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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 901 records · Page 50Linked to original sources

Inhibitions of acid secretion by E3810 and omeprazole, and their reversal by glutathione.

A substituted benzimidazole ([4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methylsulfinyl)- 1H-benzimidazole sodium salt (E3810), is a gastric proton pump (H+, K(+)-ATPase) inhibitor. E3810 and omeprazole inhibited acid accumulation dose dependently as measured with aminopyrine uptake in isolated rabbit gastric glands, their IC50 values being 0.16 and 0.36 microM, respectively. The addition of exogenous reduced glutathione (GSH) to the gland suspension reactivated dose dependently the acid secretion which had been inhibited by 2 microM E3810 or omeprazole as a function of the incubation time. Furthermore, GSH at 1 and 3 mM reversed the antisecretory effect of E3810 more quickly than it did that of omeprazole. The antisecretory effect of E3810 was slightly greater than that of omeprazole in histamine-stimulated fistula dogs in vivo. The duration of the antisecretory activity of E3810 at concentrations of 2 and 4 mg/kg was shorter than that of omeprazole at the same concentrations in pentagastrin-stimulated fistula dogs. The reversal of the antisecretory activity of the inhibitors in dogs is suggested to be due to the action of endogenous extracellular GSH, in addition to de novo synthesis of the proton pump, because bullfrog gastric mucosae were found in the present study to secrete GSH into the mucosal solution at the rate of about 0.25 nmol/min/g tissue.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Functional participation in M1 receptor subtype on chronotropic and dromotropic responses to vagus stimulation in anesthetized dogs.

We investigated blocking effects of pirenzepine, AF-DX 116 and atropine on the negative chronotropic and dromotropic responses to stimulation of the intracardiac vagus nerves in the anesthetized, open-chest dogs. Stimulation of the intracardiac vagus nerves to the sinoatrial nodal region (stimulation of the intracardiac parasympathetic nerves to the sinoatrial nodal region) or to the atrioventricular nodal region (stimulation of intracardiac nerves to the atriventricular region) selectively decreased heart rate or increased atrioventricular conduction time, respectively. Pirenzepine at lower doses (0.3-3 microgram/kg i.v.) attenuated the stimulation of the negative chronotropic response to the intracardiac parasympathetic nerves to the sinoatrial nodal region to 80% of the control response significantly but did not affect the negative dromotropic one. Similarly, higher doses (10-1000 micrograms/kg i.v.) of pirenzepine inhibited the chronotropic and dromotropic responses to each stimulation in a dose-dependent manner. AF-DX 116 (0.3-300 microgram/kg i.v.) inhibited the chronotropic and dromotropic responses to each stimulation in a similar dose-dependent manner. Atropine (1-30 microgram/kg i.v.) blocked the cardiac responses to each stimulation. However, the ID50 of atropine for the chronotropic response was less than that for the dromotropic one, although ID50s of pirenzepine and AF-DX 116 for the chronotropic and dromotropic responses were not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Monitoring of intracellular ammonium in perfused rat salivary gland by nitrogen-14 nuclear magnetic resonance spectroscopy.

We have observed the changes in the intracellular ammonium (NH4+) content and the intracellular pH during administration of 20 mM NH4Cl (the ammonium pulse experiment) using nitrogen-14 and phosphorus-31 nuclear magnetic resonance spectroscopy (14N and 31P NMR) at 8.45 T. In the isolated perfused rat mandibular salivary gland, resonances of trimethylamines (-328 p.p.m.) and betaine (-329 p.p.m. from the resonance of NO3-) were detected. A chemical shift reagent, 10 mM of dysprosium triethylenetetramine-N,N,N',N",N"',N"'-hexaacetic acid (Dy(TTHA], was used to discriminate between the resonances from the extracellular NH4+ (-352 p.p.m.) and the intracellular NH4+ (-355 p.p.m.). During the NH4Cl application, the intracellular NH4+ content [( NH4+]i) increased quickly to ca. 50 mmol per litre intracellular fluid (ICF), then increased gradually to ca. 70 mmol per litre ICF. The intracellular pH (pHi), calculated from the 31P chemical shift of inorganic phosphate, increased transiently by 0.5 pH units and then decreased gradually in spite of the high level of [NH4+]i. The initial increase of [NH4+]i, which was observed by 14N NMR, was larger than that calculated from the intracellular pH on an assumption of a non-ionic diffusion process for ammonia. These results suggest a possibility of influx of NH4+, and also suggest an activation of cellular buffering mechanism that extrudes the excess bases from the cells.

Ammonia↗

NMR relaxation characteristics of rubidium-87 in perfused rat salivary glands.

Rubidium is a good substitute for potassium in many biological systems, and it has been suggested that rubidium-87 nuclear magnetic resonance (87Rb-NMR) spectroscopy could be used to measure K+ fluxes across membranes in intact tissues. To evaluate this possibility, isolated rat mandibular salivary glands were perfused with solutions containing Rb+ in place of K+. The 87Rb signals arising from the intra- and extracellular compartments were first separated by spectral subtraction and then subjected to line-shape analysis. The narrow extracellular signal was a single Lorentzian (line-width 156 Hz), whereas the broader intracellular signal consisted of two Lorentzian components (ca. 530 and 3080 Hz). Double-quantum filtering of the 87Rb signal from the glands revealed two components of transverse relaxation in antiphase (rate constants 1.8 and 13.3 ms-1), showing the probable involvement of quadrupolar interactions in the relaxation of intracellular Rb+. We conclude, therefore, that both line-shape analysis and double-quantum filtering could provide a basis for the measurement of unidirectional K+ fluxes in intact tissues.

Animals↗

Calcium-dependent regulation of cyclic GMP phosphodiesterase by a protein from frog retinal rods.

In vertebrate photoreceptors, light reduces cyclic GMP concentration and closes cGMP-activated channels to induce a hyperpolarizing response. As Ca2+ can permeate the channels and the Na(+)-Ca2+ exchanger continuously extrudes Ca2+, closure of the channel results in a reduction of the inter-rod Ca2+ concentration. This is believed to be one of the mechanisms of light-adaptation produced by activation of guanylate cyclase. Effects of Ca2+ on the cGMP phosphodiesterase (PDE) have been reported, but their physiological significance has remained unclear. We have perfused the inside-out preparation of a frog rod outer segment (I/O ROS, originally termed truncated ROS, and find that Ca2+ in a physiological range regulates the light-activation of PDE. Therefore, PDE regulation by Ca2+ must be involved in light-adaptation in rods. The effect is mediated by a newly found protein which binds to disk membranes at high Ca2+ concentrations and prolongs PDE activation.

3',5'-Cyclic-GMP Phosphodiesterases↗

[Fast MR imaging of liver metastasis using FLASH and FISP--optimal sequences for T1- and T2*-weighted images].

This paper deals with a study to obtain the optimal sequence of gradient echo (GE) for T1- and T2*-weighted images similar to T1- and T2-weighted images of spin echo (SE). Two GE sequences, fast low angle shot (FLASH) and fast imaging with steady-state precession (FISP), were performed in 15 cases of liver metastasis in various combination of flip angle (FA), repetition time (TR), and echo time (TE). The optimal combinations were summarized as follows: 1) T1-weighted FLASH image with FA of 40 degrees, TR of 22 msec and TE of 10 msec, 2) T1-weighted FISP image with FA of 70 degrees, TR of 100 msec, TE of 10 msec, 3) both T2*-weighted FLASH and FISP images with FA of 10 degrees, TR of 100 msec and TE of 30 msec. Not only to provide the adequate T1- and T2*-weighted images but also to enable breath-holding MR imaging, GE sequences can optionally take place SE in cases of deteriorated images caused by moving artifacts. Other applications support the re-examination and further detailing when required, conveniently rather in short time.

Adult↗

Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo.

The School Health Law of Japan was passed in 1974 mandating urine screening of elementary and junior high-school students for the detection of renal disease. A first morning urine was obtained on an annual basis for each individual student for the time period 1974-1986. The prevalence of proteinuria and haematuria among elementary school children was 0.08% and 0.54%, respectively, while junior high-school students demonstrated corresponding prevalences of 0.37% and 0.94%. The theoretical merits of this screening programme include the detection of glomerulonephritis with possible early therapeutic intervention. However, a limitation to this approach is its over-sensitivity where asymptomatic urine abnormalities is found to be 10 times greater in frequency than glomerulonephritis histologically.

Adolescent↗

Effects of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brain in vivo.

The effect of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brain was investigated in vivo. After administration of HA1077, at doses of 0.1, 0.3, and 3 mg/kg, 5-hydroxyindoleacetic acid (5-HIAA) levels increased in most regions except midbrain. In the striatum, parallel increases of both serotonin (5-HT) and 5-HIAA levels were observed at 0.3 mg/kg, but only the 5-HT level increased at 0.1 mg/kg. These results suggest that HA1077 may activate the turnover or synthesis of 5-HT. After administration of HA1077 at 0.3, 1, and 3 mg/kg, the dopamine (DA) level was increased in the striatum, but 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid levels were unchanged. After HA1077 administration at 1 mg/kg, both DA and DOPAC levels increased in the hypothalamus and only DA level increased in the cerebral cortex. By contrast, DOPAC level decreased in the midbrain after HA1077 treatment at 0.1 and 0.3 mg/kg, and in the brainstem at 0.1 and 10 mg/kg. The ratio of [3H]-N-methylspiperone accumulation relative to that in the cerebellum did not change after HA1077 treatment at any of the doses employed. Thus, the effects of HA1077 on neurotransmitter metabolism are complex and vary depending on the dosage and sites of the brain. Although the dose-dependent effects of HA1077 on neurotransmitter metabolism are similar to those of calcium entry blockers, HA1077 can facilitate DA synthesis in the hypothalamus and striatum, unlike the calcium entry blockers.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Occurrence of beta-turn potentials around nuclear and nucleolar localization sequences.

The biological significance of turn structures is now of great topical interest. By using the protein conformational prediction method of Chou and Fasman, the present work predicts that 17 nuclear localization signals and a nucleolar localization signal reported so far contain turn potentials. Two nuclear localization signals, human lamin A and c-myc protein (peptide M1), however, cannot be predicted as containing beta-turns by the prediction method. To date, no physical characterization of any nuclear or nucleolar location signal by X-ray crystallography and nuclear magnetic resonance spectroscopy has been performed. Employing conformation prediction methods, therefore, would be useful for elucidating structural features of nuclear and nucleolar location signals.

Amino Acid Sequence↗

Effect of parasympathectomy on the histochemical maturation of myoepithelial cells of the rat sublingual salivary gland.

This effect of parasympathectomy was assessed by fluorescent microscopy using nitrobenzoxadiazole-phallacidin, which is known for its specific binding to actin filaments. Resection of the chorda tympani within 48 h after birth inhibited the normal formation of actin in the myoepithelial cells and the maturation of myoepithelial cells. The effect of denervation decreased progressively if the operation was delayed. Denervation 30 days after birth had no effect on development and differentiation of myoepithelial cells. Moreover, the procedure produced no histochemical changes in the myoepithelial cells in mature rats, even two months later. These findings suggest that the parasympathetic innervation is closely involved in the maturation of myoepithelial cells. Further, its involvement is limited to the first 48 h after birth, during which it exerts its neurotrophic effect on the myoepithelial cells present in all the acinar buds.

Actin Cytoskeleton↗

TRH-Gly, a precursor of TRH, alters GH secretion in acromegaly.

We explored effects of a precursor of thyrotropin (TSH)-releasing hormone (TRH), TRH-Gly, on growth hormone (GH) secretion in acromegaly. Intravenous injection of TRH-Gly produced a profound increase in GH secretion in eight, decrease in two, and no response in five out of a total fifteen patients. The magnitude of GH responsiveness to TRH-Gly was significantly correlated with that induced by TRH (r = 0.824, P less than 0.01). In contrast, TRH-Gly did not induce secretion of TSH or prolactin. The present data suggest that TRH-Gly may participate in regulating GH secretion in some patients with acromegaly and that TRH-Gly-induced GH secretion may be due at least in part to TRH-associated mechanisms underlying GH secretion.

Acromegaly↗

Synaptic inputs to turtle horizontal cells analyzed after blocking of gap junctions by intracellular injection of cyclic nucleotides.

Intracellular injection of cAMP or cGMP into turtle horizontal cells significantly increased the input resistances, and the cells could thus be easily polarized by current injection, suggesting that the cyclic nucleotides blocked gap junctions between cells. Then, synaptic inputs onto triphasic chromaticity-type cells were analyzed. Hyperpolarizing and depolarizing light responses were all reduced with depolarizing current, and their polarities were reversed by further depolarization. Their reversal potentials coincided at around 0 mV. This level was the same as observed in luminosity-type and biphasic chromaticity-type cells, suggesting that the ionic mechanisms of synaptic transmission are common among horizontal cell types.

Animals↗

Reversal potentials of color opponent responses in horizontal cells of the carp retina.

Reversal potentials of color opponent responses were measured in H2 and H3 horizontal cells of the carp using Ca2+ action potential method. All responses reversed around -5 mV, suggesting that the ionic mechanisms of light responses are common among all types of horizontal cells. Glutamate-induced depolarizations in H2 and H3 cells had the same reversal potentials as those of light responses, consistent with the idea that these cells receive glutamate-mediated inputs from the cones. Simultaneous recordings showed that depolarization of H1 cells by Ca2+ action potential was transmitted to H2 cells in sign-inverted manner through a negative feedback interposed between these cells.

Action Potentials↗

Hemangioma of the temporalis muscle: case report and review of the literature.

A 51 year-old man presented with a 10-year history of a painless, slowly growing mass (35 x 25 x 15 min) in the right temporal fossa. The T1-weighted image on magnetic resonance imaging demonstrated a partial, low-signal intensity lesion with high intensity in the lower part and significant enhancement with contrast medium. The tumor, which lay within the temporal muscle, was totally excised, and histological examination confirmed the lesion to be an intramuscular, cavernous type of hemangioma. The therapeutic options are described.

Angiography, Digital Subtraction↗

Recognition by anti-idiotypic anti-thyrotropin-releasing hormone (TRH) antibody of rat TRH receptors.

We asked whether anti-idiotypic antibodies raised against anti-TRH antibody could bind to TRH receptors in the rat anterior pituitary and brain. Six rabbits were immunized with IgG from a rabbit anti-TRH antiserum. One anti-idiotypic antibody caused strong, dose-dependent inhibition in anti-TRH antibody-binding to [125]I-TRH. This inhibition was not observed after treatment with goat anti-rabbit IgG antibody. The anti-idiotypic anti-TRH antibody significantly immunoprecipitated digitonin-solubilized pituitary TRH receptors. When eluates of digitonin-solubilized membranes which were adsorbed by either an anti-idiotypic anti-TRH IgG-, normal rabbit IgG-linked affinity column or control column were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and visualized by silver stain, only the former eluate showed two bands under nonreducing conditions; one corresponded to a molecular weight marker of 200K, the other to 100K. Western blotting analysis with an anti-idiotypic anti-TRH antiserum showed a single band of molecular weight 56K under reducing conditions. The present study indicates that one can make anti-idiotypic antibodies that specifically recognize TRH receptors.

Animals↗