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Biomedical subjects

M B Lopes

Publications and source records attributed to M B Lopes.

At least 55 records · Page 3Linked to original sources

Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein is increased in reactive and neoplastic glial cells.

alpha 2-Macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2M-R/LRP) is a multi-functional cell-surface receptor that has been implicated in diverse physiologic processes. In normal human brain, alpha 2M-R/LRP is expressed principally by pyramidal neurons with localization to cell bodies and proximal processes. By contrast, alpha 2M-R/LRP is not present in either the cell bodies or processes of most normal macroglia (including astrocytes). In this investigation, we studied the expression of alpha 2M-R/LRP in the brain, following tissue injury or neoplastic transformation, by immunohistochemistry. Significantly increased alpha 2M-R/LRP immunoreactivity was identified in reactive astrocytes, indicating the expression of this receptor is regulated in vivo in response to brain injury. alpha 2M-R/LRP immunoreactivity was also detected in glial cell tumors; this finding is novel since malignant transformation is typically thought to turn off expression of this receptor.

Astrocytes↗

Dysembryoplastic neuroeptihelial tumor (DNT): an immunohistochemical and ultrastructural study.

To assess the range of differentiation of the cells comprising dysembryoplastic neuroepithelial tumor (DNT), particularly the oligodendrocyte-like cells (OLC), 14 DNT were immunochemically studied with a spectrum of neuronal and glial markers. Eight tumors were also studied ultrastructurally. Neurofilament protein, class III beta-tubulin, and synaptophysin preparations stained a few OLC in two, six and one lesion, respectively. In addition, many OLC within a single cortical nodule were reactive for class III beta-tubulin. The vast majority of OLC were strongly S-100 protein positive. Glial fibrillary acidic protein labeled a fair number of OLC in two cases and one nodule consisted almost entirely of immunoreactive astrocytes. Ultrastructurally, many OLC resembled oligodendrocytes in exhibiting microtubules, prominent Golgi and short cell processes; pericellular lamination of cell processes, a characteristic of oligodendroglia, was noted in only one tumor. In two cases, OLC with astrocytic features were seen to contain small numbers of intermediate filaments. In four cases, a few OLC resembled immature neurons with scant dense-core granules or synapses. This study confirms the glioneuronal nature of DNT, a lesion composed of heterogeneous cells, many resembling oligodendrocytes and a few showing early astrocytic and neuronal differentiation. Although their relation to OLC is unclear, the presence and peculiar distribution of mature neurons is nonetheless an integral diagnostic feature of the lesion.

Adolescent↗

Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas.

Forty-one human pituitary adenoma specimens were examined for the presence of estrogen receptor (ER) messenger ribonucleic acid and protein using a combination of ribonuclease protection assay, [3H] estradiol ([3H]E2) binding, and ER immunohistochemistry. ER messenger ribonucleic acid prevalence was high in PRL-immunoreactive tumors (2 of 2), moderate in GH/PRL tumors (2 of 5), and low or absent (0 of 4) in GH tumors. In the GH/PRL-immunostaining tumors, the presence of the ER was uniformly associated with elevated serum PRL levels. Among the gonadotropin-immunostaining tumors, 10 of 17 were ER positive; within this group, those with gonadotroph adenoma characteristics were ER positive, whereas those with null cell/oncocytic characteristics were ER negative. Of the tumors that did not immunostain for any known anterior pituitary hormones, 3 of 11 were ER positive. ER immunohistochemistry in 14 tumors revealed a 100% correlation with ribonuclease protection assay results, whereas [3H]E2 binding, determined in 9 tumors, showed an 87% correlation. In summary, it appears that PRL and a specific class of gonadotropin-immunostaining tumors (identifiable by specific characteristics on electron microscope) contain ER, whereas GH-immunostaining tumors are ER negative. ER expression in normal pituitary paralleled that in macroadenomas (GH, 2.3%; PRL, 50%; FSH, 70%; LH, 83%; TSH, 4%; ACTH, 1%). The ER-positive tumors represent a subset whose growth and secretory profiles may be influenced by the gonadal steroidal milieu or by pharmacological agents that affect E2 levels or ER function.

Adenoma↗

Differential expression of retinal proteins in a pineal parenchymal tumor.

The pineal gland and retina share histogenetic features that reflect a similar neurosensory/photosensory ontogeny. Pineal parenchymal tumors demonstrate a highly variable and incomplete photosensory differentiation evidenced by specific cytoarchitectural features and the expression of photosensory retinal S-Antigen (S-Ag). Despite these neuro-ontogenetic parallels, pineal parenchymal tumors have not been well studied for the neuroretinal phenotypes that accompany normal neuroretinal development. The investigation of photoreceptor gene expression may provide an important insight into the histogenesis of pineal parenchymal neoplasms. In this study, a pineal parenchymal tumor of the "mixed pineoblastoma/pineocytoma" type was examined for the expression of several photoreceptor, glial and neuronal proteins including: interphotoreceptor retinoid-binding protein (IRBP), rod opsin, cone opsin, S-Ag and cellular retinaldehyde-binding protein (CRA1BP). The detection of IRBP and its mRNA, the earliest photoreceptor-associated protein expressed during retinal development, corroborated the rudimentary photosensory differentiation of this tumor which had limited cytoarchitectural evidence for pineal differentiation. The analysis of IRBP expression may facilitate the diagnostic recognition of primitive pineal neoplasms and further define the neuroretinal differentiation which occurs in pineal parenchymal tumors.

Adolescent↗

Pit-1 messenger ribonucleic acid is differentially expressed in human pituitary adenomas.

Thirty-four human pituitary adenomas were examined for the presence of Pit-1 mRNA via Northern analysis. All tumors that were immunoreactive with either human (h) PRL or hGH antiserum contained Pit-1 mRNA (8 of 8) as did a small percentage of alpha-subunit only (1 of 3) and null tumors (1 of 9). Two tumors that contained TSH beta mRNA by RNAse protection assay also contained Pit-1 mRNA. Tumors that were immunoreactive with antiserum for hACTH, hFSH beta, or hLH beta without containing PRL, GH, or TSH beta were uniformly Pit-1 negative (0 of 14). Although RNA from the majority of Pit-1-positive tumors (10 of 11) contained primarily a 2.4-kilobase (kb) Pit-1 mRNA transcript, 1 tumor appeared to contain a 1.6-kb mRNA. Analysis of human pituitary autopsy specimens revealed no 1.6-kb Pit-1 mRNA, indicating that this variant may be tumor specific. The wide variety of serum PRL, GH, and insulin-like growth factor-I levels in patients with Pit-1-positive tumors suggests that although Pit-1 is necessary for PRL and GH production, it is not uniformly associated with hormone production, as determined by either immunohistochemistry or elevated serum levels. The expression of Pit-1 mRNA in a small fraction of null and alpha-subunit only tumors indicates that there may be a previously unsuspected diversity of origin within these particular subsets of adenomas.

Adenoma↗

Pallidoluysian atrophy: dystonia and basal ganglia functional anatomy.

The clinical correlates of "pure" pallidoluysian atrophy are not well described. A 59-year-old man presented with 20 years of progressive generalized dystonia, dysarthria, gait disorder, supranuclear vertical gaze palsy, and bradykinesia. At autopsy there was severe bilateral atrophy of the external pallidum and subthalamic nucleus with neuronal loss and marked gliosis. This syndrome may epitomize the consequences of "pure" pallidoluysian atrophy. In this case, dystonia appears to occur in the setting of decreased excitation (increased inhibition) of medial pallidal neurons, a pathophysiologic condition common to several hyperkinetic states.

Atrophy↗

The presence of neuron-associated microtubule proteins in the human U-251 MG cell line. A comparative immunoblot and immunohistochemical study.

U-251 MG, a permanent cell line derived from human glioblastoma multiforme with the capacity to maintain glial fibrillary acidic protein (GFAP) production over repeated in vitro passages, was evaluated for the expression of three neuron-associated proteins (Class III beta-tubulin, MAP2, and tau) in three different in vitro systems: as free-floating suspensions, on coverslips, and on a gelatin foam (Gelfoam) matrix. Cells grown under the three in vitro conditions were analyzed by immunoblotting techniques, whereas immunohistochemical analyses were performed on cells grown on Gelfoam. By immunohistochemistry, cells were positive for Class III beta-tubulin isotype, a neuron-associated beta-tubulin, for microtubule-associated protein 2 (MAP2), but not for tau. Immunoblotting studies confirmed the presence of Class III beta-tubulin in extracts of cells grown under the three in vitro conditions. MAP2 and tau were clearly evident only in cell extracts grown in Gelfoam cultures. GFAP expression was observed in all three in vitro conditions by immunoblotting and also in foam matrix cultures by immunohistochemistry. In matrix cultures, Class III beta-tubulin- and GFAP-positive cells were found immediately adjacent to each other, but coexpression of these proteins was not observed, and the cells were morphologically indistinguishable. Our findings confirm the heterogeneity of malignant gliomas in vitro, and the implications of these observations require further study.

Animals↗

Cytoskeletal immunohistochemistry of central neurocytomas.

Central neurocytomas are rare intraventricular tumors. Patients with such tumors have a favorable prognosis after surgical removal. These tumors may be misdiagnosed as neuroblastomas or gliomas, risking the complications of adjuvant therapy. Diagnosis of central neurocytoma requires that the tumor shows the ultrastructural features of mature neuronal differentiation, including the presence of synapses and dense-core and clear vesicles in addition to profiles of neuritic processes with microtubules. The cytoskeletal phenotype of central neurocytomas has not been previously characterized, but it may facilitate their definitive recognition when ultrastructural examination is not possible. Ten central neurocytomas were examined by immunohistochemistry for phosphorylation-dependent/independent neurofilament epitopes, neuron-associated class III beta-tubulin, microtubule-associated proteins (MAP2, tau), and glial fibrillary acidic protein (GFAP). The neuronal nature of all neoplasms was documented by immunoreactivity for synaptophysin in nine tumors and for phosphorylation-independent neurofilament-H/M in the remaining case. Electron microscopy in four cases showed synapses and dense core vesicles. All tumors were immunoreactive for class III beta-tubulin and MAP2, which were seen in cytoskeletal structures by immunoelectron microscopy. Two thirds of the cases were immunohistochemically positive for neurofilament epitopes. None of the tumor cells displayed GFAP immunoreactivity, although reactive astrocytes were present. These data suggest that central neurocytomas may be recognized by synaptophysin immunoreactivity and that the expression of cytoskeletal epitopes indicates that these tumors are well-differentiated neuronal neoplasms.

Adolescent↗

Pathology of the central nervous system in patients infected with the human immunodeficiency virus (HIV): a report of 252 autopsy cases from Brazil.

The central nervous system (CNS) was studied in 252 HIV-infected patients from the States of Rio de Janeiro and São Paulo in Brazil, the regions with the highest incidence of AIDS in the country. We compared the frequency and morphology of opportunistic infections and CNS changes caused by the HIV, with those described in other series and briefly analysed the risk factors involved in our cases. There were CNS lesions in 230 cases (91.3%), 30 (11.9%) with multiple infections and/or tumours. Most infections were opportunistic (65.4%), including 15.4% viral and 50% bacterial, fungal or protozoal infections. The most frequent was toxoplasmosis (34.1%), followed by cryptococcosis (13.5%), cytomegalovirus (CMV) infection (7.9%) and nodular encephalitis (6.7%). Primary lymphomas were observed in 4% of the cases and HIV encephalitis or leukoencephalopathy in 10.7%. Other opportunistic and HIV associated lesions were present in a limited number of cases and there were also vascular and non-specific lesions. Our study confirms the high frequency of CNS lesions in HIV infected patients. They are morphologically similar to those previously described. However, the higher incidence of toxoplasmosis and cryptococcosis, a lower incidence of viral opportunistic and HIV-associated lesions, and the presence of rarer lesions such as histoplasmosis and chagasic encephalitis, differ from other series, and may reflect geographical and/or socio-economic factors.

AIDS-Related Opportunistic Infections↗

Fatal meningoencephalitis caused by reactivation of Trypanosoma cruzi infection in a patient with AIDS.

We report a case of fatal chagasic meningoencephalitis in an AIDS patient. Acute exacerbation of chronic Chagas' disease with involvement of the CNS is uncommon and occurs only in immunocompromised patients. This is the third such reported reactivation and it underscores the importance of considering Chagas' disease in HIV-positive patients from endemic regions.

Acquired Immunodeficiency Syndrome↗

Expression of developmentally defined retinal phenotypes in the histogenesis of retinoblastoma.

Retinoblastoma, the most common intraocular tumor of childhood, is a malignant neoplasm that arises during retinal development. The embryonal cell target for neoplastic transformation is not yet clearly defined. To better understand the histogenetic potential of this tumor, the expression of photoreceptor and glial cell-associated proteins were examined in 22 primary retinoblastomas. Interphotoreceptor retinol-binding protein (IRBP), cone and rod opsins were selected as the photoreceptor specific proteins due to their different temporal patterns of expression during normal retinal development. Neoplastic Müller cell differentiation, and non-neoplastic reactive astrocytes were identified using cellular retinaldehyde binding-protein (CRAlBP), and glial fibrillary acidic protein (GFAP), respectively. Photoreceptor proteins were present in 16 cases and showed different cellular patterns of expression. IRBP and cone opsin were usually abundant. Although rod opsin was clearly identified in eight tumors, its expression was more restricted than either IRBP or cone opsin. This differential pattern of expression, opposite to the normal pattern of photoreceptor gene expression in the adult retina, corresponded to a marked decrease in mRNA for rod opsin. Cone opsin and IRBP colocalized in fleurettes demonstrating that neoplastic human cone cells are capable of IRBP synthesis. Müller cell differentiation was present in 12 of the 16 cases in which photoreceptor proteins were detected. In contrast, GFAP was only present in reactive, stromal astrocytes associated with blood vessels. Our data suggest that the retinoblastoma has the histogenetic potential of the immature neural retinal epithelium which can give rise to both photoreceptor and Müller cell lineages. The differential expression of cone and rod phenotypes in retinoblastoma is consistent with the "default" mechanism of cone cell differentiation.

Blotting, Northern↗

Characterization and immunohistochemical localization of alpha 2-macroglobulin receptor (low-density lipoprotein receptor-related protein) in human brain.

Proteinase inhibitors have been implicated in brain development and in degenerative processes such as Alzheimer's disease. Low-density lipoprotein receptor-related protein (LRP) is a multifunctional cell-surface receptor that binds activated forms of the proteinase inhibitor, alpha 2-macroglobulin (alpha 2M) and apolipoprotein E. Solubilized plasma membranes of human cerebral cortical gray matter were subjected to affinity chromatography on alpha 2M-methylamine-sepharose. A single receptor was purified; this protein was LRP as determined by molecular mass, peptide structure, and immunoreactivity with monoclonal and polyclonal antibodies. In adult human brain, LRP immunoreactivity was abundant on neuronal cell bodies and proximal processes. Other cells within the neuropil, including glia and microvascular cells (endothelium and pericytes), were immunonegative. Weak LRP immunoreactivity was identified in a perivascular pattern corresponding to the location of astrocytic foot processes. The distribution of LRP in the central nervous system is consistent with the potential function of this receptor in the regulation of proteinase activity, cytokine activity, and cholesterol metabolism.

Blotting, Western↗

Aluminium maltol-induced neurocytoskeletal changes in fetal rabbit midbrain in matrix culture.

We have developed a neuronal culture system to evaluate the neurotoxic effects of aluminium maltol on fetal rabbit midbrain sections containing the oculomotor nucleus. Cultures were treated with 5, 7, 9, 11, 13 and 15 mumol/l aluminium maltol or 39 and 45 mumol/l maltol (molal equivalents to 13 and 15 mumol/l aluminium maltol). Control cultures were maintained in nutrient medium alone. Silver-positive neuritic swellings and occasional perikaryal neurofibrillary tangles were observed in cultures treated with 11, 13 and 15 mumol/l aluminium maltol. The number of tangles (involved neurons) produced in aluminium maltol treated cultures were counted and compared to (untreated) controls. We observed a total of 3, 7 and 7% of involved neurons following treatment with 11, 13 and 15 mumol/l aluminium maltol respectively, and none in the control group. By immunohistochemistry, neurofibrillary tangles were immunoreactive with MAbs to phosphorylated (SMI-31), non-phosphorylated, phosphorylation dependent (SMI-32) and phosphorylation independent (SMI-33) epitopes of the high (-H) and middle (-M) molecular weight neurofilament subunits (NF-H/M). By contrast these lesions were nonreactive with MAbs recognizing tau, MAP2 or different beta-tubulin isotypes. The perikaryal tangles consisted of focal accumulations of 10 nm straight filaments by electron microscopy. These findings are in agreement with previous data from rabbit in vivo studies after the administration of aluminium maltol intravenously (Bertholf et al., 1989) or intraventricularly (Katsetos et al., 1990). Using this in vitro system, aluminium-induced neurofibrillary tangles can be consistently produced, and changes in the distribution of neurofilament proteins evaluated. These studies may aid in the assessment of the possible role of aluminium in the aetiology of human neurodegenerative disorders.

Aluminum↗

Glial fibrillary acidic protein and cytokeratin in choroid plexus tumors. An immunohistochemical study.

Ten cases of choroid plexus tumors (3 papillomas and 7 carcinomas) were tested for the presence of glial fibrillary acidic protein (GFAP) and cytokeratin. None of the papillomas and one of the carcinomas were positive with GFAP antisera. Cytokeratin-positive cells were present in 2 of 7 carcinomas and in all papillomas. There seems to be a positive correlation between the degree of the tumor differentiation and the expression of intermediate filaments.

Carcinoma↗

[Spinal cord compression caused by Cladosporium trichoides. An anatomo-clinical case report].

The authors report a case concerning a 25-year-old man who presented a cervical cord compression. The pathologic examination of the mass disclosed a chronic granulomatous meningitis with dense fibrosis. Septate and pigmented hyphae of Cladosporium trichoides were present among the inflammatory infiltrate. A review of the literature concerning the involvement of the central nervous system by this agent is performed. This is the first case in which the disease started as a compressive cord syndrome.

Adult↗

Childhood Degos disease with prominent neurological symptoms: report of a clinicopathological case.

Degos disease is a rare disorder, characterized by a vasculopathy of unknown origin that leads to typical skin lesions and involves other organ systems. It is frequently a lethal condition; death occurs as a consequence of intestinal perforation. In about 20% of cases, the central nervous system is involved and the neurological symptoms can be prominent. The incidence of the disease in children is very uncommon. We report the case of teenage girl who had Degos disease with prominent neurological involvement.

Adolescent↗

Neuropathology of acquired immunodeficiency syndrome (AIDS). Analysis of 22 Brazilian cases.

The neuropathologic study of 22 Brazilian cases of acquired immuno-deficiency syndrome (AIDS) was performed. Thirteen cases (59%) showed neuropathologic lesions. These included infection by Toxoplasma (n = 4), Cryptococcus neoformans (n = 3), viral encephalitis (n = 4), primary lymphomas (n = 2), isolated cerebral infarct (n = 1), and reactive gliosis (n = 1). In 2 cases, primary lymphoma and viral encephalitis were associated. Axonal spheroids in the gracilis and cuneatus nuclei were present in a case of toxoplasmosis. Mammillary bodies lesions consistent with Wernicke's encephalopathy were found in a case of viral encephalitis. In addition, circulatory changes (focal cortical infarcts) were associated lesions in 3 cases. These findings were compared with the main series reported in American and European literature.

Acquired Immunodeficiency Syndrome↗

Fatal encephalopathy due to Lagochilascaris minor infection.

A 14-year-old boy with a tetralogy of Fallot showed a subacute, progressive encephalopathy characterized by headache, stupor and coma. Death occurred three months after the beginning of the illness. Neuropathologic examination revealed diffuse foci of necrosis of the cerebral hemispheres and cerebellum, and the presence of the nematode Lagochilascaris minor in the parenchyma and in the cisterns at the base of the brain. In almost all 28 cases of human lagochilascaris previously reported, the worms were located in the soft tissues of the neck and throat, tonsils, mastoids and paranasal sinuses. This is the first reported case in which Lagochilascaris infected the brain. Since the life cycle of the worm is unknown the pathogenesis of the central nervous system lesions is obscure.

Adolescent↗