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Biomedical subjects

A Mikami

Publications and source records attributed to A Mikami.

At least 73 records · Page 4Linked to original sources

Primary structure and functional expression from complementary DNA of a brain calcium channel.

The primary structure of a voltage-dependent calcium channel from rabbit brain has been deduced by cloning and sequencing the complementary DNA. Calcium channel activity expressed from the cDNA is dramatically increased by coexpression of the alpha 2 and beta subunits, known to be associated with the dihydropyridine receptor. This channel is a high voltage-activated calcium channel that is insensitive both to nifedipine and to omega-conotoxin. We suggest that it is expressed predominantly in cerebellar Purkinje cells and granule cells.

Amino Acid Sequence↗

Unique oscillatory activity related to visual processing in the temporal pole of monkeys.

To examine the role of the temporal pole of monkeys in visual processing, the activity of single neurons was extracellularly recorded while the monkey performed a visual discrimination task. Various colored photographs were used as visual stimuli. We found neurons with oscillatory activity coupled to visual stimuli in the ventral part of the temporal pole. Oscillatory activity tended to be elicited by objects familiar to the monkey, such as familiar human faces, familiar foods and familiar non-food objects related to the experiment. The frequencies of oscillations changed depending upon the nature of the visual stimulus. The results suggest that oscillatory activity generated by the activation of a certain circuit is involved in the recognition of complex visual stimuli, leading to the production of certain psychological states.

Animals↗

Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains.

To enzymatically synthesize vitamin D derivatives, we screened about 300 Streptomyces sp. strains. Streptomyces sclerotialus FERM BP-1370 and Streptomyces roseoporus FERM BP-1574 were found to have the ability to convert 25-hydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3, respectively, to 1 alpha, 25-dihydroxyvitamin D3. The average rates of 1 alpha hydroxylation of 25-hydroxyvitamin D3 were 6.9 micrograms liter-1 min-1 with FERM BP-1370 and 7.0 micrograms liter-1 min-1 with FERM BP-1574. The specific cytochrome P-450 inhibitors carbon monoxide, SKF-525-A, and metyrapone inhibited the hydroxylation of 1 alpha- and 25-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by FERM BP-1370 and FERM BP-1574. The cytochromes P-450 of these strains were detected by reduced CO difference spectra in the whole-cell suspensions. The appearance of cytochrome P-450 suggests that the cytochromes P-450 of FERM BP-1370 and FERM BP-1574 carry out the hydroxylation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3.

Biotransformation↗

Direction selective neurons respond to short-range and long-range apparent motion stimuli in macaque visual area MT.

To examine the involvement of macaque visual area MT in the short-range process and the long-range process of visual motion (Braddick 1974), direction selective MT neurons responding to alternating slits and alternating random dots were analyzed. Experiments were performed in awake macaque monkeys trained to fixate a pair of small stationary lines. Visual stimuli were presented on a CRT display screen. About 82% of direction selective MT neurons showed directional responses to alternating slits and/or alternating random dots. The maximum spatial separation for eliciting directional responses (Dmax) was determined for each neuron. In most of cases, Dmax for the alternating random dots was smaller than Dmax for the alternating slits. The Dmax for both alternating random dots and alternating slits increased when retinal eccentricity increased. It is suggested that MT neurons might be involved in the long-range process rather than the short-range process of the apparent motion.

Animals↗

Intramembrane charge movement restored in dysgenic skeletal muscle by injection of dihydropyridine receptor cDNAs.

The skeletal muscle dihydropyridine (DHP) receptor is essential in excitation-contraction (EC) coupling. The receptor is postulated to be the voltage sensor giving rise to the intramembrane current, termed charge movement. We have now tested this hypothesis using myotubes from mice with the muscular dysgenesis mutation, which alters the skeletal muscle DHP receptor gene and prevents its expression. Our results indicate that charge movement is deficient in dysgenic myotubes but is fully restored following injection of an expression plasmid carrying the rabbit skeletal muscle DHP receptor complementary DNA, strongly supporting the hypothesis that the DHP receptor is the voltage sensor for EC coupling in skeletal muscle. Additionally, our data obtained for normal and chimaeric DHP receptor constructs demonstrate that DHP receptors with widely differing abilities to function as calcium channels and to mediate EC coupling produce very similar charge movements.

Animals↗

Cardiac-type excitation-contraction coupling in dysgenic skeletal muscle injected with cardiac dihydropyridine receptor cDNA.

There are dihydropyridine (DHP)-sensitive calcium currents in both skeletal and cardiac muscle cells, although the properties of these currents are very different in the two cell types (for simplicity, we refer to currents in both tissues as L-type). The mechanisms of depolarization-contraction coupling also differ. As the predominant voltage-dependent calcium current of cardiac cells, the L-type current represents a major pathway for entry of extracellular calcium. This entry triggers the subsequent large release of calcium from the sarcoplasmic reticulum (SR). In contrast, depolarization of skeletal muscle releases calcium from the SR without the requirement for entry of extracellular calcium through L-type calcium channels. To investigate the molecular basis for these differences in calcium currents and in excitation-contraction (E-C) coupling, we expressed complementary DNAs for the DHP receptors from skeletal and cardiac muscle in dysgenic skeletal muscle. We compared the properties of the L-type channels produced and showed that expression of a cardiac calcium channel in skeletal muscle cells results in E-C coupling resembling that of cardiac muscle.

Animals↗

Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel.

In cardiac muscle, where Ca2+ influx across the sarcolemma is essential for contraction, the dihydropyridine (DHP)-sensitive L-type calcium channel represents the major entry pathway of extracellular Ca2+. We have previously elucidated the primary structure of the rabbit skeletal muscle DHP receptor by cloning and sequencing the complementary DNA. An expression plasmid carrying this cDNA, microinjected into cultured skeletal muscle cells from mice with muscular dysgenesis, has been shown to restore both excitation-contraction coupling and slow calcium current missing from these cells, so that a dual role for the DHP receptor in skeletal muscle transverse tubules is suggested. We report here the complete amino-acid sequence of the rabbit cardiac DHP receptor, deduced from the cDNA sequence. We also show that messenger RNA derived from the cardiac DHP receptor cDNA is sufficient to direct the formation of a functional DHP-sensitive calcium channel in Xenopus oocytes. Furthermore, higher calcium-channel activity is observed when mRNA specific for the polypeptide of relative molecular mass approximately 140,000 (alpha 2-subunit) associated with skeletal muscle DHP receptor is co-injected.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Directionally selective response of cells in the middle temporal area (MT) of the macaque monkey to the movement of equiluminous opponent color stimuli.

Based on the fact that a great majority of cells in the middle temporal (MT) area of the macaque respond to movement of luminance contours with directional selectivity, this area has been thought to be concerned with the analysis of visual motion. However, objects can be discriminated from the background not only by differences in luminance but also by differences in color. It is possible that color signals are also used for motion analysis in MT. In the present study, we examined whether MT cells respond to movement of a pattern composed of pure color-contours. Using a color TV system, a moving color bar was displayed on a uniform background whose color was opponent with that of the bar. The main bar/background color combination we examined was magenta/cyan. Yellow/blue and cyan/magenta combinations were also examined for some cells. The response of MT cells to movements of opponent-color stimuli was recorded while the bar/background luminance ratio was changed from 1/10 to 10/1. In half of 89 cells tested in 3 monkeys, the response decreased considerably (disappeared completely in some cells) at a luminance ratio close to the human equiluminous condition. In the other half, a directional response persisted at any bar/background luminance ratio, though the response decreased to a varied extent (30-90% of the maximum response) near the ratio 1 (human equiluminous condition). The average magnitude of the equiluminous response to the magenta/cyan stimulus for the overall population was about 35% of the maximal response when the length of the bar (0.5 degrees in width) and the movement amplitude were set to be optimal for individual cells, i.e. smaller than 15 degrees and 10 degrees of visual angle, respectively. This fall to 23% when the bar length and movement amplitude were limited to 2 degrees. The same cell responded to pure color-contours of yellow/blue as well as of cyan/magenta combinations. Thus, MT can detect the direction of movement of pure color-contours, although the sensitivity is less than for luminance contours.

Animals↗

Induction of mRNA for low-density lipoprotein receptors in heterozygous Watanabe heritable hyperlipidemic rabbits treated with CS-514 (Pravastatin) and cholestyramine.

We administered CS-514, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alone and in combination with cholestyramine to heterozygous Watanabe heritable hyperlipidemic rabbits. This rabbit model for heterozygous familial hypercholesterolemia has hepatic low-density lipoprotein receptors that are assumed to be half as many as in normal rabbits. CS-514 alone lowered plasma low-density lipoprotein cholesterol levels by 50%, and in combination with cholestyramine, it lowered levels by 80%. The membrane-binding assay showed these drugs caused 1.5- and 1.8-fold increases in the number of hepatic low-density lipoprotein receptors, respectively. We also measured the amount of mRNA for low-density lipoprotein receptor by S1 nuclease protection assay in the same livers as above. These drugs induced mutant mRNA for the low-density lipoprotein receptor, which has an in-flame deletion of 12 nucleotides, as well as normal receptor mRNA. CS-514 alone produced a 1.8-fold increase in the amount of mRNA for the normal receptor and a 2.3-fold increase for the mutant mRNA, whereas CS-514 in combination with cholestyramine produced 1.9- and 3.1-fold increases, respectively. We conclude that CS-514 induces mRNA for the low-density lipoprotein receptor, subsequently increasing the receptor protein in the liver, and then reduces the levels of plasma cholesterol, and that the induction is augmented when the drug is administered in combination with cholestyramine.

Animals↗

The concentration of serum lipids in Zen monks and control males in Japan.

The concentrations of total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol, triglyceride and apoprotein B have been examined in Zen monks whose intake of animal products was almost negligible for 2 to 8 years, and in age-matched (24 to 35 years) control Japanese males who eat Western style food. The mean levels of total, LDL- and HDL-cholesterol, and apoprotein B were 135.1 +/- 16.7, 73.0 +/- 11.6, 50.4 +/- 9.6, and 70.6 +/- 15.6 mg/dl, respectively in Zen monks. These levels were 28.5, 32.8, 18.8, and 23.9% lower in Zen monks than in control Japanese males. These values are statistically significant compared to those of the controls (p less than 0.01). There were no significant changes in the level of triglyceride in both groups.

Adult↗

[A case report of hereditary angioedema and studies on the serum components of complement, C1-inactivator and proteinase inhibitors during edema attack].

Sixteen years old girl was admitted because of for the past ten years' frequent edema attack and abdominal pain. Laboratory examination revealed hypocomplementemia, marked depletion of the fourth component of complement and low level of C1-inactivator. Familial studies revealed that her mother was also hypocomplementemic and in low level of C1-inactivator. Serial studies performed on the alterlation of components of complement, C1-inactivator, alpha 1-antitrypsin, antithrombin III, and alpha 2-macroglobulin during edema attack. The fourth component of complement and C1-inactivator were markedly depleted in remission and attack. Remarkable depletion was found in antithrombin III and esterase inhibition activity of C1-inactivator during attack. In contrast, alpha 1-antitrypsin and alpha 2-macroglobulin did not change. The present study may explain that Hageman factor fragments, activated by C1s, promotes kinin generation via kalikrein activation. And the condition that complete functional deficiency of C1-inactivator was main role in this circuit. Fibrynolysis and late components of complement was less influence on edema attack.

Adolescent↗

Motion selectivity in macaque visual cortex. I. Mechanisms of direction and speed selectivity in extrastriate area MT.

Mechanisms of direction selectivity and speed selectivity were studied in single neurons of the middle temporal visual area (MT) of behaving macaque monkeys. Visual stimuli were presented in both smooth and stroboscopic motion within a neuron's receptive field as the monkey fixated a stationary point of light. Direction selectivity, speed selectivity, and the spontaneous discharge characteristics of MT neurons in behaving monkeys were similar to those reported in previous studies in anesthetized monkeys. Stroboscopic motion stimuli were sequences of flashes characterized by the spatial and temporal intervals between each flash. The spatial and temporal intervals were systematically varied so that suppressive and facilitatory interactions could be studied in both the preferred and null directions. Suppression and facilitation were measured by subtracting the peak discharge rate elicited by a single flash from the peak discharge rate elicited by a stroboscopic train of flashes. The dominant mechanism of direction selectivity in MT was a pronounced suppression of discharge for motion in the null direction which we interpreted as inhibition. The inhibition was sufficiently potent to abolish the responses to single flashed stimuli when they were embedded in a series of flashes in the null direction, and it frequently reduced the neuronal discharge to a level below the spontaneous firing rate. Facilitation in the preferred direction was a prominent feature of the responses of some, but not all, MT neurons. The peak discharge rate for stroboscopic motion in the preferred direction was more than twice the peak rate to a single flash for approximately 50% of the neurons in our sample. The direction selectivity of most MT neurons showed the effects of both inhibitory and facilitatory mechanisms, and it was not possible to segregate MT neurons into distinct groups on the basis of these measures. Suppressive mechanisms contributed to speed tuning as well as direction tuning. The low-speed cutoff for motion in the preferred direction resulted from suppression in 82% of the neurons tested. The high-speed cutoff resulted from suppression in 32% of the neurons tested. The latter mechanism appeared to be distinct from the inhibitory mechanism which acted in the null direction in that large spatial intervals were required for its activation.

Animals↗