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Biomedical subjects

K Matsunaga

Publications and source records attributed to K Matsunaga.

At least 19 recordsLinked to original sources

Xestoquinone activates skeletal muscle actomyosin ATPase by modification of the specific sulfhydryl group in the myosin head probably distinct from sulfhydryl groups SH1 and SH2.

Xestoquinone isolated from a sea sponge Xestospongia sapra inhibited both Ca2+ and K(+)-(EDTA) ATPase of skeletal muscle myosin. The inhibition was abolished in the presence of dithiothreitol. Xestoquinone reacted with 2-mercaptoethanol, a sulfhydryl (SH) compound. Unlike N-ethylmaleimide, a well-known SH reagent, modification of 2 mol of SH groups per myosin by xestoquinone caused a marked increase in the actomyosin ATPase activity. Kinetical analysis of stimulatory effects of xestoquinone indicates a decrease in the actin concentrations which gives half of the maximum velocity (Vmax) of actomyosin ATPase reaction without affecting the Vmax, suggesting an increase in the affinity of myosin for actin. N-Ethylmaleimide can still modify both the SH1 and SH2 groups after modification of 2 mol of SH groups by xestoquinone. Xestoquinone modified myosin SH groups which caused changes in the tryptophan fluorescence intensity and circular dichroism. These results suggest that xestoquinone modifies the specific SH groups in myosin distinct from SH1 and SH2, resulting in activation of actomyosin ATPase. It is also suggested that xestoquinone strengthens the interaction between actin and myosin through conformational change in the myosin molecule.

Actins

Sympathetic skin responses evoked by magnetic stimulation of the neck.

We studied sympathetic skin responses (SSRs) following magnetic stimulation of the neck in 40 normal subjects and 54 patients with neurological diseases and active sweat gland densities (ASGDs) at the foot induced by pilocarpine in 39 patients. SSRs at the hand following magnetic stimulation showed the lowest coefficients of variability of the latencies and amplitudes in eight consecutive responses compared with SSRs following other types of stimuli (electrical and auditory stimulation, and deep inspiration) in 12 normal subjects. Fourteen of 38 patients with neuropathies (37%) showed the presence of SSRs after magnetic stimulation, but not after median nerve stimulation, although SSRs to magnetic stimulation corresponded with those to nerve stimulation in all patients with multiple sclerosis or multiple system atrophy. These results suggest that the absence of SSRs after nerve stimulation in patients with neuropathies may be due to abnormalities of the peripheral sensory afferent fibers. ASGDs significantly correlated with SSRs at the foot following magnetic stimulation, but not with those following nerve stimulation in patients with neuropathies. Magnetic stimulation of the neck is the highly reproducible method of evoking SSRs because this technique is able to produce strong sensory afferent inputs proximally. Furthermore, SSRs following magnetic stimulation, little influenced by sensory afferent fiber involvement, are very useful for evaluating the postganglionic sympathetic function in patients with neuropathies.

Action Potentials

Effect of sleep stage on somatosensory evoked potentials by median nerve stimulation.

The effects of sleep stage on early cortical somatosensory evoked potentials (SEPs) and short-latency components elicited by median nerve stimulation were studied in 12 normal volunteers. The latency of P13 in the awake stage was not significantly different from that in any sleep stage. The latencies of N16, N20 and P20 were significantly prolonged while the amplitude of N20 was decreased during the non-rapid eye movement (NREM) sleep stage. P22, P23 and N24 components showed double peaks (P23a, P23b, N24a, N24b) during the NREM sleep stage in 6 subjects, while N24 showed a single peak and only P22 and P23 showed double peaks in 5 other subjects. The latencies and morphologies of SEPs during rapid eye movement sleep stage were almost the same as those during the awake stage. These findings suggest that NREM sleep affects the latency, amplitude and morphology of N16 and early cortical components.

Adolescent

Vitamin K prodrugs: 1. Synthesis of amino acid esters of menahydroquinone-4 and enzymatic reconversion to an active form.

The efficacy and toxicity of vitamin K depends on the pathway and the extent of enzymatic reductive activation to vitamin K hydroquinone, which is an essential cofactor for the synthesis of clotting factors. Parenteral use of vitamin K is impaired by its water insolubility. With the aim to improve delivery problems associated with menahydroquinone-4 (MKH, 2), an active form of menaquinone-4, N,N-dimethylglycine esters of 2 (1-mono, 4-mono, and 1,4-bis) were synthesized and assessed as potential water-soluble prodrugs for parenteral use. The esters can deliver the hydroquinone to its active site without a quinone reductive activation step. The hydrochloride salts of the esters were found to be quite soluble in water. The hydrolysis of the esters in 20% rat liver homogenate 9000 x g supernatant, rat plasma and phosphate buffer, pH 7.4, at 37 degrees C was kinetically studied in the presence and absence of an esterase inhibitor. The hydrolysis was catalyzed by esterases located in the rat liver and rat plasma and quantitatively yielded 2. These results suggest that esterification of 2 with N,N-dimethylglycine is a promising way for obtaining water-soluble prodrug forms of 2. Based on the high susceptibility to liver esterase, the esters are potential prodrugs for achieving the site-specific delivery of 2.

Animals

[Intrapleural bleomycin for management of malignant pleural effusions].

We studied the efficacy of intrapleural administration of bleomycin for the management of malignant pleural effusions of non-small cell lung cancer in 24 cases. Bleomycin 60 mg was administered into the pleural space after tube drainage. If the effusion continued, one additional dose was given. The efficacy was seen in 18 cases (75%). The main adverse drug reaction was transient fever among others. There was little toxicity and no cases of pulmonary fibrosis. Intrapleural administration of bleomycin is useful in management of malignant pleural effusions.

Aged

NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene.

Expression of the human monocyte chemoattractant protein-1 (hMCP-1) is ubiquitous in various cell types and is increased by a wide variety of stimuli. We initially found that the effects of various stimuli, including IL-1 beta, TNF-alpha, and 2-O-tetradecanoylphorbol 13-acetate, on the expression of hMCP-1 mRNA were quite different among A172 glioblastoma cells, HT1080 fibrosarcoma cells, and SKLMS1 leiomyosarcoma cells. These findings suggested that hMCP-1 expression is regulated both in a stimulus-specific and a tissue-specific manner. To elucidate the mechanism underlying this stimulus-specific and tissue-specific regulation, we isolated a hMCP-1 5'-flanking genomic DNA fragment and sequenced it extensively up to bp 3011 upstream from the transcriptional start site. Among many putative cis-elements, we identified two cis-elements critical for the transcription of the hMCP-1 gene. The first element is a remote kappa B binding site located far upstream between bp -2612 and -2603 that was important for IL-1 beta-, TNF-alpha-, and 2-O-tetradecanoylphorbol 13-acetate-induced enhancer activity. Mutation at the kappa B consensus site resulted in a complete loss of these stimulus-induced enhancer activities. The second element is a GC box located between bp -64 and -59 that was important for the maintenance of basal transcriptional activity. Overexpression of rSp1 resulted in increased hMCP-1 transcriptional activity, possibly suggesting the role of Sp1 in controlling basal hMCP-1 transcription via this GC box. These results together indicate that hMCP-1 expression is controlled by at least two distinct regulatory elements: a kappa B site and a GC box that seem to be associated with stimulus-specific and tissue-specific regulation, respectively.

Base Sequence

Ameliorating effects of sigma receptor ligands on the impairment of passive avoidance tasks in mice: involvement in the central acetylcholinergic system.

Three sigma receptor ligands were examined for their ameliorating effects on p-chloroamphetamine-induced amnesia in mice. p-Chloroamphetamine was administered intraperitoneally 30 min before the training session of the passive avoidance response. Each sigma receptor ligand was administered 60 min before or immediately after the training session, or 60 min before the retention test. (+)-N-Allylnormetazocine ((+)-SKF-10,047), a prototype benzomorphan sigma receptor ligand, significantly reduced the p-chloroamphetamine-induced amnesia in these three administration schedules, as do acetylcholinesterase inhibitors. On the contrary, the significant anti-amnesic effects elicited by non-benzomorphan sigma receptor ligands, 1,3-di-(2-tolyl)guanidine (DTG) or (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperizine ((+)-3-PPP), were observed depending upon the timing of their administration. In addition, the ameliorating effect of (+)-SKF-10,047 against the p-chloroamphetamine-induced amnesia was superior to that of (-)-SKF-10,047. The (+)-SKF-10,047-induced anti-amnesic effect was significantly antagonized by the concurrent administration of either scopolamine, a muscarinic receptor antagonist, or hemicholinium-3, an inhibitor of the Na(+)-dependent high-affinity choline uptake site. These findings indicated that sigma receptor ligands had anti-amnesic effects against drug-induced memory impairment. In addition, the anti-amnesic effect of (+)-SKF-10,047 was superior to those of other sigma receptor ligands, and was mediated by both the sigma receptor and the central acetylcholinergic system.

Acetylcholine

23Na- and 1H-NMR studies of the action of chlorpromazine and imipramine on nigericin-mediated Na+ transport across phosphatidylcholine vesicular membranes.

In order to elucidate the action of chlorpromazine (CPZ) and imipramine (IMP) on nigericin-mediated Na+ transport across phosphatidylcholine vesicular membranes, 23Na nuclear magnetic resonance was applied to the exchange system of Na+ ions present at the same concentration inside and outside unilamellar vesicles. CPZ and IMP added to the vesicles in micromolar concentrations produced an equal increase in the carrier-transport rate. The kinetic analysis, together with 1H-NMR observations of the reduction in membrane fluidity produced by the drugs and on the direct interaction between drugs and nigericin, allowed us to conclude that the drug-induced promotion of transport occurred not from the formation step of the Na(+)-nigericin complex nor from its diffusion step, but from its dissociation step. The formation of an adduct between drug and nigericin could be the cause of the drug effect and this proceeded much more efficiently at a membrane-water interface (stability constant Kb; 3 x 10(5) M-1) than in methanol (Kb; 5 x 10(2) M-1). The reason for the difference is also discussed.

Chlorpromazine

Influence of looking at hazard lights on car-driving performance.

The purpose of the present study was to determine what effect (if any) looking at an automobile's hazard lights has on the direction in which a car is driven. Eight Japanese drivers participated in this experiment. Analysis indicated that (a) at night drivers passed closer to a forward-facing stationary car than during the day and (b) when instructions were given to look at the hazard lights of a forward-facing stationary car, drivers passed closer than when no such instructions were given or when the hazard lights were off. The relationship between looking at the visible targets in a visually poor environment and the direction in which a car is driven was discussed.

Adult

[Clinical and serological studies in six cases of chlamydial pneumonia].

Clinical and serological studies of chlamydial pneumonia were done in six patients (three men and three women). The other three patients had no avian contact and showed almost the same clinical symptom. Acute infection with Chlamydia psittaci and Chlamydia pneumoniae were diagnosed in two patients and in one patient, respectively, by MFA. Because in some cases Chlamydia psittaci pneumonia and Chlamydia pneumoniae pneumonia are difficult to differentiate, it is necessary to use a test that allows different chlamydia species to be distinguished.

Adult

[Exercise-nitroglycerine technetium-99m-2-methoxy isobutyl isonitrile tomoscintigraphic imaging for identifying diseased coronary vessels: comparison with thallium-201 standard exercise-redistribution study].

A same-day double injection protocol employing 99mTc-methoxy isobutyl isonitrile (MIBI) and myocardial single-photon emission computed tomography (SPECT) for detecting coronary heart disease (CAD) was assessed in 21 patients. Our exercise-nitroglycerin (NTG) MIBI study was performed as follows: 150 MBq 99mTc-MIBI was injected at peak exercise, and after 5 minutes 0.3 mg of NTG was sublingually administered. Then, SPECT was performed 1 hour later. Immediately after the 1st imaging, patients were injected of 750 MBq 99mTc-MIBI and were reimaged 1 hour later. Within 1 month, all patients were underwent standard exercise redistribution SPECT thallium (Tl) study. Of the 126 myocardial segments evaluated, 81 were judged as normal by both techniques, while the presence of stress defects were demonstrated in 37 segments (Agreement: 94%). Vessel sensitivities were 75% by MIBI and 67% by Tl. Specificities were 90% by MIBI and 93% by Tl. For the pattern of reversibility in myocardial segments with stress defects, the agreement was 73%. In conclusion, our exercise-NTG MIBI may be safely performed, giving results equivalent to those of standard stress-redistribution thallium studies.

Angina Pectoris

[Myocardial SPECT with iodine-123-labeled beta-methyl-branched fatty acid in patients with angina pectoris].

To evaluate the usefulness of 123I-BMIPP as a tracer of fatty acid metabolism in patients with angina pectoris, we performed rest BMIPP myocardial SPECT and stress 201Tl SPECT in 20 patients with angina pectoris. BMIPP SPECT was evaluated in the defected regions with Tl redistribution. Abnormal findings in BMIPP were observed in 11 of 20 patients and in 14 of 29 myocardial segments with Tl redistribution. Such decreased uptake was observed more often in patients with multivessel disease (64% vs. 12%). In addition, the decreased BMIPP uptake was seen more often in the segments exhibiting hypokinesis than the segments showing with normal wall motion. Thus, BMIPP imaging may be available to detect myocardial ischemia, particularly in patients with severe coronary disease.

Aged