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Biomedical subjects

C Geny

Publications and source records attributed to C Geny.

At least 37 records · Page 2Linked to original sources

Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction.

Muscle biopsy specimens were obtained from 48 human immunodeficiency virus-infected patients suffering from various neuromuscular symptoms. Microscopic examination by conventional and electron microscopy revealed a characteristic structural myopathy associated with mitochondrial changes in 13 patients, all of whom had received long-term zidovudine therapy. The mean cumulative dose they had received (498 +/- 145 gm) was significantly higher than that of the other 14 zidovudine recipients of the study. They suffered from a progressive, usually painful, proximal myopathy with pronounced wasting, normal-to-moderately elevated creatine kinase levels, and a myopathic electromyographic pattern. The condition usually improved after withdrawal of the drug. Assay of mitochondrial enzymes, including succinate-cytochrome c reductase, cytochrome c oxidase, and citrate synthase, showed a decline in respiratory chain capacity. Southern blot analysis of mitochondrial DNA showed no abnormality. It is likely that mitochondrial dysfunction, probably resulting from drug-induced inhibition of the mitochondrial DNA polymerase, is implicated in the pathogenesis of this complication of zidovudine therapy.

Adult↗

Prominent cortical atrophy with neuronal loss as correlate of human immunodeficiency virus encephalopathy.

A 25-year-old homosexual AIDS patient presented with progressive cognitive, motor and behavioral disturbances consistent with HIV encephalopathy. CT scans demonstrated progressive diffuse brain atrophy. Neuropathology showed predominant cortical changes including severe neuronal loss corroborated by morphometry. Only minimal changes were found in the white matter and basal ganglia. Immunocytochemistry for HIV stained occasional microglial cells more markedly in the cerebral cortex. This suggests that HIV infection of the brain may cause predominant cortical nerve cell loss, and that HIV encephalopathy is not necessarily due to white matter lesions.

AIDS Dementia Complex↗

Muscle mitochondrial DNA in encephalomyopathy and ragged red fibres: a Southern blot analysis and literature review.

Various mitochondrial DNA abnormalities have been described in patients with encephalomyopathies. We performed Southern blot analysis of skeletal muscle mitochondrial DNA in nine adult patients with clinical features and ragged red fibres suggesting mitochondrial dysfunction. Two patients with encephalomyopathy and two with the MERRF syndrome (myoclonus epilepsy with ragged red fibres) had the normal PvuII restriction pattern of muscle mitochondrial DNA. In contrast, mitochondrial DNA deletion was observed in two of six patients with ophthalmoplegia. One suffered from typical Kearns-Sayre syndrome and the other from isolated external ophthalmoplegia. None of these patients had affected relatives. The detection of mitochondrial DNA deletion in external ophthalmoplegia and their site and size support previously reported data.

Blotting, Southern↗

Multifocal multinucleated giant cell myelitis in an AIDS patient.

A 19-year-old male intravenous drug abuser, was admitted to hospital with a one-week history of lower limb weakness and urinary retention. He was known to have been HIV-seropositive for 3 years and had been treated for cerebral toxoplasmosis. Neurological examination confirmed flaccid paraparesis with weak ankle jerks and bilateral extensor plantar responses. There was no obvious sensory deficit. Neurological examination was otherwise normal. CSF contained 63 mg/dl protein and 10 leucocytes/mm3. Myelography was normal. He died 1 month later from septic peritonitis. Neuropathological examination showed chronic lesions of toxoplasmosis in brain. Small necrotic foci with myelin loss, proliferation of microglia, macrophages and multinucleated giant cells (MGC) were disseminated in the whole spinal cord, mostly in the white matter, but the brain was spared. Immunohistochemistry demonstrated p24 and p17 HIV antigens in macrophages, MGC and microglial cells. These lesions resemble those of so called 'multifocal giant cell encephalitis'. The present case demonstrates that HIV-related multifocal inflammatory changes may be restricted to the spinal cord and may be a cause of myelopathy in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Antibody to reverse transcriptase of human retroviruses in multiple sclerosis.

HTLV-1, HIV-1 and HIV-2 western blot analysis of sera from patients with multiple sclerosis (MS), from patients with other neurological diseases and from blood donors, revealed a rather frequent cross-reactivity with retroviral proteins in the MS group, though no patient was positive with the corresponding specific ELISA serology. Statistical analysis revealed a significant difference between the MS group and the two control groups for HIV-1 and HIV-2 reverse transcriptase fragments and for HTLV-1 p24. The general significance of these observations is discussed in the light of a retroviral hypothesis for the aetiology of MS. It is suggested that, if a retrovirus is present in MS patients, it does not necessarily belong to the HTLV sub-family and could as well be a lentivirus, like Visna virus, the causative agent of a demyelinating disease in sheep which is one--natural--model for MS.

AIDS Serodiagnosis↗

[Neuropathologic study of 135 adult cases of acquired immunodeficiency syndrome (AIDS)].

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.

Acquired Immunodeficiency Syndrome↗

[Rhomboencephalitis caused by Listeria monocytogenes: a case studies with magnetic nuclear resonance].

Central nervous system infections due to Listeria monocytogenes result in a variety of clinical syndromes ranging from meningitis to rhomboencephalitis. We report the case of a previously healthy patient with rhomboencephalitis in whom the CT scan was normal, while magnetic resonance imaging (MRI) confirmed the diagnosis. We review the literature and emphasize the value of MRI for timely diagnosis.

Encephalitis↗

[Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) co-infection, of multinucleated giant cells in acquired immunodeficiency syndrome (AIDS) encephalopathy].

A 31-year-old HIV-1-seropositive Haitian male presented with HIV-nephropathy and typical features of subcortical dementia. He died 4 months after the onset of neurological signs. Neuropathological examination revealed HIV encephalitis with diffuse progressive leukoencephalopathy, diffuse poliodystrophy and massive calcifications of white matter, basal ganglia and dentate nuclei probably partly related to renal failure. It was associated with focal, subependymal CMV encephalitis. In the periventricular regions, morphologically characteristic multinucleated giant cells, positive for CD68, and negative for GFAP, contained early CMV antigens (E13) in their nuclei and HIV antigens (gp41 and p24) in their cytoplasm. The co-infection of a single cell by both viruses was confirmed by electron microscopy. The finding that HIV and CMV can co-infect in vivo the same cell raises the question of a direct cooperation of both viruses at the single cell level, and suggests the possibility of a role for CMV as co-factor in the pathogenesis of HIV encephalopathy.

AIDS Dementia Complex↗

In vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient.

We have recently isolated an apparently novel retrovirus (LM7) from a patient with multiple sclerosis (MS). We present here results showing that (1) LM7 retrovirus can be transmitted in vitro to a normal human leptomeningeal cell culture and that (2) specific antibody against this retroviral strain can be detected in MS cases. Our results suggest that, if this virus is an endogenous retrovirus, it is different from human endogenous elements already described.

Antibodies, Viral↗

Leptomeningeal cell line from multiple sclerosis with reverse transcriptase activity and viral particles.

A leptomeningeal cell line (clonal but not immortal) was isolated from lumbar-punctured cerebrospinal fluid in a patient with definite multiple sclerosis (MS). This cell line, named LM7, was characterized by immunocytochemical and ultrastructural analyses and was found to produce specific viral reverse transcriptase activity, whereas electron microscopy revealed the presence of viral particles. This patient had no antibodies against human T-leukaemia virus type 1 (HTLV-I) or human immunodeficiency viruses types 1 and 2 (HIV-1, HIV-2). Moreover, monoclonal antibodies against HTLV-I and HIV-1 failed to recognize epitopes in induced LM7 cells. The possible relationship between MS and the virus present in LM7 cells is discussed.

Antibodies, Monoclonal↗