Objective: To investigate the expression of toll-like receptor (TLR)-2, 4 and 9 in idiopathic inflammatory myopathies (IIMs). Methods: The expression of TLR-2, 4 and 9 was measured by real-time RT-PCR and immunohistochemical stain (IHS) from muscle tissues in patients with IIMs and controls. Results: The expression levels of TLR-2, 4 and 9 in IIMs were significantly higher than controls. TLR-2, 4 and 9 were mainly expressed on sarcolemma of muscle fibers, perimysial vascular endothelium and infiltrating inflammatory cells in dermatomyositis, whereas, they were mainly expressed on sarcolemma of muscle fibers, destructed muscle fibers, and enodmysial infiltrating inflammatory cells in polymyositis. Conclusion: TLR-2, 4 and 9 were highly expressed in muscle tissue of IIMs. These results suggest that TLR-2, 4 and 9 play a role in pathogenesis of IIMs.
Dermatomyositis ; Endothelium, Vascular ; Humans ; Myositis* ; Polymyositis ; Sarcolemma ; Toll-Like Receptors*

Cap myopathy is pathologically characterized by cap structures comprising well-demarcated areas under the sarcolemma and containing deranged myofibrils and scattered Z-disks. Clinically it presents with slowly progressive muscle weakness, myopathic face, and frequent respiratory insufficiency. Four genes have been reported to be associated with the disease: TPM2, TPM3, ACTA1, and NEB. Here we describe that a patient presenting with mild limb weakness with facial affection showed cap structures on muscle pathology and carried a heterozygous TPM3 mutation.
Extremities ; Humans ; Muscle Weakness ; Muscular Diseases* ; Mutation, Missense* ; Myofibrils ; Pathology ; Respiratory Insufficiency ; Sarcolemma ; Tropomyosin

BACKGROUND: Cadmium, an environmental pollutant, has implicated in the pathogenesis of cardiovascular diseases. Biochemical and pathophysiological changes characterized by arterial hypertension, accelerated cholesterol plaque formation on arterial walls, cardiac conduction abnormalities, and reduction in myocardial contractility have been reported in experimental animals chronically exposed to low concentration of cadmium. This study was undertaken to evaluate the ultrastructural changes of the cardiac muscle in rats exposed to cadmium chloride and to ascertain whether these changes are modified after discontinuation of cadmium feeding. METHOD: Wistar strain rats(body weight 200~250gram) were injected intraperitoneally once weekly with 3.75mg/kg of cadmium chloride for 10 weeks and were sacrificed at 1 day, 1 week and 2 weeks after discontinuation of cadmium administration. RESULT: Ultrastructure if rat cardiac muscle fibers after cadmium administration revealed that mitochondria were increased in number and their cristae were severely damaged. Cardiac myofibrils and myofilaments were reduced. Z-disc were partly dislocated and A-bands and I-bands were not clearly defined. Irregularly arranged intercalated disc and disrupted sarcolemma were also found. These structural alterations resulting from cadmium feeding were partly reduced after removal of cadmium exposure for 2 weeks. These structural alterations resulting from cadmium feeding were partly reduced after removal of cadmium exposure for 2 weeks. CONCLUSIONS: It is suggested that exposure to cadmium chloride was associated with cardiac ultrastructural changes which might be responsible for physiologic abnormalities and these alterations may be partly reversible after discontinuation of cadmium administration.
Animals ; Cadmium Chloride* ; Cadmium* ; Cardiovascular Diseases ; Cholesterol ; Hypertension ; Mitochondria ; Myocardium* ; Myofibrils ; Rats* ; Sarcolemma

BACKGORUND: Capacitive calcium entry involves the influx of Ca2+ across the sarcolemma in response to the depletion of intracellular Ca2+ stores. Presently, little is known about the nature of the intracellular Ca2+ store (s) in pulmonary arterial smooth muscle cells (PASMCs), even though the unique contractile response of this tissue to hypoxia may at least partially involve the intracellular release of Ca2+ . The authors aimed to investigate the effects of nicardipine on capacitative calcium entry. METHODS: isolated pulmonary smooth muscle cells were obtained from enzymatically treated canine pulmonary artery. Currents were recorded at room temperature using the dialyzed whole cell recording technique. The protocol used to deplete intracellular Ca2+ stores and to monitor the development of the store-operated Ca2+ currents, involved cells being were voltage-clamped at 0 mv to inactivate any voltage-dependent calcium currents, which were recorded in response to a 200 ms voltage step from 120 to 40 mV in 20 mV increments. RESULTS: Simultaneous depletion of intracellular Ca2+ leads to linear store-operated Ca2+ current (iSOC) reversal near 0 mV. Nicardipine does not affect iSOC. CONCLUSiONS: in canine PASMCs, the depletion of intracellular Ca2+ stores leads to the activation of iSOC, which is not inhibited by nicardipine, a voltage-dependent Ca2+ channel (VDCC) blocker, indicating that VDCC blocked by nicardipine does not contribute to CCE in canine PASMCs.
Anoxia ; Calcium Channels ; Calcium* ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Nicardipine* ; Patch-Clamp Techniques ; Pulmonary Artery ; Sarcolemma

Childhood onset nemaline myopathy, first described in 1963 by Shy, et al and Conen, et al, is rare congenital myopathy, characterized by nonprogressive or slowly progressive muscle weakness associated with rod-like structures in muscle fibers, often with dysmorphic features. This myopathy was confirmed by muscle biopsy. The light microscopic features noted generally small round fibers that showed variation in size and occasional internal nuclei and characteristic rod bodies that could be demonstrated in the longitudinal sections stained with modified Gomori trichrome stain. Electromicroscopically there were accumulations of numerous irregular electron dense materials scattered between the myofibrils, particularly under the sarcolemma and enlargement and streamimg of the Z disk. We report a case of childhood onset nemaline myopathy in Korea in a 7 year- old boy who had nonprogressive muscle weakness of the limbs with a waddling gait.
Biopsy ; Extremities ; Gait ; Humans ; Korea ; Male ; Muscle Weakness ; Muscular Diseases ; Myofibrils ; Myopathies, Nemaline* ; Sarcolemma

OBJECTIVETo evaluate the histopathological characteristics and clinical implication of sarcolemma tissue in prepubertal concealed penis.

METHODSAfter measurement of the penile length, 10 prepubertal children with congenital concealed penis underwent modified Devine's operation (treatment group), and another 10 normal prepubertal children received circumcision (control group). The anatomic features of the penile sarcolemma tissue was observed intraoperatively, and its fibrosis was evaluated by Masson trichrome staining.

RESULTSThe penile length of the treatment group was significantly shorter than that of the control group preoperatively ([1.49 +/- 0.17 ] cm vs [4.26 +/- 0.23 ] cm, P < 0.01). The degree of penile concealment was correlated with the distal point of the attachment of its sarcolemma fibrous tissue: the closer the distal attachment point was to the coronary ditch, the more serious was penile concealment. The proportion of the area of collagen fibers in the penile sarcolemma tissue was significantly higher in the treatment group than in the control ([65.6 +/- 6.9]% vs [37.1 +/- 4.7]%, P < 0.01).

CONCLUSIONSarcolemma fibrosis was obvious in congenital concealed penis, and the key to its management is drastic removal of all the fibrous sarcolemma tissue.

Child ; Circumcision, Male ; Fibrosis ; Humans ; Male ; Penis ; abnormalities ; pathology ; surgery ; Phimosis ; pathology ; surgery ; Sarcolemma ; pathology

Animals ; Heart Ventricles ; cytology ; Lipid Bilayers ; Potassium Channels ; Sarcolemma ; physiology ; Swine

The purpose of this study was undertaken to test if alteration of calcium flux across the sarcolemma or sarcoplasmic reticulum change subsequent relaxation of rat aorta in tissue model of ischemia. Thoracic aorta ring segments(2-3mm wide) were studied with solution that mimicked real ischemia condition(hypoxia, acidosis, elevated lactate levels and zero sub strate). During ischemic condition, the effect of treatments thought to decrease cytosolic cal cium were tested. Half time(t(1/2)) and degree of stabilized relaxation were 2.4+/-0.9 minutes and 17.6+/-12.1%(NE 10-7 M precontraction as 100%) for verapamil(10-6 M), 3.3+/-0.7 min- utes, 22.2+/-3.9% for low Ca2+(0.75mM) in ischemic solution. Interventions aimed to elevat- ing cytosolic calcium were also tested. 3.8+/-0.9 minutes and 68.6+/-8.1% for high (10.0 mM) Ca2+ in ischemic solution, 3.7+/-0.7 minutes, 72.8+/-3.9/. for ryanodine(3X10-9 M). 3.8+/-0.5 minutes, 53.4+/-2.6% for isoproterenol. Without any treatment or agents during ischemia, hlaf time and degree of relaxation were 4.0+/-1.7 minutes, 74.6+/-13.2%, enothelium and time independent. These data support that treatment or agent thought to reduce influx of cytosolic calcium levels exaggerated the severity of relaxation. The mechanism of relaxation in ischsmia is not completely clear, but it is suggested that a reduction of calcium influx may involved and directly related.
Acidosis ; Animals ; Anoxia ; Aorta ; Aorta, Thoracic ; Calcium ; Cytosol ; Ischemia* ; Isoproterenol ; Lactic Acid ; Rats* ; Relaxation* ; Sarcolemma ; Sarcoplasmic Reticulum

BACKGROUND: The effects of various concentrations (10, 25 micrometer) of azumolene, an analogue of dantrolene, were studied in isolated guinea pig ventricular papillary muscles by measuring the effects on myocardial contractility and electrophysiologic parameters. METHODS: Isometric forces were studied in normal and 26 mM K Tyrode's solution. Rapid cooling contracture, an index of SR Ca2 content, was performed. Normal and slow action potentials (APs) were evaluated by using conventional microelectrode technique. RESULTS: Ten and 25 micrometer azumolene depressed peak force and maximum rate of force development ( 30 40%). Dose-dependent depression was shown at 2 and 3 Hz stimulation rate. Rapid cooling contractures following 10 and 25 micrometer azumolene was not altered compared to control while peak force at 2 Hz stimulation rate just prior to cooling was depressed similarly to normal Tyrode's solution. In 26 mM K Tyrode's solution, 10 and 25 micrometer azumolene caused depression of early (10 micrometer: 20%) and late (10 micrometer: 50%) force development. In slow APs, shortening of AP duration at 20, 50, and 90% of the repolarization phase, as well as a small but significant reduction of dV/dt-max ( 20%) were shown at 0.25 Hz stimulation rate. There was no alteration in AP parameters in normal APs. CONCLUSIONS: The direct myocardial depressant action of azumolene seems to be at least in part caused by inhibition of Ca2 influx via the Ca2 channel in sarcolemma. It seems likely that azumolene does not alter the sarcoplasmic reticulum function such as Ca2 uptake and release in cardiac muscle.
Action Potentials ; Animals ; Contracture ; Dantrolene ; Depression ; Guinea Pigs ; Malignant Hyperthermia ; Microelectrodes ; Myocardium* ; Papillary Muscles ; Sarcolemma ; Sarcoplasmic Reticulum

Although the mechanism of the development of hypertension has not been fully elucidated, abnormal ion transport across the cardiovascular musle membrance may play some role in this mechanism. The elevation of intraceular sodium by inhibition of the Na(+), K(+)-ATPase diminshes the sodium gradient for calcium extrusion and/or increase Na(+)/Ca(++) exchange across the cell membrance. In any event, contractility and vascular tone of cardiovascular system can be incresed as reslut of an increase of intracellular calcium. Recently it is reported that the defects of Na(+), K(+)-ATPase occur in spontaneously hypertensive rat(SHR) hearts, compared to control normotensive Spargue Dawley(SD) rat hearts. However, one missing, unresolved question arose in the previous reports in whether the reduced Na(+)-pump activity in the heart of SHR is associated with the development of hypertension itself in these animals or is a consequence of inhertied pathological features that later reslut in a reduced pump activity. In order to clearify this question it is attempted to measured to measure the change of the Na(+), K(+)-ATPase activities in cardiac sarcolemma purified from both the normotensive SD rats and SHR rats during growth ; Simultaneously the charge of cation concentration in both intracellular space(RBC) and extracelluar space(ECF) are measured to the erythrocyte test(Garay and Meyer) applied to the clinical investiation of hypertension. The results obtained are summarized as follows ; 1) The systolic blood pressure of 7 week old SHR was 120-130mmHg, which was not significantly different from that of the age-matched SD rats. However, the blood pressure was elevated to 160-170mmHg in 13-15 week old SHR, even elevated to 190mmHg in one of 19 week old SHR. On the other hand, SHR, in which hypertension was well established had pronounced cardiac hypertrophy. 2) The Na(+), K(+)-ATPase activities in cardiac sarcolemma of the SHR rats were decreased gradually as hypertension established.The decrease of Na(+), K(+)-ATPase was well associated with the increase of intracellular potassium concentration.By contrast, thr Na(+), K(+)-ATPase activities and cation transports og the normotensive SD rats were not significanlty chaged during growth. 3) The charges of Na(+), K(+)-ATPase activities in SHR were specific because the activities of Ca(++)-ATPase which is one of the membrance bound enzyme were not changed during growth appeared to be a major fator which generated hypertension in SHR rats. However, question on how the Na(+), K(+)-ATPase activities are decreased and which event is initiative between reduction of Na(+), K(+)-ATPase and development of hypertension are still remained unclear. Recent literature suggests the there might be a genetic factor, so-called Na(+)-pump inhibitor, involved in the meachanism.
Animals ; Blood Pressure ; Calcium ; Cardiomegaly ; Cardiovascular System ; Erythrocytes ; Hand ; Heart ; Hypertension ; Ion Transport ; Potassium ; Rats ; Rats, Inbred SHR* ; Sarcolemma ; Sodium