papain-E-64-c complex.

Based on the crystal structure of the papain-E-64-c complex, 3-dimensional binding modes of a series of epoxysuccinyl amino acid derivatives to the papain active site have been constructed and the structure-inhibitory activity relationship has been analyzed using the accessible surface area and nonbonded energy parameters. The result indicates the importance of the hydrophobic interaction between the amino acid side chain of the inhibitor and the papain Val-157 residue for revealing the potent inhibitory activity.

Amino Acid Sequence↗
PubMed1990

Molecular dynamics simulation of papain-E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine) complex.

To investigate the possible binding mode of E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine), a potent cysteine protease inhibitor, to papain active site, molecular dynamics simulations were applied to two complex forms: R- and S- configurational forms of E-64 C2 atom for the covalent bond formation with the papain Cys-25 SH group. The tertiary structures of the papain-E-64 complexes were built by visual interactive modelling and the energy minimization technique, and were subjected to the dynamics simulations of 10 ps. Although no significant difference was observed between the potential energies of energy-minimized R- and S-complex forms, the molecular dynamics simulations suggested that the hydrogen bonding mode of the former form is more advantageous than that of the latter one. Comparing with the hydrogen bonds observed in the papain-E-64 complex crystal, it could be concluded that the present molecular dynamics simulation reflects well the three-dimensional structure concerning the interaction of E-64 with the papain active site. The conformational characteristics of E-64 and its possible interaction mode with papain were also discussed.

Computer Simulation↗
PubMed1989

Properties of single chloride channels in primary neuronal cultures of Drosophila.

An anion channel from Drosophila neurons had the selectivity sequence: NO3- (1.97) greater than Br- (1.12) approximately equal to I- (1.03) approximately equal to Cl- (1) greater than F- (0.32) much greater than glutamate (less than 0.02) as estimated by the permeability ratio based on the reversal potential measurement. 4-Acetoamido-4'-isothiocyanostilbene-2,2'-disulfonic acid applied internally at 10 microM blocked the channel. We suggest that the chloride channel identified here may provide a pathway for Cl- in the resting membrane of Drosophila neurons.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1989

Mode of binding of E-64-c, a potent thiol protease inhibitor, to papain as determined by X-ray crystal analysis of the complex.

The three-dimensional structure of the E-64-c-papain complex has been determined by X-ray crystal analysis at 2.5 A resolution (conventional R = 26.9%). The structure determined indicates that: (i) the C2 atom of the oxirane ring of E-64-c is covalently bound by the S gamma atom of Cys-25 of papain; (ii) this covalent bond formation results in a configurational conversion of the oxirane C2 atom from the S- to the R-form; and (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the specific interaction of the E-64-c molecule with papain.

Binding Sites↗
PubMed1989

Two distinct mechanisms are responsible for single K channel block by internal tetraethylammonium ions.

Tetraethylammonium (TEA) ions blocked the unitary currents through the delayed rectifier potassium channels of Drosophila neurons from the cytoplasmic side of inside-out membrane patches by two distinct mechanisms. First, TEA attenuated the single-channel conductance, probably by producing very rapid block-unblock reactions at the inner mouth of the potassium pore. Second, TEA markedly enhanced the slow inactivation, making the incidence of channel openings highly nonrandom; blank traces with no channel openings during repetitive depolarizations showed a significant tendency to be clustered in the presence of TEA. This second action accounts for almost half of the reduction of average current produced by 10 mM internal TEA.

Animals↗
PubMed1989

Characterization of single non-inactivating potassium channels in primary neuronal cultures of Drosophila.

Permeability and gating properties of single, non-inactivating, K+ channel currents in cultured Drosophila neurons were studied using the gigaohm-seal patch-clamp technique. The non-inactivating K+ currents were activated by depolarizing the membrane to -30 mV or to more positive potentials. The slope conductance of the channel was estimated to be 17.6 +/- 3.70 pS when the cytoplasmic side of the inside-out membrane patch was perfused with solutions containing 145 mmoll-1 K+. The single-channel conductance was temperature-sensitive, with a Q10 of 1.44 between 10 and 20 degrees C. Single-channel currents could be recorded when the cytoplasmic K+ was replaced with NH4+, Rb+ or Na+, but not with Cs+. The conductance ratio of the channel for these cations was: K+ (1) greater than NH4+(0.53) greater than Rb+ (0.47) greater than Na+ (0.44). Tetraethylammonium (TEA+) ions applied at a concentration of 10 mmoll-1 to the cytoplasmic side of the membrane increased the frequency of 'blank' traces which contained no channel openings during repetitive depolarization. In addition, single-channel amplitude was reduced by about 20%. The open-time distribution was fitted by a single exponential function, whereas the closed-time distribution required a three-exponential fit. Permeability and gating properties of single, non-inactivating K+ channel currents in neurons of eag, a mutant which has defects in the delayed rectifier K+ channel, were indistinguishable from those recorded from wild-type neurons.

Action Potentials↗
PubMed1989

Crystal structure and molecular conformation of E-64, a cysteine protease inhibitor.

In order to elucidate the conformational characteristics of cysteine protease inhibitors contributing to their inhibitory activities, the conformation of E-64 (N-[N-(L-3-trans-carboxyoxiran-2-carbonyl)-L-leucyl]-agmatine), a potent inhibitor of papain, was determined by X-ray crystal structure analysis. The molecules were packed in the crystal through electrostatic forces and hydrogen bonding between the oppositely charged terminal groups and between the amide groups. Two crystallographically independent E-64 molecules both took a flattened and slightly curved structure, which is similar to that of loxistatin, a related cysteine protease inhibitor. Based on the present results, a possible inhibitory mechanism of E-64 is proposed, with reference to the binding mode observed in the crystal structure of papain-substrate analogue complex.

Crystallization↗
PubMed1988

Leucomyosuppressin, a novel insect neuropeptide, inhibits evoked transmitter release at the mealworm neuromuscular junction.

The action of leucomyosuppressin (LMS: pGlu-Asp-Val-Asp-His-Val-Phe-Leu-Arg-Phe-NH2) on the glutamate-mediated neuromuscular transmission in the mealworm, Tenebrio molitor, was studied by the microelectrode current-clamp and voltage-clamp techniques. Submicromolar concentrations of LMS reversibly attenuate evoked release of transmitter from the motor nerve terminals, as evidenced by a decrease in the quantum content estimated by the number of failures of extracellular EPSPs. LMS has no effect on the glutamate-induced depolarization. Possible intracellular mediators for the LMS action are discussed.

Action Potentials↗
PubMed1988

Activation of protein kinase C promotes glutamate-mediated transmission at the neuromuscular junction of the mealworm.

1. Actions of protein kinase C activators, 1,2-oleoylacetylglycerol (OAG) and 12-O-tetradecanoylphorbol-13-acetate (TPA), on the glutamate-mediated neuromuscular transmission in the mealworm, Tenebrio molitor, were studied by the microelectrode current-clamp and voltage-clamp techniques. 2. The activators OAG and TPA stimulate the evoked and spontaneous transmitter releases from the presynaptic terminal, as evidenced by an increase in the quantum content estimated by the number of failures of extracellular excitatory postsynaptic potentials (EPSPs), and in the frequency of miniature EPSPs. 3. Both OAG and TPA act on the postsynaptic membrane to enhance responses to the transmitter L-glutamate. Protein kinase C activators increased the apparent maximum of the ionophoretic dose-response curve for glutamate-induced depolarization, without affecting the reversal potential and the voltage-dependent decay rate for the excitatory postsynaptic current (EPSC) under voltage-clamp conditions. 4. The postsynaptic effect of OAG and TPA is distinctly different from that of activators of cyclic nucleotide-dependent protein kinases, such as octopamine, forskolin, CPT-cyclic AMP (8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate), and 8-bromo-cyclic GMP (8-bromoguanosine 3',5'-cyclic monophosphate) which decreased the postsynaptic sensitivity to L-glutamate. 5. I suggest that the responsiveness of the receptor to L-glutamate is under the control of these counteracting enzyme systems in the insect neuromuscular junction.

Action Potentials↗
PubMed1988

Structure-activity relationship of aldose reductase inhibitors based on X-ray crystal structures of oxazolecarbamate derivatives.

In order to elucidate the key atoms and/or stereostructures necessary for the inhibitory emergence of aldose reductase, crystal structure determinations were carried out for 11 oxazolecarbamate analogues, which have similar chemical and physicochemical properties but different inhibitory activities. The molecular conformations, revealed by X-ray analyses, were also ascertained to be energetically stable from theoretical conformational energy calculations. A surprising degree of conformational similarity was observed for the potent inhibitors. The analyses of the quantitative structure--activity relationships showed that the molecular conformation and the dipole moment, as well as the hydrophobicity at the oxazole C5-site, were important for high activity.

Aldehyde Reductase↗
PubMed1987

Blockage of chloride channels by HEPES buffer.

Chloride channels of neurons of Drosophila are blocked when the cytoplasmic side of the membrane is exposed to the commonly used buffering agents 4-(2-hydroxyethyl)-1-piperazine ethanesulphonic acid (HEPES) and 4-morpholinepropanesulphonic acid (MOPS). In the presence of these compounds, chloride channels appear to function as a complex of multiple protochannels.

Animals↗
PubMed1987

Pancreatic lysosomal thiol proteinases and inhibitors in acute pancreatitis induced in rats.

When examining the level of esterolysis and that of cathepsin B or H, a significant positive correlation was found in the rat pancreas with inflammation induced by a closed duodenal loop, whereas there was a significant negative correlation between the activity of cathepsin B or H and that of its endogenous inhibitors. The levels of endogenous inhibitors of cathepsins B and H in rats with a pancreatitis were lower than in the sham-treated group. The endogenous inhibitors of cathepsins B and H were destroyed by incubation with the supernatant fraction obtained from the inflamed pancreas. These observations indicate that the activities of pancreatic cathepsins B and H are closely related to the severity of acute pancreatitis and that lesser levels of thiol proteinase inhibitors in the pancreatitis group than in the sham-treated group are due to destruction of the inhibitors by the enhanced protease activity.

Acute Disease↗