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  • 1
    ISSN: 1432-0533
    Keywords: Key words Thrombomodulin ; Paraneoplastic phenomenon ; Endothelial cell ; Myalgia ; Thrombophlebitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We found a microvascular endothelial abnormality in a biopsy specimen from the gastrocnemius muscle of a patient with gastric cancer, who had severe myalgia and angialgia in the calf region with the symptoms of thrombophlebitis. There were no definite findings of inflammatory myopathy in histochemical and immunohistochemical studies. Electron microscopic examination revealed the accumulation of abnormal mitochondria in the subsarcolemmal area, and a fair number of degenerating capillaries. Immunohistochemical analysis of procoagulant or anticoagulant factors revealed marked reduction of thrombomodulin (TM) expression on small vessels and capillaries. Although a reduction of TM on small vessels has been observed around perifascicular atrophic fibers in patients with dermatomyositis, histochemical findings of the present patient showed no perifascicular atrophy or severely degenerating fibers. These pathological findings in the patient may be related to a malignant neoplasm and may be one of the causes of disseminated intravascular coagulation (DIC), which is the main complication of malignant neoplasms. Further studies are necessary to determine whether the reduction of TM on the small vessels and capillaries in skeletal muscle is a predictor of some severe condition such as DIC or a rare pathological finding in some special condition such as scirrhous carcinoma with thrombophlebitis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1459
    Keywords: Key words HTLV-I associated myelopathy ; Macrophage ; Microglia ; MRP14 ; MRP8
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1459
    Keywords: Human T-cell lymphotropic virus type I associated myelopathy/tropical spastic paraparesis ; Virus-specific antibodies ; Immunoglobulin G ; Intrathecal antibody formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The humoral immune response against human T-cell lymphotropic virus type I (HTLV-I) in the central nervous system (CNS) compartment and in the blood was investigated by enzyme immunoassay using 16 synthetic peptides corresponding to HTLV-I core and envelope sequences. We evaluated paired samples of cerebrospinal fluid and serum from HTLV-I seropositive Japanese patients, classified as follows: HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP;n = 39), patients with spinal cord disease ascribed to either HAM/TSP or to some concomitant, HTLV-I-unrelated disease (possible HAM/TSP;n = 6) or carriers without any clinical signs of HAM/TSP (n = 15). HTLV-I-peptide-specific intrathecal antibody synthesis was found in 79% of HAM/TSP patients, but only in 20% of carriers without HAM/TSP. The group of carriers without HAM/TSP showed local synthesis for some peptides (on average 0.3 peptides per patient). In most HAM/TSP patients, however, there was a diverse intrathecal immune response to several HTLV-I synthetic peptides (on average against 3.6 peptides per HAM/TSP patient), most frequently againstgag p19 100–130,env gp21 458–488, andenv gp46 175–199 and 288–317. The intrathecal antibody synthesis against several HTLV-I determinants may represent a pathogenic immune response in HAM/TSP and is possibly related to the infiltration of virus-infected T-cells in the spinal cord.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Key words Human T lymphotropic virus type I ; HTLV-I-associated myelopathy/tropical spastic paraparesis ; Quasispecies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To understand the mechanisms involved in the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), three in vivo phenomena which have been observed in the peripheral blood of patients and differing from that in asymptomatic HTLV-I carriers must be taken into consideration: (a) the presence of increased HTLV-I viral load, (b) a higher immune responsiveness against HTLV-I antigens, and (c) biased nucleotide substitutions in the HTLV-I pX region which indicate a decreased selection pressure for viral amino acid changes. We now propose a hypothesis which focuses on the in vivo dynamics of HTLV-I infected lymphocyte migration and which incorporates these features. In addition, the hypothesis assumes the existence of a deviation in immune surveillance for HTLV-I in the central nervous system (CNS) in spite of the presence of frequent specific immune effectors. We suggest that in the active phase of HAM/TSP, accompanied with or following autoaggressive interactions between infected lymphocytes and immunocompetent cells in the CNS, there is a consequential reflux of the infected lymphocytes to the peripheral blood. The reflux of infected cells would be expected to provide peripheral blood with tissue-derived HTLV-I proviruses which have been indulged and propagated in an immune-privileged site. This process would result in and account for the observed increase in viral load and the substitution bias in HTLV-I sequences in the peripheral blood.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Key words Adhesion molecules ; HTLV-1-associated ; myopathy/tropical spastic paraparesis ; Monocyte ; chemoattractant protein-1 ; Vascular cell adhesion ; molecule-1 ; Very late antigen-4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leukocyte adhesion molecules to endothelium plays an important role in the pathogenesis of inflammatory diseases, including HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). To help define the role of adhesion molecules in HAM/TSP, we studied the expression of lymphocyte function-associated antigen-1 (LFA-1), Mac-1, very late antigen-4 (VLA-4), Sialyl Lewisx (SLex), intercelluar adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1) and monocyte chemoattractant protein-1 (MCP-1) in the spinal cord lesions of HAM/TSP. The results indicate that spinal cord lesions of HAM/TSP have greater VCAM-1 expression on endothelium compared with those of controls. Infiltrating mononuclear cells, especially perivascular lesions, expressed VLA-4. Although the expression of ICAM-1 in the spinal cords was not distinctive between HAM/TSP and controls, infiltrating mononulcear cells in the spinal cords of HAM/TSP strongly expressed LFA-1 and Mac-1. ELAM-1 was expressed on endothelium in the inactive-chronic lesions from three of five HAM/TSP, but was not detectable in the spinal cords of controls. SLex reaction was detectable on occasional perivascular cells in the spinal cord of HAM/TSP, but not in those of controls. MCP-1 was detectable on perivascular infiltrating cells and vascular endothelium in active-chronic lesions. This study suggests that VLA-4/VCAM-1 interaction may play an important role for lymphocyte migration into the central nervous system (CNS), and MCP-1 may also be involved in inflammatory cell recruitment to the CNS in HAM/TSP.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Key words Neuronal ceroid lipofuscinosis ; Sural ; nerve ; Mitochondrial ATP synthase subunit c ; Muscle ; Curvilinear profile
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a case of late infantile neuronal ceroid lipofuscinosis (NCL). Abnormal granules were found in the skeletal muscle fibers, Schwann cells, perineurial cells, endothelial cells, fibroblasts, and perivascular smooth muscle cells in the sural nerve. Electron microscopy revealed that these granules showed fingerprint profiles, curvilinear profiles or membrane-bound membranous structures. Acid phosphatase reaction was increased in these cells. Immunohistochemical studies for mitochondrial ATP synthase subunit c showed a strong reaction in these cells, suggesting abnormal accumulation of subunit c. Immunohistochemistry for subunit c in muscle may be useful in the diagnosis of late infantile NCL.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0533
    Keywords: Key wordsα-Sarcoglycan ; γ-Sarcoglycan ; Sarcoglycanopathy ; Immunohistochemistry ; Gene ; mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the expression of α-sarcoglycan, β-sarcoglycan, γ-sarcoglycan, and δ-sarcoglycan immunohistochemically in three patients with mutations of the α-sarcoglycan gene and a patient with a mutation of the γ-sarcoglycan gene. Although each of the four sarcoglycans were decreased on the muscle membranes of all the patients, different expression patterns for each were seen among the patients. In patients with mutations of the α-sarcoglycan gene, β-, γ- and δ-sarcoglycans were relatively preserved as compared to greatly reduced α-sarcoglycan. However, the patient with a mutation of the γ-sarcoglycan gene showed marked reduction of γ-sarcoglycan as compared to partially preserved α- and β-sarcoglycans, and well-preserved δ-sarcoglycan. These results suggest that each sarcoglycan component in sarcoglycanopathy does not decrease in the same manner, and that mutations of the sarcoglycan gene can be predicted, at least in part, by means of sensitive immunohistochemistry for each sarcoglycan.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0533
    Keywords: Key words Mixed gonadal dysgenesis ; Polyneuropathy ; Minifascicle ; Sural nerve ; Mental retardation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0533
    Keywords: Key words HTLV-I ; HTLV-I-associated myelopathy/ ; tropical spastic paraparesis ; Microglia/macrophage ; Rat model ; In situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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