Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

An immunohistochemical, clinical and electroneuromyographic correlative study of the neural markers in the neuritic form of leprosy

The nerve biopsies of 11 patients with pure neuritic leprosy were submitted to routine diagnostic procedures and immunoperoxidase staining with antibodies against axonal (neurofilament, nerve growth factor receptor (NGFr), and protein gene product (PGP) 9.5) and Schwann cell (myelin basic protein, S-100 protein, and NGFr) markers. Two pairs of non-adjacent histological cross-sections of the peripheral nerve were removed for quantification. All the fascicles of the nerve were examined with a 10X-ocular and 40X-objective lens. The immunohistochemistry results were compared to the results of semithin section analysis and clinical and electroneuromyographic data. Neurofilament staining was reduced in 100 percent of the neuritic biopsies. NGFr positivity was also reduced in 81.8 percent, PGP staining in 100 percent of the affected nerves, S100 positivity in 90.9 percent, and myelin basic protein immunoreactivity in 90.9 percent. Hypoesthesia was associated with decreased NGFr (81.8 percent) and PGP staining (90.9 percent). Reduced potential amplitudes (electroneuromyographic data) were found to be associated with reduced PGP 9.5 (63.6 percent) and nerve fiber neurofilament staining (45.4 percent) by immunohistochemistry and with loss of myelinated fibers (100 percent) by semithin section analysis. On the other hand, the small fibers (immunoreactive dots) seen amid inflammatory cells continued to be present even after 40 percent of the larger myelinated fibers had disappeared. The present study shows an in-depth view of the destructive effects of leprosy upon the expression of neural markers and the integrity of nerve fiber. The association of these structural changes with the clinical and electroneuromyographic manifestations of leprosy peripheral neuropathy was also discussed.

Quantitative evidence for neurofilament heavy subunit aggregation in motor neurons of spinal cords of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown etiology, affects motor neurons leading to atrophy of skeletal muscles, paralysis and death. There is evidence for the accumulation of neurofilaments (NF) in motor neurons of the spinal cord in ALS cases. NF are major structural elements of the neuronal cytoskeleton. They play an important role in cell architecture and differentiation and in the determination and maintenance of fiber caliber. They are composed of three different polypeptides: light (NF-L), medium (NF-M) and heavy (NF-H) subunits. In the present study, we performed a morphological and quantitative immunohistochemical analysis to evaluate the accumulation of NF and the presence of each subunit in control and ALS cases. Spinal cords from patients without neurological disease and from ALS patients were obtained at autopsy. In all ALS cases there was a marked loss of motor neurons, besides atrophic neurons and preserved neurons with cytoplasmic inclusions, and extensive gliosis. In control cases, the immunoreaction in the cytoplasm of neurons was weak for phosphorylated NF-H, strong for NF-M and weak for NF-L. In ALS cases, anterior horn neurons showed intense immunoreactivity in focal regions of neuronal perikarya for all subunits, although the difference in the integrated optical density was statistically significant only for NF-H. Furthermore, we also observed dilated axons (spheroids), which were immunopositive for NF-H but negative for NF-M and NF-L. In conclusion, we present qualitative and quantitative evidence of NF-H subunit accumulation in neuronal perikarya and spheroids, which suggests a possible role of this subunit in the pathogenesis of ALS.

Effects of chronic heart disease on skeletal muscle fiber size

Size changes in muscle fibers of subjects with chronic heart disease (CHD) have been reported, although a consensus has not been achieved. The aims of the present study were to investigate a possible association between CHD and fiber size changes in the brachial biceps compared to subjects without heart disease. Forty-six muscle samples were obtained in autopsies of individuals (13 to 84 years) without neuromuscular disorders, 19 (10 males and 9 females) with, and 27 (14 males and 13 females) without CHD. In all cases muscle sections were stained with hematoxylin and eosin and processed for the visualization of myofibrillar ATPase activity. The lesser diameter of type 1 and type 2 fibers was obtained tracing their outlines (at least 150 fibers of each type per sample) onto an image analyzer connected to a computer. The results were analyzed statistically comparing males and females with and without CHD. Type 1 fiber mean lesser diameters were 51.51 and 54.52 æm in males (normal range 34-71 æm) and 45.65 and 55.42 æm in females (normal range 34-65 æm) without and with CHD, respectively; type 2 fibers measured 54.31, 58.23, 41.15, and 49.57 æm, respectively (normal range 36-79 æm for males and 32-59 æm for females). No significant difference in fiber size was detected in 24 males with and without CHD, while in 22 females there was a significant increase in size in those with cardiomyopathy. We concluded that CHD does not determine significant changes in fiber size. However, in females, there is some hypertrophy which, despite within normal range, may reflect morphologic heterogeneity of the sample, or the daily life activities in the upper limbs as a compensatory mechanism to fatigability that affect predominantly the lower limbs in subjects with CHD.

Vírus da estomatite vesicular (Sorotipo Indiana 2) como modelo experimental para o estudo de encefalite aguda: aspectos morfológicos / Vesicular stomatitis virus (Indiana 2 Serotype) as experimental model to study acute encephalitis: morphological features

O vírus da estomatite vesicular (VEV) é um vesiculovírus da família Rhabdoviridae que infecta mamíferos e causa lesões vesiculares semelhantes às observadas na febre aftosa. A encefalite experimental pode ser induzida em roedores e os sintomas são semelhantes aos observados na raiva; entretanto, as lesões observadas no encéfalo dos animais são diferentes. Corpúsculos de inclusão não são observados, há necrose especialmente da região do bulbo olfatório e em alguns casos, ventriculite. Observamos que o padrão temporal de disseminação do VEV e os aspectos morfológicos das lesões são similares aos descritos na literatura. O vírus parece se disseminar através dos ventrículos cerebrais, multiplicando-se em células do epêndima e em neurônios, além de utilizar o transporte retrógrado e anterógrado. Constatamos que devido à facilidade de manipulação do vírus, este modelo experimental tem sido utilizado em inúmeros trabalhos de pesquisa em diversas áreas. Se por um lado, os relatos sobre a patogenia da infecção são numerosos, por outro lado, ainda existem muitas lacunas que envolvem, por exemplo, aspectos sobre a transmissão do vírus, a recuperação dos animais infectados e a participação de células gliais durante a fase aguda e a fase de recuperação dos animais

Modulation of fibronectin expression in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis

Fibronectin (FN), a large family of plasma and extracellular matrix (ECM) glycoproteins, plays an important role in leukocyte migration. In normal central nervous system (CNS), a fine and delicate mesh of FN is virtually restricted to the basal membrane of cerebral blood vessels and to the glial limitans externa. Experimental autoimmune encephalomyelitis (EAE), an inflammatory CNS demyelinating disease, was induced in Lewis rats with a spinal cord homogenate. During the preclinical phase and the onset of the disease, marked immunolabelling was observed on the endothelial luminal surface and basal lamina of spinal cord and brainstem microvasculature. In the paralytic phase, a discrete labelling was evident in blood vessels of spinal cord and brainstem associated or not with an inflammatory infiltrate. Conversely, intense immunolabelling was present in cerebral and cerebellar blood vessels, which were still free from inflammatory cuffs. Shortly after clinical recovery minimal labelling was observed in a few blood vessels. Brainstem and spinal cord returned to normal, but numerous inflammatory foci and demyelination were still evident near the ventricle walls, in the cerebral cortex and in the cerebellum. Intense expression of FN in brain vessels ascending from the spinal cord towards the encephalon preceded the appearance of inflammatory cells but faded away after the establishment of the inflammatory cuff. These results indicate an important role for FN in the pathogenesis of CNS inflammatory demyelinating events occurring during EAE

Aspecto citológico de tumores intracranianos e do canal vertebral / Cytologic aspects of intracranial and spinal canal tumors

We present the cytologic aspects of 137 tumors operated by neurosurgeons, including 12 astrocytomas, 4 anaplastic astrocytomas, 26 glioblastomas, 7 oligodendrogliomas, 5 medulloblastomas, 8 schwannomas, 17 meningiomas, 13 pituitary adenomas, 20 metastatic tumors and 18 assorted tumors and nonneoplastic lesions. We have also analysed cytologically samples of normal nervous tissue obtained from autopsies, aiming at its recognition and distinction from the neoplastic tissue in biopsies. The tumors were analysed in smears which were subsequently compared with the histological sections. Although it is important to observe cytological details in the tumor, occasionally cells are arranged in such a way, that an overview of the smear practically allows the diagnosis of the tumor.

Valor do esfregaço no diagnóstico per-operatório dos tumores provenientes de neurocirurgias / Value of the smear in the peroperative diagnosis of tumors removed in neurosurgeries

The smear technique has been used for rapid diagnosis of tumors removed in neurosurgeries in many neuropathological centers. In order to assess the diagnostic accuracy of this technique, we examined 137 smears and made a cytohistological correlation. Our cases include 12 astrocytomas, 4 anaplastic astrocytomas, 26 glioblastomas, 7 oligodendrogliomas, 5 medulloblastomas, 8 schwannomas, 17 meningiomas, 13 pituitary adenomas, 20 metastatic tumors and 18 assorted tumors and non neoplastic lesions. The correct diagnosis was made in 91.2% of the cases which coincides to the literature. The knowledge of the localization and the characteristic morphologic features of some tumors were important for the diagnosis. The ability to recognize normal nervous tissue in smears was important even to help the surgeon to reach the tumor. We believe that the use of smears should be encouraged in our country in view of the simplicity of its preparation and accuracy of results.

Neuropatia diabética: I. Conceito, epidemiologia, classificaçäo, quadro clínico e eletroneuromiográfico: estudo de 210 casos / Diabetic neuropathy: I. Definition, epidemiology, classification, clinical features and electrophysiologic changes: study of 210 patients

Os autores fazem revisäo da neuropatia diabética, seu conceito, sua prevalência e citam as várias classificaçöes existentes. Referem-se aos principais quadros clínicos apresentando 210 pacientes com neuropatia diabética estudados num período de quatro anos (1987-1991). As polineuropatias compreendem 184 casos. A forma sensitiva foi a predominante ocorrendo em 135 enfermos. Seguiram-se com menor número as formas sensitivo-motora, atáxica, motora e autonômica. Os distúrbios autonômicos estiveram presentes 63 vezes, sendo as alteraçöes pupilares as mais freqüentes. Os nervos cranianos foram acometidos 20 vezes, predominando a paralisia do VII e III nervos. O nervo mediano foi acometido em 20 oportunidades e a plexopatia lombar unilateral ocorreu em 10 pacientes. A eletroneuromiografia foi realizada em 63 pacientes, predominando a lesäo axonal sensitivo-motora (43 vezes)

Anoxia perinatal. Estudo anatomopatologico do encefalo. / Perinatal anoxia Anatomopathological study of the encephalon

O trabalho visa a analise de lesoes iniciais do tecido nervoso, nas mortes precoces por anoxia perinatal, quando ainda nao sao frequentes necroses extensas no encefalo. Foram estudados anatomopatologicamente os encefalos de 46 recem-nascidos com historia de anoxia perinatal.As lesoes observadas guardaram relacao com a idade gestacional e com o tempo de sobrevida.Nos recem-nascidos a termo predominaram as lesoes na substancia cinzenta do cortex e nos prematuros as lesoes nas substancias branca periventricular e as de natureza hemorragica. O tempo de sobrevida, em todos os casos, relacionou-se diretamente com a intensidade das lesoes encefalicas