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Biomedical subjects

T Kitazawa

Publications and source records attributed to T Kitazawa.

At least 127 records · Page 7Linked to original sources
PubMed1985

Calcium and sodium distribution and movements in smooth muscle.

Electron probe microanalysis (EPMA) has been used to study the subcellular distribution of Ca, Na, K, Cl, and Mg in smooth muscle. The EPMA results indicate that the sarcoplasmic reticulum (SR) is the major intracellular source and sink of activator Ca: norepinephrine decreases the Ca content of the junctional SR in portal vein smooth muscle. Mitochondria do not play a significant role in regulating cytoplasmic free Ca2+, but mitochondrial Ca content can be altered to a degree compatible with suggestions that fluctuations in matrix Ca contribute to the control of mitochondrial metabolism. The rise in total cytoplasmic Ca during a maintained, maximal contraction is very much greater than the rise in free Ca2+, and is probably in excess of the known binding sites available on calmodulin and myosin. Cell Ca is not increased in normal cells that are Na-loaded. The non-Donnan distribution of Cl is not due to compartmentalization, but reflects high cytoplasmic Cl. Na-loading of smooth muscle in K-free solutions is temperature dependent, and may exhibit cellular heterogeneity undetected by conventional techniques. The total cell Mg is equivalent to approximately 12 mM, and less than 50% of it can be accounted for by binding to ATP and to actin. Mitochondrial monovalent cations in smooth muscle are relatively rapidly exchangeable.

Animals↗
PubMed1985

Effects of catecholamines on spinal motoneurones and spinal reflex discharges in the isolated spinal cord of the newborn rat.

The effects of catecholamines on spinal motoneurones and spinal reflex discharges were investigated in the isolated spinal cord of newborn rat. Noradrenaline (NA), adrenaline (Adr), dopamine (DA) and isoproterenol (Iso) caused depolarization of the motoneurones in a dose-dependent manner. The depolarizing action persisted in Ca2+-deficient Krebs solution. The order of potency was Adr greater than NA greater than DA much greater than Iso. The effects of NA and Adr on the monosynaptic reflex discharge varied; depression, potentiation or depression followed by potentiation. The polysynaptic reflex discharge was consistently depressed. DA depressed both the mono- and polysynaptic reflex discharges in all the preparations. Tyramine and adamantanamine induced a response similar to that to DA rather than to NA. Depolarization of the motoneurones and the effects on the spinal reflex discharges induced by all the catecholamines were decreased by phentolamine or phenoxybenzamine but not by propranolol or haloperidol. It is suggested that the endogenous catecholamines, mainly DA, depolarize the motoneurones and depress the mono- and polysynaptic reflex discharges through an alpha-adrenoceptor in the spinal cord of the newborn rat.

Animals↗
PubMed1985

Effects of vitamin C on tumor induction by diethylnitrosamine in the respiratory tract of hamsters exposed to cigarette smoke.

A large dietary supplement (1%) of vitamin C was given to male Syrian hamsters exposed to cigarette smoke and receiving 12 weekly subcutaneous injections of diethylnitrosamine (DEN) to determine whether or not high doses of vitamin C can prevent the development of tumors by DEN in the respiratory tract. Treatment with DEN developed various types of tumors in the respiratory tract of hamsters and cigarette smoke exposure potentiated the tumor development in the nasal cavity, larynx and trachea. In comparison with the smoke-exposed hamsters treated with DEN, the vitamin C-supplemented hamsters showed significantly lower incidence of nasal cavity tumors and exhibited significantly earlier appearance of tracheal tumors. In addition, the laryngeal tumors also tended to develop earlier in the vitamin C-supplemented hamsters. The results indicate that high doses of vitamin C may inhibit tumor induction by DEN and exposure to cigarette smoke in the nasal cavity, but the development of laryngeal and tracheal tumors appeared to be accelerated by vitamin C supplement.

Animals↗
PubMed1985

Isoproterenol-induced desensitization to the positive inotropic effect of isoproterenol in ventricular strips isolated from carp heart (Cyprinus carpio).

Whether the positive inotropic effect of isoproterenol in ventricular strips of carp heart is altered by previous exposure to the agonist was studied. Isoproterenol produced a concentration-dependent positive inotropic effect in these preparations which was competitively antagonized by propranolol. Isoproterenol dose-response curves were shifted significantly downward and to the right after previous treatment with and removal of isoproterenol. The desensitization could be demonstrated after 5 min incubation and near maximal desensitization was observed after 30 min exposure to 1000 nM isoproterenol. The responsiveness was only partially recovered after 180 min incubation in drug-free medium. Isoproterenol produces a rapidly developing desensitization to inotropic effects of the beta-adrenergic agonist. This phenomenon may be mediated by alterations in beta-adrenergic receptors, adenylate cyclase and/or the beta receptor-adenylate cyclase coupling mechanism.

Animals↗
PubMed1985

[Focal nodular hyperplasia-like lesion of the liver associated with thorotrast liver disease--report of a case].

A 66-year-old man with Thorotrast liver disease underwent a partial hepatectomy for a small tumor of the liver, which was demonstrated by digital subtraction angiography. The resected specimen was grossly a sharply circumscribed, gray-yellow nodule, 7.5 mm in diameter. Microscopically, the nodule was an ill-defined hepatic cell mass, which was divided by fine fibrous septa irregularly and incompletely. Central veins and Glisson's capsules were not observed inside the nodule. Bile duct proliferation and infiltration of lymphocytes were found in the fibrous septa. There were Thorotrast depositions within the fibrous tissues around the nodule. Because a typical fibrous boundary and central scar were not found, we have termed this condition a focal nodular hyperplasia-like lesion. A relationship between focal nodular, hyperplasia as a precancerous state and Thorotrast liver disease was suggested.

Aged↗
PubMed1984

The effects of valinomycin on ion movements across the sarcoplasmic reticulum in frog muscle.

The effects of valinomycin on the elemental composition and the fractional volume of the terminal cisternae (t.c.) of the sarcoplasmic reticulum (s.r.) were determined in rapidly frozen frog semitendinosus muscles. The concentrations of valinomycin used for the electron probe studies (5 microM) had no effect on tetanus tension or t.c. volume (2.% of fibre volume). Mitochondria were markedly swollen and their K content was significantly increased in both the resting and the tetanized valinomycin-treated muscles. Valinomycin had no effect on the concentration of Na, Mg, P, Cl, K and Ca in the t.c. of resting muscles. In untreated, tetanized muscles, Ca2+ release was accompanied by the uptake of K and Mg into the t.c. in an amount that was significantly less than the positive charge removed through Ca2+ release, confirming previous observations showing an apparent charge deficit (Somlyo, Gonzalez-Serratos, Shuman, McClellan & Somlyo, 1981). Valinomycin abolished the apparent charge deficit: in tetanized, valinomycin-treated muscles, the uptake of K into the t.c. was significantly (P less than 0.001) greater than in the untreated muscles and Mg uptake also remained highly significant. It is suggested that Ca2+ release from activated muscle is an electrogenic process and that the K+ conductance of the s.r. in untreated frog muscles is insufficient to allow charge neutralization of the Ca2+ current during release. The increase in K+ permeability caused by valinomycin permits the greater counter movement of K+ under the combined influence of the electrical potential generated by outward Ca2+ movement and the acidic cation binding proteins in the lumen of the s.r. The results are consistent with the proposal (Somlyo et al. 1981) that in normal frog muscles not treated with valinomycin, the apparent positive charge deficit observed after a tetanus reflects the movement of protons and, possibly, organic cations.

Animals↗
PubMed1984

Effect of extracellular calcium on contractile activation in guinea-pig ventricular muscle.

The problem of whether or not the alterations in twitch tension of mammalian cardiac muscle induced by changes in extracellular Ca concentration ([Ca]o) are due to the Na-Ca exchange process across the surface membrane and/or the changes in the amount of Ca in the sarcoplasmic reticulum has been re-examined by using thin bundles (70-120 micron diameter) dissected from guinea-pig papillary muscle. The observed time course of the change in the twitch tension due to a step change in [Ca]o was compared with that computed on a basis of the diffusion process of Ca ions in a circular cylinder and of the steady-state relation between [Ca]o and twitch tension. After a sudden decrease in [Ca]o from 2 mM to various lower concentrations, the isometric twitch tension of the thin bundles first fell rapidly and monotonically and then showed a much smaller and slower secondary fall. The correspondence of the observed time course of the rapid phase with the predicted time course and the observed half-time of the rapid phase ranging from 1.0 to 2.5 s indicate that the rapidity of the twitch response may be dominated by simple diffusion of Ca ions through the extracellular space. If so, the effective diffusion constant of Ca ions inside the bundles was 1.4 +/- 0.2 X 10(-6) cm2/s (mean +/- S.E., n = 9). The magnitude and direction of the step change in [Ca]o or the change at different stimulus frequencies gave rise to dissimilar time courses of the contractile change; the difference in the rapid time courses due to these factors could be explained by the simple diffusion models, but not in the much slower phase. The half-time for the Ca effect was the same as that for the rapid effect of Na ions in the external solutions. The time course of twitch decline due to [Ca]o decrease in the Na-free (Li) solution was identical to that predicted from the time course measured in the Na-rich solution and the steady-state relation between [Ca]o and tension in the Na-free solution. The half-time of Ca leak from the sarcoplasmic reticulum in the skinned cardiac muscle was 40-60 s in the presence of 10 mM-EGTA, much shorter than that of the Ca leak in the skinned amphibian skeletal muscle, but much longer than that of twitch responses due to step changes in [Ca]o in the intact cardiac muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Release and recycling of calcium by the sarcoplasmic reticulum in guinea-pig portal vein smooth muscle.

The amplitude of interrupted contractions evoked by noradrenaline or caffeine in Ca2+-free, high-K+ solutions containing EGTA or La3+ was determined in small (40-60 micron thick) bundles of guinea-pig portal anterior mesenteric vein. Interrupted contractions were produced by removing the stimulating agent as soon as the amplitude of the tension record reached its peak. The distribution of intracellular Ca2+ was determined, with electron probe X-ray microanalysis, in cryosections of preparations frozen in the relaxed state and at the peak of noradrenaline-induced contractions. Interrupted contractions of maximal or near-maximal amplitudes could be evoked every 2 min for up to 15 min in the virtual absence of extracellular Ca2+. If noradrenaline was allowed to remain in the solution throughout the period of spontaneous relaxation, a subsequent contraction could no longer be evoked in the absence of extracellular Ca2+. Interrupted contractions, similar to those evoked by noradrenaline, could also be stimulated by caffeine. The amplitude of reproducible interrupted contractions in Ca2+-free, high-K+ solution was graded with noradrenaline concentration. The ability of these smooth muscles to contract repeatedly and maximally in Ca2+-free solutions indicates the recycling of Ca2+ released from an intracellular store. The occurrence of these contractions in high-K+ (depolarizing) solutions supports the conclusion (Devine, Somlyo & Somlyo, 1972) that the release of intracellular Ca2+ is one of the mechanisms of pharmacomechanical coupling. The number of subplasmalemmal regions in which high Ca concentrations (greater than 10 mmol/kg dry wt.) were detected, with approximately 75 nm diameter electron probes, was reduced in muscles frozen at the peak of contraction, from 4.7/cell periphery in the relaxed to 1.4/cell periphery in the contracted preparations. In freeze-substituted smooth muscles, in which the membranes of the junctional sarcoplasmic reticulum could be visualized, the regions containing high Ca were identified as part of the sarcoplasmic reticulum (s.r.), indicating that the s.r. is the store from which noradrenaline and caffeine release Ca2+.

Animals↗
PubMed1984

[Successful resection of giant hepatocellular carcinoma with hypoglycemic attack].

We experienced a 68 years-old male who had frequent hypoglycemic attacks. The diagnosis of a giant hepatoma associated with hypoglycemia was established by oral glucose tolerance test (O-GTT), angiography and computed tomography. The cavography demonstrated the invasion or depression of the tumor. It was ascertained by an operative exploration that the tumor occupied most of the right trisegments of the liver and infiltrated into a part of the left lateral segment. The right hepatic trisegmentectomy along 1.5cm left side line apart from the falciform ligament was performed. Resected tumor showed 11 X 13 X 10cm in size and 1200g in weight. Microscopic findings demonstrated hepatocellular carcinoma as Edmondson's Type II. After the operation, this patient became free from the hypoglycemic attack. A fasting blood sugar became within normal limits and O-GTT demonstrated a normal blood sugar level and insulin response. No concentration of immuno-reactive insulin was found in the resected tumor, however, the blood sugar in rats which received the intravenous injection of the tumor extracts was remarkably decreased in 20 minutes. From these observation, hypoglycemia in this patient seemed to depend mainly on the factor of insulin-like activity of the tumor. In the literature, the hepatocellular carcinoma associated with paraneoplastic phenomenon, e.g. hypoglycemia, has rarely been resected because of accompanied liver cirrhosis or giant size of the tumor. This is the second patient in our country in whom the tumor was fortunately resected and the paraneoplastic syndrome disappeared postoperatively.

Aged↗
PubMed1983

Ultrastructure, function and composition of smooth muscle.

Filamentous myosin is present in both relaxed (myosin light chains unphosphorylated) and contracted (light chains phosphorylated) vascular smooth muscle. The organization of myosin and actin filaments and the insertion of the latter on cytoplasmic and plasma membrane bound dense bodies is consistent with a mini sarcomere-like organization and a sliding filament mechanism of contraction in smooth muscle. Mitochondria are high capacity, low affinity Ca stores in smooth muscle. They do not play a role in the regulation of cytoplasmic Ca2+ at physiological levels. The localization and Ca content of the junctional sarcoplasmatic reticulum (SR) is consistent with this organelle being the major intracellular source of activator Ca released by excitatory transmitters. Repeated contractions in the absence of extracellular Ca2+ (thought to represent recycling of intracellular activator Ca2+) can be demonstrated if the excitatory agent is not allowed to remain in contact with the smooth muscle throughout relaxation.; the demonstration of "recycling" is facilitated if the efflux of cellular Ca2+ is blocked. The rise in total cytoplasmic calcium measured with electron probe analysis during a maintained (30 min) contracture in rabbit portal-anterior mesenteric vein smooth muscle (approximately 0.9 mol/kg dry cytoplasm) is greater than the amount of Ca that could be bound to calmodulin.

Actins↗
PubMed1982

Selective inhibition by methysergide of the monosynaptic reflex discharge in the isolated spinal cord of the newborn rat.

In the isolated spinal cord of the newborn rat, methysergide and LSD-25 depressed the monosynaptic reflex discharge selectively. Cyproheptadine and dimethothiazine did not inhibit the monosynaptic reflex. The selective inhibitory effect of methysergide on the monosynaptic reflex was not due to a presumptive low safety factor of this reflex. The inhibition was restored under a condition such as the compound action potential in the dorsal root was enhanced by 4-aminopyridine. Methysergide did not decrease the sensitivity of the motoneuron to substance P and L-glutamic acid. It is suggested that methysergide acts at the presynaptic terminal of Ia afferent fibers and depresses evoked transmitter release.

Action Potentials↗
PubMed1982

Calcium and magnesium binding to thin and thick filaments in skinned muscle fibres: electron probe analysis.

Electron probe analysis of ultrathin cryosections with high spatial resolution was used to determine in situ the concentrations of Ca2+ and Mg2+ bound in the absence of ATP to myofilaments in the I and A-bands of skinned frog skeletal muscle. At 2.2 x 10(-11) M Ca2+ and 2.7 x 10(-9) M Mg2+, the inexchangeably bound Mg2+ in the I-band was equivalent to the amount of divalent cations known to be inexchangeably bound to F-actin, while the Ca2+ bound to the I-band was not significantly above zero. The bound Mg2+ in the I-band was not exchangeable with Ca2+ even when the skinned fibres were exposed to 10 mM Ca2+ solution. These results clearly indicate that Mg2+, rather than Ca2+, is the divalent cation bound to F-actin in the thin filaments in situ. In the presence of 1 mM Mg2+, the exchangeable Ca2+ bound to the I-band was increased as a function of the free Ca2+, while that in the A-band was not significantly changed with [Ca2+] up to 2 x 10(-5) M, and increased to approximately 0.8 mol Ca2+ per mol myosin at 10(-4) M Ca2+. At a saturating free Ca2+ in Tris-Cl solution, the bound Ca2+ content (2-3 mol Ca2+ per mol troponin) of the nonoverlapping I-band was unexpectedly low; the replacement of Tris with Na+ enhanced Ca2+ binding to the level equivalent to 3-4 mol Ca2+ per mol troponin. The depressant effect of Tris on Ca2+ binding was greater in the absence of Mg2+. High concentrations of Tris also reduced the maximum tension induced by 10(-4) M Ca2+ buffered with 10 mM EGTA. At 1.3 x 10(-7) M Ca2+, thought to be close to the cytoplasmic free Ca2+ in resting muscle, the I-band bound a significant amount of Ca2+: equivalent to about 1 mol Ca2+ per mol troponin. In rabbit myofibrils there was a significant amount (approximately 1.5 mol/mol myosin) of Ca2+ bound by the A-band at a free Ca2+ of 10(-4) M.

Animals↗