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D Yamamoto

Publications and source records attributed to D Yamamoto.

At least 109 records · Page 6Linked to original sources
PubMed1986

Ion permeation and selectivity of squid axon sodium channels modified by tetramethrin.

The pyrethroid tetramethrin greatly prolongs the sodium current during step depolarization and the sodium tail current associated with step repolarization of the squid axon membrane. Non-linear current-voltage relationships for the sodium tail current were analyzed to assess the open sodium channel properties which included the permeation of various cations, calcium block and cation selectivity. Tetramethrin had no effect on any of these properties. It was concluded that tetramethrin modifies the sodium channel gating machinery without affecting the pore properties.

Animals↗
PubMed1986

Dynamics of strychnine block of single sodium channels in bovine chromaffin cells.

The kinetics of strychnine block of single Na channels in bovine chromaffin cells were studied using the gigohm seal, patch-clamp technique, under the condition in which the Na current inactivation had been eliminated by treatment with N-bromoacetamide (NBA). Strychnine, applied to the cytoplasmic face of Na channels at concentrations ranging from 25 to 100 microM, caused repetitive rapid transitions (flickering) between open and blocked states within single openings of Na channels, without affecting the amplitude of the single-channel current. Average currents in the presence of strychnine accompanied 'hooked' tail currents upon repolarization. The histograms for blocked times and the histograms for open times could be fitted with a single-exponential function. The mean open time (to) became shorter as the drug concentration was increased, while the mean blocked time (tb) was concentration independent. The association (blocking) rate constant, k, calculated from the slope of the curve relating the reciprocal mean open time to strychnine concentration was 7.6 X 10(6) M-1 S-1 at -40 mV in a typical experiment. to-1 and tb-1 had opposite voltage dependences: tb-1 became larger as the membrane was hyperpolarized whereas to-1 became smaller. The voltage dependence suggests that a first-order blocking site is located 35% of the way through the membrane electric field from the cytoplasmic surface. An increase in the external Na+ concentration greatly decreased to-1 without affecting tb-1. The voltage dependence of both to-1 and tb-1 did not change when the external Na concentration was changed. It is suggested that the strychnine block of single Na channels is not 'current-dependent'. All of the features of strychnine block of single Na channels are compatible with the sequential model, in which strychnine molecules block open Na channels, and the blocked channels could not close until strychnine molecules had left the blocking site in the channels.

Acetamides↗
PubMed1985

Interactions of permeant cations with sodium channels of squid axon membranes.

To determine how the permeant cations interact with the sodium channel, the instantaneous current-voltage (I-V) relationship, conductance-ion concentration relationship, and cation selectivity of sodium channels were studied with internally perfused, voltage clamped squid giant axons in the presence of different permeant cations in the external solution. In Na-containing media, the instantaneous I-V curve was almost linear between +60 and -20 mV, but deviated from the linearity in the direction to decrease the current at more negative potentials. The linearity of instantaneous I-V curve extended to more negative potentials with lowering the external Ca concentration. The I-V curve in Li solution was almost the same as that in Na solution. The linearity of the I-V curve improved in NH4 solution exhibiting only saturation at -100 mV with no sign of further decrease in current at more negative potentials. Guanidine and formamidine further linearized the instantaneous I-V curve. The conductance of the sodium channels as measured from the tail current saturated at high concentrations of permeant cations. The apparent dissociation constants determined from the conductance-ion concentration curve at -60 mV were as follows: Na, 378 mM; Li, 247 mM; NH4, 174 mM; guanidine, 111 mM; formamidine, 103 mM. The ratio of the test cation permeability to the sodium permeability as measured from the reversal potentials of tail currents varied with the test cation concentration and/or the membrane potential. These observations are incompatible with the independence principle, and can be explained on the basis of the Eyring's rate theory. It is suggested that the slope of the instantaneous I-V curve is determined by the relative affinity of permeant cations and blocking ions (Ca) for the binding site in the sodium channel. The ionic selectivity of the channel depends on the energy barrier profile of the channel.

Animals↗
PubMed1984

Voltage-dependent calcium block of normal and tetramethrin-modified single sodium channels.

The mechanisms by which external Ca ions block sodium channels were studied by a gigaohm seal patch clamp method using membranes excised from N1E-115 neuroblastoma cells. Tetramethrin was used to prolong the open time of single channels so that the current-voltage relationship could be readily determined over a wide range of membrane potentials. Comparable experiments were performed in the absence of tetramethrin. Increasing external Ca ions from 0.18 to 9.0 mM reduced the single channel conductance without causing flickering. From the dose-response relation the dissociation constant for Ca block at 0 mV was estimated to be 32.4 +/- 1.05 mM. The block was intensified by hyperpolarization. The voltage dependence indicates that Ca ions bind to sodium channels at a site located 37 +/- 2% of the electrical distance from the outside. The current increased with increasing external Na concentrations but showed a saturation; the concentration for half-maximal saturation was estimated to be 185 mM at -50 mV and 204 mM at 0 mV. A model consisting of a one-ion pore with four barriers and three wells can account for the observations that deviate from the independence principle, namely, the saturation of current, block by Ca ions, and rectification in current-voltage relationship. The results suggest that the Ca-induced decrease of the macroscopic sodium current results from a reduced single sodium channel conductance.

Animals↗
PubMed1984

Kinetics of 9-aminoacridine block of single Na channels.

The kinetics of 9-aminoacridine (9-AA) block of single Na channels in neuroblastoma N1E-115 cells were studied using the gigohm seal, patch clamp technique, under the condition in which the Na current inactivation had been eliminated by treatment with N-bromoacetamide (NBA). Following NBA treatment, the current flowing through individual Na channels was manifested by square-wave open events lasting from several to tens of milliseconds. When 9-AA was applied to the cytoplasmic face of Na channels at concentrations ranging from 30 to 100 microM, it caused repetitive rapid transitions (flickering) between open and blocked states within single openings of Na channels, without affecting the amplitude of the single channel current. The histograms for the duration of blocked states and the histograms for the duration of open states could be fitted with a single-exponential function. The mean open time (tau o) became shorter as the drug concentration was increased, while the mean blocked time (tau b) was concentration independent. The association (blocking) rate constant, kappa, calculated from the slope of the curve relating the reciprocal mean open time to 9-AA concentration, showed little voltage dependence, the rate constant being on the order of 1 X 10(7) M-1s-1. The dissociation (unblocking) rate constant, l, calculated from the mean blocked time, was strongly voltage dependent, the mean rate constant being 214 s-1 at 0 mV and becoming larger as the membrane being hyperpolarized. The voltage dependence suggests that a first-order blocking site is located at least 63% of the way through the membrane field from the cytoplasmic surface. The equilibrium dissociation constant for 9-AA to block the Na channel, defined by the relation of l/kappa, was calculated to be 21 microM at 0 mV. Both tau -1o and tau -1b had a Q10 of 1.3, which suggests that binding reaction was diffusion controlled. The burst time in the presence of 9-AA, which is the sum of open times and blocked times, was longer than the lifetime of open channels in the absence of drug. All of the features of 9-AA block of single Na channels are compatible with the sequential model in which 9-AA molecules block open Na channels, and the blocked channels could not close until 9-AA molecules had left the blocking site in the channels.

Acetamides↗
PubMed1983

Modification of single sodium channels by the insecticide tetramethrin.

(+)-trans-Tetramethrin, a pyrethroid insecticide, markedly prolongs the open time of single sodium channels recorded by the gigaohm-seal voltage clamp technique in a membrane patch excised from the N1E-115 neuroblastoma cell. Single channel conductance is not altered by tetramethrin. The modification by tetramethrin occurs in an all-or-none manner in a population of sodium channels. The observed tetramethrin-induced modification of single sodium channels is compatible with previous sodium current data from axons.

Animals↗
PubMed1983

Factors associated with actinomyces-like organisms on Papanicolaou smear in users of intrauterine contraceptive devices.

To determine the factors associated with the presence of actinomyces-like organisms on cervicovaginal Papanicolaou smears in users of the intrauterine contraceptive device (IUD), we carried out a case-control study. Among about 80,000 Papanicolaou smears examined in one year in a large cytology laboratory, actinomyces-like organisms were identified on 107 smears; all but three smears were from IUD users. Compared with IUD users who did not have actinomyces-like organisms on Papanicolaou smears, those with actinomyces-like organisms had used the IUD for more years. An increased risk of actinomyces-like organisms on Papanicolaou smear was not apparent until 7 years of IUD use, however. No significant association of actinomyces-like organisms with the type of IUD was found after controlling for differences in duration of use between users of various IUDs. The percentage of women reporting gynecologic symptoms (vaginal discharge, pelvic pain, abnormal bleeding) also did not differ significantly between IUD users with and without actinomyces-like organisms on Papanicolaou smear (p = 0.5).

Actinomyces↗
PubMed1979

Curare has a voltage-dependent blocking action on the glutamate synapse.

The skeletal muscle of members of Orthoptera and Diptera receives an innervation which is probably glutaminergic. Recent study of the ventral muscle fibres in the larvae of the beetle, Tenebrio molitor, has revealed that the transmitter action can be mimicked by the iontophoretic application of L-glutamate to the junctional sites at which the extracellular excitatory postsynaptic potentials (e.p.s.ps) could be recorded (D.Y. and H.W., unpublished observation). Contrary to the evidence favouring glutamate as a transmitter of junctional excitation in insects, some investigators have found that curare (+)tubocrarine, TC), a classic acetylcholine (ACh) antagonist, suppresses the neurally evoked muscle potentials in the fly Sacophaga, and Tenebrio. Here, we have analysed the action of curare on the neuromuscular junction of Tenebrio larvae and found that curare blocked the glutaminergic transmission by antagonising the transmitter at the postsynaptic site.

Action Potentials↗
PubMed1979

Permeation of sodium through calcium channels of an insect muscle membrane.

The contribution of Na ions to the electrically excited response was studied in the muscle fibres of mealworm larvae, Tenebrio molitor, using microelectrode techniques. When Ca ions were omitted from the external solution, no action potential could be elicited. However, addition of Na ions to Ca-free medium rendered the fibre excitable again. The amplitude of these action potentials increased with a slope of about 40 mV for a 10-fold elevation of external Na concentrations. Tetrodotoxin had no effect on the initiation of the spike, and Co ions completely suppressed it. Therefore, it seems likely that a Ca-channel, which is utilized by both Na and Ca ions, is the sole factor responsible for the action potential in the mealworm larval muscle fibre membrane.

Action Potentials↗
PubMed1978

Recruitment and retention program for minority and disadvantaged students.

Attracting ethnic minority and disadvantaged students to health careers and facilitating their successful completion of training program requirements have been major activities of the University of Colorado Medical Center since 1969. As a result of extensive college campus recruitment efforts, high school and college level preprofessional programs, and the participation of ethnic minority faculty members in the medical school admissions process, the number of applicants to the medical school increased from 45 in 1971 to 265 in 1977. Concurrently, medical school matriculants increased from 12 in 1971 to 24 in 1977, with a maximum of 30 in 1975. However, significantly fewer minority students have shown interest in nursing, dentistry, or allied health professions careers. Because of support programs for matriculants (including preadmission and postadmissions personal, academic, study skills, and test-taking counseling and a prefreshman year summer orientation course), 71 percent of the minority students entering medical school in 1971-73 have received the M.D. degree.

Colorado↗
PubMedDate not supplied

Cataractogenesis in neonatal Sprague-Dawley rats by N-methyl-N-nitrosourea.

Cataract was induced by a single intraperitoneal injection of 100 mg/kg N-methyl-N-nitrosourea (MNU) to 0-, 5-, 10-, 15-, or 20-day-old male and female Sprague-Dawley rats. In day 0, 5, 10, and 15 MNU-treated rats, mature cataracts were constantly seen 7, 14, 14, and 30 days after dosing, respectively. In the day 20 MNU-treated rats, only subcapsular cataract was seen 30 days after dosing. Therefore, the rats exposed to MNU at an earlier age caused cataract more rapidly and severely. In the day 0 MNU-treated rats, 7-methyldeoxyguanosine DNA adduct was detected in the lens epithelial nuclei 12 hours after MNU dosing, followed by apoptosis, which was confirmed by morphology, by TUNEL signals, and by DNA ladder and peaked 3 days after MNU dosing. In the apoptosis cascade, upregulation of Bax, downregulation of Bcl-2, and increased CPP32 protease (caspase-3) activity were seen 12 hours after MNU dosing. Therefore, the pathogenesis of MNU-induced cataract was associated with DNA adduct formation in the lens epithelial cell nuclei leading to apoptosis by upregulation of Bax protein, downmodulation of Bcl-2 protein, and activation of caspase-3.

Animals↗
PubMedDate not supplied

Prognostic significance of Bcl-2, Bcl-xL/S, Bax and Bak expressions in colorectal carcinomas.

The immunohistochemical expressions of the apoptosis-related proteins Bcl-2, Bcl-xL/S, Bax and Bak were investigated in tumor specimens selected from 58 consecutive patients undergoing surgery for advanced colorectal carcinoma. The expression patterns in 50 specimens of adjacent normal colonic mucosa were also examined. In the normal colonic mucosa, Bcl-2-positive epithelial cells tended to be located at the base of the crypts, while the Bcl-xL/S-, Bax- and Bak-positive epithelial cells tended to be located at the luminal surface. The intracellular expression patterns of Bcl-2 and Bax were diffuse cytoplasmic, whereas those of Bcl-xL/S and Bak were granular cytoplasmic. In the adenocarcinomas, the intracellular expression patterns of all antibodies were diffuse cytoplasmic, and the percentages of Bcl-2-, Bcl-xL/S-, Bax- and Bak-positive cases (>20% of cancer cells labeled) were 29%, 43%, 45% and 69%, respectively. Bax expression was significantly correlated with less lymph vessel invasion (p=0.02) and less depth of invasion (p=0.04). In relation to prognosis (5-year-survival), the patients with Bax-positive tumors had significantly better prognoses than the patients who had Bax-negative tumors (p<0.05). However, the Bcl-2, Bcl-xL/S and Bak expressions were not related to any clinicopathological factors examined. Thus, Bax expression may be an additional prognostic marker in colorectal carcinomas.

Adult↗
PubMedDate not supplied

Cycloprodigiosin hydrochloride, a H+/Cl- symporter, induces apoptosis in human colon cancer cell lines in vitro.

Recently, we reported that cycloprodigiosin hydrochloride (cPrG.HCl), a novel H+/Cl- symporter, induces acidification of the cytosol and leads to apoptosis on rat and human liver cancer cells. In the present study, the effects of cPrG.HCl, a H+/Cl- symporter, were examined in colon cancer cell lines in vitro. In the MTT assay, cPrG.HCl inhibited the growth of two colon cancer cell lines (WiDr and SW480) in a dose- and time-dependent manner. The cPrG.HCl treatment of both types of cells induced apoptosis as confirmed by the appearance of a sub-G1 population and intranucleosomal DNA fragmentation. In addition, cPrG.HCl lowered pHi (below pH 6.8) respectively. Therefore, these results suggest that cPrG.HCl may be useful for the treatment of colon cancer cells.

Antiporters↗
PubMedDate not supplied

The organization of extrinsic neurons and their implications in the functional roles of the mushroom bodies in Drosophila melanogaster Meigen.

Although the importance of the Drosophila mushroom body in olfactory learning and memory has been stressed, virtually nothing is known about the brain regions to which it is connected. Using Golgi and GAL4-UAS techniques, we performed the first systematic attempt to reveal the anatomy of its extrinsic neurons. A novel presynaptic reporter construct, UAS-neuronal synaptobrevin-green fluorescent protein (n-syb-GFP), was used to reveal the direction of information in the GAL4-labeled neurons. Our results showed that the main target of the output neurons from the mushroom body lobes is the anterior part of the inferior medial, superior medial, and superior lateral protocerebrum. The lobes also receive afferents from these neuropils. The lack of major output projections directly to the deutocerebrum's premotor pathways discourages the view that the role of the mushroom body may be that of an immediate modifier of behavior. Our data, as well as a critical evaluation of the literature, suggest that the mushroom body may not by itself be a "center" for learning and memory, but that it can equally be considered as a preprocessor of olfactory signals en route to "higher" protocerebral regions.

Animals↗