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The Stüve-Wiedemann syndrome (SWS) comprises short stature, congenital bowing of the long bones, respiratory distress, and recurrent episodes of unexplained hyperthermia. The skeletal radiographic changes include short and broad long bones, large metaphyses, internal cortical thickening, and angulation primarily of tibiae and femora, but also of humeri and forearm bones. We report 3 cases of SWS from 2 different unrelated consanguineous gypsy families. All 3 cases fulfilled the clinical and radiological criteria of SWS. Two patients died shortly after birth, whereas the third one was alive at the age of one year. Besides hyperthermic episodes, one patient had hyperaminoaciduria, hepatic failure, and megaloblastic anemia which prompted us to investigate mitochondrial respiratory chain in 2 cases. Abnormal results consisting of decreased activities of complex I and IV were found in both. The simultaneous occurrence of both SWS phenotype and abnormal mitochondrial metabolism in two unrelated cases strongly supports the hypothesis of a pathogenetic relationship between the two events. These cases may also be related to recent reports on the effects of the mitochondrial respiratory chain defects on embryogenesis.

We present a new experimental model of Staphylococcus aureus infective endocarditis in guinea pigs. Permanent aortic valve damage was produced by electrocoagulation after catheterization of the right carotid artery, which allowed avoidance of the intracardiac catheter to produce cardiac vegetations. Our model closely mimics pathological mechanisms of native valve endocarditis.

Exercise intolerance associated with myalgias, muscle cramps or myoglobinuria may be associated with a dystrophinopathy. A search for abnormal dystrophin expression (using immunohistochemistry, immunoblot and DNA analysis) was carried out in a series of 15 patients. They were selected because they presented exercise intolerance, negative biochemical tests (lipid, glycogen and mitochondrial metabolism) and abnormal immunohistochemistry with at least one anti-dystrophin antibody (anti-Dys 1, rod domain; anti-Dys 2, C terminus; anti-Dys 3, N terminus). Lack of anti-Dys 1 immunoreactivity was seen in three patients and abnormal immunoreactivity with all three anti-dystrophin antibodies in two. Immunoblot confirmed the dystrophinopathy in these five patients only, and multiplex polymerase chain reaction DNA analysis revealed a deletion in the dystrophin gene in two of these patients, affecting the proximal part of the rod domain in one and the distal part of this domain in the other. The clinical, biological and histopathological features of the five patients reported here, together with the previous cases reported in the literature, are described and reveal that exercise intolerance associated with dystrophinopathy displays characteristic clinical, biological and immunohistochemical features and defines a new dystrophinopathy phenotype. The absence of staining in the rod domain provides a secure diagnosis of this syndrome. Dystrophinopathy is one etiology of idiopathic myoglobinuria, requiring genetic counseling.

We report two cases of gastrocnemius muscle vasculitis revealing Crohn's disease. Gastrocnemius muscle biopsy evidenced a necrotizing vasculitis resembling panarteritis nodosa in one case; a nonnecrotizing vasculitis was found in the other case. Neither of the patients had systemic vasculitic involvement, and the muscle disease resembled calf muscle-located panarteritis nodosa. Our literature review shows five cases of calf-located myalgia occurring during Crohn's disease characterized by heterogenous histopathological findings including vasculitic and myositic lesions. Thus, faced with calf-located myalgia with vasculitis or myositis, a search for Crohn's disease is probably necessary to determine precisely the frequency and the etiopathogenic mechanisms of this association.

The incidence of neurosyphilis has been increasing since AIDS has appeared but acute gummatous necrotizing progression is so far exceptional. We report a second case of "quaternary neurosyphilis" in a 29-year-old patient without serologic nor CT scan evidence of treponema. Diagnosing neurosyphilis is particularly difficult in HIV-1 infected patients, specially in spirochetes-poor injuries.

Integrins form a family of cell adhesion molecules. CD44 glycoproteins are found in a wide variety of isoforms; the most common, CD44s (standard) is widely distributed, and functions as an adhesion molecule. In this study, we have investigated immunohistochemically the distribution of some VLA integrins (alpha2, alpha5 and alpha6 chains of beta1 integrins) and CD44s in 44 meningioma specimens and normal arachnoid villi. Meningiomas were of meningothelial (16), transitional (13) and fibroblastic (15) subtypes. There were 13 grade I, 19 grade II and 12 grade III (27%). Immunoprecipitates were quantified by image analysis and correlated with clinical (age, sex, location) and morphological data (histological subtypes and grades). VLA alpha5 chain was expressed by normal arachnoid villi (mainly cap cells) and by 42 out of 44 meningioma specimens. Expression was lower in fibroblastic meningiomas (P=0.02). VLA alpha2 and alpha6 chains were not observed in normal arachnoid villi. VLA alpha2 was expressed by 15 meningiomas, VLA alpha6 by 10. Interestingly, meningiomas expressing either VLA alpha2 or alpha6 were usually of grade III (P< or =(0.05). CD44s was found on various parts of arachnoid villi and in all meningiomas although expression was higher in meningothelial and transitional than in fibroblastic (P< or =0.001). These results show that VLA alpha5 and CD44s are widely expressed by arachnoid villi and meningiomas, in contrast to VLA alpha2 and VLA alpha6. It was noted that high grade meningiomas (III) express VLA alpha2 and alpha6 suggesting that changes in integrin pattern expression are a feature of these meningiomas. Moreover, strong CD44s expression characterizes meningothelial and transitional meningiomas. Previous studies have shown that high NCAM expression is a feature of fibroblastic meningiomas whereas meningothelial and transitional meningiomas expressed mainly E-Cadherin, and that polysialylated NCAM expression was restricted to high grade meningiomas. Taken together these features suggest that each cell adhesion molecule has a characteristic pattern of expression according to meningioma subtype and grade. No correlation was seen between integrins and CD44s expression and clinical data.

The authors report two cases of aortic angiosarcomas. These cases were similar and characterized by a typical pejorative clinical course, with peripheric emboli and many osteolytic metastasis. Immunohistochemical study was in favour of an endothelial origin, electronic microscopy indicated a mixed tumor with myofibroblasts and poorly differentiated endothelial cells. Differential diagnosis between angiosarcoma, leiomyosarcoma and intimal sarcoma are reviewed.

The clinical and pathological findings of a 43-year-old woman, diagnosed as having acute hemorrhagic leukoencephalitis at postmortem examination, are presented. The acute hemorrhagic leukoencephalitis affects mainly young adults and is the most fulminant from of demyelinating disease. It is frequently preceded by a respiratory infection. Diagnosis is facilitated by CT scanning and MRI, which reveal the massive lesion in the cerebral white matter. Many cases terminate fatally in 2 or 4 days, but in others survival is longer. The pathological findings are distinctive.

Muscle biopsy is a simple procedure of great diagnostic interest when correct processing is obtained. Specimens for molecular genetics are very important. Paraffin embedded material is not sufficient in most of the cases except in some inflammatory processes. Histochemical techniques on frozen material are of major interest. Immunohistochemistry and electron microscopy can also be used. The aim of this paper is to describe the procedure of the muscle biopsy, the various techniques and the possible artefacts.

Clinicopathological, immunohistochemical and biochemical studies were performed on seven patients from five families showing an abnormal accumulation of desmin in the muscle fibers. Late onset myopathy was observed in all the cases studied. The clinical features were heterogeneous and usually nonspecific. However, some patients presented with dysphonia, dysphagia or cardiomyopathy. These features are highly suggestive of desmin myopathy. Using electron microscopy, desmin myopathy is characterized by an accumulation of granulofilamentous material. Depending on the distribution of the material, however, three different patterns of desmin accumulation can be observed: (1) large circumscribed inclusions, (2) intermyofibrillar areas of diffusely distributed material, and (3) deposits around large spheroid bodies. The second pattern is characterized by a rubbed-out appearance using oxidative enzyme reactions. For all the patients studied here, the immunohistochemical data showed that the desmin accumulation fitted these three patterns of distribution. For six patients, immunoblot analysis confirmed the desmin accumulation patterns and showed that an increase in the expression of the 53-kDa protein had occurred. The third pattern of desmin accumulation confirms the pathological heterogeneity of cytoplasmic and spheroid bodies. Desmin does not accumulate in all cytoplasmic and spheroid body myopathies, as observed in two other familial cases presented here.

31-P MR spectroscopy has been used to investigate metabolic events surrounding muscular contraction in a patient with an unusual myopathy characterized by clinical signs of muscle stiffness and swelling after prolonged exercise. Histological assays demonstrated a predominance of type II fibers with tubular aggregates. These structures had low calcium content although calcium-ATPase protein was present. Metabolic measurements were normal at rest except for the presence of a marked signal in the phosphodiester region which could reflect membrane abnormalities. Exercise-induced PCr consumption was in the normal range but the extent of the related intracellular acidosis was abnormally large. Kinetics of PCr and PCr/Pi ratio post-exercise recovery were delayed, but were likely to reflect the effect of the very low end-of-exercise pH rather than an aerobic deficiency. Finally, proton efflux from muscle to bloodstream, measured during the initial recovery period, was delayed, indicating altered mechanisms of proton handling. The most prominent metabolic abnormality recorded is the large glycogenolysis-induced pH decrease which might be linked to either abnormal activation of glycogenolysis and/or impaired proton and lactate handling within the muscle. The association between tubular aggregates and hyperacidosis is of interest but the exact causal relationship remains to be elucidated.

Construction of animal models of human inherited diseases is particularly important for testing gene therapy approaches. Towards this end, we constructed a mouse model for Charcot-Marie-Tooth disease type 1A by pronuclear injection of a YAC containing the human PMP22 gene. In one transgenic line, the YAC DNA is integrated in about eight copies and the PMP22 gene is strongly expressed to give a peripheral neuropathy closely resembling the human pathology. The disorder is dominant, causes progressive weakness of the hind legs, and there is severe demyelination in the peripheral nervous system including the presence of onion bulb formations. This approach will be valuable for pathologies produced by over-expression of a gene including trisomy and amplification in cancer. Such models will be particularly useful for testing gene therapy approaches if the transgene is human.

The purpose of this study was to use our newly developed mock circulation loop to determine the effects of cryopreservation on the common carotid artery (CCA) and the superficial femoral artery (SFA). Fourteen healthy arteries (7 CCA and 7 SFA) harvested from multiple organ donors between the ages of 18 and 35 years were tested before and after cryopreservation at -140 degrees C using dimethyl sulfoxide and the vapor phase of liquid nitrogen. Mean storage time was 4.2 months. The mock pulse rate was 60 beats/min and the following four systolic/diastolic pressures settings were used: 50/110, 80/140, 110/170, and 140/200 mm Hg. Simultaneous measurements of intra-arterial pressure and external arterial diameter were made using an intra-arterial pressure sensor and external piezoelectric sensors. Measured data were used to calculate pulsatility, volumetric compliance, stiffness, midwall radial arterial stress, Young's modulus, and the incremental modulus. After SFA cryopreservation, no significant changes were observed. Conversely, CCA cryopreservation led to a significant decrease in compliance and pulsatility and a significant increase in stiffness. Young's modulus, the incremental modulus, and midwall radial arterial stress did not change significantly. A clearcut decrease in hysteresis was observed after cryopreservation in the CCA. No evidence of structural changes was detected on light and scanning electron microscopy. Baseline findings in this study were consistent with classification of the CCA as an elastic artery and the SFA as a muscular artery. Cryopreservation had no effect on the viscoelastic properties of muscular arteries (SFA). Cryopreservation affected only values related to the cylindrical shape of the elastic arteries (CCA). It had no effect on values related to wall structure.

Acute myopathy occurred in a 49-year-old woman hospitalized in the intensive care unit for status asthmaticus. She was given high-dose intravenous steroid therapy and intubated. Pancuronium bromide was used for prolonged curarization. Flaccid quadriplegia developed with preservation of the deep tendon reflexes. Muscle biopsy showed a myogenic process with disorganized myofibrils and selective loss of thick myosin filaments. This mainly myogenic process would result from the toxic effect of corticosteroids favored by prolonged curarization although the effect of other factors still remains unknown.

We report three cases of patients who complained of myalgia showing histological features similar to tubular aggregates in their muscle biopsies. All had an elevated erythrocyte sedimentation rate without any evidence of infectious or autoimmune disease. On electron microscopy, small areas of myofibrillar degeneration, selectively in type II fibres, were found in all patients, but no tubular aggregates were seen. Although the pathogenesis of these lesions is unclear, it does seem that this condition is acquired and transient.

Eight elderly patients developed progressive paravertebral muscle weakness with bent spine on standing but normal supine posture. Computed tomography showed pronounced hypodensity of the paraspinal muscles. Serum creatine kinase was moderately increased, paraspinal EMG non-specific, and biopsy myopathic. The syndrome was familial in two patients and may be caused by a late onset paraspinal muscle dystrophy. In the absence of specific pathological changes, such cases could be classified as having "bent spine syndrome".

In order to study the biomechanical properties of the arterial wall and to compare arteries with different histologic structures, we designed a device that allows testing of arterial segments under near-physiologic conditions. A hydrodynamic generator simulates systolo-diastolic pressures in an open loop. An intraarterial pressure sensor and a sonomicrometer connected to two piezoelectric crystals placed in diametric opposition on the arterial wall allow computer calculation of compliance, stiffness, midwall radial arterial stress, Young modulus, and incremental modulus for a given arterial segment at a given pressure setting. Seven healthy common carotid artery (CCA) segments and seven healthy (superficial) femoral artery (FA) segments were studied immediately after removal from brain-dead donors between the ages of 18 and 35 years. Histologic examination was performed to determine the density of elastic fibers in the arterial wall. Hysteresis was observed in all segments regardless of pressure settings. Compliance was greater and modulus values and stiffness were lower in CCA than in FA. No evidence of structural change was noted after testing in the circulation loop. These preliminary results open the way to a wide variety of applications for our hydrodynamic circulation loop. Experiments will be undertaken to compare the mechanical properties of arteries before and after cryopreservation.

CD24 is a glycoprotein with an unusual structure consisting of a small protein core extensively glycosylated and linked to the outer surface of the plasma membrane by a glycosylphosphatidylinositol (GPI) lipid anchor. Its murine homolog mCD24 is transiently expressed during the development and differentiation of the hematopoietic and neural cell lineages. We have searched for the expression of CD24 in the developing and in the mature human brain as well as in a wide range of neuroectodermal tumors. Neuroblastomas, a subgroup of tumors able to maturate from undifferentiated features towards mature ganglioneuromas, were more extensively studied. Immunohistochemical studies demonstrated that CD24 is transiently expressed by neurons during human brain development. In neuroectodermal tumors, CD24 is a marker of neuronal tumors. Furthermore, in neuroblastomas, CD24 expression decreases as tumors differentiate. In non-neuronal neuroectodermal tumors, CD24 expression is mostly absent. When present, it correlates with the emergence of anaplastic histological features. Reverse transcriptase -polymerase chain reaction (RT-PCR) demonstrated the presence of an unique transcript identical in both hematopoietic, developing and tumoral nervous tissue. RT-PCR and in situ hydridization techniques showed that CD24 expression is transcriptionally regulated. Interestingly, Western blot analysis demonstrated differential CD24 isoforms according to the tissue (hematopoietic versus nervous), the differentiation status, and the origin of neuroblastomas likely reflecting variations in the extent of glycosylation. This indicates an additional level of regulation of CD24 involving post-translational modifications.

The viscoelastic properties of the arterial wall are responsible for the blood pressure wave propagation throughout the arterial system. Arterial diseases may cause disorders in this propagation. We have developed a mock circulation system that allows assessment of viscoelastic properties in fresh or cryopreserved human arteries. It includes the following components:--a hydrodynamic generator that can simulate physiological pressure variations in fresh segments of human arteries;--a lightweight miniature flexible probe that can be placed around the artery to measure changes in the external diameter during systolo-diastolic cycles;--a computer program to analyse pressure and diameter data measured during a cardiac cycle. Using this system, it is possible to evaluate the main viscoelastic properties of the arterial wall (arterial compliance, arterial stiffness, midwall aortic stress, Young elastic modulus, incremental modulus). Human arterial samples were collected during organ harvesting in subjects from 18 to 35 years of age. Correlation between viscoelastic properties, arterial wall status, and histological aspect in nitrogen vapor (-140 degree C) were established. No statistically significant difference was observed in femoral arteries characteristics. Compliance decreased, while stiffness increased with statistically significant difference after cryopreservation in carotid arteries. No histological difference was observed in both arteries before and after cryopreservation.

The case of a 41 years old man presenting with mitochondrial myopathy associated with calcification of the basal ganglia (Fahr's disease) neurosensorial and endocrine-deficits is reported. These different symptoms could share a common physiopathological process.

Expression of some developmentally regulated cytoskeleton components (desmin, vimentin and myosin heavy chain isoforms) and cell surface proteins (including neural cell adhesion molecule (NCAM), its polysialylated (PSA) isoform and CD24) have been studied by immunohistochemical detection in a series of 23 infantile spinal muscular atrophies (SMA). According to the clinical classification established by Byers and Banker in 1961, 8 cases were type I SMA (Werdnig-Hoffmann's disease), 10 cases were type II (intermediate form), and 5 cases were type III (Kugelberg-Welander's disease). In 15 cases, the percentage of immunoreactive fibers with the various antibodies used has been quantified and the results correlated with clinical data. The aim of the study was to search for variations in the pattern of expression of the proteins to improve the accuracy of diagnosis and prognosis, and to gain an understanding of the pathological processes involved in SMA. The results showed that the pattern of expression of these cytoskeleton and cell surface proteins is abnormal in all types of SMA. However, it was strikingly different in type I and II SMA as opposed to type III. In type I and II SMA, strong NCAM and developmental myosin heavy chain (MHC) expression was observed in atrophic fibers. Numerous atrophic fibers co-expressed desmin and vimentin as well as slow and fast adult MHC. Very few of them expressed PSA NCAM, fetal MHC and CD24. In type III SMA, the number of fibers expressing NCAM, developmental MHC and co-expressing slow and fast adult MHC was low and virtually none of them expressed vimentin or desmin. These findings are in favor of a denervation process occurring very early in life, probably even in utero, in type I and II SMA and leading to a severe impairment of muscle fibers maturation. In contrast, in type III SMA, the process is initiated well after birth and affects mature muscle fibers. In all types of SMA, the ability of muscle fibers to regenerate is low, although some fibers may be reinnervated. Immunohistochemical data was not related to the patients follow-up and thus has no prognostic value.

Cerebral angiotropic large cell lymphoma is a rare fatal neurologic disorder characterized by multifocal intravascular proliferation of large pleomorphic cells within vessels of all caliber, predominantly skin and nervous system. Clinical manifestations in previously reported cases were dominated by focal neurologic signs, epilepsia and progressive dementia. We report a case of a 70 year-old man with subacute dementia, epileptic seizures and cerebrovascular events. There was no evidence of a systemic disease outside the nervous system. Cerebrospinal fluid contained 13 leukocytes/mm3 (49% of lymphocytic cells) and more than 100 mg/dl of protein. Cytology was negative. Cranial MRI demonstrated cerebral atrophy and an increased paraventricular signal in T 2 weighted images. A frontal brain biopsy revealed only neuronal dystrophy and astrocytic gliosis. Despite treatment with corticosteroids the patient died 18 months after the onset of the first symptoms. Autopsy was performed and revealed B cell lymphoma.

Unlabelled: We studied a 3-month-old girl who was admitted to hospital because of respiratory distress. The clinical course was characterized by a rapidly progressive generalized hypotonia with lactic acidosis and she died at 4 months of age. A muscle biopsy showed few ragged-red fibres and lack of histochemical cytochrome c oxidase reaction in all fibres. Enzyme activities of the respiratory chain complexes containing subunits encoded by the mitochondrial DNA (mtDNA) were markedly decreased. A quantitative Southern blot analysis revealed 99% depletion of mtDNA in muscle and normal amounts in blood. There was no family history and the dizygotic twin sister of the patient was no symptomatic., Conclusion: This new case confirms the rapidly fatal evolution associated with severe depletion of muscle mtDNA.

Lafora disease and Unverricht-Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht-Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North-African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht-Lundborg disease may be facilitated by molecular genetic analysis.

A series of frozen specimens of 18 ependymomas and 7 choroid plexus tumors were examined for their expression of cell adhesion molecules, such as neural cell adhesion molecule (NCAM), its polysialylated isoforms (PSA NCAM), and epithelial (E-) cadherin, and of intermediate filament proteins, such as glial fibrillary acidic protein (GFAP) and cytokeratin, using various monoclonal and polyclonal antibodies. Normal choroid plexus and ependyma were taken as controls. Anti-E-cadherin immunoreactivity was observed on the basolateral part of most adult choroid plexus and benign choroid plexus papilloma cells. However, a small number of atypical papillomas and carcinoma cells showed anti- E-cadherin immunoreactivity throughout their cell surface membrane. NCAM were not expressed by adult choroid plexus and benign papilloma cells. Only a few cells expressed NCAM and PSA NCAM in developing choroid plexus, atypical papillomas and carcinomas. Cytokeratin expression was always observed in choroid plexus and their tumors; GFAP expression was variable from case to case. In contrast, ependymal cells and their tumors never expressed E-cadherin but strongly expressed NCAM. PSA NCAM was found in ependymomas exhibiting anaplastic features. All ependymomas strongly expressed GFAP and a few demonstrated slight expression of cytokeratin. These data suggest that, besides GFAP and cytokeratin, NCAM and E-cadherin are of potential diagnostic value in distinguishing choroid plexus tumors from ependymomas. E-cadherin and NCAM may play a role in the functional organization of normal choroid plexus and ependyma, respectively. In particular, incomplete or irregular anti-E-cadherin expression in choroid plexus tumors and PSA NCAM immunoreativity in ependymomas and choroid plexus tumors correlates with the emergence of anaplastic histological features.

We analyzed the mitochondrial DNA of patients with polymyalgia rheumatica, a disease frequently associated with mitochondrial myopathy. In an attempt to study the deletions, we have developed a qualitative PCR method using a highly thermostable polymerase in order to amplify multiple mitochondrial DNA large fragments (up to 12 kb). PCR serves to observe both deleted and normal fractions of the mitochondrial DNA. We found multiple deletions of the mitochondrial DNA in all of the patient muscles. Although these muscles harbored many ragged red fibers, we found no point mutations of the tRNA(Leu)(UUR)) and the mutation at nucleotide position 8344 was not present.

Quantitative imaging of estrogen receptors (ER's), progesterone receptors (PR's), estrogen-regulated protein (pS2), and growth fraction (Ki67) immunocytochemical assays were performed in 52 meningiomas. The results were correlated with clinical (age, sex, hormonal status, and tumor volume and location) and morphological (histological types and grades) data. The authors observed a lack of ER's in all meningiomas but the presence of PR's in 53% of these meningiomas. The immunoreactivity was restricted to tumor cell nuclei. The PR immunocytochemical assay was correlated with tumor location, histological type, histological grade, and pS2 immunocytochemical assay, but not with Ki67 immunocytochemical assay; high PR content was observed in cisternae, transitional, meningothelial, and low-grade meningiomas. Only 11 meningiomas showed more than 1% Ki67 immunoreactive nuclei. These meningiomas were usually located in the convexity and were of high histological grade. Estrogen-regulated protein immunoreactivity was observed in 34 meningiomas but the number of immunoreactive nuclei was low. The pS2 immunocytochemical assay was not related to clinicopathological features but was preferentially observed in PR-negative meningiomas. The results of this study are compared with those previously reported, and the function and regulation of PR's in meningiomas is discussed. The results indicate that 1) regulation of PR's and pS2 proteins in meningiomas differs from regulation in estrogen-dependent tissues such as breast or endometrium; 2) interruption of hormonal therapy in women presenting with a meningioma is not absolutely necessary; 3) meningiomas have different biological properties according to their clinicopathological features; and 4) future studies of hormonal clinical trials should be performed on well-defined meningioma subgroups.

We report three cases of mitochondrial encephalomyopathy affecting predominantly the central nervous system; two patients had the MELAS syndrome and one had "ophthalmoplegia plus". Histoenzymatic analysis of muscle biopsy and biochemical studies of muscle mitochondria demonstrated myopathy associated with partial deficiency of complex I of the electron transfer chain in three cases, complex IV in two cases and complex III in one case. Molecular analysis of mtDNA in the first case did not revealed any abnormality. Coenzyme Q10 therapy improved exercise tolerance but not the central nervous signs.

PDGFs and their receptors expression were examined in a series of 46 meningiomas by using specific monoclonal antibodies. The immunostaining was quantified by an image analyser and the results correlated with clinical and morphological data (histological type and grade). In addition, since the PDGFB chain is encoded by the c-sis proto-oncogene localized on chromosome 22 and because monosomy 22 has been frequently reported in meningiomas, PDGFs and PDGFRs expression have been correlated with cytogenetic analysis performed in 29 cases. The results demonstrate PDGF A and PDGF B expression in most meningioma specimens and co-expression of these growth factors in numerous cells. PDGF A and B immunoreactivity was related to histological grade. PDGFR beta expression was strong in almost all meningiomas whereas PDGFR alpha was low. PDGFR alpha expression was related to tumour location and grade and PDGFR beta to histological subtype only. The cytogenetic analysis was not related to PDGFB chain expression. Taken together these data further confirm PDGF and PDGFR expression in human meningioma; PDGF may exist as an heterodimer (AB) as well as its receptor. The lack of correlation between cytogenetic analysis and PDGF values, the low level of PDGFB in recurrent meningiomas suggests that it is unlikely that the c-sis proto-oncogene plays an important role in the genesis of meningiomas.

Meningiomas are derived from arachnoidal cells exhibiting both epithelial and mesenchymal properties. The expression of epithelial cadherin and neural cell-adhesion molecule isoforms was examined in 47 meningioma specimens and normal arachnoid villi by using immunohistochemistry and immunoblot procedures. For immunohistochemistry, the percentage of immunostained surface versus counterstained surface and the intensity of labeling were quantified by image analysis and correlated with clinical and morphological data. Neural cell-adhesion molecule, 140-kDa, was expressed by all meningiomas examined and by cap cells and the fibrous capsule forming the arachnoid villi. Neural cell-adhesion-molecule immunostaining was correlated to tumor location, histological type, and grade. The expression of polysialylated isoforms was related to tumor location and grade, with a higher expression on convexity meningiomas and high-grade tumors. Epithelial cadherin was expressed with various intensity. In arachnoid villi, its expression was restricted to cap cells, but it was found in all meningiomas, whatever their histological type or grade. However, the expression was stronger in whorls and meningiotheliomatous areas versus fibroblastic areas. No correlation was observed with the tumor location or the grade. These data suggest that neural cell-adhesion molecule and epithelial cadherin play a role in the morphogenesis and histogenesis of human meningiomas.

We studied mitochondrial respiratory chain function in skeletal muscle taken from 27 patients with idiopathic Parkinson's disease (PD; 21 Dopa-treated PD patients and 6 de novo patients), 5 patients with multiple system atrophy (MSA) and from 43 age-matched controls in order to determine the occurrence of mitochondrial respiratory chain abnormalities in parkinsonian syndromes. In our control subjects, we found a significant age-related decrease in the activity of respiratory chain complex I. As compared to carefully age-matched control subjects, activity of complex (NADH:ubiquinone reductase) was significantly lower in muscle mitochondria from patients with PD and MSA and a mean remaining activity < 30% of controls was observed. Mean activities of complexes III (ubiquinol:cytochrome c reductase) and IV (cytochrome c oxidase) were also lower in PD patients than controls, but a low activity (remaining activity < 30% of controls) was observed in only 5 PD patients for complex I and III or I and IV. No deficit in complex II activity (succinate:ubiquinone reductase) was observed. Our results support the hypothesis of a wide-spread mitochondrial complex I deficiency in PD and MSA as compared to age-matched controls, who showed age-related deficiency. This deficit can be found in de novo PD patients as well as in treated patients. The observed respiratory enzyme chain deficiency could not be explained by the dose and duration of L-Dopa or dopaminergic agonist treatment, the severity of the disease, anxiety or depression since no significant correlation was found between these parameters and enzyme complexes activities.

The evaluation of molecular markers in breast carcinomas can be routinely assessed by (i) histochemistry for ploidy measurement (Feulgen stain) and for AgNORs counts, and by (ii) immunocytochemistry (Ki67, cathepsin D, pHER-2/neu, EGFR, ER, PR, pS2, p53). Immunocytochemical assays are correlated to biochemical assays and are particularly relevant in small tumors in which only small amount of tissue is available. Immunocytochemical assays provide for data additional to current histological methods, useful for prognostic evaluation and for the selection of node negative patients who may benefit from adjuvant therapy. Nevertheless, immunocytochemical assays can be used for clinical purposes only if they are standardized (frozen sections, image analysis).

Since age 12 years, a 25-year-old woman had a syndrome with myoclonic epilepsy, cerebellar signs, and spontaneous myoclonus. Skin biopsy showed typical Lafora bodies (LB), but she lacked a progressive course and mental impairment, hallmarks of Lafora disease. Lysosomal enzyme assays showed low level arylsulfatase A (ASA) activity. DNA study disclosed a homozygous ASA Pd genotype. Both parents carried one Pd allele. The still-unknown relationship between the pathologic level of ASA activity and myoclonic epilepsies suggests introduction of ASA assays in patients with PME.

Objective: To assess the significance of an isolated vasculitis of vasa vasorum on temporal artery biopsy., Methods: A diagnostic procedure was performed with 28 patients presenting clinical and biological inflammatory process and an isolated vasculitis of vasa vasorum on temporal artery biopsies., Results: Panarteritis nodosa was diagnosed in 5 cases: polymyalgia rheumatica was evidenced in 4 cases; temporal arteritis was strongly suspected in 2 cases; various types of underlying disease were found in 12 patients; a noncharacterized systemic disease was found in 5 cases., Conclusion: Isolated vasculitis of vasa vasorum on temporal artery is a meaningful lesion frequently indicating a systemic vasculitic disorder.

The authors report four cases of cardiac amyloidosis, the diagnosis of which was confirmed by endomyocardial biopsy. They underline the value of immuno-histological studies with labelling of the biopsy fragments with anti-transthyretin and anti-light chain immunoglobulin antibodies. This approach provides a more precise typing of amyloidosis and a more accurate evaluation of the prognosis.

Objectives: Diagnosis of polymyalgia rheumatica requires the elimination of other inflammatory diseases due to the lack of a specific diagnostic criteria. Since results of muscle biopsy have been considered non-specific, we evaluated the full spectrum of histological, histochemical and biochemical data observed in 24 patients with suspected polymyalgia rheumatica., Methods: From January 1989, the diagnosis of polymyalgia rheumatica was suspected in 24 patients (4 males, 20 females; mean age 67.8 years, range 50-88) hospitalized in our unit for inflammatory joint and muscle pain with a current duration of 6-30 months. Muscle biopsies were obtained in each case., Results: Based on the histological, histo-enzymatic, ultrastructural and biochemical analyses, 19 patients fulfilled the criteria defining mitochondrial myopathies. After favourable outcome (reduced pain, involution of biochemical inflammatory syndrome) following prednisone therapy (0.5 mg/kg/day) a second muscle biopsy revealed identical abnormalities., Conclusion: These muscular diseases have been described mainly as hereditary encephalo-myopathies, but in our series the mitochondrial myopathy may have preceded the polymyalgia rheumatica or been acquired, aggravating the inflammatory process. Muscle biopsy might act as a referee for diagnosis.

The granular cell tumor was first described by Abrikossoff who referred to that lesion as myoblastoma. This lesion is mainly observed in soft tissues and is exceptionally found in the mammary gland. Among the 159 cases of breast granular cell tumor reported in the literature, only 121 have been well documented. Tumors occurred in 15 to 74 year old patients and in only 9.8% of the tumors discovered in males. In breast this tumor may mimic a carcinoma like in the three cases reported. The intra-operative diagnosis on frozen sections may be particularly difficult and the risks to overdiagnose a carcinoma are not negligible and must be known. The diagnosis on paraffin sections is much more easier than on frozen sections. The immunostaining procedures (anti p S100) and electron easier than on frozen section. The immunostaining procedures (anti p S100) and electron microscopy are mainly interesting to document the histogenetic hypotheses. The schwannian origin of the tumor is favoured in most of the recent studies. The granular cell tumors are usually benign and malignant tumors account for only 2.5% of those diagnosed in the breast.

Mechanisms of peripheral neuropathies in polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome are poorly understood. A peripheral nerve biopsy was performed in 22 patients. Of these 9 had histological features of Castleman's disease on lymph node biopsies, and 19 had a monoclonal lambda light chain in their serum. Certain nerve fragments were paraffin embedded, others were frozen and studied by direct immunofluorescence, and others were fixed for ultrastructural examination. Paraffin-embedded fragments did not show any amyloid deposits, and at direct immunofluorescence there was no immunoglobulin fixation. At ultrastructural examination, features of uncompacted myelin lamellae (UML) were present in 19 patients, and their frequency varied from 1% to 16% of myelinated fibres. Up to now UML have been reported only in 7 patients with POEMS syndrome in the literature. UML have also been noticed in a few cases of inflammatory demyelinating polyradiculoneuritis and inherited tendency to pressure palsy.

Three cases of chronic limb-girdle myasthenia gravis (one man and two women) are reported. The duration of the disease was three, five and 20 years respectively. None had oculobulbar weakness during this period nor fluctuating symptoms. The primary diagnosis was myopathy in two cases and myelopathy in the other one. In view of this diagnosis, several features were atypical: absence of marked wasting, preservation of tendon reflexes and normal serum creatine kinase activity. Finally, diagnosis of myasthenia gravis was established by the occurrence of a characteristic decremental muscular response to repetitive stimulation and by positive edrophonium test. It seems that the rate of positivity of acetylcholine receptor antibody is lower than in the common form of the disease. Two patients responded to acetylcholinesterase inhibitors and one to high-doses intravenous human immunoglobulins. These and previous cases described in the literature raise the problem of the definition of an unusual form of myasthenia gravis or of a new type of neuromuscular disease characterized by the presence of distinctive changes on muscular biopsies, specially tubular aggregates as in one of our cases. However, this unusual form of chronic limb-girdle weakness has to be recognized because treatments are effective in most cases.

The pathological findings in 165 patients explored for malignant hyperthermia (MH) susceptibility are reported. The first group of 120 subjects were patients investigated for MH. These patients had suffered an attack of MH under anaesthetic or were members of families in which a subject had died of MH. In vitro contracture tests revealed 25 malignant hyperthermia susceptible (MHS) subjects, with positive contracture tests for halothane and caffeine, 5 malignant hyperthermia subjects with reaction to caffeine only (MHC), 3 malignant hyperthermia subjects with reaction to halothane only (MHH) and 87 malignant hyperthermia negative (MHN) subjects with normal contracture tests. The second group of 45 subjects had exertional heat stroke. In vitro contracture tests performed at least 3 months after the exertional heat stroke revealed 11 MHS, 6 MHC, 2 MHH subjects and 26 MHN. In both groups, whatever the in vitro contracture test results, pathological findings were heterogeneous and revealed various changes: rhabdomyolysis, mitochondrial myopathy, denervation, type II atrophy, AMPase deficiency, non-specific findings or normal features. Central core myopathy was only observed in the first subgroup and was the only disease significantly associated with MH. In contrast to previous reports, this study demonstrates the absence of a specific malignant hyperthermia or exertional heat stroke myopathy. Furthermore, the discovery of MHS subjects among the EHS group of patients highlights the need for systematic exploration of all these patients.

A 68 year old man presented with a clinical and biological picture that suggested polymyalgia rheumatica. Temporal artery biopsy disclosed no inflammatory change but massive light chain amyloid deposits in the media. Further exploration showed a malignant lymphoplasmacytic haemopathy with a triclonal gammopathy and a muscular, rectal, and probable cardiac amyloidosis. Cryoglobulinaemia and high concentrations of soluble interleukin 2 receptor (sIL-2R) were also found. This is the fifth case with confirmed involvement of the temporal artery. The especially high sIL-2R concentration was thought to reflect the tumour mass rather than lymphocyte activation.

A patient experienced an axonomyelinic peripheral neuropathy during a long-term allopurinol treatment. The symptoms and signs regressed after drug withdrawal, and the nerve conduction velocities and distal latencies improved. The incidence of allopurinol-induced peripheral neuropathy is very low. Thus, facilitatory factors have to be sought.

A case of peripheral neuropathy following treatment with piroxicam is reported. The patient developed muscle pain and asymmetrical sensory distal neuropathy of the lower limbs a few months after the onset of the treatment. Piroxicam was withdrawn and full recovery was achieved within one year. The simultaneous appearance in the same patient of erythroderma with microvasculitis on nerve and skin biopsies suggests a common type III hypersensitivity mechanism in the pathogenesis of these two side-effects of piroxicam.

The expression of the CD24 molecule, a glycoprotein expressed at the surface of most B lymphocytes and differentiating neuroblasts, was studied in developing nerve and muscle (after 16 weeks of gestation), normal adult and various diseased human muscles using immunohistochemistry and Western blot analysis. Immunohistochemical studies demonstrated that: (1) in developing muscles, fibers did not express CD24, whereas only some mesenchymal areas, also expressing neural cell adhesion molecule (N.CAM) and vimentin, and developing nerves were positive; (2) in normal adult muscles, CD24 immunoreactivity was observed only in some unmyelinated nerve fibers--intra and extra fusal muscle fibers, satellite cells and neuromuscular junctions were negative; and (3) in all diseased muscles studied here, CD24 expression was always associated with a subpopulation of regenerative fibers. These fibers also expressed vimentin, desmin, developmental myosin heavy chain, N.CAM and its polysialylated isoforms (PSA-N.CAM). The number of CD24-positive fibers was always lower than that of PSA-N.CAM-positive fibers. Denervated fibers and vacuolated muscle fibers never expressed CD24. Western blot analysis indicated that the apparent molecular mass of CD24 antigen was different between muscle and developing nervous tissues, suggesting that CD24 glycosylation is tissue specific. Since the molecule was not expressed in developing human muscle fibers, it strongly suggests that regenerative and fetal myotubes are different with respect to the CD24 molecule expression.

A primary extraspinal medulloepithelioma with lung metastases is reported. The tumour was located in the presacral area. Microscopically, it showed typical features of medulloepithelioma with focal ependymal differentiation. Medulloepitheliomas are malignant tumours of primitive neuro-epithelium usually involving the cerebral hemispheres. This report demonstrates their possible extraspinal presacral occurrence. By immunohistochemistry, neuron-specific-enolase, S100 protein, vimentin, cytokeratin and glial fibrillary acidic protein were found in some tumour cells. Electron microscopy demonstrated poorly differentiated cells forming stratified epithelium resting on a basal lamina and short junctional complexes at the apical pole. Ultrastructural evidence of ependymal differentiation was observed. Presacral medulloepithelioma may arise from undifferentiated embryonic cells forming the presacral remnants of the neurenteric canal.