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Biomedical subjects

S Kurihara

Publications and source records attributed to S Kurihara.

At least 55 records · Page 3Linked to original sources

A case of anaphylactoid purpura with multiple blister formation: possible pathophysiological role of gelatinase (MMP-9).

A 10-year-old Japanese male with multiple blister formation and palpable purpura in the course of anaphylactoid purpura is described. Histologically, the lesions showed leukocytoclastic vasculitis in the upper dermis with subepidermal clefts. Blister fluid showed matrix metalloproteinase (MMP) 2 and MMP-9 gelantinolytic activities using zymography. These enzymatic reactions, especially that involving MMP-9 derived from polymorphonuclear leukocytes, might play an important role in the pathophysiology of this condition.

Blister↗

[Hypoparathyroidism in maintenance dialysis patients (Pts)--a clinical study].

With the recent development of measurement in intact PTH, increases of hypoparathyroidism and adynamic bone disease have been reported in patients on chronic maintenance dialysis. To clarify the frequency of hypoparathyroidism in maintenance dialysis patients, the present study investigates the relationship between the occurrence of hypoparathyroidism and clinical background, several bone metabolic markers and the bone mineral density. We divided 298 maintenance dialysis patients (HD 270, CAPD 28) without parathyroidectomy into 4 groups based on intact PTH. Group A was absolutely hypo (intact PTH < 60 pg/ml), group B was relatively hypo (60 < or = intact PTH < 160), group C was normal (160 < or = intact PTH < 300), and group D was hyperparathyroidic (300 < or = intact PTH). Groups A and B together accounted for 71.8% of the patients. The mean age in groups A and B was higher than in group D (p < 0.05), and the dialysis duration was shorter (p < 0.01). The concentration of 1, 25 (OH)2D was significantly higher in groups A and B than in group D (p < 0.01), and remarkably higher in group A than in group C. The level of Ca, i-P did not differ among the groups. In our investigation of bone metabolic markers, group D was found to have significantly higher Al-p, intact-BGP, and P 1 PC compared with the other 3 groups (p < 0.01), and the concentration of intact BGP was lower in group A than in groups B and C (p < 0.01). The bone mineral density measured by DEXA did not differ among the groups. The results suggest that, due to multiple factors, the actual occurrence of hypoparathyroidism in maintenance dialysis patients is higher than the predicted occurrence.

Alkaline Phosphatase↗

Length dependence of Ca(2+)-tension relationship in aequorin-injected ferret papillary muscles.

The possible contractile proteins, which are related to the length-dependent change in the relationship between intracellular Ca2+ concentration ([Ca2+]i) and tension, were investigated using aequorin-injected ferret papillary muscles. Tetanic contraction was produced by applying repetitive stimulation to the ryanodine-treated preparations, and the relationships between [Ca2+]i and tension were measured. When the muscle length was decreased from maximal length (Lmax), at which maximal tension is produced, to 95 and 90% Lmax, the maximal tension was significantly decreased. [Ca2+]i required for producing 50% of the maximal tension was significantly increased from 1.05 +/- 0.04 microM (Lmax) to 1.17 +/- 0.04 microM (95% Lmax) and to 1.22 +/- 0.04 microM (90% Lmax). Isoproterenol (Iso) accentuated the length-dependent change in the [Ca2+]i-tension relationship. The decrease in the Ca2+ sensitivity induced by Iso was larger at shorter muscle lengths compared with that at Lmax. It is, therefore, suggested that adenosine 3',5'-cyclic monophosphate-dependent phosphorylation of troponin I and/or C protein alters the length dependence of the [Ca2+]i-tension relationship and that troponin I and/or C protein might be involved in the length-tension-dependent change in the affinity of the contractile elements for Ca2+.

Aequorin↗

Contribution of mitochondria to the removal of intracellular Ca2+ induced by caffeine and rapid cooling at low temperatures in ferret ventricular muscles.

We investigated the role of mitochondria in the removal of intracellular Ca2+ which was increased by caffeine (15 mM, Caf), rapid lowering of the solution temperature from 30 to 4 degrees C (rapid cooling, RC), and electrical stimulation (0.07 Hz, ES). For this purpose, the intracellular Ca2+ concentration ([Ca2+]i) was measured using aequorin from the superficial cells of ferret papillary muscles. The three maneuvers induced transient changes in [Ca2+]i with different time courses. The decay time of the aequorin light signal (DT) in the Caf-induced Ca2+ release was significantly prolonged by the inhibitors for Na+-Ca2+ exchanger (Ni2+, Na+-free solution) at higher temperatures (> or = 12 degrees C). In the caffeine application at lower temperatures (< or = 12 degrees C), the inhibitors for mitochondria (ruthenium red, NaN3) significantly prolonged the DT but other inhibitors were ineffective. In the RC-induced Ca2+ release, DT was significantly prolonged by the mitochondrial inhibitors but other inhibitors were not effective. In the ES-induced Ca2+ release, each inhibitor for the sarcoplasmic reticulum (SR) (thapsigargin and 2,5-di(tert-butyl)-1,4-benzohydroquinone) prolonged the DT at all temperatures. The inhibitors for Na+-Ca2+ exchanger slightly prolonged the DT only at higher temperatures, and the mitochondrial inhibitors did not alter the DT at any temperature. These results suggest that mitochondria substantially transport Ca2+ when the Ca2+ uptake by the SR and Na+-Ca2+ exchanger are inhibited and [Ca2+]i is increased with a slower time course.

Aequorin↗

Effects of ruthenium red on the cellular functions and ultrastructure in intact ferret ventricular muscles.

The effects of ruthenium red (RR) on the cellular functions (intracellular Ca2+ handling and contraction) and permeation of the dye through the cell membrane were investigated in intact ferret papillary muscles. The intracellular Ca2+ concentration ([Ca2+]i), measured using aequorin, was simultaneously recorded with tension. The permeation of the dye through the cell membrane was studied with electronmicroscopy. The preparation was continuously stimulated at 0.2 Hz and treated with 50 microM RR at 30 degrees C. [Ca2+]i was increased by electrical stimulation (0.07 and 2 Hz) and rapid cooling (from 30 to 4 degrees C) (RC). In electrical stimulation, RR time-dependently decreased the peak light of aequorin without a significant change in the time course at 30 degrees C. However, in RC, treatment with RR for about 100 min significantly prolonged the decay time of the light signal and increased the peak light. The peak tension in RC was decreased after treatment with RR for a longer time. The pCa-tension relation of skinned preparations was significantly shifted to the right by 50 microM RR. In the RR (50 microM)-treated specimens, mitochondrial outer membranes were darkly stained if OsO4 was used for fixation. Even though the specimen treated with 500 microM RR was fixed without OsO4 and electron staining, the matrices of mitochondria became electron dense. We concluded that RR could penetrate into intact mammalian cardiac myocytes, and that RR inhibits the release of Ca2+ from the sarcoplasmic reticulum in electrical stimulation, inhibits mitochondrial Ca2+ uptake, and decreases the Ca2+ sensitivity of the myofilaments.

Aequorin↗

Evidence for association between the class I subset of the insulin gene minisatellite (IDDM2 locus) and IDDM in the Japanese population.

Although the shortest (class I) minisatellite (i.e., variable number of tandem repeats [VNTR]) alleles in the 5' region of the insulin gene are positively associated with IDDM in Caucasians, the majority of Japanese are homozygous for class I alleles. Here, we determined the exact length, in number of repeat units (RUs), of class I alleles in Japanese subjects. The distribution of class I alleles in Japanese was trimodal, with peaks located at 32/33, 41, and 44 RUs. The shortest component (i.e., 1S [25-38 RUs]) alleles were significantly increased in the IDDM group compared with the control group (54 vs. 46%; P = 0.040). The 1S/1S genotype was significantly increased in the IDDM patients (34 vs. 20%; P = 0.005; relative risk 2.1). Furthermore, the transmission disequilibrium test of Japanese families with 1S/1M or 1S/1L heterozygous parents confirmed the association of 1S alleles; 17 alleles of 1S and 6 alleles of 1M (39-41 RUs) or 1L (42-44 RUs) were transmitted to affected offspring (P = 0.022). In addition, we found tight linkage of 1S with allele 9 of the tyrosine hydroxylase gene microsatellite and allele (-) of the IGF-II gene Apa I polymorphism, but neither 9 nor (-) alleles were significantly associated with IDDM. The present study suggests that a class I subset may have a role in IDDM susceptibility in Japan. It was revealed that the difference between 1S alleles and 1M or 1L alleles is almost consistently characterized by a sequence variation generated by deletion of two copies of an ACAGGGGTCC CGGGG repeat element, implying that sequence variation of class I alleles may influence disease susceptibility.

Adolescent↗

Is the bone mass of hemodialysis patients genetically determined?

Polymorphism of the vitamin D receptor gene (VDR) has been linked to bone mineral density in twins, postmenopausal osteoporosis, and premenopausal woman. We examined the possibility that the bone mass in hemodialysis (HD) patients might be determined by VDR. The study consisted of 229 HD patients with a mean age of 53.3 years (range 21 to 83), who were dialyzed three times a week for an average of 8.65 (range 0.2 to 24) years. We determined their VDR using DNA of peripheral white blood cells by restriction enzyme BsmI and the polymerase chain reaction-restriction fragment length polymorphism method. Bone mineral content (BMC) was estimated at 1/3 of the radius using dual energy X-ray bone absorptiometry, and expressed in z-scores standardized by gender and age. Distributions of VDR in this hemodialysis population were BB (9.9%), Bb (13.1%), and bb (77.0%), showing no significant different from those in 105 healthy volunteers (BB, 7.6%; Bb, 13.3%; and bb, 79.0%). Multiple regression analysis revealed that gender, age, duration on HD, and serum osteocalcin are major determinants of BMC (r = 0.762, P < 0.001), while VDR and serum parathyroid hormone are not. In a subgroup with younger (< 65 years) patients dialyzed for less than 8.65 years, the z-score of BMC of patients with BB allele was less than those with Bb and bb allele (N = 77, P = 0.020). We conclude that vitamin D receptor polymorphism is not one of the main determinants of BMC of HD patients, though it might partially effect bone mass in a subgroup of younger HD patients with shorter HD histories. Further studies with longitudinal observation will be needed to confirm these possibilities.

Adult↗

Magnesium and hydrogen ions inhibit sarcoplasmic reticulum function in cardiac muscle.

We investigated the direct effects of magnesium and hydrogen ions (Mg2+ and H+) on cardiac sarcoplasmic reticulum (SR) functions using saponin-treated ferret ventricular muscles. Ca2+ uptake function and the Ca(2+)-induced Ca2+ release (CICR) mechanism were examined. For the analysis of Ca2+ uptake, the SR was loaded with Ca2+ under various conditions and the Ca2+ content of SR was estimated by releasing Ca2+ with 50 mM caffeine. To determine CICR, following Ca2+ loading of the SR, solutions with various free Ca2+ concentrations ([Ca2+]) were applied to the preparation to release Ca2+, and the Ca2+ remaining in the SR was estimated. The amount of the released Ca2+ was measured with the fluorescent indicator fluo-3. Mg2+ (10mM) and H+ (pH 6.6) inhibited both Ca2+ uptake and CICR. The rate of Ca2+ accumulation was decreased but the steady-state Ca2+ content of the SR was not significantly altered in the loading solutions with a high [Mg2+] or low pH. CICR at around 1 microM [Ca2+] was clearly inhibited by a moderately low pH 6.6 but Mg2+ (0.6-4mM) did not significantly inhibit CICR except for at a very high [Mg2+] (10 mM). At the high [Ca2+] which shows maximal CICR, the Ca2+ release was not inhibited by either Mg2+ or H+. It is suggested that the elevation of intracellular H+ more profoundly influences the Ca2+ regulation mechanisms of the SR compared to the elevation of intracellular [Mg2+] under ischemic conditions.

Aniline Compounds↗

Effect of developed tension on the time courses of Ca2+ transients and tension in twitch contraction in ferret myocardium.

OBJECTIVES: The aim of the study is to test the hypothesis that tension-dependent change in the affinity of cardiac troponin-C influences the time courses of Ca2+ transients and tension in twitch contraction. METHODS: The Ca(2+)-sensitive photoprotein, aequorin, was microinjected into superficial cells of ferret papillary muscles and the Ca2+ transients and tension were simultaneously measured. The peak of developed tension was altered by changing the extracellular Ca2+ concentration, initial muscle length, and the application of 2,3-butanedione monoxime. RESULTS: In each maneuver, the decay time of Ca2+ transients was prolonged and the tension relaxation time was shortened when the peak of developed tension was decreased. In contrast, when the peak of developed tension was increased, the decay time of Ca2+ transients was shortened and the tension relaxation time was prolonged. The decay time of Ca2+ transients measured with different maneuvers was negatively correlated with the peak tension and the tension relaxation time was positively correlated with the tension peak. CONCLUSIONS: The changes in the decay time of Ca2+ transients and the tension relaxation time indicate that developed tension modulates the affinity of troponin-C for Ca2+ in normal twitch contraction.

Aequorin↗

Mechanisms of the inotropic effects of UD-CG 212 Cl, an active metabolite of pimobendan, on ferret papillary muscles.

We investigated the effects of an active metabolite of pimobendan, UD-CG 212 Cl, on Ca(2+) transients and tension using the aequorin method. When extracellular [Ca(2+)] ([Ca2+]o) in the Tyrode's solution was 2 mM, UD-CG 212 C1 (10(-7)-10(-4)M) increased the peak of Ca(2+) transients, accompanying a slight increase in peak tension. When [Ca(2+)]o was decreased to 0.5 mM, the twitch-potentiating effect of UD-CG 212 C1 was more remarkable, but the increase in the Ca(2+) transients at low concentrations of UD-CG 212 C1 (10(-7)-10(-6)M) was not significant as it was at 2 mM [Ca2+]o. The effects of UD-CG 212 Cl on the time courses of Ca(2+) transients and tension were evaluated at 0.5 mM [Ca2+]o. UD-CG 212 Cl shortened the decay time of Ca(2+) transients and the time to peak tension. However, the relaxation time was not significantly altered. UD-CG 212 C1 (10(-6)M) did not significantly change the relation between [Ca(2+)]i and tension in tetanic contraction. Therefore, the twitch-potentiating effect of UD-CG 212 Cl might not be due to an increase in the Ca(2+) sensitivity of the contractile elements. The slight increase in cyclic AMP due to the inhibition of phosphodiesterase type III by UD-CG 212 Cl could explain the twitch-potentiating effect and the faster time courses of Ca(2+) transients and tension.

Animals↗

Two cases of atypical bullous disease showing linear IgG and IgA deposition in the basement membrane zone.

Patients showing coexistent linear IgG and IgA deposition along the basement membrane zone on direct immunofluorescence have been described as either bullous pemphigoid, epidermolysis bullosa acquisita, linear IgA bullous dermatosis, or cicatricial pemphigoid, depending on the clinical features and laboratory findings. In the present report, we describe two cases showing atypical clinical features distinct from those of other known bullous diseases. No circulating antibodies were detected by indirect immunofluorescence of normal human skin. Indirect immunofluorescence of 1 M NaCl split skin revealed IgG and/or IgA antibodies reactive with the dermal side of the split. Immunoblotting of normal human epidermal and dermal extracts showed no apparent reactivity with known autoantigens. The results suggest that there may be a unique and distinct bullous disease with linear IgG and IgA deposition at the basement membrane zone.

Adult↗

Cross-bridge-dependent changes in the intracellular Ca2+ concentration in mammalian cardiac muscles.

A change in muscle length significantly alters the developed tension in mammalian cardiac muscle compared to that in skeletal muscle fibers. The intracellular mechanisms related to the length-dependent change in developed tension have been studied using Ca2+ indicators in intact preparations; a cross-bridge-dependent change in the affinity of troponin-C for Ca2+ is a possible mechanism. This hypothesis is further supported by the measurement of Ca2+ bound to troponin-C in skinned preparations. The molecular mechanism of the cross-bridge-dependent change in the affinity of troponin-C for Ca2+ is not fully understood although the studies which employ the substitution of troponin-C in skinned preparations, transgenic animals and in an animal model with heart disease have been performed. We reviewed the current studies by analyzing the intracellular mechanism responsible for the length-dependent change in tension development in mammalian cardiac muscle.

Animals↗