Protective effect of pravastatin on vascular endothelium in patients with systemic sclerosis: a pilot study.
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Adult↗
Biomedical subjects
T Horita
Publications and source records attributed to T Horita.
Cerebral imaging by magnetic resonance imaging and single photon emission computed tomography in systemic lupus erythematosus with central nervous system involvement.
OBJECTIVE: To assess the significance of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) abnormalities in patients with systemic lupus erythematosus (SLE). METHODS: Forty-four patients with SLE were retrospectively analysed. Patients were classified into three groups [1 and 2: patients with central nervous system (CNS) manifestations before and after starting high-dose steroid therapy, respectively; 3: patients without CNS manifestations. MRI was performed in all 44 patients and SPECT in 31. RESULTS: Abnormal findings in MRI were found in 19 patients. MRI abnormalities were significantly more frequent in patients with CNS manifestations than in those without [71 vs 17%, odds ratio (OR) 11.9, confidence interval (CI) 2.8-49.9, P=0.0003]. After the initiation of steroid therapy, patients with CNS manifestations also had an increased frequency of abnormal MRI. No correlation was found between SPECT findings and CNS manifestations. However, patients with CNS manifestations after starting steroids showed a markedly increased frequency of abnormal MRI and SPECT compared with those without CNS manifestations (80 vs 7%; OR 56, CI 4.4-719, P=0.0003). The positive predictive value of abnormality in both techniques in developing CNS manifestations after starting steroids was 89%. CONCLUSION: MRI findings correlated with CNS manifestations in SLE. Where there is a high suspicion of CNS involvement, the combination of MRI and SPECT may be useful in predicting CNS manifestations after starting steroid therapy.
Adolescent↗
Exhausting stretch-shortening cycle (SSC) exercise causes greater impairment in SSC performance than in pure concentric performance.
The purpose of the present study was to investigate the fatigue effect of repeated exhaustive stretch-shortening cycle (SSC) exercise on concentric muscle function. Ten healthy male subjects performed SSC exercise [92 (30) jumps] on a special sledge apparatus. Exhaustion occurred on average within 3 min. A squat jump (SJ) test utilizing a concentric-only action was performed immediately before and after the SSC exercise, and then 10 min, 20 min, 2 days and 4 days later. In addition, a drop jump (DJ) test using an SSC was also performed immediately before and 20 min after the SSC exercise, and 2 days and 4 days later. During jump tests, lower limb joint moment, power, and work contributions were analyzed by using the kinetic and kinematic data. The fatigue exercise was characterized by a relatively high blood lactate concentration [7.2 (0.8) mmol x l(-1)] and a 2-day delayed increase in serum creatine kinase activity [486 (300) U x l(-1)]. SJ performance decreased markedly immediately after the SSC exercise (P<0.05) and then recovered within 10 min. In contrast, DJ performance and knee joint contribution showed a delayed decrease 2 days after the SSC exercise bout. The surface electromyographic (EMG) activity of the lower limb muscles showed no obvious change in the SJ in comparison to the DJ, although in the latter there was a delayed decrease of knee extensor EMG during the pre-activation and braking phases. The results suggest that isolated concentric muscle function is affected mainly by acute metabolic fatigue after SSC exercise. During a follow-up period after the exercise, changes in hip and knee joint contribution in SJ showed a different recovery pattern compared to those in eccentric DJ. It could be suggested that exhaustive SSC exercise would mainly influence the relative power-work balance between the hip and knee joints during the eccentric phase of SSC. Thus different motor control strategies may account for the distinctive fatigue responses observed in SJ and DJ.
Adult↗
Interaction between pre-landing activities and stiffness regulation of the knee joint musculoskeletal system in the drop jump: implications to performance.
The purpose of the present study was to investigate the interaction between the pre-landing activities and the stiffness regulation of the knee joint musculoskeletal system and the takeoff speed during a drop jump (DJ). Nine healthy male subjects performed a DJ test from the height of 50 cm. The surface electromyographic (EMG) activity of the vastus lateralis (VL) muscle was recorded to evaluate both the pre-landing and post-landing muscle activation levels. Simultaneous recording of the jumping motion and ground reaction force was performed by a high-speed video camera (100 frames x s(-1)), and a force platform was employed to allow joint moment analysis. Joint stiffness was calculated by a linear regression of the knee joint moment/angle relationship. Elasticity of the knee extensor muscle during DJ was estimated by means of a four-element muscle model consisting of a parallel elastic component, a series elastic component (SEC), a viscous damper, and a contractile element. DJ performance correlated positively with the positive peak power of the knee joint (P < 0.01) and with the moment of the knee joint at the end of stretch (P < 0.01). However, there was no significant relationship between DJ performance and the positive peak power of the ankle joint. The knee joint moment at the end of stretch correlated with the SEC stiffness during the transmission phase from the end of the initial impact to the onset of the concentric action (P < 0.01) and with the maximum rate of isometric force development of the knee extensors (P < 0.01). Multiple regression analysis showed that the SEC stiffness during the transmission phase of the knee joint can be explained by a combination of the pre-activity of the VL muscle and the knee joint angular velocity at touchdown (F = 5.76, P < 0.05). These results seem to emphasize the functional significance of the pre-programmed activity for controlling the subsequent stiffness regulation and then contributing to the performance in DJ. Thus, it can be suggested that the centrally pre-programmed activity and the associated elastic behavior of the SEC in the knee extensor muscle in conjunction with the muscle contractile property play a major role in regulating the performance in DJ.
Adult↗
Significance of magnetic resonance imaging in the diagnosis of nodular regenerative hyperplasia of the liver complicated with systemic lupus erythematosus: a case report and review of the literature.
Nodular regenerative hyperplasia of the liver (NRH), characterized by multiple hepatic nodules in the absence of fibrosis, is a rare but important complication of systemic lupus erythematosus (SLE) associated with non-cirrhotic portal hypertension. The diagnosis of NRH is based on the pathological examination, and radiological findings of NRH are poorly documented. We report a case of a 40-year-old woman with SLE complicated with NRH. Sixteen years after diagnosis of SLE, esophageal varices were incidentally found and diagnosis of portal hypertension due to NRH was made by magnetic resonance imaging (MRI) and confirmed by needle liver biopsy. Although MRI showed the lesions as significant nodules, neither computed tomography nor ultrasonography could demonstrate the nodules. However, serial MRI showed significant enlargement of the nodules for 2 years Because NRH may lead to portal hypertension with life-threatening variceral haemorrhage in patients with SLE, MRI is a useful, non-invasive examination to screen the patients for its presence and follow-up. We reviewed the literature regarding NRH in SLE and discuss the management of the affected patients.
Adult↗
Theoretical analysis of array-enhanced stochastic resonance in the diffusively coupled FitzHugh-Nagumo equation.
The array-enhanced stochastic resonance (AESR) in the diffusively coupled FitzHugh-Nagumo equation is investigated. The two properties of AESR, namely, the scaling of the optimal noise intensity and the enhancement of the maximum value of the correlation coefficient as a function of the coupling strength, are analyzed theoretically. By transforming the dynamics of N elements into that of the mean and the deviation from it, it is found that AESR is caused by the correlation between them. A low-dimensional model that reproduces the above properties is constructed.
Animals↗
Circulating matrix metalloproteinases and their inhibitors in premature coronary atherosclerosis.
To investigate the clinical significance of circulating matrix metalloproteinases (MMPs) and their tissue inhibitos (TIMPs) in patients with premature coronary atheroscrelosis, we studied 53 consecutive male patients with angiographically defined premature (<65 years) and stable coronary artery disease. Plasma levels of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 were determined in peripheral blood by a sandwich enzyme immunoassay, and the results were compared with those from 133 age-matched control males. There were significant differences in all the MMPs and TIMPs (p<0.001) between patients and controls. In the patient group, the levels of MMP-9 (mean +/- SD (ng/ml) 27.2 +/- 15.2/21.8 +/- 15.2) and TIMP-1 (130.4 +/- 55.7/94.5 +/- 26.3) were significantly higher, and the levels of MMP-2 (632.5 +/- 191.6/727.6 +/- 171.4), MMP-3 (53.1 +/- 31.2/79.6 +/- 29.9), and TIMP-2 (24.7 +/- 15.2/35.4 +/- 16.4) were significantly lower than those of controls. We found significant positive correlation between plasma MMP-9 levels and low-density lipoprotein (LDL)-cholesterol levels (Rs = 0.168, p = 0.022), and significant negative correlation between plasma MMP-9 levels and high-density lipoprotein (HDL)-cholesterol levels (Rs = -0.164, p = 0.026) by Spearman rank correlation test. In contrast, plasma MMP-2 (Rs = 0.181, p = 0.014) and MMP-3 (Rs = 0.260, p = 0.0004) levels were positively correlated with HDL-cholesterol levels. TIMP-2 levels were negatively correlated with total cholesterol (Rs = -0.197, p = 0.007) and LDL-cholesterol (Rs = -0.168, p=0.022) levels. These results suggest that the circulating levels of MMPs and TIMPs are altered in patients with premature coronary atherosclerosis and that plasma lipoprotein cholesterol levels correlate with these, possibly as a result of the lipoprotein-vessel wall interactions.
Biomarkers↗
[Severe neuro-Behçet with perforation of the intestine].
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Behcet Syndrome↗
beta(2)-glycoprotein I deficiency: prevalence, genetic background and effects on plasma lipoprotein metabolism and hemostasis.
beta(2)-glycoprotein I (beta(2)-GPI=apolipoprotein H) is an important autoantigen in patients with the antiphospholipid syndrome. It also plays a role in lipoprotein metabolism, such as anti-atherogenic property, triglyceride removal, and enhancement of lipoprotein lipase. Serum beta(2)-GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with complete beta(2)-GPI deficiency were identified. In one family, all affected had increased serum LDL-cholesterol levels or smaller particle sizes of LDL, while the other had no apparent abnormality in lipid metabolism. Individuals investigated had no history of thrombosis or overt abnormalities in hemostatic tests. A thymine corresponding to position 379 of the beta(2)-GPI cDNA was deleted in every beta(2)-GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6. 3% in Japanese and none in Caucasians. Heterozygotes had significantly lower concentrations of serum beta(2)-GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration of beta(2)-GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.
Adult↗
Effect of exhausting stretch-shortening cycle exercise on the time course of mechanical behaviour in the drop jump: possible role of muscle damage.
The purpose of the present study was to investigate the effect of stretch-shortening-cycle-induced muscle damage on the time course of mechanical behaviour in the drop jump. Ten healthy male subjects performed submaximal stretch-shortening cycle (SSC) exercise on a special sledge apparatus. Exhaustion occurred on average within 3 min. A drop jump (DJ) test from a 50-cm height was performed before and immediately after the sledge exercise as well as 2 h, 2 days and 4 days later. The fatigue exercise showed relatively high blood lactate concentration [12.5 (SD 2.6) mmol x l(-1)] and an increase of serum creatine kinase (CK) activity delayed by 2 days [540 (SD 407) U x l(-1)]. The initial decline in the jump performance (before - immediately after) was related negatively to the early recovery in performance (immediately after 2 h) (P < 0.05). The early recovery of the knee joint moment at the end of stretch showed a negative correlation to the delayed decrease in DJ performance (2 h 2 days) (P < 0.01). Thus, the DJ performance showed an initial decline followed by an early recovery and a secondary decline. Both the initial decline and early recovery in the knee joint moment at the end of stretch were related to the corresponding initial (after 2 h) (P < 0.05) and secondary increases (2 h - 2 days) (P < 0.01) in CK. It is suggested that the early recovery as well as the initial decline in the knee joint function could depend on the degree of muscle damage. Delayed decrease in initial stiffness (2 h - 2 days) was negatively related to the corresponding changes in the knee joint angle at touch down in DJ (P < 0.001). These interactions would imply that the decrease in the stiffness regulation and the modulation of the prelanding motor control might be attributable to secondary muscle damage during 2 days after the SSC exercise. Therefore, it may be suggested that the changes in the DJ performance after the exhausting SSC exercise accompany the progress of muscle damage observed by the corresponding increase in serum CK concentration and the corresponding deterioration of stiffness regulation and motor control in DJ.
Adult↗
Large deviation properties of on-off intermittency.
The large deviation property of on-off intermittency is investigated by introducing a two-dimensional piecewise linear map, which can be mapped to an infinite Markov chain. It is shown that nonanalyticity, in the q-weighted average of the portion of time spent in burst state, appears as a second-order phase transition for an interval of control parameter with the bifurcation point of on-off intermittency as its end point.
Journal Article↗
Reflex sympathetic dystrophy in a patient with the antiphospholipid syndrome.
We describe a 50-year-old woman who developed severe pain of the left lower limb after an episode of thrombophlebitis. Bone scintigraphy and thermography showed results indicative of reflex sympathetic dystrophy. Laboratory analysis revealed the presence of the lupus anticoagulant. The patient was diagnosed as antiphospholipid syndrome complicated with reflex sympathetic dystrophy of the left lower limb. To our knowledge, this is the first report of a patient with reflex sympathetic dystrophy with underlying antiphospholipid syndrome.
Antiphospholipid Syndrome↗
Effects of XT-44, a phosphodiesterase 4 inhibitor, in osteoblastgenesis and osteoclastgenesis in culture and its therapeutic effects in rat osteopenia models.
We have reported that denbufylline, a phosphodiesterase 4 (PDE4) inhibitor, inhibits bone loss in Walker256/S tumor-bearing rats, suggesting therapeutic potentiality of a PDE4 inhibitor in osteopenia. In the present study, effects of a new PDE4 inhibitor, 1-n-butyl-3-n-propylxanthine (XT-44), in bone were evaluated in cell cultures and animal experiments. In rat bone marrow culture, XT-44 stimulated mineralized-nodule formation, whereas it inhibited osteoclast-like cell formation in mouse bone marrow culture. In Walker256/S-bearing rats (6-week-old female Wistar Imamichi rats), rapid decrease in bone mineral density (BMD) was prominent, and oral administration of XT-44 (0.3 mg/kg, every 2 days) inhibited the decrease in BMD. In the second animal experiment, female Wistar rats (6-week-old) were sciatic neurectomized, and XT-44 was orally administered to these rats every 2 days for 4 weeks. XT-44 administration (0.3 mg/kg) recovered BMD in these neurectomized animals. Furthermore, 19-week-old, female Wistar rats were ovariectomized (OVX), and 15 weeks after surgery, these rats were orally administered XT-44 every 2 days for 8 weeks. XT-44 treatment (1 mg/kg) increased the BMD of OVX rats. These results indicate that XT-44 could be a candidate as a therapeutic drug for treating osteopenia including osteoporosis.
1-Methyl-3-isobutylxanthine↗
Synthesis and degradation of 1-aminocyclopropane-1-carboxylic acid by Penicillium citrinum.
1-Aminocyclopropane-1-carboxylic acid (ACC), which is a precursor of ethylene in plants, has never been known to occur in microorganisms. We describe the synthesis of ACC by Penicillium citrinum, purification of ACC synthase [EC 4.4.1.14] and ACC deaminase [EC 4.1.99.4], and their properties. Analyses of P. citrinum culture showed occurrence of ACC in the culture broth and in the cell extract. ACC synthase was purified from cells grown in a medium containing 0.05% L-methionine and ACC deaminase was done from cells incubated in a medium containing 1% 2-aminoisobutyrate. The purified ACC synthase, with a specific activity of 327 milliunit/mg protein, showed a single band of M(r) 48,000 in SDS-polyacrylamide gel electrophoresis. The molecular mass of the native enzyme by gel filtration was 96,000 Da. The ACC synthase had the Km for S-adenosyl-L-methionine of 1.74 mM and kcat of 0.56 s-1 per monomer. The purified ACC deaminase, with a specific activity of 4.7 unit/mg protein, showed one band in SDS-polyacrylamide gel electrophoresis of M(r) 41,000. The molecular mass of the native ACC deaminase was 68,000 Da by gel filtration. The enzyme had a Km for ACC of 4.8 mM and kcat of 3.52 s-1. The presence of 7 mM Cu2+ in alkaline buffer solution was effective for increasing the stability of the ACC deaminase in the process of purification.
Amino Acids↗
Haemophagocytic syndrome in a patient with dermatomyositis.
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Dermatomyositis↗
Role of phosphodiesterase 4 isoenzyme in alkaline phosphatase activation by calcitonin in porcine kidney LLC-PK1 cells.
To confirm the intracellular signal transduction in regulation of alkaline phosphatase (ALP) activity by calcitonin in kidney tubular cells, effects of several inhibitors of cyclic nucleotide phosphodiesterase (PDE) isoenzymes and cyclic AMP-dependent protein kinase (PKA) on the action of salmon calcitonin in porcine kidney tubular epithelial cells LLC-PK1 were examined. A confluent culture of LLC-PK1 cells was treated with calcitonin and inhibitors in Dulbecco's modified Eagle's medium supplemented with 0.1% bovine serum albumin, and intracellular cyclic AMP content and ALP activity were measured after incubation for 30 min and 48 hr, respectively. Calcitonin and PDE 4 inhibitors increased cyclic AMP level and ALP activity in the cells, and PDE 4 inhibitors synergistically potentiated the effects of calcitonin. Calcitonin induced ALP activation by treatment for the first 1 hr, as well as continuous treatment for 48 hr, while it never increased the enzyme activity just after 1-hr exposure. Rolipram, an inhibitor of PDE 4 isoenzyme, induced ALP activation by itself and in combination with calcitonin by only a long term treatment (48 hr). The activation of ALP by calcitonin and rolipram each alone and in combination was completely abolished by a PKA inhibitor, H-89. These results confirm that calcitonin induces ALP activation through the cyclic AMP-PKA pathway and that PDE 4 isoenzyme is closely associated with the calcitonin-receptor system and plays a major role in hydrolysis of cyclic AMP produced in the kidney tubular cells.
3',5'-Cyclic-AMP Phosphodiesterases↗
Reduction of bone loss by denbufylline, an inhibitor of phosphodiesterase 4.
The effects of denbufylline, a xanthine derivative with selective inhibitory activity on the phosphodiesterase (PDE) 4 isoenzyme, on bone loss in Walker 256/S-bearing rats and on mineralized nodule formation and osteoclastlike cell formation in bone marrow culture systems were examined. Serial oral administrations of denbufylline inhibited the decrease in the bone mineral density of femurs from Walker 256/S-bearing rats, without influence on the healthy rats. Denbufylline restored the bone mass and the number of osteoclasts and osteoblasts per trabecular surface in the femur metaphysis. Among PDE inhibitors, only PDE4-selective inhibitors increased the number of mineralized nodules and decreased the number of osteoclastlike cells in the in vitro bone marrow culture systems, and dibutyryl cyclic AMP mimicked these effects in the in vitro systems. These results suggest that the PDE4 isoenzyme may play an important role in bone turnover through cyclic AMP and that its inhibitors are candidates for therapeutic drugs for the bone loss diseases.
1-Methyl-3-isobutylxanthine↗
Dual regulation of alkaline phosphatase activity by calcitonin in porcine kidney cells.
Intracellular signal transduction for regulation of alkaline phosphatase (ALP) activity in renal epithelial cells treated with calcitonin is not yet completely understood, although it is known that calcitonin receptors couple to cyclic AMP-dependent protein kinase (PKA) and calcium/phospholipid-dependent protein kinase (PKC). Salmon calcitonin increased the cyclic AMP content in LLC-PK1 porcine kidney cells in a concentration-dependent manner. When the confluent cells were incubated for 47 h after a 1 h-pulse exposure or continuously exposed to calcitonin and forskolin for 48 h, ALP activity in the cells was increased by calcitonin about 2-fold compared with the basal activity at the maximum level but was not dependent on the exposure time; it was markedly increased by forskolin in parallel with the exposure time. The increase in activity produced by calcitonin was abolished by a PKA inhibitor H-89, and, in contrast, potentiated by a PKC inhibitor, NA-382 to near the forskolin-induced level. These results indicate that calcitonin exerts a dual-regulation of ALP activity in LLC-PK1 cells, positively through the PKA pathway and negatively through PKC.
Alkaline Phosphatase↗