Quantitative morphometric study of muscle in inclusion body myositis.

Clinical and electromyographic findings do not clearly distinguish inclusion body myositis (IBM) from chronic polymyositis (PM). The rimmed vacuoles and filamentous nuclear and cytoplasmic inclusions that characterize IBM are often sparse and may be overlooked; conversely, these features may occasionally be seen in other diseases. Preliminary studies suggested that muscle fiber hypertrophy occurred more frequently in IBM than in PM. To investigate whether fiber hypertrophy can be used to improve the ability to separate IBM from PM, we report a morphometric analysis of 28 IBM cases, 22 PM and 22 dermatomyositis (DM) cases. The analysis, using a computer automated system, included proportion of hypertrophied fibers and also fiber type proportions, average fiber diameter, proportion of atrophic and angulated fibers, and the co-dispersion index (CDI). The proportion of hypertrophied fibers was greater in IBM than the other two conditions (IBM (mean +/- SEM) 31.0 +/- 4.7% and 12.2 +/- 2.4% for type 1 and type 2 fibers, respectively, compared to 9.8 +/- 3.0% and 3.3 +/- 1.7% in PM, and 7.7 +/- 2.7% and 3.9 +/- 1.9% in DM). These differences were statistically significant (P < 0.05) in both sexes for type 1 fibers and in women for type 2 fibers. Also, the average fiber size and hypertrophy factors for type 1 and type 2 fibers were increased in IBM compared to PM and DM. This study confirms that the presence of muscle fiber hypertrophy in biopsies from IBM patients may help differentiate them from other clinically similar inflammatory myopathies.     

Clinical, immunopathologic, and therapeutic considerations of inflammatory myopathies.

The inflammatory myopathies encompass a group of heterogenous muscle diseases which have in common an acquired myopathy with histological signs of endomysial inflammation. We present evidence based on recently emerged clinical, histologic, immunopathologic, demographic and therapeutic observations that these myopathies comprise three major and distinct groups: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM). Immune-mediated mechanisms characteristic for each group appear to play a primary role in the pathogenesis of these diseases. In DM there is an intramuscular microangiopathy mediated by the C5b-9 membranolytic attack complex, leading sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis and perifascicular atrophy. In contrast, in PM and IBM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize MHC-I restricted muscle antigens, leading to phagocytosis and fiber necrosis. Among the viruses implicated in the cause of inflammatory myopathies, only the retroviruses, HIV, HTLV-1 and simian retroviruses, have been convincingly associated with PM. Retroviruses, therefore, appear to be the leading group of viruses capable of triggering these diseases. The treatment of inflammatory myopathies has been largely empirical. A detailed therapeutic plan based on our experience with a large number of patients is presented. Patients with bona fide PM or DM respond to steroids to some degree and for some period of time. In contrast, patients with IBM do not respond to any therapy and the disease should be suspected when a patient with presumed PM has failed treatment. Methotrexate and cyclophosphamide are disappointing. Cyclosporine and Azathioprine are commonly used but they are of uncertain benefit. Plasmapheresis is ineffective. High-dose intravenous immunoglobulin is a promising new therapeutic modality.     

Chemokine-like factor expression in the idiopathic inflammatory myopathies

Objectives –  We evaluated the expression of chemokine-like factor (CKLF) in biopsied muscle fibers in inflammatory myopathies, non-inflammatory myopathies and neurologically diseased controls.
Materials and methods –  We studied the expression of CKLF in 15 polymyositis (PM), five dermatomyositis (DM), 15 non-inflammatory myopathies and nine neurologically diseased patients by immunohistochemistry.
Results –  Chemokine-like factor was mostly expressed in small diameter muscle fibers surrounded by infiltrated lymphocytes of inflammatory myopathies patients. Parts of them were also positive for the staining of the developmental form of myosin heavy chain, a maker of regenerating muscle fibers. Thrombin immunoreactivity was observed in endomysium in PM and perimysium in DM. In vitro differentiation study showed a constitutive expression of CKLF in myoblasts that was abolished in myotubes during differentiation process and was induced again by thrombin. Thrombin regulates CKLF expression through protease-activated receptor-1 in myotubes. Treatment of a protein kinase C inhibitor partially blocked CKLF expression in myoblasts, while it remarkably inhibited that in myotubes.
Conclusion –  Chemokine-like factor expression is differentially regulated in myoblasts and myotubes. Thrombin could be a strong regulator for its expression. As CKLF is immunohistochemically positive in regenerating muscle fibers, we postulate here that CKLF is a useful marker for regenerating muscle fibers in inflammatory myopathies.     

B7-H1分子免疫病理在多发性肌炎中的临床研究

目的 通过免疫组化染色了解协同刺激分子B7-H1蛋白在多发性肌炎(PM)和肢带型肌营养不良2B型(LGMD 28)患者肌组织中的表达情况,探讨其在PM诊断和鉴别诊断中的意义.方法 选择苏州大学附属第一医院神经内科自2006年1月至2009年12月收治的43例PM患者(PM组),26例LGMD 2B型患者(LGMD 2B组)及21例肌活检正常者(对照组).对所有成员行肌肉活检,冰冻切片后进行常规HE染色、免疫组织化学染色,检测肌组织中B7-H1蛋白的表达.结果 (1)PM组与LGMD 2B型组肌肉活检普通病理染色结果相似,表现为不同程度的坏死、吞噬、再生现象,伴有不同程度的炎细胞浸润.(2)PM组B7-H1蛋白阳性表达主要定位于细胞膜,呈棕黄色至棕褐色,主要集中在有炎细胞浸润的变性、坏死肌纤维上;其肌组织中B7-H1蛋白表达水平比较LGMD2B型组和对照组成员肌组织中水平明显增高(分别为69.77%、26.92%、4.76%),差异有统计学意义(P<0.05).结论 协同刺激分子B7-H1在PM患者肌组织中高表达,参与了PM的免疫学发病机制,可成为PM与继发性炎细胞浸润性肌病相鉴别的免疫病理标志.     

B7-H1分子免疫病理在多发性肌炎中的临床研究

目的 通过免疫组化染色了解协同刺激分子B7-H1蛋白在多发性肌炎(PM)和肢带型肌营养不良2B型(LGMD 28)患者肌组织中的表达情况,探讨其在PM诊断和鉴别诊断中的意义.方法 选择苏州大学附属第一医院神经内科自2006年1月至2009年12月收治的43例PM患者(PM组),26例LGMD 2B型患者(LGMD 2B组)及21例肌活检正常者(对照组).对所有成员行肌肉活检,冰冻切片后进行常规HE染色、免疫组织化学染色,检测肌组织中B7-H1蛋白的表达.结果 (1)PM组与LGMD 2B型组肌肉活检普通病理染色结果相似,表现为不同程度的坏死、吞噬、再生现象,伴有不同程度的炎细胞浸润.(2)PM组B7-H1蛋白阳性表达主要定位于细胞膜,呈棕黄色至棕褐色,主要集中在有炎细胞浸润的变性、坏死肌纤维上;其肌组织中B7-H1蛋白表达水平比较LGMD2B型组和对照组成员肌组织中水平明显增高(分别为69.77%、26.92%、4.76%),差异有统计学意义(P<0.05).结论 协同刺激分子B7-H1在PM患者肌组织中高表达,参与了PM的免疫学发病机制,可成为PM与继发性炎细胞浸润性肌病相鉴别的免疫病理标志.     

B7-H1分子免疫病理在多发性肌炎中的临床研究

目的 通过免疫组化染色了解协同刺激分子B7-H1蛋白在多发性肌炎(PM)和肢带型肌营养不良2B型(LGMD 28)患者肌组织中的表达情况,探讨其在PM诊断和鉴别诊断中的意义.方法 选择苏州大学附属第一医院神经内科自2006年1月至2009年12月收治的43例PM患者(PM组),26例LGMD 2B型患者(LGMD 2B组)及21例肌活检正常者(对照组).对所有成员行肌肉活检,冰冻切片后进行常规HE染色、免疫组织化学染色,检测肌组织中B7-H1蛋白的表达.结果 (1)PM组与LGMD 2B型组肌肉活检普通病理染色结果相似,表现为不同程度的坏死、吞噬、再生现象,伴有不同程度的炎细胞浸润.(2)PM组B7-H1蛋白阳性表达主要定位于细胞膜,呈棕黄色至棕褐色,主要集中在有炎细胞浸润的变性、坏死肌纤维上;其肌组织中B7-H1蛋白表达水平比较LGMD2B型组和对照组成员肌组织中水平明显增高(分别为69.77%、26.92%、4.76%),差异有统计学意义(P<0.05).结论 协同刺激分子B7-H1在PM患者肌组织中高表达,参与了PM的免疫学发病机制,可成为PM与继发性炎细胞浸润性肌病相鉴别的免疫病理标志.

Abstract：

Objective To analyze the protein expression of costimulatory molecule B7-H1 in muscular tissues of patients with polymyositis (PM) and limb-girdle muscular dystrophy-2B type (LGMD-2B), and investigate its relevance to the pathogenesis of PM and its role in the diagnosis and identification of PM. Methods Forty-three patients with PM, 26 patients with LGMD -2B and 21 with normal muscle biopsy were recruited. Muscle biopsy was performed before frozen sections, and then, HE staining and immunohistochemistry were employed to detect the protein expression of B7-H1 in muscle tissues of each group. Results The results of HE staining of muscle tissues in the PM group and LGMD 2B group were very similar; varying degrees of necrosis, phagocytosis and regeneration phenomenon were noted with varying degrees of inflammatory cell infiltration. In PM group,muscle-related expression of B7-H1 was observed on the surface of muscle fibers (the cytomembrane). It was localized in areas where inflammatory cells lay in close apposition to damaged or non-necrotic muscle fibers. The B7-H1 protein in the PM muscular tissue was significantly increased as compared with that in the LGMD -2B tissue and normal tissue (69.77%, 26.92%, 4.76%, P<0.05). Conclusion Costimulatory molecule B7-H1 is highly expressed in the muscular tissue of patients with PM and it may be involved in the immunological pathogenesis of PM. It can be used to make a distinction between PM and other myopathies that have secondary inflammatory changes.     

Extrajunctional acetylcholine receptors. Alterations in human and experimental neuromuscular diseases.

Diffuse extrajunctional acethycholine receptors (AChR) of skeletal muscle fibers were readily visualized by light and electron microscopy in muscle biopsy specimens of experimental denervation and human denervating diseases by use of an alpha-bungarotoxin immunoperoxidase technique. In peripheral neuropathies and various motor neuron diseases, a significant number of muscle fibers appearing denervated by histochemical criteria have diffuse extrajunctional AChR like those experimentally denervated by cutting the motor nerve supply. In portions of muscle fibers experimentally deprived of neuronal influence by direct injury, diffuse extrajunctional AChR developed, demonstrating that a denervation-like diffuse appearance of extrajunctional AChR can develop other than with neuronal damage, ie, it can be myogenous. Similar extrajunctional AChR was seen in some regenerating fibers of human myopathies, especially inflammatory myopathies.     

Immunolocalization of FAS and FAS ligand in inflammatory myopathies

Fas/Fas ligand (FasL) interaction can induce apoptosis, have a costimulatory role or act as a mechanism by which cytotoxic T cells produce target cell lysis. We used several commercially available antibodies to study Fas and FasL expression in polymyositis (PM), inclusion body myositis (IBM), dermatomyositis (DM) and normal controls. A strong Fas signal occurred on the sarcolemma, and to a lesser extent in the sarcoplasm of neural cell adhesion molecule (NCAM)-positive or developmental myosin heavy chain-positive regenerating muscle fibers and of injured fibers with presumed abortive regenerative activity, including some nonnecrotic invaded fibers in PM and IBM and some of the atrophic perifascicular fibers in DM. Most fibers within groups of atrophic fibers in IBM were strongly Fas-positive, and statistically more muscle fibers were Fas-positive in IBM compared to PM. A subset of the actively invading CD8+ T cells in nonnecrotic muscle fibers in PM and IBM, and scattered CD4+ cells in each inflammatory myopathy, had up-regulated Fas expression, probably reflecting costimulation. No FasL antibody consistently labeled the positive control tissue (testis) or intramuscular elements in control or inflammatory myopathy specimens. Our study identifies regenerating muscle fibers as the main site of Fas immunoreactivity in inflammatory myopathies, and Fas expression may be part of an activated or reactivated developmental program of new gene expression in regenerating or denervated muscle fibers. Our data plead against a specific role of Fas/FasL interaction in the immunopathogenesis of the inflammatory myopathies.     

Pleomorphic mitochondrial and different filamentous inclusions in inflammatory myopathies associated with mtDNA deletions

Mitochondrial changes are frequently observed in muscle fibers of patients with inclusion body myositis (IBM) and polymyositis (PM), suggesting that mitochondrial function may be especially impaired in these forms of inflammatory myopathies. Intranuclear and cytoplasmic tubulofilamentous inclusions are characteristic, although not totally specific for IBM. In the present cases, the inclusions were strikingly pleomorphic when chloroquine had been given for long periods. The nuclear inclusions were always tubular, whereas the cytoplasmic filaments had either a tubular, a helical, or a cross-striated structure with different diameters and arrangements in association with myelin-like figures, and vacuoles. Abnormal mitochondria containing paracrystalline, globoid, and other inclusions, noted in IBM, were occasionally also seen in PM or vasculitis. By contrast, in the latter, no intranuclear or cytoplasmic tubulofilamentous inclusions were apparent in muscle fibers. This study reports for the first time the presence of membrane-bound crystalloid inclusions in a muscle fiber with numerous abnormal mitochondria; similar structures have thus far only been observed in macrophages. The identity and function of these inclusions remains unknown. Using PCR analysis we detected different mtDNA deletions not only in IBM, but also in PM and vasculitis, indicating at least some degree of association between the structural mitochondrial abnormalities and the mtDNA mutations. There was no topographical correlation between the presence of tubular or helical filaments and the mitochondrial abnormalities. As already noted by others, the mitochondrial changes in IBM were more frequent than expected in this age group. It is suggested that the presence of the mtDNA deletions in IBM and PM are not primary, but rather the result of the underlying, presumably immunological disorder causing nuclear and secondary or simultaneous mitochondrial changes. Received: 12 May 1997 / Revised, accepted: 17 February 1998     

肌纤维内脂滴增多在炎性肌病中的意义

目的　了解在炎性肌病中肌纤维内脂滴增多的发生频率、影响因素及临床意义。方法回顾性分析53例多发性肌炎和皮肌炎患者的临床病理资料,通过油红O染色显示肌纤维脂滴,依据肌纤维内脂滴的含量将患者分为大致正常和明显增多两组,比较各组患者肌力、肌酶谱、肌肉组织病变程度、病程和用皮质类固醇治疗情况。结果　在53例肌肉标本中, 37 7%有脂滴明显增多。与脂滴正常组相比,脂滴明显增多组肌纤维坏变程度和临床肌力下降程度差异有统计学意义。虽然用激素治疗患者出现脂滴明显增多的几率增加,但无统计学意义。结论　部分肌炎患者有肌纤维内脂滴增多,主要与肌纤维病变有关,细胞能量代谢的异常又可能促进肌纤维的病变,加重肌肉无力。     

Peripheral neuropathy of mitochondrial myopathies.

Peripheral neuropathy has attracted relatively little attention in mitochondrial myopathy. However, mitochondrial myopathies are clinically heterogeneous disorders that can affect multiple systems including peripheral nerves other than the skeletal muscle. In addition to the survey of the literature, we studied 6 cases of mitochondrial myopathy with peripheral neuropathy; 3 cases of oligo-systemic involvement confined mainly to skeletal muscles and peripheral nerves, and 3 cases of multi-systemic involvement diagnosed as myoclonus epilepsy with ragged-red fibers (MERRF) or mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). This study suggests that peripheral neuropathy may be relatively common and has similar clinical and laboratory features in a broad spectrum of mitochondrial myopathies. The clinical manifestation is usually of mild sensorimotor neuropathy with frequent subclinical involvement. Sensory disturbances are more evident than manifestations of motor neuropathy which is usually subclinical. It is also noteworthy that there exist some cases of oligo-systemic involvement, which present with peripheral neuropathy as main clinical manifestations. Electrophysiological findings include decreased nerve conduction velocities and neuropathic electromyograms. Peripheral nerves show loss of myelinated fibers, particularly of large ones, and the remaining fibers have disproportionately thin myelin sheaths with or without onion-bulb formation. Thus the pathological process is axonal degeneration with demyelination resulting from involvement of both neurons (axons) and Schwann cells.     

Expression of tumor necrosis factor-α in regenerating muscle fibers in inflammatory and non-inflammatory myopathies

The expression level of tumor necrosis factor (TNF)-alpha is elevated in idiopathic inflammatory myopathies and Duchenne muscular dystrophy (DMD), but the precise role of TNF-alpha is unknown. To elucidate the possible role of TNF-alpha, we investigated the expression of TNF-alpha and its receptor in polymyositis (PM), dermatomyositis (DM), and DMD using in situ hybridization (ISH) and immunohistochemistry. We showed that TNF-alpha mRNA and protein were present in muscle fibers. TNF-alpha-positive fibers were observed in all cases of PM, DM and DMD, but were rare or absent in neurogenic disorders and normal controls. The proportion of TNF-alpha-positive fiber showed a significant positive correlation with the proportion of regenerating fibers that were positive for the developmental form of myosin heavy chain (MHC-d). The number of TNF receptor-positive fibers was small. Some muscle fibers expressed both TNF-alpha and its receptor simultaneously. Our results indicate that TNF-alpha is produced and expressed by muscle fibers and associated with muscle regeneration.     

Expression of the costimulatory molecule BB-1 and its receptors in patients with scleroderma-polymyositis overlap syndrome

We investigated expression of costimulatory molecules BB-1, B7-1 (CD80), B7-2 (CD86), and their counter-receptors CD28 and CTLA-4 (CD152) in muscle biopsy specimens of patients with scleroderma-polymyositis overlap syndrome (SSc-PM), primary polymyositis (PM), and other related diseases to examine whether the muscle fibers in patients with SSc-PM behave as antigen-presenting cells (APCs). The major histocompatibility (MHC) class II-positive muscle fibers of SSc-PM patients reacted with monoclonal antibodies (mAb) against BB-1 but not against B7-1 or B7-2. The CD4+ T cells expressed the counter-receptors CD28 and CTLA-4, and bound with the BB-1-positive muscle fibers in cell-to-cell contact. Our findings show that muscle fibers in patients with SSc-PM function as "professional" APCs in a way distinct from muscle fibers in patients with primary PM.     

肌萎缩侧索硬化患者血清对器官型培养脊髓片的影响

目的　观察肌萎缩侧索硬化(ALS)患者的血清对器官型培养的脊髓片的影响,探讨ALS运动神经元损伤的机制。方法　取120只生后8d乳鼠的腰段脊髓切片240片做器官型培养,在培养液中分别加入健康对照血清(对照组120片)和含有较高浓度谷氨酸(Glu)的ALS患者血清(ALS组120片),培养4周,计数脊髓前角α运动神经元和后角中间神经元的数目,琥珀酸脱氢酶(SDH)染色观察线粒体酶活性改变,测定培养液中乳酸脱氢酶(LDH)、Glu、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量,两组间进行比较。结果　对照组脊髓片在体外生长良好,α运动神经元(约15个/张脊髓片)和后角中间神经元(约40个/2 5mm2 )的数目稳定。而ALS组的脊髓片在培养4周时前角α运动神经元的数目明显减少(约7个/张脊髓片),SDH染色明显减弱。用ALS患者血清干预后,培养液中LDH、MDA的含量在培养3周后较对照组分别升高了22 4%和48 2%,而SOD则下降了12 6%;ALS组培养液中的Glu含量在各时点均较对照组显著升高(P<0 .01 )。结论　Glu兴奋毒、自由基损伤在ALS的发病中起重要作用,脊髓的器官型培养技术为ALS损伤机制的探讨提供了有效手段。     

Expression of myositis specific autoantigens during post-natal myogenesis

Idiopathic inflammatory myopathies such as polymyositis (PM) and dermatomyositis (DM) are a group of rare autoimmune diseases, characterized by an inflammatory infiltrate within the skeletal muscle and high titer of circulating autoantibodies in the patient's serum. The etiopathogenesis of these diseases is not known and the relationship between the specific muscle involvement and the ubiquitary presence of the targeted antigens is still unclear. The enhanced expression of myositis specific autoantigens in regenerating muscle fibers from biopsies of PM and DM patients compared to normal muscle has been recently demonstrated. In order to understand whether candidate autoantigens in myositis are expressed during post-natal myogenesis, we performed immunolocalization studies of myositis specific autoantigens in skeletal muscle from newborn and adult rats. Our observations indicate the presence of myositis specific autoantigens during post-natal myogenesis, with possible implications for the induction and/or amplification of the immune-inflammatory response, in patients affected with autoimmune myositis.     

Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies

The inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), and sporadic inclusion-body myositis (s-IBM). In DM, the main immune effector response appears to be humoral and directed against the microvasculature, whereas in both PM and s-IBM, cytotoxic CD8+ T cells and macrophages invade and eventually destroy nonnecrotic muscle fibers expressing major histocompatibility complex class I. The need for more specific and safer therapies in inflammatory myopathies has prompted researchers to better decipher the molecular events associated with inflammation and muscle fiber loss in these diseases. The complex specific migration of leukocyte subsets to target tissues requires a coordinated series of events, namely activation of leukocytes, adhesion to the vascular endothelium, and migration. Cell adhesion molecules (CAM) and chemokines play a major role in this multistep process. In addition, cytokines by stimulating CAM expression and orchestrating T-cell differentiation also influence the immune response. This review focuses on recent advances in defining the molecular events involved in leukocyte trafficking in inflammatory myopathies. Specific topics include a concise summary of clinical features, pathological findings and immunopathology observed in inflammatory myopathies, background information about cytokines, chemokines and cell adhesion molecules, and the expression of these molecules in inflammatory myopathies.     

Muscle biopsy correlated with electromyography. Study of 100 cases

To find what the correlation is and verify if it is possible to avoid extensive electromyographic examination, studying only one muscle, 100 patients with neuromuscular disorders (58 primary myopathies, 32 neurogenic disorders and 10 myotonic dystrophies) were submitted to quantified electromyography (EMG) and muscle biopsy (MB) with fresh-frozen section plus histochemistry in the same muscle, but on the opposite side. The EMG was abnormal in 98% and MB in 93% of the cases. EMG and MB had a concordance of 84.3% in the neurogenic disorders and 84.77% in the primary myopathies. A correlation of 80% was obtained between all MB and EMG (including the cases of myotonic dystrophies), regarding the origin of the pathogenic process (p less than 0.01). The EMG had 5% inconsistencies and the MB 11%, with respect to the pathogenic process. When the myotonic dystrophy was separated from the primary myopathies and from the denervation disorders, a complete concordance was found in all MB and had only 3.4% inconsistencies in the denervation disorders and 3.1% in the primary myopathies.     

Multifactorial study of inflammatory myopathies. Report of 29 cases

We made a comparative clinical, immunopathological and therapeutic evaluation in 17 patients with polymyositis (PM) and 12 patients with dermatomyositis (DM), followed up at our Neuromuscular Center. DM can be distinguished by its clinical appearance and pathological changes. Current evidence suggests that it results from vasculopathy. For studying these inflammatory myopathies we used multifactorial diagnostic criteria, evaluating the therapeutic response by means of a composite clinical and functional score in a longitudinal study. In muscle biopsy specimens we characterized with monoclonal antibodies T lymphocyte subpopulations (CD4, CD8), macrophages, IgG, IgM, C1q, C3, C4 complement fractions, MHC-I, MHC-II. In PM the cell-mediated immunity was more pronounced and in sowithin muscle fibers. Our patients were treated with steroids; in resistant cases azathioprine, cyclophosphamide, plasmapheresis, high-dose intravenous immunoglobulins (ivIgG) and total body irradiation were added to the therapeutic schedule. Paper presented at the National Congress at Sorrento in 1991 and selected by the Editorial Board of the Journal     

Myopathy with trabecular muscle fibers.

A systematic review of muscle biopsies over a 15 year period in a large neurological hospital revealed 21 cases (7% of the total of non-inflammatory myopathies) with a distinctive pattern of myopathology and a limb-girdle clinical phenotype. The muscle pathology was dominated by a large prevalence (20-90%) of trabecular or lobulated fibers in which maldistribution of intermyofibrillar mitochondria produced a lobulated pattern of oxidative enzyme activity on transverse sections. The clinical picture was characterized by adult onset, slowly progressive muscle weakness affecting mainly proximal limb musculature, although mild distal weakness was also present in 60% of the cases. The trabecular pattern of oxidative enzyme reaction reflects maldistribution of the intermyofibrillar mitochondria; this may be caused by malfunction of a putative anchoring mechanism. While trabecular fibers can occur as a nonspecific alteration of muscle fibers in many diverse myopathies, the high prevalence of trabecular fibers as the dominant pathology in trabecular fiber myopathy makes it a distinctive (though not necessarily etiologically homogeneous) clinico-pathological entity.     

Immunocytochemical localisation of complement components C8 and C9 in human diseased muscle. The role of complement in muscle fibre damage

The localisation of the complement components C8 and C9 was studied immunocytochemically in human diseased muscle to determine the role of complement in muscle fibre damage. Monoclonal antibodies to 2 epitopes of C9 and a monoclonal antibody to the alpha subunit of C8 were applied to frozen sections of muscle biopsies from 9 cases of dermatomyositis, 5 cases of polymyositis, 7 cases of Duchenne muscular dystrophy and 4 cases of Becker muscular dystrophy. These were compared with 6 control biopsies which were morphologically normal. In all cases of inflammatory myopathies several non-necrotic fibres showed discrete peripheral patches of C9 and to a lesser extent C8. In the muscular dystrophies peripheral C9 was observed on a few non-necrotic fibres and basophilic fibres showed C9 between the fibres as well as at the periphery. In all cases necrotic fibres labelled intensely with C9 and C8 but intensities varied with the different monoclonal antibodies. This was thought to result from differences in the polymerisation of the C9 molecule in the membrane attack complex. Complement C8 and C9 were also localised to blood vessels in 3 cases of muscular dystrophy, 2 cases of polymyositis and all cases of juvenile dermatomyositis. No complement was observed in the control samples. Our results provide evidence for the sublytic formation of the membrane attack complex (MAC) on non-necrotic fibres in inflammatory myopathies and muscular dystrophy. This sublytic formation of the MAC may induce sublethal metabolic damage, mediated by calcium, and suggests a primary role of complement in muscle damage not only in inflammatory disorders but also muscular dystrophy.