Progressive Multifocal Leukoencephalopathy

Nagashima, Kazuo; Yamaguchi, Kazuyoshi; Yasui, Kohichiroh; Ogiwara, Hiroshi

doi:10.1111/j.1440-1827.1981.tb02009.x

Cited by 15 publications

(9 citation statements)

References 14 publications

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“…In culture, JCV can be most efficiently propagated in fetal glial cells (Nagashima et al, 1981), an observation consistent with the notion that most people acquire the virus at an early age. Presumably, sequence rearrangement could predipose JCV to activation of replication in adult oligodendrocytes.…”

Section: Discussionsupporting

confidence: 79%

Internalization of Exogenous Human Immunodeficiency Virus-1 Protein, Tat, by KG-1 Oligodendroglioma Cells Followed by Stimulation of DNA Replication Initiated at the JC Virus Origin

Daniel¹,

Kinoshita²,

Khan³

et al. 2004

dna cell biol

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JC virus (JCV) is the etiological agent of an opportunistic brain infection, progressive multifocal leukoencephalopathy (PML), in AIDS. PML is fatal in approximately 4% of HIV-infected individuals, and although the overall incidence has fallen due to highly aggressive antiretroviral therapy (HAART), this percent has remained steady. It has been shown that the Tat protein of human immunodeficiency virus-1 (HIV-1) interacts in cells with cellular protein Pur␣. This interaction can stimulate transcription of both HIV-1 and JCV genes. HIV-1, however, infects primarily microglia and astrocytes in the brain, whereas JCV infects primarily oligodendrocytes. Although HIV-1 has been shown capable of infecting oligodendrocytes in vitro (Albright et al., 1996), no instance of viral coinfection of such cells with JCV has been reported. Tat is known to be secreted from cells in which it is made. Here we ask whether such exogenous Tat can influence JCV replication in oligodendrocytes. We find that glial cells infected with either HIV-1 or JCV are in proximity at the outer edge of PML lesions. Exogenous Tat is avidly incorporated into cultured KG-1 oligodendroglioma cells over a 72-hperiod and is colocalized with endogenous Pur␣ both nuclear and juxtanuclear. At concentrations in the medium well below the pM range, Tat stimulates several-fold the replication in vivo of DNA initiated at the JCV origin. These results define a pathway by which a protein made by HIV-1 can directly affect the course of infection by another disease-causing virus.

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Section: Discussionsupporting

confidence: 79%

Internalization of Exogenous Human Immunodeficiency Virus-1 Protein, Tat, by KG-1 Oligodendroglioma Cells Followed by Stimulation of DNA Replication Initiated at the JC Virus Origin

Daniel¹,

Kinoshita²,

Khan³

et al. 2004

dna cell biol

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“…Here, we have characterized subtypes 2A and 2B, and a possible new subtype represented by strain F230. The first subtype 2A strain was isolated in Japan from a PML brain and termed the Tokyo-1 strain (Nagashima et al, 1981(Nagashima et al, , 1982. The subtype 2B prototype was obtained from a PML patient in Germany, and the DNA sequences of both brain and kidney isolates were reported (Loeber & Do$ rries, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…We now report the complete genome DNA sequence of nine Type 2 strains and a tenth sequence which may represent a new genotype most closely related to Type 2B. These ten isolates include nine urinary strains and the JCV (Tokyo-1) strain obtained from the brain of a Japanese PML patient (Nagashima et al, 1981(Nagashima et al, , 1982. In order to establish a representative system for the definition of major JCV types and subtypes in clinical samples, sequences obtained were compared with the prototype Type 2 sequence, GS\B, and we show how typing based on the short fragment within the VP1 gene corresponds to phylogenetic relationships based on entire coding region genomes.…”

Section: Introductionmentioning

confidence: 99%

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JC virusType 2: definition of subtypes based on DNA sequence analysis of ten complete genomes.

Agostini¹,

Shishido‐Hara²,

Baumhefner³

et al. 1998

Journal of General Virology

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Five major genotypes of JC virus (JCV) have been defined based on nucleotide differences in the VP1 gene of the DNA sequence. These types are probably a result of virus evolution in geographically isolated population groups. One of the first genotypes identified, Type 2, was found to represent strains of Asian origin. In order to further define the spectrum within Type 2 strains, the entire 5n1 kb genome of nine urinary strains of JCV was amplified by PCR with one pair of primers. These urine samples were obtained in the USA (California and New Mexico) from three European Americans, three Native Americans, two African Americans and one Hispanic American. The complete genome of an Asian JCV strain (Tokyo-1) isolated from progressive multifocal leukoencephalopathy (PML) brain in

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“…21 As for progressive multifocal leukoencephalopathy (PML), multiple, sometimes confluent, foci of demylination are usually observed with abnormal astrocytes around the lesions. 22 Most leukodystrophies involve the whole brain and are not limited to the frontal lobes. The Alexander type of leukodystrophy reveals diffuse demyelination and rarefaction of the white matter, 23 similar to that of the lobotomized brain.…”

Section: Discussionmentioning

confidence: 99%

An autopsy case of the schizophrenic 32 years after lobotomy

et al. 2001

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technique and introduced the 'standard leucotomy ' or 'lobotomy' in 1942. 2-4 A great number of schizophrenics and patients with other mental disorders had been treated with psychosurgery for the purpose of the recovery and improvement of their symptoms during the 1930s to the early 1960s. Negative factors against undertaking lobotomy have since been shown. These include a number of sideeffects such as post-lobotomized syndromes, the advent of effective pharmacotherapy and the rise of sociopolitical views against psychosurgeries. Therefore, lobotomy showed a rapid decrease in the 1960s. 2,5,6 In Japan, psychosurgery was first undertaken in 1939 and spread rapidly until the early 1960s, before the number of psychosurgeries was reduced for the above reasons. 7 Although a number of studies described histopathological findings of the lobotomized schizophrenics in the late 1930s to 1950s, most of the articles were descriptive and presented mainly illustrated figures. 8,9 Recently, there have been several studies concerning clinicopathological aspects of lobotomized patients such as the relationship between clinical psychiatric symptoms and neuroradiological findings, 10-12 the prognosis of the lobotomized patients 13-15 and new methods such as stereotactic surgery. 16,17 However, histopathological studies are very rare. We report the neuropathological examinations of a post-mortem lobotomized schizophrenic brain. CLINICAL SUMMARYThe patient was a 69-year-old man. He had been diagnosed as schizophrenic at the age of 24, and had undergone a prefrontal lobotomy in 1964 at 37 years of age. Since then he had been treated with psychological and psychopharmacological therapies at some hospitals, but his detailed past histories were uncertain. The patient had shown a symptom of poriomania several years before death. He left home and wandered during early October 1997, and was Neuropathology 2001; 21, 53-60 An autopsy case is reported here of a 69-year-old patient with schizophrenia, who was known retrospectively to have had a prefrontal lobotomy 32 years previously. The patient was diagnosed as schizophrenic at the age of 24 and the lobotomy was undertaken 13 years later. The patient was recently found outside in a dehydrated condition and admitted to a general hospital, where he died of respiratory failure. Bilateral cystic lesions were found in the deep white matter of the frontal lobe. The cyst walls consisted of glial fibrous tissues, and severe demyelination with axonal destruction was diffusely observed in the white matter of the frontal lobe. In the thinner frontal cortex without arcuate fibers (U fibers) close to the cavities, cytoarchitectural abnormalities were observed. In the thalamic nuclei marked retrograde degeneration and astrocytic gliosis were observed. The detailed neuropathological findings of a lobotomized schizophrenic brain are reported here. It is proposed that one should be reminded of a lobotomized brain if bilateral cysts are found.

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Progressive Multifocal Leukoencephalopathy

Cited by 15 publications

References 14 publications

Internalization of Exogenous Human Immunodeficiency Virus-1 Protein, Tat, by KG-1 Oligodendroglioma Cells Followed by Stimulation of DNA Replication Initiated at the JC Virus Origin

Internalization of Exogenous Human Immunodeficiency Virus-1 Protein, Tat, by KG-1 Oligodendroglioma Cells Followed by Stimulation of DNA Replication Initiated at the JC Virus Origin

JC virusType 2: definition of subtypes based on DNA sequence analysis of ten complete genomes.

An autopsy case of the schizophrenic 32 years after lobotomy

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