Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HAM (HTLV-I-associated myelopathy) rat disease, HAM/TSP (HTLV-I-associated myelopathy/tropical spastic paraparesis)-like myelopathy in rats, occurred in 8 of 8 HTLV-I (Human T cell leukemia virus type I) carrier rats of WKAH strain inoculated with MT-2 cells at either neonates or 4 to 6 months of age. We report here ultrastructural findings of the affected spinal cords and the peripheral nerves of perfusion-fixed HAM rats. They were infected at the age of 4 to 6 months old and showed gait disturbance and hind leg paraparesis 15 months after infection. Pathological alterations of HAM rat disease were mainly confined to marginal areas of white matter of the spinal cord. The affected lesion was rather symmetrical and distributed in the anterior and the lateral columns. A prominent ultrastructural change in the spinal cord was separation of myelin lamellae at the intraperiod line and vacuolation of myelin sheath. Many myelin-debris-filled macrophages and a marked astrogliosis were also observed. In the gliotic areas, lots of demyelinated and remyelinated axons were intermingled. Axons were relatively preserved, however, some of them had tubulo-reticular inclusions. Astrocytes appeared ultrastructurally normal. Lymphocytic infiltration was virtually absent. Ultrastructural alterations of the peripheral nerve were basically similar to those of the spinal cord. Separation of myelin lamellae, macrophages infiltration, demyelination, and remyelination were observed. Schwann cells had also alterations. We observed some apoptotic cell death of the oligodendrocytes and Schwann cells with condensed nucleus and phagocytosis of apoptotic bodies by macrophages. Collective evidence suggests that a series of demyelinating process described above may be caused by apoptosis. No virus particles were seen in the spinal cord and peripheral nerve. Although the precise mechanism of apoptosis is not known at present, possible pathogenetic pathway involving apoptosis in HAM rat disease may contribute greatly to a better understanding of mechanisms implicated in the pathogenesis of HAM/TSP in humans.
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PMID:[Rat model of HTLV-I infection--ultrastructural study of HAM rat disease]. 770 50

Human T-cell leukemia virus type I (HTLV-I) gives rise to a neurologic disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the pathogenesis of the disease is unknown, the presence of a remarkably high frequency of Tax-specific, cytotoxic CD8 T cells may suggest a role of these cells in the development of HAM/TSP. Antigen-mediated signaling in a CD8 T-cell clone specific for the Tax(11-19) peptide of HTLV-I was studied using analog peptides substituted in their T-cell receptor contact residues defined by x-ray crystallographic data of the Tax(11-19) peptide in the groove of HLA-A2. CD8 T-cell stimulation with the wild-type peptide antigen led to activation of p56lck kinase activity, interleukin 2 secretion, cytotoxicity, and clonal expansion. A Tax analog peptide with an alanine substitution of the T-cell receptor contact residue tyrosine-15 induced T-cell-mediated cytolysis without activation of interleukin 2 secretion or proliferation. Induction of p56lck kinase activity correlated with T-cell-mediated cytotoxicity, whereas interleukin 2 secretion correlated with [3H]thymidine incorporation and proliferation. Moreover, Tax peptide analogs that activated the tyrosine kinase activity of p56lck could induce unresponsiveness to secondary stimulation with the wild-type peptide. These observations show that a single amino acid substitution in a T-cell receptor contact residue of Tax can differentially signal CD8 T cells and further demonstrate that primary activation has functional consequences for the secondary response of at least some Tax-specific CD8 T cells to HTLV-I-infected target cells.
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PMID:Differential activation of proliferation and cytotoxicity in human T-cell lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand. 773 26

Human T-cell lymphotropic virus type I (HTLV-I) can be associated with either adult T-cell leukemia or HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic progressive immune-mediated myelopathy. Skin manifestations such as xerosis and erythema may be associated with HAM/TSP. Infective dermatitis due to Staphylococcus aureus or beta-hemolytic Streptococcus has recently been described as a marker for HTLV-I infection and as a probable risk factor for the development of adult T-cell leukemia and lymphoma in Jamaican children. We report a case of folliculitis decalvans, a rare chronic follicular inflammatory process of bacterial origin that is extremely resistant to treatment, in a patient with HAM/TSP. This case suggests the possibility that the disturbance of the immune system that was observed in patients with HAM/TSP can play a role in the persistence of this severe skin lesion. In addition, the findings of our case cast doubt on the hypothesis that the cause of infective dermatitis in persons infected with HTLV-I is immunosuppression due to congenital or perinatal infection of the immature immune system.
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PMID:Folliculitis decalvans and human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. 775 98

An association between HTLV-1 infection and infective dermatitis (ID) a relapsing eczematous condition of Jamaican children, was reported in 1990. These patients are at risk of developing other known HTLV-1 related diseases. We have observed the development of HTLV-1 associated myelopathy/tropical spastic paraparesis in two patients, ages 14 and 35 years, who were diagnosed with ID at ages 2 and 10 years, respectively. Infective dermatitis of children serves as an early marker of HTLV-I infection and may predict later development of either the malignant outcome, adult T-cell leukaemia/lymphoma or the neurologic manifestation HAM/TSP among adult carriers of HTLV-1 infection.
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PMID:Tropical spastic paraparesis occurring in HTLV-1 associated infective dermatitis. Report of two cases. 779 13

Tumaco, Colombia, is an area with elevated rates of tropical spastic paraparesis/human T-cell leukemia virus type I (HTLV-I)-associated myelopathy (TSP/HAM). We have identified a mutation in nucleotide 7959 of the tax gene of 14 Tumaco HTLV-I isolates (14 positive of 14 tested) that was present in 5 of 14 (35%) TSP/HAM patients from Japan and in 8 of 11 (72%) TSP/HAM patients from other geographic locations. In contrast, this mutation was found in only 2 of 21 (9.5%) HTLV-I-infected subjects outside of Tumaco who did not have TSP/HAM. tax clones with nucleotide mutations including one at nucleotide 7959 showed a greater ability to transactivate the HTLV-I U3 promoter. However, this effect was not observed when two clones that differed only in nucleotide 7959 were compared. These results suggest that HTLV-I-infected individuals carrying isolates with this tax mutation are at higher risk for developing TSP/HAM.
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PMID:Tax mutation associated with tropical spastic paraparesis/human T-cell leukemia virus type I-associated myelopathy. 763 41

A quantitative method utilizing polymerase chain reaction was employed to evaluate the amount of human T-cell leukemia virus type I (HTLV-I) proviral DNA in the affected spinal cords from patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Central nervous system (CNS) tissues were obtained at post-mortem from five patients with HAM/TSP, who vary in the duration of illness from 2.5-10 years, and one patient with adult T-cell leukemia (ATL), who had leukemic cell infiltration in the CNS. The presence of HTLV-I pX and pol sequences in the CNS tissues were demonstrated in all patients examined. In HAM/TSP, the proviral DNA quantified in the thoracic cord was 0.002-2 copies per 100 tissue cells, and that in the peripheral blood mononuclear cells (PBMC) was 2-8 copies per 100 PBMC. The proviral DNA amount in the thoracic cord of the patient with ATL was 0.4 copies per 100 tissue cells. An apparent propensity for the amount of integrated HTLV-I in the thoracic cord to decrease with the disease duration in patients with HAM/TSP was observed. The decline in HTLV-I proviral DNA amount in the thoracic cord lesions was paralleled with the alteration of proportion of CD4+ T lymphocytes in patients with HAM/TSP. These findings suggest that preferential virus reservoir may be infiltrating CD4+ T lymphocytes in the spinal cord lesions of patients with HAM/TSP, and HTLV-I infection in the CNS of patients is declining with the disease duration in spite of the chronic course of neurological manifestations at least in some patients with HAM/TSP.
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PMID:HTLV-I proviral DNA amount correlates with infiltrating CD4+ lymphocytes in the spinal cord from patients with HTLV-I-associated myelopathy. 791 11

The pX gene of human T-cell leukemia virus type I (HTLV-I) is known to be a potent transactivator of the viral gene and the host genes which are important for cell proliferation in vitro. It has been reported that various diseases occur in transgenic mice harboring either tax, pX, or env-pX gene, such as mesenchymal tumor, neurofibroma, thymic atrophy, muscle degeneration, exocrinopathy and arthropathy. We previously demonstrated that rat but not mouse CD4 positive T cells could be easily infected and immortalized by HTLV-I and infectious transmission of HTLV-I induced HAM/TSP-like myelopathy in WKAH rats after long incubation periods of 16 months. These observations prompted us to produce a series of transgenic rats that expressed the pX gene products under the control of mouse H-2Kd promotor in order to evaluate further the biological and pathological function of the pX gene in vivo. In various tissues of pX transgenic rats (pX rats), pX mRNA was constitutively expressed irrespective of age. PX rats developed mammary tumors with massive infiltration by neutrophils as early as 9 months of age. Pathological and immunohistochemical examination revealed that the tumors were undifferentiated carcinomas of the mammary gland origin. They were transplantable into pX rats, but not into normal syngenic rats. High levels of mRNA expression of not only the pX transgene but also the host genes such as Gro (melanoma growth-stimulatory activity/KC), MIP-2 (macrophage inflammatory protein-2) and IL-1 alpha were demonstrated in the tumor tissues. Gro and MIP-2 which were known as IL-8 families were likely to be produced by tumor cells and appeared to be responsible for neutrophil infiltration in the tumor tissues. Lastly, pX rats described here appear to be suitable animal models for elucidating mechanisms involved in the tumorigenesis and the transactivation of the cellular genes by HTLV-I, especially by the pX gene products in vivo.
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PMID:[Pathological and molecular analyses of mammary tumors induced in HTLV-I pX transgenic rats]. 792 76

We analyzed the serum levels of C-terminal parathyroid hormone-related protein (C-PTHrP) in asymptomatic carriers of human T lymphotropic virus type 1 (HTLV-1) and patients with three HTLV-1 related diseases; adult T-cell leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU). Serum C-PTHrP levels were significantly elevated in HTLV-1-infected individuals, irrespective of whether they were symptomatic or asymptomatic, when compared with that of the seronegative controls. In ATL patients, a good correlation was demonstrated between the serum C-PTHrP level and serum calcium or lactic dehydrogenase (LDH) level. Thus the elevated serum C-PTHrP level could be a characteristic marker of HTLV-1 carrier state, and the determination of its level in ATL patients could be useful for the assessment of the prognosis and as one of the tumor markers. The determination of the serum level of C-PTHrP in various stages of the HTLV-1 carrier state would help to understand the mechanism of the development of hypercalcemia in ATL.
Leukemia 1994 Oct
PMID:Increased serum levels of C-terminal parathyroid hormone-related protein in different diseases associated with HTLV-1 infection. 793 67

We describe the clinical and laboratory features of nine patients born in Chile with HTLV-I-positive adult T-cell leukemia/lymphoma (ATLL). All were adults (median age 51 years) of Caucasian origin without evidence of Indian or foreign extraction and none had been out of the country. The main disease features were organomegaly, cutaneous lesions, hypercalcemia and leukemia with atypical polylobed lymphocytes displaying a CD2+, CD3+, CD4+, CD8-, CD7- T-cell phenotype. Eight patients presented with acute type ATLL and one had a chronic form lasting for 16 months prior to the development of the acute phase. Lymph node histology (three cases) was consistent with a T-cell non-Hodgkin's lymphoma (large and small cells). Antibodies to HTLV-I were detected by ELISA and particle agglutination in the serum from eight of nine patients. DNA analysis showed HTLV-I proviral DNA in all seven cases investigated, including the single serologically negative patient. In five cases, HTLV-I was monoclonally integrated and in one case oligoclonal. In the seventh case viral DNA clonal status was ambiguous. Response to therapy was poor and median survival was 3 months (range 2-20 months). This study provides further evidence that HTLV-I is endemic in Chile, a non-tropical country where the two main diseases associated with HTLV-I, ATLL and TSP, are found.
Leukemia 1994 Oct
PMID:HTLV-I positive adult T-cell leukaemia/lymphoma (ATLL) in Chile. 793 73

Human T cell leukemia virus type I (HTLV-I) can be transmitted into several inbred strains of rats. Adult rats inoculated with HTLV-I immortalized human T cell line MT-2 at 8-37 weeks of age become seropositive HTLV-I carrier rats. Seropositive HTLV-I carrier rats of WKAH strain developed myelopathy similar to HAM/TSP (HTLV-I associated myelopathy/Tropical spastic paraparesis), designated as HAM rat disease. Neuropathological and immunohistochemical features of the affected spinal cord showed symmetrical white matter degeneration characterized by loss of myelin, vacuolar degeneration, infiltration with foamy macrophages and astrocytic gliosis. Lymphocytic infiltration was virtually absent throughout the disease process, and apoptotic cells were observed in the affected spinal cord. Clinical findings and pathological changes in seropositive HAM rats were, in general, milder than findings in seronegative HAM rats as previously described. Provirus genome in the affected spinal cord was evident in 1 of 2 seropositive HAM rats by polymerase chain reaction, but localization of HTLV-I antigen could not be detected by immunohistochemical staining. The collective evidence suggests that development of HAM rat disease is under strict genetic restriction of the host strain, and the primary cause is not mediated by immunological process with effector T cells as suggested in human HAM/TSP, and there seems to be a direct or indirect neurotoxicity for oligodendrocytes mediated by HTLV-I infection.
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PMID:[Analysis of HAM rat disease developed in HTLV-I carrier rat as an animal model of HAM/TSP in human]. 795 97


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