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L Chimelli

Publications and source records attributed to L Chimelli.

At least 19 recordsLinked to original sources
PubMed1999

Microwave-stimulated recovery of myosin-V immunoreactivity from formalin-fixed, paraffin-embedded human CNS.

The lability of brain myosin-V (BM-V) to aldehyde-fixation has hindered immunohistochemical (IH) studies of this actin-based motor. We show here that BM-V immunoreactivity (IR) can be retrieved from formalin-fixed, paraffin-embedded human tissue. BM-V IR was optimally retrieved by boiling 5 microm cerebellar tissue sections in 10 mM sodium citrate buffer, pH 6, for 15 min, using a microwave oven set at 900 W and 2.45 GHz. A polyclonal, affinity purified anti-BM-V antibody, raised in rabbits against the tail domain of chicken BM-V, was shown here to recognize a single band in Western blots of human cortical homogenates. The combined use of this monospecific antibody and of the antigen retrieval (AR) method above allowed us to verify that BM-V IR is strongly expressed in human Purkinje cell bodies and dendrites, and in granule cells. The same pattern of BM-V IR expression was consistently and maximally detected in tissues stored in 10% formalin from 1 week to 2.5 months. The AR protocol for BM-V described here permits its IH study in formaldehyde-fixed tissues. It is a valuable tool to study BM-V in well fixed tissues, as occurs with the large collection of human archival tissue available.

Adult↗
PubMed1999

Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients.

Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters its channel properties, and may enhance or reduce neuronal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n = 16), non-HS (n = 10), and autopsy hippocampi (n = 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell. Furthermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per CA2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chronic temporal lobe seizures are associated with differential changes in hippocampal NR1 and NR2A-D hybridization densities that vary by subfield and clinical-pathological category. In temporal lobe epilepsy patients, these findings support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases.

Adolescent↗
PubMed1999

Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy.

OBJECTIVE: Sodium-coupled transporters remove extracellular neurotransmitters and alterations in their function could enhance or suppress synaptic transmission and seizures. This study determined hippocampal gamma-aminobutyric acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal lobe epilepsy (TLE) patients. METHODS: Hippocampal sclerosis (HS) patients (n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compared with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynaptic GABA terminals), GABA transporter-1 (GAT-1; presynaptic GABA transporter), GAT-3 (astrocytic GABA transporter), excitatory amino acid transporter 3 (EAAT3; postsynaptic glutamate transporter), and EAAT2-1 (glial glutamate transporters). RESULTS: Compared with autopsies, non-HS cases with similar neuron counts showed: 1) increased GAD IR gray values (GV) in the fascia dentata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-1 OML GVs; 3) increased astrocytic GAT-3 GVs in the hilus and Ammon's horn; and 4) no IR differences for EAAT3-1. HS patients with decreased neuron densities demonstrated: 1) increased OML and inner molecular layer GAD puncta; 2) decreased GAT-1 puncta relative to GAD in the stratum granulosum and pyramidale; 3) increased GAT-1 OML GVs; 4) decreased GAT-3 GVs; 5) increased EAAT3 IR on remaining granule cells and pyramids; 6) decreased glial EAAT2 GVs in the hilus and CA1 stratum radiatum associated with neuron loss; and 7) increased glial EAAT1 GVs in CA2/3 stratum radiatum. CONCLUSIONS: Hippocampal GABA and glutamate transporter IR differ in TLE patients compared with autopsies. These data support the hypothesis that excitatory and inhibitory neurotransmission and seizure susceptibility could be altered by neuronal and glial transporters in TLE patients.

ATP-Binding Cassette Transporters↗
PubMed1998

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients.

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.

Adult↗
PubMed1998

Increased hippocampal AMPA and NMDA receptor subunit immunoreactivity in temporal lobe epilepsy patients.

This study determined if hippocampal AMPA and NMDA subunit immunoreactivity (IR) in temporal lobe epilepsy patients was increased compared with nonseizure autopsies. Hippocampi from hippocampal sclerosis patients (HS; n = 26) and nonsclerosis cases (non-HS: n = 12) were compared with autopsies (n = 6) and studied for GluR1, GluR2/3, NMDAR1, and NMDAR2 IR gray values (GV) along with fascia dentata and Ammon's horn neuron densities. Compared with autopsies, non-HS cases with similar neuron densities and HS patients with decreased neuron densities showed: (a) Increased GluR1 GVs in the fascia dentata molecular layer: (b) increased NMDAR1 GVs in the CA3-1 stratum radiatum and greater IR within pyramids; and (c) increased GluR2/3 and NMDAR2 GVs throughout all hippocampal subfields. Furthermore, HS patients showed that relative to the outer molecular layer: (a) GluR1 GV differences were decreased in the CA4/hilar region and CA1 stratum radiatum compared with autopsies; and (b) NMDAR2 GV differences were increased in the inner molecular layer compared with non-HS cases. In temporal lobe seizure patients, these results indicate that AMPA and NMDA receptor subunit IR was increased in HS and non-HS hippocampi compared with nonseizure autopsies. In humans, these findings support the hypothesis that glutamate receptor subunits are increased in association with chronic temporal lobe seizures, which may enhance excitatory neurotransmission and seizure susceptibility.

Adult↗
PubMed1998

[Neurocysticercosis: contribution of autopsies in the consolidation of mandatory notification in Ribeiräo Preto-SP,Brazil].

Neurocysticercosis is a serious public health problem in several countries of Asia, Africa and Latin America. The objective of the present study is to present autopsy findings of neurocysticercosis in the Pathology Division of the University Hospital, Medical School of Ribeirão Preto, University of São Paulo, from 1992 to 1997. Neurocysticercosis was detected in 38 (1.5%) of 2522 autopsies. In twenty two (57.9%) of these, the diagnosis was made post-mortem, while 16 (42.1%) had a previous diagnosis of cysticercosis based on laboratory and imaging studies. Reviewing the medical records, we found that 21 patients (55.2%) were neurologically asymptomatic, while the various clinical manifestations in the others were in accordance with the literature. The high frequency of asymptomatic individuals detected only post-mortem indicates the importance of autopsies as an additional source of data to consolidate the compulsory notification of cysticercosis. Considering the results of this study, the new coefficient of prevalence of cysticercosis in Ribeirão Preto is 67 cases/100,000 inhabitants.

Aged↗
PubMed1998

Lipoblastic meningioma. Case report.

We describe the case of a patient presenting a right parietal mass lesion with an heterogeneous aspect on computed tomography, with hyperdense contrast uptake areas and hypodense areas with fat density. The unusual aspect of the lesion prevented preoperative and intraoperative diagnosis. The final histopathological examination revealed a meningothelial neoplasia with adipose differentiation, characterizing a lipoblastic meningioma.

Humans↗
PubMed1998

Disseminated muscular cysticercosis with myositis induced by praziquantel therapy.

Cysticercosis, the infestation with the encysted larval stage of Taenia solium, is increasingly recognized as a major problem in most countries in Latin America, Asia, and Africa, involving mainly the central nervous system. Muscle involvement is also common, although it usually remains asymptomatic. We describe a case of disseminated muscular cysticercosis followed by myositis (fever, diffuse myalgia, weakness of the lower limbs, and inflammatory reaction around dying cysticerci) induced by praziquantel therapy, an event not described previously.

Adult↗
PubMed1997

Experimental benznidazole encephalopathy: II. Electroencephalographic and morphological alterations.

We describe electroencephalographic (EEG) and morphological alterations in the CNS of dogs treated with benznidazole. The relationship between dose, duration of treatment and intensity of lesions observed was examined and used to establish anatomo-clinical associations. Two predominant EEG patterns were noted in treated dogs. Most of the animals (Group I) that received acute treatment with high doses (30 mg/kg/day) for 15 days followed by treatment at a lower dose (10 mg/kg/day) exhibited a type 2, EEG pattern, i.e., low voltage desynchronized with fast activity (LVFA). In contrast, most of the animals (Group II) that received short-term acute treatment with high doses (40 mg/kg/day) for 7 days followed by chronic treatment at lower doses (20 and 5 mg/kg/day) presented a type 1 EEG pattern. high voltage diffuse with slow activity (HVSA). Even after the drug was discontinued, the animals presented mild EEG alterations. These alterations. observed during and after treatment with benznidazole, suggest the presence of encephalopathy with multifocal characteristics. Several morphological alterations were observed in the animals, the most important being: lymphocytic inflammatory infiltrate, neuronal degeneration, satellitosis, demyelination and axonal degeneration, microglial proliferation, necrosis and gliosis. Such alterations involved the meninges, cerebral cortex, hemispheric white matter and subcortical gray matter, brain stem, cerebellum, and, less frequently, the spinal cord. No histopathological alterations were detected in the peripheral nerves. All encephalic levels were involved in all animals treated although the use of the high doses for 15 days (Group I) appeared to result in more lesions in the subcortical gray matter and the lower brainstem when compared to the use of high doses for 7 days (Group II) which led to greater involvement of the cerebral cortex, hemispheric white matter, cerebellum and medulla.

Animals↗
PubMed1997

Value of nerve biopsy in the diagnosis and follow-up of leprosy: the role of vascular lesions and usefulness of nerve studies in the detection of persistent bacilli.

Nerve biopsy specimens from 53 patients with leprosy and neuropathy were taken from the sural, the dorsal branch of the ulnar, or the superficial radial nerves and processed for light and electron microscopy. There was inflammation in 40 cases (75%), 7 with a granulomatous reaction, various stages of fibrosis in 35 (66%), and endoneurial vascular neoformation in 7. In two cases, small focal infarcts were associated with marked endoneurial inflammation compressing the vessels, in addition to endoneurial lymphocytic vasculitis. Most had an axonal neuropathy of varying degree, some with total fibre loss, others with predominant small myelinated and unmyelinated fibre loss. Signs of demyelination and remyelination were the main findings in 9 cases (17%). Bacilli were present in endothelial, perineurial, Schwann cells and in macrophages. On two occasions, they lost their alcohol acid resistance, were suspected in semithin sections, and confirmed ultrastructurally. The biopsy was decisive for the diagnosis of leprosy in 15 cases (28%), most without skin lesions. We evaluated the effectiveness of the treatment in 20 (37.7%), 12 without and 8 with bacilli, despite negativity in the skin. The diagnosis of leprosy based on skin lesions was confirmed with the nerve biopsy in 9 cases, 6 had an inflammatory neuropathy suggestive of leprosy in the absence of bacilli, and 3 had nonspecific changes in the sural nerve since the neuropathy was in the upper limbs. We conclude that nerve biopsy is indicated for the diagnosis of leprosy in cases without clinically visible skin lesions and to evaluate the effectiveness of the treatment. In these cases the ultrastructural studies are important for recognition of the bacilli. Vascular lesions may play an important role in the progression of the nerve damage, including the occurrence of focal nerve infarcts which, to our knowledge, have not been previously reported in association with leprosy.

Biopsy↗
PubMed1997

Trypanosomiasis.

African (sleeping sickness) and American (Chagas' disease) trypanosomiasis, caused by protozoa of the family Trypanosomatidae, are diseases that are endemic in parts of Africa and Latin America, respectively. Physicians in developed countries may occasionally see cases because of extensive travel and immigration from endemic countries. Although neurological involvement is common in both, its incidence and clinical presentation differ considerably. African trypanosomiasis, caused by subspecies of Trypanosoma brucei (T b rhodesiense, T b gambiense), is transmitted by the tsetse fly and causes meningoencephalitis, in which somnolence is a prominent feature. Parasites may reach the brain parenchyma through the choroid plexus or the Virchow Robin spaces. American trypanosomiasis, caused by Trypanosoma cruzi is transmitted by reduviid bugs. While lesions in the central nervous system are not prominent, except in the reactivated forms which occur in immunodeficient patients, the peripheral nerve, mainly the autonomic nervous system, is frequently involved, leading to the cardiomegaly and the digestive megaviscera. Congenital infections may also occur. In this paper we give an account of the epidemiology, clinical presentation and pathological features of these two protozoal infections based on human and experimental studies of both the central and peripheral nervous system.

Animals↗
PubMed1997

Fungal infections.

Fungal infections have increased in frequency in the last decades because of the growing number of immunocompromised patients who survive longer periods of time than in the past, the widespread use of immunosuppressive drugs, a large aging population with increased numbers of malignancies, and the spread of AIDS. Although fungi are present everywhere, some mycoses predominate in the tropics, not only in view of warm temperature and humid climate, which favor their growth, but also because of inadequate hygienic and working conditions brought about by poverty. Mycotic diseases in the brain are usually secondary to infections elsewhere in the body, usually the lungs, less often from other extracranial sites, and in the vast majority of the cases spread via blood circulation. Only occasionally they result from direct extensions from infections of the sinuses or bone, and less frequently from prosthetic heart valves. Candida may be endogenous in origin, inhabiting the digestive tract. Most fungi cause basal meningitis or intraparenchymal abscesses. Direct extension from the cribriform plate cause necro-hemorrhagic lesions in the base of the frontal lobe. Although fungi are common in our environment, few are pathogenic. In this paper mycotic infections are divided into opportunistic and pathogenic; although most of the latter have also been described in immunosuppressed patients, some of those caused by opportunistic organisms, have also occurred in the absence of predisposing factors.

Antifungal Agents↗
PubMed1996

Intramedullary spinal cord paracoccidioidomycosis. Report of two cases.

Two cases of intramedullary paracoccidioidomycosis are reported. Paracoccidioidomycosis is a systemic disease that involves the buccopharyngeal mucosa, lungs lymph nodes and viscera and infrequently the central nervous system. Localization in the spinal cord is rare. Case 1: a 55-year old male admitted with crural pararesis, tactile/painful hypesthesia and sphincter disturbances of 15 days duration. Cutaneous-pulmonary blastomycosis was diagnosed 17 years ago. Myelotomography showed a blockade of T3-T4 (intramedullary lesion). The lesion surgically removed was a Paracoccidioides brasiliensis granuloma. Treatment with sulfadiazine was started after the surgery. Follow-up of 15 month showed an improvement of the clinical signs. Case 2: a 57-year old male was admitted elsewhere 6 months ago and, with a radiologic diagnosis of pulmonary paracoccidioidomycosis, was treated with amphotericin B. He progressively developer paresthesia and tactile/pain anaesthesia on the left side, sphincter disturbances and tetraparesis with bilateral extensor plantar response and clonus of the feet. Myelotomography showed a blockade of C4-C6 (intramedullary lesion). The lesion was not found during surgical exploration and the patient deteriorated and died. Post-mortem examination revealed an intramedullary tumor above the site of the mielotomy (Paracoccidioides brasiliensis granuloma). The preoperative diagnosis of intramedullary paracoccidioidomycotic granulomas is difficult because the clinical and radiologic manifestations are uncharacteristic. Clinical suspicion was possible in our cases based on the history of previous systemic disease. Contrary to intracranial localizations, paracoccidioidomycotic granulomas causing progressive spinal cord compression may require early surgery because response to clinical treatment is slow and the reversibility of neurological deficits depends on the promptness of the decompression.

Granuloma↗
PubMed1996

[Peripheral neuropathies in childhood: a neuropathological approach].

Peripheral neuropathies affect children more often than the young and middle age adults, but less frequently than the elderly. They differ from those in the adults because of the high incidence of hereditary neuropathies, including those associated with metabolic and degenerative disorders of the central nervous system; the low incidence of toxic neuropathies and those associated with systemic disorders; and a lower incidence of chronic acquire polineuropathies. Nerve biopsies are indicated if the diagnosis has not been made with clinical and electrophysiologic studies and other methods, and should only be performed in laboratories with appropriated techniques for the study of the nerve. It is important to know the normal development of the nerve, the thickness of the myelin sheath and the distribution of small and large fibers, according to the age. The main morphological aspects of the most frequent neuropathies in children--acquired (inflammatory, demyelinating) and hereditary (sensory-motor, sensory-autonomic, ataxic, and those associated with metabolic and degenerative disorders), are reviewed.

Adult↗
PubMed1995

[Charcot-Marie-Tooth disease. Study of sural nerve biopsy in 41 patients].

We studied the pathological findings of sural nerve biopsy in 41 patients with Charcot-Marie-Tooth (CMT) disease. They were previously classified by the median motor conduction velocity (MCV) in two types. Type I (demyelinating) with 9 patients and type II (axonal) with 32 cases. In type I we found loss of myelinated fibers (unimodal histogram), demyelinated and remyelinated axons with numerous onion bulb formations. In one case there was thickness of myelin with thin axons (axonal atrophy). In type II there were seven patients with normal sural nerve biopsy. In 25 cases there were mild to severe loss of myelinated fibers. In 5 patients the number of myelinated fibers was increased due to the great regeneration of the axons. The electron microscopic studies in type II showed in a few cases small onion bulbs and in one case axonal atrophy. In type I there was no correlation between clinical severity and the loss of myelinated fibers, but there was relationship between the low MCV and the intensity of myelinated fibers. In type II we did not found any correlation between clinical course, MCV and pathological findings.

Adult↗