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Biomedical subjects

S Kurihara

Publications and source records attributed to S Kurihara.

At least 73 records · Page 4Linked to original sources

[Oscillatory changes in the intracellular Ca2+ concentration in cardiac muscles].

Contraction of cardiac muscle is regulated by intracellular Ca2+ concentration ([Ca2+]i) change. The Ca2+ increased by the action potential is removed by Ca2+ removal mechanisms (sarcoplasmic reticulum, Na-Ca exchanger and Ca pump of the surface membrane) and is also bound to troponin. However, under some specific conditions which induced an overload of Ca2+, oscillatory changes in [Ca2+]i, which are considered to be due to regenerative Ca2+ release from the sarcoplasmic reticulum, appear. In Ca2+ overload, a transient increase in [Ca2+]i is observed after the falling phase of the Ca2+ transient which is induced by electrical stimulation. In accordance with the transient increase in [Ca2+¿i, the membrane transiently depolarizes (delayed after-depolarization). This membrane depolarization is considered to be due to the inward currents through the Na-Ca exchanger and non-specific cation channels. If the depolarization is large enough to reach the threshold, the action potentials are triggered (triggered activity). Thus, an increase in [Ca2+]i is one of possible factors in triggering of arrhythmia.

Action Potentials↗

[Acute effects of human recombinant erythropoietin on cardiovascular dynamics and vasoactive substances].

Treatment with human recombinant erythropoietin (r-EPO) can dramatically improve renal anemia, whereas it has been reported that such improved anemia may involve or worsen hypertension. When we administered a single dose of r-EPO at 9,000 units to 16 patients with end-stage renal failure requiring examination with a right cardiac catheter immediately before the introduction of dialysis, we measured cardiovascular dynamics and various vasoactive substances. The mean blood concentration of EPO was 3,035 units/ml 15 minutes after administration. As compared with the value of 107.6 +/- 3.2 mmHg obtained before administration, the mean arterial blood pressure significantly increased following the administration of r-EPO to 111.5 +/- 3.8 mmHg after 5 minutes, 112.4 +/- 4.2 mmHg after 10 minutes, 113.7 +/- 4.3 mmHg after 20 minutes, and 113.6 +/- 4.3 mmHg after 30 minutes (p < 0.05). The mean pulmonary arterial blood pressure tended to increase to 17.9 +/- 1.8 mmHg after 10 minutes from the level of 16.3 +/- 1.8 mmHg before administration (p = 0.096). The pulmonary vascular resistance index (PVRI) was 165.0 +/- 18.0 mmHg before administration and significantly increased to 193.2 +/- 19.0 and 199.0 +/- 16.6 dyn.S.cm-5.m2 after 10 and 30 minutes, respectively (p < 0.01, p < 0.05). The systemic vascular resistance index (SVRI) also significantly increased to 2,587 +/- 195 dyn.S.cm-5.m2 after 30 minutes from the level of 2,454 +/- 207 dyn.S.cm-5.m2 before administration (p < 0.05). Changes in SVRI showed a bimodal pattern, as with changes in PVRI. Angiotensin-II concentration significantly decreased to 13.7 +/- 4.4 pg/ml after 15 minutes from the level of 15.7 +/- 3.2 pg/ml before administration (p < 0.05). There were no significant changes in endothelin, prostaglandin, or adrenaline concentration after the administration of r-EPO. From these results, it was revealed that pulmonary intra-arterial administration of r-EPO has the acute effect of increasing pulmonary vascular resistance, thereby pointing to a direct effect of r-EPO in pulmonary vasoconstriction. Although no changes in vasoactive substances were observed in the present investigation, further studies with more sensitive measuring methods may be necessary.

Angiotensin II↗

Tension-dependent changes of the intracellular Ca2+ transients in ferret ventricular muscles.

1. We measured the change in intracellular Ca2+ transients, using aequorin, in response to muscle length change during twitch contraction in ferret ventricular muscles. 2. Intracellular Ca2+ concentration ([Ca2+]i) was transiently increased when the muscle length was quickly shortened to 92% of maximum length (Lmax) at various times after stimulation (this increase in [Ca2+] is termed extra-Ca2+). The magnitude of extra-Ca2+, measured at different extracellular Ca2+ concentrations ([Ca2+]o), showed a dependence upon the magnitude of tension reduction and upon [Ca2+]i immediately before the length change. 3. In the presence of caffeine (5 mM), the difference between the Ca2+ transient at Lmax and at shorter lengths showed a time course similar to the difference between the developed tension at both lengths. A quick release in the caffeine-treated preparation produced the extra-Ca2+ with a slower time course compared with that observed in the absence of caffeine. Stretching the muscle from 96% Lmax to Lmax produced more active tension and decreased [Ca2+]i. 4. These results indicate that the affinity of troponin-C, a major Ca2+ binding protein, which controls contraction, is influenced by developed tension i.e. cross-bridge attachment and detachment.

Aequorin↗

Effects of a new inotropic drug (DN-9693) on Ca2+ transients and contraction in ferret ventricular muscles.

We investigated the mechanisms of the effects of a newly synthesized cyclic AMP phosphodiesterase inhibitor (PDEI: 1,5-dihydro-7-(1-piperidinyl)imidazo[2,1-beta]quinazolin- 2(3H)-one dihydrochloride hydrate, DN-9693) on intracellular Ca2+ transients and tension in ferret papillary muscles. We used the aequorin method to measure Ca2+ transients in intact preparations. DN-9693 (1-100 microM) increased the peaks of both Ca2+ transients and tension. The potentiation of Ca2+ transients by DN-9693 was significant at lower concentrations (1-10 microM) but not at higher concentrations (50 and 100 microM). The peak of tension was significantly increased when the concentration of DN-9693 was increased (1-100 microM). In addition, the time to peak light was shortened at lower concentrations (1 and 5 microM). Other parameters of Ca2+ transients were not significantly altered. The time course of tension was not affected by DN-9693. In Triton X-100-treated skinned preparations, DN-9693 decreased the Ca2+ concentration required for half-maximal activation of the pCa-tension relation. These results suggest that the positive inotropic effect of DN-9693 is attributable to the alteration in Ca2+ handling of sarcoplasmic reticulum (SR) and Ca2+ sensitization of the myofilaments.

Animals↗

Treatment of granuloma annulare with tranilast.

Three cases of granuloma annulare which did not exhibit a self-limited course were treated with tranilast at the dose of 300 mg/daily. The treatment resulted in the resolution of skin lesions within three months of administration. Although spontaneous resolution is often observed in granuloma annulare, tranilast may provide an alternative therapy for the treatment of cases resistant to spontaneous healing.

Adult↗

Late-onset focal dermal elastosis: clinical and histological features.

We describe two patients with lesions clinically resembling pseudoxanthoma elasticum and histologically exhibiting focal elastosis, with normal-appearing elastic fibres in the mid- and deep dermis. We consider that these skin lesions represent a previously undescribed entity, whose pathogenesis appears to be related to the ageing process.

Aged↗

Laparoscopic mesenterioadhesiotomy and Tenckhoff catheter placement in patients with predisposing abdominal surgery.

Peritoneoscopic surgery has been performed widely for a variety of abdominal surgical diseases. We describe here a safe and reliable technique of laparoscopic-assisted mesenterioadhesiotomy and peritoneal Tenckhoff catheter placement in patients who have previously undergone abdominal surgery. Five patients suffering from end-stage renal failure previously underwent single and/or polyabdominal surgery. The surgical procedures included hysterectomy, ovarian resection, appendectomy, and transabdominal right nephrectomy. Under general endotrachial anesthesia, a laparoscope was placed down through a direct cut made using a trocar. After CO2 gas insufflation, another one or two trocars were put in place for surgical procedures. To avoid intestinal injury, mesenterioadhesiotomy was performed carefully using a high-frequency hook electrode, forceps, and scissors forceps, and the Tenckhoff catheter was subsequently inserted with forceps directly into Douglas' fossa. Peritoneal equilibration tests performed 30-70 days after the initiation of continuous ambulatory peritoneal dialysis (CAPD) treatment revealed moderate to good peritoneal effectiveness. This procedure permits the surgeon to perform safe and exact catheter placement into Douglas' fossa even when there is a possibility that peritoneal and mesenterial adhesion are present. We believe that this technique of catheter placement may extend the indication for CAPD treatment in patients with predisposing lower abdominal surgery.

Aged↗

Effect of age on blood pressure response to cigarette smoking.

The plasma nicotine level and hemodynamic parameters were evaluated after cigarette smoking in young (group I, 17 men) and middle-aged habitual smokers (group II, 17 men). The amount of increase in plasma nicotine concentration after smoking was related to the percent change of mean blood pressure in both groups. The total peripheral vascular resistance index (TPRI) increased significantly at 10 min after smoking and reduced thereafter in group I, whereas the TPRI increased till 30 min after in group II. Thus, smoking raised the TPRI for a longer time in the middle-aged subjects due to a decrease in aortic elasticity with aging.

Adult↗

Synthesis and structure-activity relationships of gelatinase inhibitors derived from matlystatins.

To investigate a series of new inhibitors of gelatinases based on matlystatin B (1b), extensive structure-activity relationship studies were performed. The new derivatives were evaluated in vitro for the ability to inhibit gelatinases. The inhibitory activities against thermolysin were also assayed to test the compounds' selectivity. Among the compounds modified at the P'3 moiety, the N-methylamide derivative 5 g was virtually twice as effective on gelatinase B as the parent compound 1b (5g, IC50 = 0.27 microM vs. 1b, IC50 = 0.57 microM). Other derivatives, including 1) esters 7a and 7b having the ester portions P'2 and P'3, 2) the cyclic amino acids, L-proline or L-pipecolinic acid (13a and 13b) bearing P'2, and 3) compounds 29a and 29b representing an attachment of the pentyl side chain at C3' (P'1 side chain) instead of C2', all showed decreased potencies. The key discovery was the observation that the introduction of a nonyl group at the P'1 position yielded a compound (31f, IC50 = 0.0012 microM) with high inhibitory activity against gelatinases and high selectivity over thermolysin. This result suggested that the S'1 subsites of the gelatinases have a locally deep hydrophobic structure, since on the basis of the optimum inhibitory activity in the alkyl series, the nonyl group seems to fit best into this hydrophobic pocket. Thus 31f exhibited a 475-fold more potent inhibitory activity than 1b towards gelatinase B.

Acetylcysteine↗

Intravenous calcitriol can increase bone mass in hemodialysis patients with osteitis fibrosa.

Intravenous calcitriol administration (IVC) suppressed parathyroid hormone (PTH) secretion and improved osteitis fibrosa (OF) in long-term hemodialysis (HD) patients, although it did not increase the mineralized bone area or the mineral apposition rate. We observed the long-term effects of IVC on OF in 8 HD patients. Bone biopsy of 7 patients revealed increased bone turnover and decreased bone mass. One microgram of calcitriol was given intravenously three times weekly after each HD session for 12 months. The dose was adjusted to maintain the serum corrected calcium level at < 11.5 mg/dl. Dual-energy X-ray bone absorptiometry (DEXA), 3rd lumbar vertebra bone density by quantitative computed tomography (QCT), and biochemical data were taken before IVC, and after 6 and 12 months of IVC. Seven HD patients were given 0.5 microgram/day 1 alpha-cholecalcitriol as controls. The serum corrected calcium levels were 9.9 +/- 0.3 (mean +/- SE) and 11.1 +/- 0.2 mg/dl at 0 and 12 months, respectively (p = 0.06). The serum phosphate levels were 6.2 +/- 0.7 and 6.6 +/- 0.6 mg/day at 0 and 12 months, respectively (p = 0.56). The serum intact PTH levels were 928 +/- 281 and 617 +/- 192 (p = 0.016) at 0 and 12 months, respectively. The bone mass of the 3rd lumbar vertebra measured by QCT was 195 +/- 17 and 218 +/- 186 g/cm3 at 0 and 12 months, respectively (p = 0.156). The bone mass of the trunk measured by DEXA was 660 +/- 44 and 706 +/- 32 g and 0 and 12 months, respectively (p = 0.156). These parameters did not change in controls. Sequential bone biopsy in 3 cases also supported these changes. We conclude that IVC not only suppresses bone turnover, but that it also restores decreased bone mass in HD patients with OF.

Adult↗

Effects of thapsigargin on aequorin-injected and skinned preparations of ferret ventricular muscles.

OBJECTIVE: We investigated the effects of thapsigargin (TG) (0.1-1 microM) on the relation between intracellular Ca2+ concentration and tension in ferret papillary muscles using aequorin-injected and skinned preparations. METHODS: Aequorin was injected into the superficial cells of ferret papillary muscles; the Ca2+ signals of aequorin and tension in twitch and those with the application of 15 mM caffeine were simultaneously measured. The alteration of Ca2+ sensitivity of the contractile elements was examined by measuring the pCa-tension relation in Triton-X-treated skinned preparations. RESULTS: TG decreased the peak of the Ca2+ signal accompanied by a prolonged decay time. However, the tension was scarcely altered even at 1 microM TG. TG inhibited the caffeine-induced Ca2+ signal. Prolongation of decay of the Ca2+ signal by TG in twitch was further enhanced by isoprenaline (10 nM). The pCa-tension relation of the skinned preparation was slightly but significantly shifted to the right by TG. CONCLUSIONS: The apparent dissociation of the effects of TG on the Ca2+ signal and tension in intact preparations is not a result of alteration of the Ca2+ sensitivity of the myofilaments. The effects of TG in multicellular preparations are probably limited to the outer layer of the preparation. The slower time course of the Ca2+ signal induced by TG is due to the inhibition of Ca2+ uptake by sarcoplasmic reticulum, which is more significantly observed when the intracellular Ca2+ transient is increased by isoprenaline.

Aequorin↗

Effects of adenosine on Ca2+ transients and tension in aequorin-injected ferret papillary muscles.

The effects of adenosine on Ca2+ transients and tension in ferret papillary muscles were investigated using the aequorin method. Adenosine (0.01-1 mM) reduced the peak of Ca2+ transients and caused a slight concentration-dependent decrease in tension. Adenosine prolonged the decay time of Ca2+ transients but did not alter the time course of tension. In isoproterenol (0.1 microM)-treated preparations, adenosine decreased the peak of Ca2+ transients but did not alter the peak of tension. Adenosine prolonged the isoproterenol-shortened decay time of Ca2+ transients. The effects of adenosine on Ca2+ transients were antagonized by the selective A1 receptor antagonist 8-cyclopentyl-1,3,-dipropylxanthine. In the presence of isoproterenol, adenosine (0.1 mM) shifted the intracellular [Ca2+]/tension relation to the left. These results can be explained by the hypothesis that adenosine inhibits the activity of adenylate cyclase via stimulation of the A1 receptor, other mechanisms however cannot be overlooked. The prolongation of the decay time of Ca2+ transients and the increase in the Ca2+ sensitivity of the contractile elements are the underlying mechanisms of adenosine which maintain developed tension in twitch response, although adenosine decreases the peak of Ca2+ transients.

Adenosine↗

Cytoplasmic free Mg2+ in rat ventricular myocytes studied with the fluorescent indicator furaptra.

To estimate cytoplasmic Mg2+ concentration ([Mg2+]i), ventricular myocytes enzymatically isolated from rat hearts were loaded with the fluorescent indicator, furaptra, and the fluorescence signals of single quiescent myocytes were measured at 32 degrees C. The excitation spectrum of furaptra measured in the myocytes was well-fitted by the spectra obtained in vitro; thus it was possible to calibrate the fluorescence signal in terms of [Mg2+]i. The analysis implied that about 20% of the indicator molecules were Mg(2+)-bound. Considering that the indicator likely reacts with Mg2+ with a larger KD value in cytoplasm than in vitro (by a factor of 1.2-2 as suggested for mouse and frog skeletal muscles), the [Mg2+]i for the resting single myocytes was estimated to be within 0.8-1.3 mM. Superfusion with a high extracellular Mg2+ concentration (20 mM) caused a slow and slight elevation in [Mg2+]i over a period of a few hours. Other experimental interventions, including application of a low extracellular Na+ concentration and isoproterenol, and CO2 acidosis, did not cause a detectable change in [Mg2+]i, whereas the application of an uncoupler, a blocker of oxidative phosphorylation in mitochondria, caused a rapid and large increase in [Mg2+]i. It is suggested that the [Mg2+]i is tightly maintained at around 1 mM, unless intracellular ATP is depleted.

Animals↗

Regulation of cardiac muscle contraction by intracellular Ca2+.

In this short review, some of the factors which influence the intracellular Ca2+ transients and contraction in mammalian cardiac muscles which we have been examining are discussed. The processes concerning the change in [Ca2+]i and contraction are divided into three steps following the scheme proposed by Blinks [6]: Upstream, Central, and Downstream. However, these processes are interrelated. Although the Ca2+ transient is an important step for triggering contraction, it is influenced by the following Central and Downstream mechanisms. The evaluation of Ca2+ sensitivity of the contractile elements (Central mechanism) in intact preparations is discussed; measurement of the relation between [Ca2+]i and tension in tetanic contraction is one of the possible methods. A change in the Ca2+ binding to troponin-C is an important factor to determine the Ca2+ sensitivity but other mechanisms are also considered to be involved. In cardiac muscles, the feedback mechanism from the Downstream, in particular the cross-bridge attachment and detachment, to the Central processes is a physiologically important mechanism in the determination of contractile properties. This feedback mechanism alternatively influences the intracellular Ca2+ transient by changing the affinity of troponin-C for Ca2+. Thus, the interpretation of the measured Ca2+ transients is not simple and the numerous factors involved must be considered. Further study is necessary to elucidate the molecular mechanisms which are responsible for the feedback from the Downstream mechanism to the Central and Upstream mechanisms.

Action Potentials↗

Matlystatins, new inhibitors of type IV collagenases from Actinomadura atramentaria. IV. Synthesis and structure-activity relationships of matlystatin B and its stereoisomers.

The first total synthesis of matlystatin B (1a), a low molecular weight inhibitor of type IV collagenases, was accomplished, and its absolute configuration was unambiguously determined. Furthermore, ten stereoisomers of 1a were synthesized, and the inhibition of the 92 kDa type IV collagenase and of other metalloproteinases by each stereoisomer was investigated.

Anti-Bacterial Agents↗

Effects of a newly synthesized dihydropyridine, NZ-105, on intracellular Ca transients and tension in ferret ventricular muscles.

We investigated the effects of a newly synthesized dihydropyridine (DHP) derivative (NZ-105) on intracellular Ca transients and contraction in ferret ventricular muscles, using the aequorin method. Low concentrations of NZ-105 (10(-9)-10(-7) M) showed no significant effects on the light signal of aequorin and tension in twitch. High concentrations of NZ-105 (10(-6)-10(-5) M) inhibited the peaks of the light signal and tension without altering their time courses. The relation between the peaks of the light signal and tension in twitch, measured in solutions with varying Ca2+ concentrations, was shifted to the left by NZ-105. The relation between [Ca2+]i and tension measured in tetanic contraction was also shifted to the left by NZ-105. These results suggest that the inhibitory effect of NZ-105 on contraction in mammalian cardiac muscle is curtailed by an increase in Ca sensitivity of the contractile elements.

Animals↗

[Quadricuspid aortic valve: three case reports and review of the literature].

Three patients with grade 3 aortic regurgitation caused by rare congenital quadricuspid valve underwent aortic valve replacement. Patients were two females (51 and 45 years old) and a 51 year-old male. The first case showed 2 equal larger and 2 equal smaller valves. In the latter two cases, 4 equal sized cusps were noted. Fibrous trabeculations bridging the aortic wall and the commissures, giving an appearance of a hammock, were noted in the third case. Small fenestations were also noted in two cusps in this case. These findings may suggest dysplastic feature of the quadricuspid aortic valve. Hypertension seemed to have played an important role in the occurrence of regurgitation in their 4th or 5th decade of life. Their postoperative courses were uneventful.

Aortic Valve↗