Biomedical subjects
M Osame
Publications and source records attributed to M Osame.
[Acute disseminated encephalomyelitis (ADEM)].
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Molecular pathologic analysis of the tonsil in HTLV-I-infected individuals.
Little is known about the role of the tonsils in HTLV-I infection. We performed molecular pathologic studies of tonsils in individuals positive or negative for anti-HTLV-I antibodies (HTLV-I-Ab) to clarify histologic characteristics of tonsils in HTLV-I infection. We collected tonsils and peripheral blood samples from patients who underwent tonsillectomy in a prospective manner. HTLV-I-Ab in serum was examined and presence of HTLV-I provirus was detected by polymerase chain reaction (PCR) in extracted DNA of both peripheral blood and tonsils. Histopathologic and immunohistochemical evaluations of tonsils were performed. HTLV-I seropositivity and PCR detection of HTLV-I provirus matched perfectly. Tonsil samples from seropositive individuals showed atrophy of the mantle zone and high numbers of T cells in the marginal zone compared with findings in HTLV-I-negative samples. HTLV-I provirus could be detected only from extracted DNA of extrafollicular areas. PCR in situ hybridization also showed positive signals in some mononuclear cells located in the marginal zone. There was a significant correlation between HTLV-I proviral load in tonsils and in peripheral blood. These results suggest the presence of characteristic histologic changes and deviated localization of HTLV-I-infected cells in the tonsils of individuals positive for HTLV-I.
Hereditary motor and sensory neuropathy with proximal dominant involvement: clinical, pathological, and genetic features.
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Increased levels of soluble Fas ligand in CSF of rapidly progressive HTLV-1-associated myelopathy/tropical spastic paraparesis patients.
The interaction of Fas ligand (FasL) with Fas-bearing cells induces apoptosis and contributes to the negative regulation of peripheral T-cell responses. Membrane-bound FasL is cleaved by a matrix metalloproteinase-like enzyme and converted to a soluble form (sFasL). Recent studies suggest that such sFasL can cause systemic tissue damage. Here we report that serum and CSF levels of soluble FasL (sFasL) are markedly higher in three active phase patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). All of these patients showed higher sFasL levels in CSF than in serum. Although the HTLV-1 proviral load of patients showed no correlation with serum or with CSF sFasL, CSF sFasL levels of 14 HAM/TSP patients correlated with the anti-HTLV-1 antibody titer and neopterin concentration in CSF. These results indicate that sFasL mediated mechanisms may contribute to the inflammatory process and subsequent spinal tissue damage seen in HAM/TSP patients.
Genetic control and dynamics of the cellular immune response to the human T-cell leukaemia virus, HTLV-I.
About 1% of people infected with the human T-cell leukaemia virus, type 1 (HTLV-I) develop a disabling chronic inflammatory disease of the central nervous system known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have a vigorous immune response to HTLV-I, and it has been widely suggested that this immune response, particularly the HTLV-I-specific cytotoxic T-lymphocyte (CTL) response, causes the tissue damage that is seen in HAM/TSP. In this paper we summarize recent evidence that a strong CTL response to HTLV-I does in fact protect against HAM/TSP by reducing the proviral load of HTLV-I. We conclude that HTLV-I is persistently replicating at a high level, despite the relative constancy of its genome sequence. These results imply that antiretroviral drugs could reduce the risk of HAM/TSP by reducing the viral load, and that an effective anti-HTLV-I vaccine should elicit a strong CTL response to the virus. The dynamic nature of the infection also has implications for the epidemiology and the evolution of HTLV-I.
A novel MPZ gene mutation in dominantly inherited neuropathy with focally folded myelin sheaths.
We found the association of a heterozygous novel MPZ gene point mutation, Ile62Phe in exon 2, with autosomal dominant motor and sensory neuropathy with focally folded myelin sheaths. Family study revealed that de novo Ile62Phe mutation on the MPZ gene occurred in the proband and was inherited by her children with early onset slowly progressive neuropathy. Our study suggests that the characteristic pathologic findings of the sural nerve in these patients are closely related to the site and nature of amino acid substitutions of the MPZ gene.
HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy.
The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM/TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus influence susceptibility to HAM/TSP. Here we show that, after infection with HTLV-I, the class I allele HLA-A*02 halves the odds of HAM/TSP (P < 0.0001), preventing 28% of potential cases of HAM/TSP. Furthermore, HLA-A*02(+) healthy HTLV-I carriers have a proviral load one-third that (P = 0.014) of HLA-A*02(-) HTLV-I carriers. An association of HLA-DRB1*0101 with disease susceptibility also was identified, which doubled the odds of HAM/TSP in the absence of the protective effect of HLA-A*02. These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.
Manganese intoxication during total parenteral nutrition: report of two cases and review of the literature.
We report two cases of manganese (Mn) intoxication during total parenteral nutrition including manganese (Mn). Both patients showed parkinsonism with psychiatric symptoms and elevated serum Mn levels. T1-weighted magnetic resonance images (MRI) revealed symmetrical high intensity lesions in the globus pallidus. Discontinuation of Mn supplementation and levodopa treatment improved the symptoms and MRI abnormalities in the both patients. Thus, careful attention should be paid to the long-term intravenous administration of Mn.
Caveolin-3 and sarcoglycans in the vacuolar myopathies and centronuclear myopathy.
Expression of dystrophin, beta-spectrin, merosin, and alpha- and beta-sarcoglycans on the vacuolar membranes in some types of vacuolar myopathies has previously been reported. We studied expression of caveolin-3; alpha-, beta-, gamma-, and delta-sarcoglycans; dystrophin; and merosin on the vacuolar membranes in various vacuolar myopathies. Caveolin-3 and dystrophin were expressed on the vacuolar membranes in lysosomal glycogen storage disease with normal acid maltase, hypokalemic myopathy, and centronuclear myopathy. Sarcoglycans and merosin were expressed only on the vacuolar membrane in lysosomal glycogen storage disease with normal acid maltase. Immunostain of caveolin-3 and sarcoglycans is therefore useful for differential diagnosis of vacuolar myopathies.
Expression of thrombomodulin, caveolin-3, and desmin on muscle fibers in neuromuscular diseases.
The expression of thrombomodulin (TM) and caveolin-3 on biopsied muscle fibers from 17 patients with various neuromuscular diseases was studied immunocytochemically. We also compared the expression of TM and caveolin-3 with that of desmin, which is a marker for muscle fiber regeneration. Most TM-positive muscle fibers strongly expressed caveolin-3 and desmin. Our results suggest that TM is expressed and caveolin-3 is upregulated during the process of muscle fiber regeneration.
Iodine-123 iodobenzofuran (I-123 IBF) SPECT in patients with parkinsonism.
I-123 IBF is a dopaminergic antagonist which is suitable for SPECT imaging of D2 receptors. The purpose of this study is to evaluate the potential usefulness of semi-quantitative parameters obtained from brain SPECT data of I-123 IBF for differential diagnosis in patients with parkinsonism (PN). Subjects were 10 patients with PN: 2 patients with striato-nigral degeneration (SND), 5 patients with Parkinson's disease (PD), 2 patients with progressive supranuclear palsy (PSP) and one patient with olivo-ponto-cerebellar atrophy (OPCA). The data were acquired with a triple-head gamma camera at 2 hours after intravenous injection of 167 MBq of I-123 IBF. Transverse images were reconstructed by means of filtered backprojection, and attenuation correction was performed by Chang's method (mu = 0.08). The basal ganglia-to-frontal cortex ratio (GFR) and the basal ganglia-to-occipital cortex ratio(GOR) on slices of 5 different thicknesses were calculated. The GFR and GOR were lower in the SND group than in the other disease groups in all slices with different thicknesses (7.2 mm, 14.4 mm, 21.6 mm, 28.8 mm and 43.2 mm). The semiquantitative parameters (GFR and GOR) obtained from brain SPECT data at 2 hours after intravenous injection of I-123 IBF may be useful for differential diagnosis in patients with PN.
A rat model of human T lymphocyte virus type I (HTLV-I) infection: in situ detection of HTLV-I provirus DNA in microglia/macrophages in affected spinal cords of rats with HTLV-I-induced chronic progressive myeloneuropathy.
To investigate the pathogenetic role of human T lymphocyte virus type I (HTLV-I) in central nervous system disease, a rat model for HTLV-I-associated myelopathy/tropical spastic paraparesis, designated as HAM rat disease, has been established. Wistar-King-Aptekman-Hokudai strain rats with induced HTLV-I infection develop a chronic progressive myeloneuropathy with paraparesis of hind limbs after an incubation period of 15 months. In the affected spinal cord in these rats, white matter degeneration, demyelination and vacuolar change with microglia/macrophage infiltration are present as are the provirus DNA and the virus mRNA. To identify infected cells in the affected lesions, we carried out in situ hybridization of amplified fragments of the provirus DNA by polymerase chain reaction on thin sections, plus immunohistochemistry on the same sections. The provirus DNA was localized in some microglia/macrophages in the spinal cord lesion. In addition, the HTLV-I provirus was clearly evident not only in ED-1-negative lymphoid cells but also in ED-1-positive macrophages from lymph nodes. These observations suggest that cells of microglia/macrophage lineage may be one of dominant viral reservoirs in the spinal cords and lymph nodes in HAM rat disease. These infected microglia/macrophages may relate to cause the myeloneuropathy through neurotoxic cytokine synthesis.
Polyneuropathy with minifascicle formation in a patient with 46XY mixed gonadal dysgenesis.
A patient with mixed gonadal dysgenesis showed glove and stocking-type sensory impairment and slowing of motor and sensory nerve conduction. Sural nerve biopsy revealed minifascicular formation with decreased density of myelinated fibers. As far as we are aware, this is the first report of polyneuropathy with minifascicular formation in 46XY mixed gonadal dysgenesis.
Multiple episodes of thrombosis in a patient with Becker muscular dystrophy with marked expression of utrophin on the muscle cell membrane.
We previously reported a patient with Becker muscular dystrophy (BMD) who exhibited a benign clinical phenotype and marked expression of utrophin on the muscle cell membrane. The patient developed multiple episodes of thrombosis (middle cerebral and femoral arteries) in the course of the disease. We re-examined the biopsy muscle specimen from the patient immunohistochemically as to the expression of procoagulant or anticoagulant factors. We found a lower expression of thrombomodulin on the muscle cell membrane in the BMD patient compared with other BMD or Duchenne muscular dystrophy (DMD) patients. Although utrophin up-regulation in muscle is thought to prevent the muscle wasting in dystrophin-deficient DMD or BMD, the data obtained in the present study indicate that up-regulated utrophin may have an unexpected influence on the function of the vascular or coagulation system.
Activation of macrophages/microglia with the calcium-binding proteins MRP14 and MRP8 is related to the lesional activities in the spinal cord of HTLV-I associated myelopathy.
Macrophages and microglia may play an important role in the pathogenesis of chronic inflammatory process in HTLV-I associated myelopathy (HAM) and tropical spastic paraparesis (TSP). However, the etiology and cellular mechanism of chronic inflammation are poorly understood in HAM/TSP. To help to define the roles of macrophages and microglia we analyzed the various patterns of macrophage and microglia activation in the central nervous system (CNS) of HAM/TSP using several monoclonal antibodies recognizing the different states of activation. The results indicate that a large number of macrophages and microglia express both MRP14 and MRP8 in active-chronic inflammatory lesions of the patients with a short duration of illness (2.5 years). In the patient whose duration of illness was 4.5 years, perivascular and parenchymal macrophages and microglia were reactive for MRP8 but not for MRP14. In contrast, MRP14 and MRP8 were negative on the perivascular and parenchymal macrophages and microglia in inactive-chronic lesions and in controls. This study suggests that (a) activated macrophages and microglia as well as CD4+ T lymphocytes and CD8+ cytotoxic T lymphocytes are main components of the inflammatory process in the CNS in HAM/TSP, (b) activation of macrophages and microglia is related to the amount of HTLV-I proviral DNA in situ.
Adult onset limb-girdle type mitochondrial myopathy with a mitochondrial DNA np8291 A-to-G substitution.
We analyzed mitochondrial DNA (mtDNA) from 7 patients in four families with adult onset limb-girdle type mitochondrial myopathy to clarify their genetic background. The patients, 2 men and 5 women, showed common clinical features, characterized by isolated skeletal myopathy, high serum creatine kinase level, ragged-red fibers and cytochrome c oxidase-defective fibers. Analysis of muscle biopsy specimens indicated that cytochrome c oxidase activity was decreased relative to that of citrate synthase in 5 of the 7 patients. Southern blotting and direct sequence analyses showed an A-to-G homoplasmic transition at np8291 and intergenic COII/tRNA (Lys) 9bp deletion in all patients. This substitution was detected in only 2 of 600 control individuals including healthy subjects and patients with other neuromuscular disorders; these 2 individuals had diabetes mellitus and myotonic dystrophy, respectively. Consequently, the mtDNA transition at np8291 was a rare polymorphism. However, the 7 patients we studied had identical clinical, pathological, biochemical, and genetic features. Therefore, limb-girdle type mitochondrial myopathy with this rare polymorphism may form a subgroup of adult onset mitochondrial myopathy.
The platelet level indicates the erythropoietic capacity for preoperative autologous blood donation.
UNLABELLED: The erythropoietic capacity for preoperative autologous blood donation (ECPABD) shows marked inter individual variability. This study was performed to evaluate factors useful to predict individual ECPABD from data available before the first donation. The subjects consisted of 74 adult patients who received autologous blood donation, with a mean of 61 +/- 12.8 yr (SD). We classified the patients into four groups using our criteria for evaluating the ECPABD and investigated the relationships among age, disease, pre-platelet count, and the rate of platelet increase. RESULTS: (1) Advanced age and the status of disease were not distinctly correlated with low ECPABD. (2) Patients with a high pre-platelet levels had a low ECPABD regardless of the haemoglobin. (3) Patients in which the platelet count increased in accordance with the level of collection exhibited low pre-platelet counts and high ECPABD. CONCLUSION: In patients with high pre-platelet levels, we reduced the amount collected, considered early use of recombinant human erythropoietin and reevaluated the application of autologous blood donation.