Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the case of a human immunodeficiency virus-infected 34-year-old man with progressive multifocal leukoencephalopathy (PML). His case displayed unusual features, including a bizarre movement disorder, predominant involvement of the subcortical U fibers on neuropathologic examination, and the absence of MRI abnormalities suggestive of PML. Anatomic-clinical correlations are discussed.
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PMID:Isolated motor control dysfunction related to progressive multifocal leukoencephalopathy during AIDS with normal MRI. 799 Nov 25

Infectious agents have been postulated as causes of multiple sclerosis for over a century. The possible role of a virus or viruses is supported by data that (1) a childhood exposure is involved and "viral" infections may precipitate exacerbations of disease, (2) experimental infections in animals and natural infections in humans can cause diseases with long incubation periods, remitting and relapsing courses, and demyelination, and (3) patients with multiple sclerosis have abnormal immune responses to viruses. The pathogenesis of three human demyelinating diseases of known viral etiology is discussed. In progressive multifocal leukoencephalopathy, a papovavirus selectively infects oligodendrocytes and causes focal areas of demyelination. In postmeasles encephalomyelitis, the virus is lymphotrophic and disrupts immune regulation that can result in an autoimmune perivenular demyelinating illness without evidence of infection of the central nervous system. In human immunodeficiency virus-encephalopathy and myelopathy virus is present in macrophages and microglia and the myelin abnormalities apparently are caused by soluble factors such as viral proteins, cytokines, or neurotoxins. These findings may have implications on how, when, and where to seek viruses in multiple sclerosis.
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PMID:The virology of demyelinating diseases. 801 89

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), the fatal demyelinating infection of oligodendrocytes, in up to 5% of AIDS patients. An intron-differential RNA PCR was developed to study the expression of alternately spliced JCV early mRNAs in brain tissues from PML patients with and without AIDS and in JCV-induced hamster brain tumors. The method utilizes primers that span the large tumor (T) and small tumor (t) antigen introns allowing amplification of specific cDNAs in the presence of contaminating viral genomic DNA. Hybridization with specific junctional probes and DNA sequence analysis confirmed the identity of the PCR products. Sequencing showed that JCV early mRNA is alternatively spliced as previously predicted by analogy to simian virus 40. Large T antigen mRNA was detected in all the brain tissues from PML patients with and without AIDS. The expression of small t antigen mRNA varied depending upon the association of PML with AIDS and upon other unknown factors. Of the 12 PML/AIDS brain tissue samples, 11 (92%) expressed small t antigen mRNA, whereas only 8 of 13 (62%) brain samples from patients with PML alone showed detectable levels of small t antigen mRNA. Human immunodeficiency virus 1 proviral DNA was detected in 10 of 12 PML/AIDS brain samples. The results indicate that alternative splicing of JCV early mRNA is regulated in the human brain and that the production of small t antigen may not be essential for the pathogenesis of PML.
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PMID:Differential expression of mRNAs for JC virus large and small tumor antigens in brain tissues from progressive multifocal leukoencephalopathy patients with and without AIDS. 805 96

Using polymerase chain reaction (PCR), 34 cerebrospinal fluid (CSF) samples from 28 patients with progressive multifocal leukoencephalopathy (PML) were analyzed. As controls, 116 samples were evaluated from 82 human immunodeficiency virus type 1 (HIV-1)-infected patients and 1 HIV-1-negative patient. Of the HIV-1-positive patients, 23 had cerebral toxoplasmosis, 10 had HIV leukoencephalopathy, and 49 had other neurologic complications. Detection of JC virus (JCV) DNA in CSF was increased 10-fold by the addition of carrier DNA before phenol-chloroform-isoamyl alcohol extraction. The primer pair JC 26/29, from the VP1/large T region, had a limit of detection of 10(5) JCV DNA molecules/100 microL. The primer pair JC 36/39, located in the large T gene region, had a 100-fold lower limit of detection. With JC 26/29, the sensitivity was 43% (12/28) and specificity was 100%. Using JC 36/39, sensitivity increased to 82% (23/28), and false-positive results were not observed. Diagnosis of PML is greatly aided by PCR analysis of CSF.
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PMID:Specific diagnosis of progressive multifocal leukoencephalopathy by polymerase chain reaction. 816 9

Six cases of AIDS-associated progressive multifocal leukoencephalopathy (PML) exhibited peculiar cellular changes in the cerebellar granular layer. These cells without discernible cytoplasm showed hypochromatic nuclei about twice as large as those of normal granule cells. They were restricted exclusively to the granular layer and always surrounded PML foci. An astrocytic, leukocytic or macrophage/microglial nature was largely excluded by immunocytochemistry. Human immunodeficiency virus (HIV) antigen p 24 could not be found in these cells and there was no unequivocal detection of JC virus (JCV) DNA and no ultrastructural evidence of papovavirus particles in them. They possibly represent altered cerebellar granule cells abortively or latently infected with JCV.
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PMID:Cellular changes in the cerebellar granular layer in AIDS-associated PML. 827 22

An "in vivo" diagnosis of progressive multifocal leukoencephalopathy (PML), a neurological opportunistic viral infection in AIDS patients, can be made only by brain biopsy. In order to identify viral particles, we examined the cerebrospinal fluid (CSF) of 15 AIDS patients with focal neurological signs by electron microscopy using negative staining technique. In 2 out of 3 patients with clinical and neuroradiological presumptive diagnosis of PML, the CSF examination revealed papova-like viral particles. Our results support the hypothesis that the severe cell-mediated immunodeficiency reactivates papovavirus from a latent state in the brain, leading to PML. Therefore, the CSF study by negative staining might be a useful test for an "in vivo" diagnosis of PML.
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PMID:Presence of papova-like viral particles in cerebrospinal fluid of AIDS patients with progressive multifocal leukoencephalopathy. An additional test for "in vivo" diagnosis. 830 80

We reviewed the clinical, radiographic, and pathologic features of 15 patients with the acquired immune deficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML). Brain tissue from 10 autopsy and 6 biopsy specimens was studied using: in situ hybridization (ISH) for JC virus (JCV), immunohistochemistry for human immunodeficiency virus (HIV) p24 antigen, and electron microscopy. Thirteen patients presented with focal neurologic deficits, while 2 presented with a rapid decline in mental status. PML was commonly the initial opportunistic infection of AIDS and produced hemiparesis, dementia, dysarthria, cerebellar abnormalities, and seizures. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions, and often showed multifocal areas of PML. CD4+ T-cell counts were uniformly low (mean 84/mm3), except in 1 patient who improved on 3'-azido-3'-deoxythymidine (AZT). PML involved the cerebral hemispheres, brain stem, cerebellum, and cervical spinal cord. The distribution of brain involvement was consistent with hematogenous dissemination of the virus. In 2 brain specimens, multiple HIV-type giant cells were present within the regions involved by PML. When co-infection by HIV and papovavirus was present, PML dominated the pathological picture. ISH for JCV showed virus in the nuclei of oligodendrocytes and astrocytes. Occasionally there was staining for JCV in the cytoplasm of glial cells and in the neuropil, the latter possibly a correlate of papovavirus spread between myelin sheaths, as seen by electron microscopy. ISH demonstrated more extensive foci of PML than did routine light microscopy.
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PMID:Progressive multifocal leukoencephalopathy in AIDS: a clinicopathologic study and review of the literature. 841 79

The authors investigated the spectrum of radiologic findings in a large series (n = 47) of patients seropositive to human immunodeficiency virus (HIV) 1 and with pathologically proved progressive multifocal leukoencephalopathy, to determine the characteristic imaging pattern of the disease. Thirty-six computed tomographic (CT) scans and 29 magnetic resonance (MR) imaging studies obtained in the 47 patients were retrospectively reviewed and correlated with pathologic and clinical findings. Contrast agents were used in 32 CT procedures and 13 MR imaging studies. Lesions typically were hypoattenuating on CT scans and were characterized by areas of increased signal intensity without mass effect on dual-echo MR images. Lesions most often involved periventricular and subcortical white matter in parietooccipital or frontal lobes. Fifteen patients had posterior fossa lesions, and disease was limited to the posterior fossa in two. Lesions were also in the corpus callosum (seven patients), thalamus (eight patients), and basal ganglia (seven patients). In comparison with CT, MR imaging demonstrated greater sensitivity for the extent and number of lesions.
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PMID:Progressive multifocal leukoencephalopathy in 47 HIV-seropositive patients: neuroimaging with clinical and pathologic correlation. 845 20

The transforming growth factor-beta family of polypeptides includes three related isoforms with pervasive effects on immune system function. In this study, the authors evaluated human brains with human immunodeficiency virus (HIV)-1 encephalitis for transforming growth factor beta (TGFbeta)1, TGFbeta2, and TGFbeta3 immunoreactivity using isoform-specific polyclonal antibodies and avidin-biotin immunohistochemistry. Normal brains and those with progressive multifocal leukoencephalopathy, toxoplasma encephalitis, and cryptococcal meningitis were used as controls. In normal controls, TGFbeta1, TGFbeta2, and TGFbeta3 immunoreactivity were confined to arachnoid cells and blood vessels. In 9 of 10 cases of HIV-1 encephalitis, all three isoforms were also detected in arachnoid cells. In addition, variable, predominantly TGFbeta2 and TGFbeta3 immunoreactivity were also detected in reactive astrocytes and mononuclear cells of white matter lesions. Extensive TGFbeta3 immunoreactivity was also detected in multinucleated giant cells in one case. In a case of cryptococcal meningitis, all three isoforms were detected in arachnoid cells and macrophages. Lesions of progressive multifocal leukoencephalopathy and toxoplasma encephalitis also exhibited TGFbeta1, TGFbeta2, and TGFbeta3 immunostaining in reactive astrocytes. These findings suggest that TGFbeta isoforms are present in HIV-1 encephalitis and may participate in the pathogenesis of this and other inflammatory central nervous system (CNS) lesions associated with acquired immunodeficiency syndrome (AIDS).
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PMID:Distribution of transforming growth factor-beta isoforms in human immunodeficiency virus-1 encephalitis. 869 6

The human polyomavirus JC virus (JCV) infects myelin-producing cells in the central nervous system, resulting in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV-induced PML occurs most frequently in immunosuppressed individuals, with the highest incidence in human immunodeficiency type 1-infected patients, ranging between 4 and 6% of all AIDS cases. Although JCV targets a highly specialized cell in the central nervous system, infection is widespread, with more than 80% of the human population worldwide demonstrating serum antibodies. A number of clinical and laboratory studies have now linked the pathogenesis of PML with JCV infection in lymphoid cells. For example, JCV-infected lymphocytes have been suggested as possible carriers of virus to the brain following reactivation of a latent infection in lymphoid tissues. To further define the cellular tropism associated with JCV, we have attempted to infect immune system cells, including CD34+ hematopoietic progenitor cells derived from human fetal liver, primary human B lymphocytes, and human tonsillar stromal cells. Our results demonstrate that these cell types as well as a CD34+ human cell line, KG-1a, are susceptible to JCV infection. JCV cannot, however, infect KG-1, a CD34+ cell line which differentiates into a macrophage-like cell when treated with phorbol esters. In addition, peripheral blood B lymphocytes isolated by flow cytometry from a PML patient demonstrate JCV infection. These results provide direct evidence that JCV is not strictly neurotropic but can infect CD34+ hematopoietic progenitor cells and those cells which have differentiated into a lymphocytic, but not monocytic, lineage.
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PMID:JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: implications for viral latency. 879 45


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