Biomedical subjects
Publications and source records attributed to J Poirier.
A 53-year-old patient with Wilsons's disease and without autonomic dysfunction presented on T2-weighted MR study an atypical decreased signal intensity of the putamina and the caudate nuclei. Possible explanations of such a signal abnormalities are discussed.
Evidence is given for altered gene expression of gamma-actin in the hippocampus in response to entorhinal cortex lesion (ECL). Time course analysis reveals a progressive repression of gamma-actin expression between 4 and 14 days post-lesion, coinciding with the early and middle phases of the hippocampal reinnervation process. RNA prevalence returns to near control values at 30 days post-lesion. Corticosterone administration, which is known to impair the reinnervation process in ECL rats, prevents the lesion-induced reduction in gamma-actin expression and blocks the induction of alpha 1-tubulin in the deafferented hippocampus. The timing of response of gamma-actin to ECL and its modulation by glucocorticoid administration support suggestions that gamma-actin has an important role to play in neuronal cytoarchitecture remodelling during hippocampal reinnervation.
A case of multiple vertebral hemangiomas with progressive neurological deficit is presented. Successful treatment was accomplished using preoperative embolization, palliative surgical decompression, and postoperative radiation therapy. The patient has remained asymptomatic for 6 years. The authors review the role of current imaging modalities and options for therapeutic intervention. Preoperative embolization, palliative surgical decompression, and postoperative radiotherapy appear to provide a satisfactory outcome in patients with multiple hemangiomas and may represent an effective alternative to more aggressive surgical intervention.
Hemosiderin deposition and vascular inflammation were evaluated in muscle specimens from 50 human immunodeficiency virus (HIV)-infected individuals with neuromuscular symptoms. Iron deposits were detected in 25 of 50 cases, and were found more frequently in the distal muscles of lower limbs than in proximal muscles (22 of 30 cases v three of 20 cases; P less than .001). The incidence was higher than in controls (P less than .01). Polyarteritis nodosa was observed in three cases and microvascular inflammation was observed in 27. Direct immunofluorescence showed deposits of both immunoglobulins (mainly immunoglobulin M) and complement in small vessel walls of 19 of 34 patients. The p17 and p24 HIV antigens were detected in three of 27 cases. Both T8 lymphocytes and macrophages were significantly more numerous in patients with Perls'-positive material; these patients also showed vascular inflammation more frequently. Other findings included noninflammatory microangiopathy (18 cases), tubuloreticular inclusions in endothelial cells (one case), and free and intracytoplasmic eosinophilic globules likely representing digested erythrocytes (seven cases). The present study shows that iron pigment deposition in skeletal muscle is a nonspecific finding, frequently observed in the lower extremities of HIV-infected individuals, where it reflects immunopathologic alterations of the microcirculation. Erythrophagocytosis, which may be observed in the muscle of some HIV-infected individuals, may also be implicated.
Evidence is given for altered gene expression in the hippocampus in response to entorhinal cortex lesioning. Three RNA markers encoding glial fibrillary acidic protein, apolipoprotein E and alpha-tubulin were isolated from a rat hippocampal cDNA library by differential screening with cDNA probes from entorhinal cortex lesioned and control rat hippocampus RNA. By Northern blot analysis, mRNA for apolipoprotein E and alpha-tubulin increased to peak around 6 days after the lesion and returned to near control level at 30 days. The increased synthesis of both mRNAs coincides with the acute phase of synaptogenesis, protein synthesis, and polyribosomes accumulation in the deafferented hippocampal area.
Entorhinal cortex lesions (ECL) that damage the perforant path to the hippocampus induce rapid increases of apolipoprotein E (apo E) mRNA in the hippocampus. Apo E mRNA was localized in astrocytes by in situ hybridization in combination with immunocytochemistry for glial fibrillary acidic protein (GFAP). Unilateral ECL also increased hippocampal GFAP mRNA, with increases preceding those of apo E mRNA. The apo E mRNA and GFAP mRNA responses were transiently bilateral in non-denervated zones. The timing of response in apo E mRNA to deafferentation supports suggestions that apo E has roles in membrane remodelling during responses to neuron injury.
Since Idiopathic Parkinson's disease (IPD) was first described more than 170 years ago, there have been major advances in the understanding of the etiology of the disease as well as in its treatment. This article will review current knowledge concerning the role of the environment, genetic hypotheses and the aging factor in the etiology of IPD and proposes a complex interaction involving all these factors. Hypotheses regarding mitochondrial inhibition and free radical generation in IPD are discussed in relation to the mechanism of action of neurotoxins known to produce parkinsonian syndromes.
A 66-year-old French homosexual man and a 42-year-old Brazilian man with no known risk factors for HIV infection developed headaches, asthenia, and neurologic episodes of abrupt onset. CT showed multiple hypodense, nonenhancing lesions. Serology for HIV was positive. They died respectively 2 months and 1 month after onset of the illnesses. Autopsy in both cases showed multiple, well-demarcated, demyelinating foci in the white matter of the cerebral hemispheres, brainstem, and cerebellum with histologic features characteristic of recent plaques of multiple sclerosis. There were no multinucleated giant cells or microglial nodules. Immunostaining for HIV was negative. Although a random coincidence of MS and HIV infection cannot be ruled out, the close temporal relationship between the 2 disorders suggests a possible etiologic association.
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We report two cases of oligodendroglioma-like meningioma revealed by symptoms of increased intracranial pressure, progressive hemiparesia and partial epileptic seizures. Brain CT-scan or scintigraphy and carotid arteriography were suggestive of a convexity meningioma. One patient had received radiation treatment for scalp tinea capitis 25 years previously. In spite of complete surgical removal, the tumor recurred in both cases respectively 17 years and 18 months later. The two patients were operated again, and one underwent a complementary radiotherapy. Pathologic diagnosis was particularly difficult in the first case where the pattern at conventional histologic technics was that of oligodendroglioma. On the occasion of recurrence, immuno-histochemistry and ultrastructural studies were performed. The tumor was positive for epithelial membrane antigen (E.M.A) and cytokeratin, but was negative for glial fibrillary acidic (G.F.A.) protein, S 100 protein (S 100), neuron-specific enolase (N.S.E.), vimentin, anti-LEU-7 (N.H.K.1), and neurofilaments (N.F.). Electron microscopy showed closely adjacent cells with tonofilaments and numerous desmosomes. These findings permitted to establish the diagnosis of oligodendroglioma-like meningioma instead of oligodendroglioma. In the second case, the histologic pattern was also reminiscent of oligodendroglioma, but presence of few cellular whorls in some part of the tumor permitted the correct diagnosis. The pathogenesis of this atypical form of meningioma, its tendency for recurrence, and usefulness of radiotherapy are discussed and literature is reviewed.
The central nervous system was examined in 135 adult AIDS patients who died between August 1982 and December 1990. Twenty two brains showed non-diagnostic changes including microglial nodules, discrete myelin pallor with reactive astrocytosis, mineralization of blood vessels and granular ependymitis. In 105 brains with specific changes, toxoplasmosis was the most frequent finding (55 cases) manifested by multifocal necrotic lesions or diffuse pseudo-encephalitic process. Other opportunists included cytomegalovirus (21 case), progressive multifocal leukoencephalopathy (1 cases), cryptococcosis (6 cases), mycobacterium avium intracellulaire (2 cases), varicella-zoster virus (2 cases), aspergillosis (1 case) and multiple bacterial microabscesses (1 case). Multinucleated giant cells were found in 52 cases. In 40 cases, they were widely disseminated throughout the brain and in 39 cases, they were associated with diffuse or multifocal white matter changes. Fifteen cases had a cerebral lymphoma, 9 hepatic encephalopathy, 1 centropontine myelinolysis and 1 focal pontine leukoencephalopathy. Three cases had a cerebral haemorrhage due to disseminated intravascular coagulation, antithrombin therapy and amyloid angiopathy. Spinal changes in 13 cases included vacuolar myelopathy (7 cases), HIV myelitis (1 case) and ganglio-radiculitis (1 cases), cytomegalovirus myelo-radiculitis (1 case) secondary spread from a lymphoma (1 case) and spinal infarcts due to disseminated intravascular coagulation (1 case). These lesions were frequently atypical and various combinations of all these pathologies were encountered in the same brain, sometimes in the same area and occasionally in the same cell. Chronological variations in the incidence of some complications could be related to changes in treatment.
The precursor to ornithine carbamyl transferase (pOCT) is cleaved at two N-terminal sites when imported into intact mitochondria but only at the N-proximal site when incubated with a membrane-free mitochondrial lysate or matrix fraction. Disruption of the mitochondrial membrane system by sonication, freeze-thaw, or lysis with non-ionic detergents blocks the processing of pOCT to its mature form. Mitoplasts prepared from protease-inactivated, import-incompetent mitochondria recover full processing activity; disruption of the inner membrane impairs the maturation process i.e. causes the loss of the mitoplasts' ability to transform pOCT into OCT. The data reveal a dependency of a maturation event on a "specific" interaction between a precursor protein and the mitochondrial inner membrane probably to position and/or to expose the correct N-distal cleavage site of the presequence.
Protein synthesis was investigated in isolated mitochondria under conditions which either inhibited electron transport or uncoupled oxidative phosphorylation. In a medium containing an exogenous source of ATP and oligomycin, an inhibitor of the ATP synthase complex, incorporation of [35S]methionine into proteins is stimulated in the presence of inhibitors of the electron transport chain; substituting uncouplers of oxidative phosphorylation for the latter leads, in contrast, to a decrease in the rate of incorporation of the labeled amino acid into mitochondrial translation products. Studies on the metabolic stability of mitochondrial translation products revealed that "mature" polypeptides made in isolated mitochondria are stable as indicated by the absence of degradation during a 50 min "chase" period. Under conditions which reduce or dissipate the membrane potential, 50-60% of the newly made polypeptides (pulse) are degraded within 50 min. The kinetics of the degradation process for individual mitochondrial gene products reveal that the largest proportion of polypeptides degraded to an acid-soluble form during the chase period are abnormal proteins, likely the result of premature chain termination. Emerging as a common denominator in these studies is a role for a transmembrane potential across the inner membrane in the production of mature "stable" mitochondrial gene products.
Spinal cord involvement in AIDS is not uncommon. Different types of lesions corresponding to varying pathogenetic mechanisms have been reported. Vacuolar myelopathy is the most frequently found. The symptoms and pathological changes resemble those of subacute combined degeneration; however, cobalamine or folate levels have always been found normal. Its frequent association with the multi-nucleated giant cells characteristic of HIV encephalitis makes it likely that the virus plays a role in its pathogenesis. Cytomegalovirus may be responsible for acute myeloradiculitis involving the spinal roots of the cauda equina and inferior part of the spinal cord. In cases of Herpes simplex virus myelitis has been reported; they are usually associated with cytomegalovirus infection and are due to herpes simplex virus type II. Secondary spread from systemic lymphomas may involve the subarachnoid space of the cord and the spinal roots. Compression of the spinal cord by epidural lymphomatous masses has also been described. Spinal infarcts may be secondary to acute or chronic vasculitis or to less specific vascular processes such as disseminated intravascular coagulation.
A 25-year-old homosexual male with AIDS presented with a cauda equina syndrome clinically suggestive of cytomegalovirus (CMV) myeloradiculitis. He was treated with ganciclovir with transient improvement of neurological signs and died 4 months after onset of neurological signs. Neuropathological examination revealed human immunodeficiency virus (HIV) encephalitis, CMV subependymal encephalitis and CMV myeloradiculitis. The latter was characterised by myelin loss, Schwann cell proliferation and presence of CMV early antigens in the nuclei of S-100 protein-positive cells in the spinal roots. In the subependymal regions, morphologically characteristic multinucleated giant cells, positive for CD68, contained early CMV antigens (E13) in their nuclei and HIV antigens (gp41 and p24) in their cytoplasm. The observation that HIV and CMV can co-infect the same cell in vivo raises the possibility of a direct synergistic interaction of both viruses at cell level. This suggests that CMV may play a role as a co-factor in the pathogenesis of HIV encephalopathy.
A hippocampal poly(A) RNA, pADHC-9, was cloned by differential screening of a human hippocampal cDNA library. By RNA blot analysis, pADHC-9 was elevated 2-fold in Alzheimer's disease hippocampus. In situ analyses identified pADHC-9 expression in pyramidal and non-pyramidal cells of the hippocampus and entorhinal cortex. Nucleotide sequence analysis identified pADHC-9 as a potential human homolog of rat sulfated glycoprotein 2 (SGP-2). SGP-2 expression increased in rat hippocampus following experimental lesions that mimic intrinsic neuronal loss and/or deafferentation. The function of pADHC-9 in brain has not been defined, but in serum, a similar protein inhibits complement-dependent cytolysis. Increased expression of pADHC-9 in Alzheimer's disease hippocampus may be a compensatory response mounted to retard a complement-driven neurodegenerative cascade.
Neuropathologic study of an 82-year-old male who died from massive cerebral hemorrhage showed extensive amyloid angiopathy, with morphologic and immunohistochemical characteristics similar to those observed in Alzheimer's disease, associated with granulomatous angiitis, including the presence of numerous giant cells. Some of the giant cells contained, in their cytoplasm, congophilic material immunoreactive for the Alzheimer A4 peptide, supporting the hypothesis that the granulomatous angiitis may, in part, represent a foreign body reaction to A4 amyloid deposition.
In vitro translation products from RNA of rat hippocampus after deafferentation by entorhinal cortex lesions were analyzed by two-dimensional gel electrophoresis. Although hippocampal total RNA yield was not affected 14 days after the lesion, analysis of the gels showed reproducible changes in the steady-state level of several transcripts. Glial fibrillary acidic protein RNA increased 2-fold over control hippocampi RNA. Moreover, seven other transcripts of unknown identity had increased prevalence in the denervated hippocampus. The changes, which ranged from 2- to 20-fold, involved mRNA encoding small slightly acidic polypeptides: 12 kDa (pI 5.6), 13 kDa (pI 6.1), 20 kDa (pI 5.8), 31 kDa (pI 5.7), 33 kDa (pI 5.7), 35 kDa (pI 5.6), and 53 kDa (pI 5.4). These results suggest new molecular markers for analyzing the complex mechanisms of synaptic reorganization in the dentate gyrus after deafferentation.