Kenshi Imoto

Ca Mobilizing Action of Sphingosine in Jurkat Human Leukemia T Cells EVIDENCE THAT SPHINGOSINE RELEASES Ca FROM INOSITOL TRISPHOSPHATE- AND PHOSPHATIDIC ACID-SENSITIVE INTRACELLULAR STORES THROUGH A MECHANISM INDEPENDENT OF INOSITOL TRISPHOSPHATE

Effects of sphingosine on Ca mobilization in the human Jurkat T cell line were examined. Sphingosine increased the cytoplasmic Ca concentration ([Ca]) in a dose-dependent manner with an ED of around 8 μM. Sphingosine and OKT3, a CD3 monoclonal antibody, transiently increased [Ca], which declined to the resting level in the absence of extracellular Ca. Under the same conditions, pretreatment with sphingosine inhibited but did not abolish an increase in [Ca] induced by the subsequent addition of OKT3 and vice versa. However, pretreatment with sphingosine did not affect an increase in [Ca] induced by OKT3 in the presence of Ca. OKT3 increased IP formation, but sphingosine did not affect the level of IP by itself nor did it cause IP formation induced by OKT3. In permeabilized Jurkat cells, the addition of IP released Ca from nonmitochondrial intracellular stores, but the addition of sphingosine did not. Sphingosine, stearylamine, and psychosine increased [Ca] and diacylglycerol (DG) kinase activation; however, ceramide did not, whereas sphingosine 1-phosphate slightly activated DG kinase without elevation of [Ca]. Pretreatment with R59022, a DG kinase inhibitor, abolished the peak but did not affect the sustained response of [Ca] to sphingosine. Phosphatidic acid (PA) elevated [Ca], after which it declined to a resting level even in the presence of extracellular Ca. In accordance with this, PA did not stimulate Ca uptake into cells, but sphingosine and OKT3 did. Pretreatment with PA partially inhibited a rise in [Ca] induced by the subsequent addition of sphingosine and vice versa in the absence of extracellular Ca. Under similar conditions, pretreatment with PA affected an elevation of [Ca] induced by OKT3 less, after which the subsequent addition of sphingosine did not increase [Ca]. In permeabilized Jurkat cells, the addition of IP did not release Ca, but PA did in the presence of heparin. Pretreatment with thapsigargin, a microsomal Ca-ATPase inhibitor, abolished the rises of [Ca] induced by the subsequent addition of sphingosine, OKT3, and PA in the absence of extracellular Ca. The present results suggest that at least two kinds of intracellular Ca stores exist in Jurkat cells, both of which are IP- and PA-sensitive, and that sphingosine mobilizes Ca from both stores in an IP-independent manner. Furthermore, the IP- but not the PA-sensitive intracellular Ca store seems to regulate Ca entry induced by sphingosine.

TETRANDRINE AS A CALCIUM ANTAGONIST

1. The Ca2+‐antagonism of tetrandrine (TET) on the Ca2+ mobilization in various types of cells were reviewed. Inositol trisphosphate (IP3)‐generating drugs were used as Ca2+‐mobilizing agonists and the effects were compared with those produced by using the microsomal Ca2+‐ATPase inhibitor thapsigargin (TG), which is a tool for analysing Ca2+ which is a tool for analysing Ca2+ store ‐regulated Ca2+ entry (capacitative Ca2+ entry).

Relation between spontaneous contraction and sarcoplasmic reticulum function in cultured neonatal rat cardiac myocytes.

The relation between spontaneous contraction, Ca2+ oscillations, and sarcoplasmic reticulum (SR) function was studied in cultured neonatal rat cardiac myocytes. Spontaneous contraction and Ca2+ oscillations were irregular at day 2 of culture but became regular at day 6 of culture in neonatal rat cardiac myocytes. The rate of spontaneous contraction and the frequency of Ca2+ oscillations were decreased by verapamil and were abolished in the absence of extracellular Ca2+ at both day 2 and day 6 of culture. Ryanodine and thapsigargin increased the rate of contraction and the frequency of Ca2+ oscillations at day 2 of culture but did not affect contractions and Ca2+ oscillations at day 6 of culture. Ultrastructural observation showed that the structure of SR developed less at day 6 of culture. The present results suggest that spontaneous contraction and Ca2+ oscillations are due mainly to extracellular Ca2+ influx but not to Ca2+ release from SR in neonatal rat cardiac myocytes.

Changes in bone resorption markers among Japanese patients with postmenopausal osteoporosis treated with alendronate and risedronate.

We compared the abilities of alendronate and risedronate to reduce levels of urinary cross-1inked N-telopeptides of type I collagen (NTX) in Japanese postmenopausal women. The patients were randomly divided into two groups (alendronate, 5 mg/day, n = 61; risedronate, 2.5 mg/day, n = 60). All patients had taken all medication prescribed for the first month and at least 90% of that prescribed for each of the following 6 months. Urinary NTX was measured at baseline, as well as at 1 and 6 months after starting treatment. According to the guidelines of the Japan Osteoporosis Society, the minimum significant change (MSC) for urinary NTX is defined as a 35% decrease from baseline and the cutoff level for a high risk of future fracture is 54.3 nmol bone collagen equivalent (BCE)/mmol·Cr. The NTX reduction rates at 1 and 6 months were greater with alendronate than with risedronate, but the difference was not significant. The rate of patients with a reduction in the MSC at 1 month was greater with alendronate than with risedronate, but the difference did not reach significance. Alendronate reduced NTX at 1 month significantly more in patients with a high risk of fracture than risedronate, but the difference was no longer significant at 6 months. The rate of MSC did not significantly differ between the two groups. In conclusion, alendronate decreases bone resorption markers more obviously and rapidly than risedronate, especially in high risk for fracture, but not significantly according to the guidelines of the Japan Osteoporosis Society.

Spinal surgery in a patient with essential thrombocythemia resulting in leg paraplegia: a case report

BACKGROUND CONTEXT Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by a relatively benign clinical course that may be complicated by conflicting thrombosis and bleeding. Postoperative spinal epidural hematoma is an uncommon, but well-known, complication after spinal surgery. PURPOSE To describe a patient with ET who underwent surgery for lumbar spinal canal stenosis resulting in leg paraplegia and discuss the perioperative management for ET. STUDY DESIGN Case report. RESULTS The patient with ET underwent laminoplasty and posterolateral fusion for degenerative spondylolisthesis and spinal stenosis at L4-L5. A hematoma was observed in the epidural cavity after surgery, and emergency surgical evacuation was performed. After revision surgery, bleeding from the wound continued for 2 months, despite transfusions of platelets and coagulation factors, and right unilateral leg paralysis developed. CONCLUSIONS This case presentation increases the awareness of this disorder to the spinal community and the need to establish guidelines for the perioperative management of patients who require surgery in similar settings.

α1-And β-adrenergic and muscarinic-cholinergic regulation in the spontaneous beating and Ca2+ oscillations in cultured neonatal rat cardiac myocytes

Abstract α 1 -and β-adrenergic and muscarinic-cholinergic regulation in spontaneous beating and Ca 2+ oscillations in neonatal rat cardiac myocytes at day 6 of culture was investigated. The spontaneous beating in myocytes decreased in the presence of 10 μM norepinephrine (NE). This negative chronotropic action was antagonized by prazosin. Carbachol (CCh) also showed negative chronotropic action which was inhibited by atropine. On the other hand, isoproterenol (ISP) increased the beating rate which was antagonized by propranolol. NE increased inositol phosphate formation whereas CCh and ISP did not. NE and CCh suppressed the frequency of the spontaneous Ca 2+ oscillations but ISP increased. The present results suggest that α 1 -adrenergic and muscarinic receptors regulate chronotropism to be negative whereas β-adrenoceptor regulates chronotropism to be positive in cultured neonatal rat cardiac myocytes.

Bilateral femoral shaft fractures in an adolescent snowboarder

A 23-year-old male snowboarder suffered bilateral femoral shaft fractures from a jumping accident. On the day following the injury, closed intramedullary nailings with static locking were inserted. Follow-up radiographs revealed that bone unions had formed in the bilateral femurs. The patient was able to walk without the help of a cane, and returned to work. Snowboard injuries most frequently involve the upper extremities, so that there have been no previous reports of bilateral femoral shaft fractures in snowboarders. Generally, femoral shaft fractures result from high-energy injury; however, in this case, the board dug into the ground on landing, and the patient was pitched forward with his lower legs bound to the ground via the board so that the indirect force caused the bilateral femoral shaft fractures. Jumping is becoming the main cause of snowboard injuries. Therefore, in order to decrease the number of snowboard-associated injuries, we should encourage snowboarders to be more cautious about jumping.