进行性肌营养不良患儿肌肉组织转化生长因子-β_1的表达

目的　进行性肌营养不良肌纤维化的病理机制不清。转化生长因子 β1(TGF β1)能诱导细胞外基质的积聚 ,对纤维发生和组织修复起调节作用。本研究探讨进行性肌营养不良患儿肌肉TGF β1表达与肌纤维化的关系 ,阐明儿童进行性肌营养不良肌纤维化慢性病理进展的部分机制。方法　采用免疫荧光和免疫印迹的方法检测 18例进行性肌营养不良患儿 [7例Duchenne肌营养不良 (DMD) ,6例福山型和 3例非福山型先天性肌营养不良 (FCMD ,nFCMD) ,2例Becker型肌营养不良 (BMD) ]和 13例非神经肌肉疾病患者肌肉组织中TGF β1表达。结果　先天性肌营养不良 (CMD)和DMD肌组织内潜伏和活性形式的TGF β1均免疫定位于肌纤维和间质的肌内膜 ,表达强度以CMD为著。免疫印迹结果显示FCMD肌肉组织TGF β1表达强于DMD和对照。结论　在儿童进行性肌营养不良的肌肉慢性病理进展中 ,肌肉纤维化可能是重要原因之一。     

An unusual case of congenital muscular dystrophy with normal serum CK level, external ophtalmoplegia, and white matter changes on brain MRI

We report a sporadic case of congenital muscular dystrophy (CMD) in a 13-year-old girl with early manifestation of muscle weakness and hypotonia, severe contractures, bulbar syndrome, progressive external ophtalmoplegia, and white matter changes on magnetic resonance imaging (MRI) of the brain, but no mental defect. Serum creatine kinase (CK) level was normal. Muscle biopsy revealed a dystrophic picture with a prominent inflammatory infiltrate mimicking inflammatory myopathy-typical histological findings in CMD. Immunostaining showed normal expression of merosin, alpha and beta-dystroglycans. Mutation analyses of calpain3, dysferlin, and SEPN1 genes were negative. An electron microscopy revealed the accumulation of abnormally enlarged mitochondria located under the sarcolemma. Measurement of respiratory chain enzyme activities did not reveal any biochemical defect and mitochondrial genetic studies, including sequencing of the entire mitochondrial genome, were unremarkable. Phenotypic presentation of our patient is very unusual and differs considerably from other CMD variants.     

Progressive pseudorheumatoid dysplasia

A rare case of progressive pseudorheumatoid dysplasia (PPD) in a 9-year-old girl is presented. Clinically, chronic painless swollen joints, accompanied by progressive motion restriction and progressive walking difficulties, were found. Radiologically, there was enlargement of the epimetaphyseal portions of the large joints, metacarpal heads, and phalanges, and generalized platyspondyly with irregular delineation of the endplates of the vertebral bodies. The radioclinical features at the peripheral joints were originally misdiagnosed as juvenile rheumatoid arthritis (JRA), and the structural spinal abnormalities were neglected and interpreted as Scheuermann's disease. However, the absence of active inflammatory parameters argues against JRA, whereas the low age of onset of the irregularities at the vertebral endplates is an argument against the diagnosis of Scheuermann's disease. The combination of the dysplastic abnormalities of the spine, with platyspondyly and Scheuermann-like lesions at an unusually low age of onset, and radiological features mimicking JRA of the peripheral joints, is the clue to the diagnosis of this rare autosomal-recessive disease. This case is the first to document the MRI features of PPD of the spine. Received: 22 February 2000; Revised: 5 May 2000; Accepted: 9 May 2000     

Pulmonary Epithelioid Hemangioendothelioma: A Case Report

A 45-year-old woman whose x-ray film revealed multiple widespreadbilateral small nodules was diagnosed as having pulmonary tuberculosisor metastatic pulmonary cancer. A conclusive histological diagnosisof pulmonary epithelioid hemangioendothelioma (PEH) was madefollowing an open-lung biopsy. PEH is a progressive diseasethat probably originates from an endothelial cell. However,there is still no effective therapeutic modality for PEH. Thepostoperative course of our patient has been uneventful withno evidence of tumor growth for four and a half years afterinitial x-ray detection of the lesions.     

Clinicopathological study of atypical motor neuron disease with vertical gaze palsy and ballism

The case of a 38-year-old patient with rapidly progressing motor neuron disease, complicated by major dysfunction of the extrapyramidal system and of vertical gaze is described. Neuropathological examination revealed a degenerative process that severely affected the lower motor neurons, as well as the neurons of the pars compacta of the substantia nigra, the nucleus of Darkschewitsch, the nucleus interstitialis of Cajal, the colliculi superiores, and the pallidum. The long tracts were unaffected at all levels of the brain stem and spinal cord. There was no convincing evidence for the presence of a multiple system atrophy or progressive supranuclear palsy; the results rather revealed a pattern of vulnerability characteristic of a variant of motor neuron disease. Received: 9 November 1999 / Revised, accepted: 10 December 1999     

Screening for HIV-associated distal-symmetric polyneuropathy in CDC-classification stages 1, 2, and 3

OBJECTIVES: A total of 670 patients were screened for distal symmetric HIV-associated polyneuropathy during CDC stages 1-3 and its correlation to immunological deterioration. MATERIAL AND METHODS: Clinical examinations of 670 patients admitted to the neurological outpatient clinic at the Department of Neurology, University of Munster. Neurophysiological investigations were performed on the sural and peroneal nerve for detection of axonal and myelin lesion. RESULTS: Clinical examination proved progressive clinical signs and symptoms indicating distal symmetric polyneuropathy from CDC 1 (32%) to CDC 3 (55%). At least one neurophysiological result was impaired in CDC 1 in 25% and in CDC 3 in 45%. Significant correlation between neurophysiological changes and CDC4(+)-cells and beta-microglobuline were detected for stage CDC 3 C. CONCLUSION: Results show stage related prevalence of distal symmetric polyneuropathy already in early stages. In late stages of HIV-infection prevalence of distal symmetric polyneuropathy seems to be directly correlated to immunodeficiency syndrome. The pathogenesis of distal symmetric polyneuropathy during HIV-infection is up to now incompletely understood, but results indicate a clear dependency between progressive immunological dysfunction and neuropathy. High active antiretroviral therapy in patients suffering from distal symmetric polyneuropathy is a main topic of future studies.     

Progressive multifocal leukoencephalopathy and oligodendroglioma in a monkey co-infected by simian immunodeficiency virus and simian virus 40

A rhesus monkey experimentally inoculated with simian immunodeficiency virus (SIV) mac₂₅₁ was killed 42 months later because of poor general condition. CD4 lymphocyte count which was 3,430/mm³ before inoculation, had decreased to 638/mm³ 2 months before death. Neuropathological examination revealed changes characteristic of progressive multifocal leukoencephalopathy (PML) in the white matter of the cerebral hemispheres and brain stem. In situ hybridization was negative for JC virus but markedly positive for simian virus 40 (SV40) in the nuclei of many oligodendrocytes. Many oligodendrocytes also expressed p53. Within an area involved by PML, there was a densely cellular tumor with honeycomb appearance and elongated vessels characteristic of oligodendrogliomas. Within the tumor in situ hybridization for SV40 and immunocytochemistry for p53 were negative. Opportunistic infection by SV40 has been occasionally reported in experimentally SIV-infected monkeys resulting in PML or malignant astrocytoma. Association of JC virus-induced PML and astrocytomas has been reported in three human cases without AIDS. In those cases, as in our monkey, polyomaviruses (SV40 or JC virus) were expressed in the areas with PML but not in the glial tumor. Association of PML and oligodendroglioma has not been reported previously to our knowledge. The relationship between oligodendrocyte proliferation and polyomavirus infection of oligodendrocytes is unclear. Our findings suggest that binding of the viral protein to p53 may result in inactivation of the pro-apoptotic protein favoring the proliferation of a randomly occurring tumoral clone of oligodendrocytes. Received: 27 October 1999 / Revised, accepted: 30 November 1999     

Morphometry of intrarenal arteries in progressive sclerosis

Summary Vessels of known position in the vascular tree of the kidneys of two cases with a long history of progressive systemic sclerosis — one normotensive, one hypertensive — were examined morphometrically.Medial thickness, intimal thickness and the relative content of collagen and elastin in the vascular media were measured. Smooth muscle nuclei were counted in the arterial cross section.These morphometric data were compared with those obtained from two autopsy cases — one with a history of essential hypertension, one without any hypertensive history. The findings suggest that progressive sclerosis induces intimal thickening in all branches of the renal artery down to a distented diameter of 200 m.In the case where progressive sclerosis was complicated by arterial hypertension increased medial thicknesses were found, similar to the findings in the case with a history of essential hypertension.     

Progressive interstitial pulmonary lobar emphysema

Progressive pulmonary interstitial lobar emphysema is a complication of artificial ventilation in premature infants with RDS. Three cases are presented who developed a progressive form of PIPE. It is demonstrated that PIPE is caused by air escaping through alveolar leaks into the pulmonary lymphatic capillary system causing dilation of lymphatic channels. Because of its increasing compressive effect on adjacent lung areas PIPE requires rapid and effective therapy. Although several types of conservative approach are suggested, lobectomy appears to be the method of choice. Lobectomy is not indicated when prolonged ventilation with high pressures and high concentrations of oxygen have caused severe bronchopulmonary dysplasia.     

Autoantibodies in SLE but not in scleroderma react with protein-stripped nucleosomes

Autoantibodies against nucleosomes (ANuA) are known to be sensitive markers for systemic lupus erythematosus (SLE), but their clinical relevance seemed to be limited because sera from patients with progressive systemic sclerosis (PSS) also showed positive reactions with conventional ANuA ELISA test systems (anti-Nu1 ELISA). It was generally assumed thatANuA were associated with both diseases. Using discontinuous sucrose gradient centrifugation to generate pure nucleosomes, we discovered by chance that at the 30-50% sucrose interface an antigen (Nu2) banded which was demonstrably free of non-histone components and histone H1. The two different nucleosome preparations, Nu1 and Nu2, were used in parallel as antigenic substrates in standardised ELISA tests to analyse sera from SLE (295 patients), PSS (119) and patients with other rheumatic diseases (101). With Nu1, 62% of the SLE and 52% of the PSS sera showed positive reactions. Two sera from patients suffering from Sj?gren's syndrome (SS) and one from polymyositis were also positive. Using the Nu2 preparation, 58% of the SLE but none of the PSS sera showed a positive reaction. One serum from a patient with SS was also positive. It could be shown that it was the PSS-specific autoantigen Scl-70 in the nucleosome preparation (Nu1) which contributed to the positive reactions of the PSS sera in conventional ANuA test systems, whereas in the Nu2 preparation no remaining Scl-70 was detectable. The present study definitely proved that ANuA are highly and specifically associated with SLE but not with PSS.