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Biomedical subjects

M Yoshii

Publications and source records attributed to M Yoshii.

At least 109 records · Page 6Linked to original sources

Hemiretinal stimuli elicit different amplitudes in the pattern electroretinogram.

Pattern electroretinograms were elicited in 13 normal eyes by half-field checkerboard stimulation of nasal-temporal and upper-lower retinal areas. With nasal-temporal visual half-field stimulation the p-q component amplitude of the nasal hemiretina was significantly larger than that of the temporal hemiretina. With upper-lower visual half-field stimulation the amplitude was significantly larger for the upper than for the lower hemiretina. No significant differences were found with respect to the component latency. Finding the p-q amplitude of the pattern electroretinogram to be closely related to the distribution of nerve cells in the innermost retinal layer supports the conclusion that the pattern response is generated in the more proximal retinal layers including the retinal ganglion cells.

Adolescent↗

Identification of 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholestanoic acid in Zellweger's syndrome.

In order to confirm the occurrence of 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholestanoic acid in Zellweger's syndrome, the nature of tetrahydroxycholestanoic acids present in a patient with this disease was studied. Urinary bile acids were extracted with a Sep-pak C18 cartridge and methylated after alkaline hydrolysis. The methyl esters were purified by silica gel column chromatography, and the methyl tetrahydroxycholestanoate fraction was analyzed by gas liquid chromatography-mass spectrometry. Along with already known side chain hydroxylated derivatives of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid, 3 alpha, 7 alpha, 12 alpha, 24- and 3 alpha, 7 alpha, 12 alpha, 26-tetrahydroxy-5 beta-cholestanoic acids, three nuclear hydroxylated derivatives of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid were found. One of them was identified as 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholestanoic acid by direct comparison with the authentic standard which was chemically synthesized from 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholanoic acid by side chain elongation.

Bile Acids and Salts↗

Synthesis of 5 beta-cholestane-3 alpha,6 beta,7 alpha,25,26-pentol and identification of a novel bile alcohol, alpha-trichechol, present in the West Indian manatee bile.

In order to confirm the structure of alpha-trichechol, the major bile alcohol of the West Indian manatee, chemical synthesis of 5 beta-cholestane-3 alpha,6 beta,7 alpha,25,26-pentol was carried out. The chain of 3 alpha-hydroxy-5 beta-chol-6-en-24-oic acid was elongated by an Arndt-Eistert reaction to form 3 alpha-hydroxy-26,27-dinor-5 beta-cholest-6-en-25-oic acid. The unsaturated C25 bile acid was converted into 3 alpha,6 beta,7 alpha-trihydroxy-25-homo-5 beta-cholan-25-oic acid by 1,2-glycol formation of the delta 6-double bond. The acetylated derivative of the trihydroxy C25 bile acid was then converted into 3 alpha,6 beta,7 alpha,26-tetraacetoxy-27-nor-5 beta-cholestan-25-one by successive treatment with thionyl chloride, diazomethane, and acetic acid. A Grignard reaction of the 25-oxo compound with methylmagnesium iodide afforded the desired bile alcohol, 5 beta-cholestane-3 alpha,6 beta,7 alpha,25,26-pentol. By direct comparison with the synthetic pentahydroxy bile alcohol, the structure of the naturally occurring alpha-trichechol was determined to be 5 beta-cholestane-3 alpha,6 beta,7 alpha,25,26-pentol.

Animals↗

[Pattern reversal electroretinogram--effect of check size, luminance, field size and defocusing].

Using a high water-content soft-contact-lens electrode we recorded pattern electroretinograms (P-ERGs) of subjects responding to reversal checkerboard stimuli and the stimulus parameters were varied in order to investigate normal P-ERG properties. The P-ERG varied with changing luminance, field size and defocusing parameters in the same way as P-VECP, but differed from P-VECP with changes in the check size parameter. These results suggest that the spatial tuning observed in P-VECP could not be discerned in this P-ERG study. It cannot be denied that P-ERG is distorted by P-VECP, which has a larger amplitude at about 100 ms after stimulation. In the future it will be necessary to investigate the origin of P-ERG under experimental conditions separating contrast-related response from luminance-related response.

Adult↗

Gating and permeation properties of two types of calcium channels in neuroblastoma cells.

The gating and permeation properties of two types of calcium channels were studied in the neuroblastoma cell line N1E-115. Calcium channel currents as carried by Ba2+ (50 mM) were recorded using the whole-cell variation of the patch electrode voltage-clamp technique. The two types of calcium channels showed similar membrane potential dependence with respect to the steady-state activation and inactivation gating properties. However, the properties of the long-lasting type II channels were shifted approximately 30 mV in the depolarizing direction compared with those of the transient type I channels. Activation of type I channels developed with a sigmoidal time course which was described by m2 kinetics, whereas the activation of type II channels was described by a single exponential function. Tail current upon repolarization followed an exponential decay in either type of calcium channels. In comparison to type I channels, the activation process of type II channels was shifted approximately 30 mV in the positive direction, while the deactivation process showed a 60 mV shift in the positive direction. The rate constants of activation obtained from the activation and deactivation processes indicated that under comparable membrane potential conditions, type II channels close 2.4 times faster than type I channels upon repolarization. When external 50 mM Ba2+ was replaced with Ca2+ or Sr2+ on the equimolar basis, the amplitudes of transient and long-lasting currents were altered without a significant change in their time courses. The ion permeability ratios determined from the maximum amplitude of the inward current were as follows: Ba2+ (1.0) = Sr2+ (1.0) greater than Ca2+ (0.7) for type I channels, and Ba2+ (1.0) greater than Sr2+ (0.7) greater than Ca2+ (0.3) for type II channels. Replacement of Ba2+ with Ca2+ caused a 10-12 mV positive shift in the current-voltage relation for type II channels. However, the shift for type I channels was much less. This suggests that negative surface charges are present around type II channels. After correction for the surface charge effect on the ion permeation, there was no significant difference between the permeability ratios of these cations for the two channel types. It was concluded that the two types of calcium channels have many common properties in their gating and permeation mechanisms despite their differential voltage sensitivity and ion selectivity.

Animals↗

Mechanisms of calcium channel block by phenytoin.

One of the proposed anticonvulsant actions of phenytoin (5,5'-diphenylhydantoin) is the suppression of calcium movement through cell membranes. However, it is not known how phenytoin interacts with calcium channels to inhibit calcium accumulation in various preparations, or to interfere with calcium-dependent neurotransmitter release. The objective of the present study was to examine whether phenytoin directly blocks voltage-dependent calcium channels of N1E-115 neuroblastoma, and if so, to determine what properties of channel gating are modified by this anticonvulsant. Calcium channel currents as carried by barium were recorded with the whole-cell voltage clamp technique. Low-threshold, transient currents ("type I") were activated at membrane potentials more positive than -50 mV. Type I currents were of maximum amplitude at -20 or -10 mV. High-threshold, sustained currents ("type II") were activated at potentials more positive than -10 mV. Application of phenytoin, at concentrations ranging from 3 to 100 microM, suppressed type I currents without changing their time course or voltage dependence of activation. Type II currents, on the other hand, were insensitive to phenytoin within this concentration range. The block of type I currents by phenytoin was enhanced when the membrane was maintained at more depolarized holding potentials, due to a hyperpolarizing shift in the steady-state inactivation relationship. In addition to the "resting block" of type I channels, phenytoin exerted an additional component of blocking at stimulation frequencies higher than 0.5 Hz. These voltage- and frequency-dependent blocking actions suggest that phenytoin shifts the channel population toward the inactivated state, allowing fewer channels to open during membrane depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Maitotoxin-induced membrane current in neuroblastoma cells.

Maitotoxin (MTX) is a potent marine toxin isolated from the toxic dinoflagellate, Gambierdiscus toxicus. We have examined the possibility of MTX activating calcium channels using cultured neuroblastoma cells (N1E-115). MTX (10 ng/ml) produced a depolarization of the membrane, which was prevented by the removal of Ca2+ from the external medium. Under voltage clamp conditions, membrane currents were recorded with 50 mM Ba2+ as a charge carrier through calcium channels. After application of MTX (1 ng/ml), an inward current necessary to hold the membrane at -90 mV increased progressively. This was followed by a gradual decrease of the transient inward Ba2+ current through type I calcium channels recorded at -30 mV which was eventually abolished. A similar tendency was observed in the long-lasting inward Ba2+ current through type II calcium channels, which was recorded at +10 mV. The MTX action was antagonized by calcium channel blockers such as verapamil (100 microM) and La3+ (1 mM). A high concentration of verapamil (500 microM) blocked both types of calcium channels persistently. After washout of verapamil but while the calcium channels were still blocked, MTX (1 ng/ml) induced a steady-state current. The MTX-induced current showed an inward-rectifying property with a reversal potential of approximately -30 mV. The results suggest that the MTX-induced current does not flow through calcium channels. Thus, MTX may create a pore in the membrane with pharmacological properties similar to those of calcium channels.

Animals↗

Characterization of two types of calcium channels in mouse neuroblastoma cells.

1. Two types of voltage-sensitive calcium channels were identified and studied in the neuroblastoma cell line N1E-115. Calcium channel currents as carried by Ba2+ (50 mM) were recorded using the whole-cell variation of the patch-electrode voltage-clamp technique. 2. A transient (type I) inward Ba2+ current was evoked by a step depolarization from a holding potential of -80 mV to potentials more positive than -50 mV. The current amplitude became maximum around -20 mV. 3. A depolarization to potentials more positive than -20 mV evoked a long-lasting (type II) component of the inward Ba2+ current. This component reached its maximum around +10 mV and did not inactivate during a prolonged depolarizing pulse lasting 400 ms. 4. When preceded by a 5 s conditioning pulse to -30 mV, step depolarization failed to evoke a transient current due to inactivation. However, it induced a long-lasting current. 5. A transient current isolated as the component sensitive to conditioning depolarization became faster in its time course and smaller in its amplitude with membrane depolarization. The current direction was still inward at +60 mV. 6. From the differential voltage sensitivity and the independent channel activity described above, calcium channels responsible for the transient current (type I channel) and those responsible for the long-lasting current (type II channel) were considered to be two different entities. 7. Cd2+ preferentially blocked type II channels, whereas La3+ was a highly potent blocker for both types of calcium channels. 8. The relative potency for block by polyvalent cations was as follows (apparent dissociation constant in microM): La3+, 1.5 much greater than Ni2+, 47 greater than Cd2+, 160 = Co2+, 160 for type I channels, and La3+, 0.9 greater than Cd2+, 7.0 much greater than Ni2+, 280 greater than Co2+, 560 for type II channels. 9. The two types of calcium channels were equally sensitive to the temperature. The current amplitude was reduced by cooling below 30 degrees C. The temperature coefficient (Q10) value was estimated to be 3.0 between 20 and 30 degrees C, and 15.0 below 20 degrees C. Above 30 degrees C, warming reduced the amplitude slightly. 10. External application of dibutyryl adenosine 3',5'-phosphate (dibutyryl cyclic AMP) (1 mM) caused an increase in the amplitude of the type II current by 30-50%, while failing to enhance the type I component.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Synchronous triple primary malignant neoplasms in a 42-year-old female].

Synchronous triple primary malignant neoplasms, namely, retroperitoneal myxoid liposarcoma, sigmoid colon carcinoma and uterocervical carcinoma in situ in a 42-year-old female is reported. The retroperitoneal sarcoma and colonic carcinoma were resected simultaneously, while a hysterectomy was performed five months later. No genetic influence could be elicited in the present case. The synchronous triple primary, malignant neoplasms in this case should be considered as having arisen by mere chance. Other cases in which triple or more primary malignancies were resected are briefly reviewed. In addition, cases of triple or more primary malignant tumors with include at least one sarcoma are also reviewed.

Adenocarcinoma↗

The relation between the after-negative potential of the pattern electroretinogram and the visually evoked cortical potential.

The relationship between the after-negative potential of the pattern electroretinogram (PERG) and the visually evoked cortical potential (VECP) was studied. The PERG was recorded through the use of Toray's high water content, soft contact lens electrode. The PERG consisted of an initial positive potential, a subsequent negative potential and then a slow positive potential. To reduce or avoid contamination of the VECP on the PERG, the most important factor was found to be the reference electrode position; special attention was paid in cases where the amplitude of the VECP was large. In the steady-state condition, the PERG was thought to be modulated by the VECP when the ear lobe was used as the reference electrode position; when the temple was used as the reference electrode position, the amplitude of the PERG was thought to represent that of the after-negative potential.

Contact Lenses↗

Preferential block of skeletal muscle sodium channels by geographutoxin II, a new peptide toxin from Conus geographus.

The effects of geographutoxin II (GTX II), a novel polypeptide toxin isolated from the marine snail Conus geographus, on nerves and muscles were studied by current clamp and voltage clamp techniques. GTX II (5 X 10(-7) M) abolished the action potential of the guinea pig skeletal muscle without change in the resting potential. However, action potentials of the crayfish giant axon, mouse neuroblastoma N1E-115 cell and guinea pig cardiac muscle were not affected by GTX II even at concentrations higher than 1 X 10(-6) M. In the voltage clamped bullfrog skeletal muscle fiber, sodium currents were almost completely blocked by GTX II (1 X 10(-6) M), and slowly recovered after washout. The time course of sodium currents was not appreciably altered by GTX II. These results suggest that GTX II selectively blocks skeletal muscle sodium channels in much the same way as tetrodotoxin.

Action Potentials↗

Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.

Leucine-enkephalin, methionine-enkephalin, and morphine caused a reversible block of Ca2+ channel currents in neuroblastoma-glioma hybrid cells (NG108-15). The long-lasting (type 2) component of the Ca2+ channel current was blocked by leucine-enkephalin, while the transient (type 1) component was not affected. The enkephalin-induced blocking action was antagonized by naloxone and appears to be mediated by delta-opiate receptors. Two different aspects of the blocking effect were detected, a resting block and a recovery from block during prolonged depolarizing pulses. Recovery from block was more complete, and its time course was more rapid, with depolarization to more positive potentials. The dose dependence of the type 2 channel block at rest indicated a one-to-one binding stoichiometry, with an apparent dissociation constant of 8.8 nM. Somatostatin exerted a similar selective blocking action on the type 2 Ca2+ channel. The time- and voltage-dependent block of type 2 Ca2+ channels may provide a mechanism underlying the enkephalinergic presynaptic inhibition of transmitter release and the somatostatin block of pituitary growth hormone release.

Animals↗

Bile alcohol profiles in bile, urine, and feces of a patient with cerebrotendinous xanthomatosis.

Bile alcohols in bile, urine, and feces of a patient with cerebrotendinous xanthomatosis have been analyzed by a combination of capillary gas-liquid chromatography and mass spectrometry after fractionation into groups according to mode of conjugation. The presence of at least 18 bile alcohols, which were excreted mainly as glucurono-conjugates in bile and urine, and as unconjugated forms in feces, was demonstrated. The following bile alcohols were identified with certainty by direct comparison with reference compounds: 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol; (23R)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,23-tetrol; 5 alpha- and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrols; 5 alpha- and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrols; 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol; (22R)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,22,25-pentol; (23R)- and (23S)-5 beta-cholestane-3 alpha,7 alpha, 12 alpha,23,25-pentols; 3 alpha,12 alpha,25-trihydroxy-5 beta-cholestane-7-one; (24R)- and (24S)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentols; 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol. Although the bile alcohol profile in urine was quite different from those in bile and feces, the determination of urinary bile alcohols as well as of biliary and fecal bile alcohols could be used for diagnosis of cerebrotendinous xanthomatosis.

Adult↗