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

Adult T-cell leukemia-lymphoma (ATL) is a unique T-cell leukemia-lymphoma that is closely associated with human T-cell leukemia virus type I (HTLV-I). HTLV-I is also associated with a benign disease, HTLV-I associated myelopathy. Main routes of the infection is through breast milk feeding from carrier mother to her baby, from carrier husband to wife, and by blood transfusion of carrier blood to recipient patients. The presence of anti-HTLV-I antibody is a definite sign of the carrier of HTLV-I, then screening of the antibody has been introduced with success to prevent the HTLV-I infection. Mechanism of leukemogenesis by the virus is not known. It is important to note that age-dependent occurrence of HTLV-I associated ATL can be simply described by a Weibull model. This suggests that ATL leukemogenesis might be the result of accumulation of numerous critical events, most likely somatic mutations, which are estimated to be five from the analysis. Although HTLV-I infection plays a primary role in the pathogenesis of ATL as an initiator, it may be only a prerequisite for accumulation of later events. The presence of HTLV-I negative ATL suggests that factor(s) other than HTLV-I infection may be involved in the leukemogenic process of ATL.
 ...
PMID:[Human T-cell leukemia virus type I and adult T-cell leukemia-lymphoma]. 218 40

Seventeen patients with adult T-cell leukemia (ATL) and 21 with tropical spastic paraparesis/human T-cell leukemia/lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) were observed during a 3-yr survey (1986-1988) in some hospitals in Paris, France. Most of them were black, originating from high-HTLV-I-endemic areas (West Indies or Africa), but two cases of TSP/HAM occurred in French Caucasians. In one case, the patient acquired the virus from a transfusion during a cardiac transplantation. Most of the ATL cases were diagnosed as acute leukemia or lymphoma, with a proliferation of CD2+, CD3+, CD4+, CD8-, DR+, and CD25+ lymphoid cells. Only three cases were diagnosed as a smoldering ATL. All of the TSP/HAM cases exhibited a spastic paraparesis with a chronic and slow evolution and high HTLV-I antibody titers in serum and cerebrospinal fluid, with a high HTLV-I antibody index and specific HTLV-I immunoglobulin = oligoclonal bands. In TSP/HAM, a high percentage of DR-expressing cells (15 to 40%) was found, with a slightly elevated CD4/CD8 ratio. This was associated with the presence of 1 to 10% abnormally shaped nuclei in lymphoid cells and a polyclonal integration of HTLV-I proviruses in these peripheral blood mononuclear cells. On the contrary, a clonal integration was always found in the ATL malignant cells (leukemic, lymph node, and cutaneous infiltrate). Long-term interleukin 2-dependent T-cell lines (CD2+, CD3+, CD4+, and WT31+) with activated T-cell markers (CD25+ and DR+) producing HTLV-I were established from ATL and TSP/HAM peripheral blood mononuclear cells.
 ...
PMID:Epidemiology and immunovirology of human T-cell leukemia/lymphoma virus type I-associated adult T-cell leukemia and chronic myelopathies as seen in France. 220 41

This may be the first documented case in the United States and in the orthopedic literature of transfusion-transmitted human T-cell leukemia virus Type I (HTLV-I)-associated myelopathy (HAM). Progressive myelopathy occurred in a 58-year-old white man with serologic and molecular evidence of HTLV-I infection after multiple trauma and subsequent transfusion with multiple units of banked blood products. Symptoms of myelopathy occurred 15 months after the transfusions. Myelopathy from HTLV-I infection simulates a disorder of orthopedic interest. Physicians should be aware of the symptoms of HAM and unexplained myelopathy.
 ...
PMID:HTLV-I viral-associated myelopathy after blood transfusion in a multiple trauma patient. 222 23

A retrovirus was isolated from a T-cell line that was established from lymphocytes in the cerebrospinal fluid of a patient with human T-cell leukemia virus type I-associated myelopathy (HAM), and its genome was sequenced. The nucleotide sequence of the 3' half of the total genome was identical in 99.5% of the nucleotides to that of the prototype human T-cell leukemia virus type I that was derived from a patient with adult T-cell leukemia. These results indicate that the same retrovirus human T-cell leukemia virus type I is associated with both a neurological disease, HAM, and a lymphoproliferative disease, adult T-cell leukemia.
 ...
PMID:Retrovirus from human T-cell leukemia virus type I-associated myelopathy is the same strain as a prototype human T-cell leukemia virus type I. 224 26

An autopsy case of HTLV-I associated myelopathy (HAM) combined with adult T-cell leukemia (ATL) was reported. Although HAM and ATL are reported to be caused by an identical virus, a combination of these two conditions is extremely rare. This is the first report of an autopsy of the case. A 42-year-old female born in Kumamoto noticed gait disturbance at age 20. Dysesthesia in her lower limbs and bladder bowel disturbance (BBD) gradually appeared at age 29 and at age 39, respectively, and slowly progressed. Neurological examination revealed spastic paraparesis, sensory disturbance in her lower limbs in all modalities and BBD. Furthermore, titers of the anti HTLV-I antibody were increased both in serum and CSF. She was diagnosed as HAM at this stage. She responded to the oral administration of prednisolone. Ten months after the initiation of prednisolone therapy, a tumor shadow appeared in the right lung and characteristic ATL cells were found in the pleural effusion. She died with respiratory failure. ATL cells were not found either in the peripheral blood or CSF throughout the course of her illness. Autopsy revealed solid tumors in both lungs, liver, kidneys, spleen, thyroid gland and para-aortic lymphnodes, composed of ATL cells with extensive necrosis. The spinal cord showed a marked loss of myelin and axons, and perivascular fibrosis in the lateral and anterior columns. These changes were most severe at the 6th and 7th thoracic segments. No ATL cell was found in the spinal cord. Concerning the sensory system, the posterior root, ganglion and posterior column were preserved, whereas the axonal degeneration was found in the biopsied specimen of the sural nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[An autopsy case of HTLV-I associated myelopathy (HAM) with adult T-cell leukemia (ATL)]. 224 29

A 52-year-old human immunodeficiency virus type 1-seropositive bisexual black man was evaluated at UCLA because of the recent onset of progressive lower-extremity weakness. Initial neurologic examination showed that the patient's distal weakness was greater than his proximal weakness, with bilateral foot drop and electrophysiologic evidence of denervation in the distal lower extremities. Magnetic resonance imaging of the brain and spinal cord disclosed no abnormalities. Subsequent neurologic evaluation 8 months later showed a myelopathy, with progression of lower-extremity weakness, spasticity, and flexor spasms, and urinary incontinence, as well as the peripheral neuropathy noted previously. A second magnetic resonance imaging scan of the brain showed patchy foci of increased signal intensity in white matter and cortex, with mild generalized cerebral and cerebellar atrophy and no lesions in the spinal cord. Specimens of the patient's serum and cerebrospinal fluid contained antibodies to human immunodeficiency virus type 1. Additionally, specimens of his serum and cerebrospinal fluid were tested for antibody to human T-cell leukemia virus type I by Western blotting and radioimmunoprecipitation, and found to be positive for human T-cell leukemia virus type I gag, env, and tax antibodies. The primary cause of severe myelopathy in this patient may be infection with human T-cell leukemia virus type I rather than with human immunodeficiency virus type 1. Treatment with prednisolone resulted in improvement of the lower-extremity weakness, reduction in flexor spasms, and slower but significant improvement in urinary symptoms. Patients who are infected with human immunodeficiency virus type 1 and have unusual motor findings should be tested for concomitant human T-cell leukemia virus type I infection.
 ...
PMID:A patient with progressive myelopathy and antibodies to human T-cell leukemia virus type I and human immunodeficiency virus type 1 in serum and cerebrospinal fluid. 232 40

Human T-cell lymphotropic virus type I (HTLV-I) causes adult T-cell leukemia and has recently been associated with HTLV-associated myelopathy/tropical spastic paraparesis. The HTLV-I is endemic throughout the Caribbean basin and parts of South America, and HTLV-associated myelopathy/tropical spastic paraparesis also seems to be common in this area. This 2-year study, 1985 and 1986, was designed to evaluate the occurrence of HTLV-I infection in all newly diagnosed cases of selected neurologic diseases in Panama City, Panama. Six (8%) of 71 patients had antibody to HTLV-I detected by immunofluorescence, enzyme-linked immunosorbent assay, radioimmunoassay, and Western blot assays; 5 patients' conditions were diagnosed as spastic paraparesis, and all 5 were seropositive and also had HTLV-I antibody in cerebrospinal fluid. The remaining seropositive patient had multiple sclerosis, and no antibody was detected in her cerebrospinal fluid. Clinical and electrophysiologic studies indicated that HTLV-I-associated spastic paraparesis is a multifocal, primarily demyelinating disease that principally involves the spinal cord.
 ...
PMID:Human T-cell lymphotropic virus type I and neurologic disease in Panama, 1985 and 1986. 234 89

A state of T-cell activation, reflected by a marked degree of spontaneous proliferation in vitro, exists among patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) but not in those with retroviral-induced adult T-cell leukemia (ATL). We wished to define the mechanism by which the immune activation of circulating cells from HAM/TSP is driven, thus gaining insight into the pathogenesis of this HTLV-I-associated disease. By using a modification of the polymerase chain reaction, we compared the levels of interleukin 2 (IL-2) and IL-2 receptor alpha chain (IL-2R alpha) mRNA expression to the transcription of the HTLV-I transactivator gene, pX, in peripheral blood mononuclear cells of HAM/TSP and ATL patients as well as seropositive carriers. Up-regulation of IL-2 and IL-2R alpha transcripts was detected in HAM/TSP and seropositive carriers that paralleled the coordinate mRNA expression of the pX transactivator. In addition, IL-2 and soluble IL-2R alpha serum levels in HAM/TSP and seropositive carriers were elevated. Despite markedly elevated levels of soluble IL-2R alpha in ATL, transcripts for IL-2 and pX were not demonstrable in the circulating cells. Finally, the marked degree of in vitro spontaneous proliferation present in HAM/TSP was profoundly inhibited by specific anti-IL-2R or anti-IL-2 blocking antibodies. Collectively, these results suggest that immune activation in HAM/TSP, in contrast to ATL, is virally driven by the transactivation and coordinate expression of IL-2 and IL-2R alpha. This deregulated autocrine process may contribute to the evolution of inflammatory nervous system damage in HAM/TSP.
 ...
PMID:Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy. 236 34

Adult T cell leukemia (ATL) is associated with human T cell leukemia virus type 1 (HTLV-1) infection, and almost all ATL patients have the complication of hypercalcemia. To understand the mechanism of the high incidence of hypercalcemia in ATL, we studied the expression of a parathyroid hormone-related protein (PTHrP) gene that has been proposed as a causative factor of hypercalcemia in some solid tumors. The polymerase chain reaction coupled with reverse transcription of mRNA was applied to RNA from peripheral blood mononuclear cells. Cells from all 13 ATL patients examined showed abundant expression of the PTHrP gene, while cells from uninfected normal subjects did not. Significant expression of PTHrP gene was also detected in HTLV-1 carriers without any symptoms and in patients with HTLV-1-associated myelopathy or tropical spastic paraparesis. PTHrP mRNA levels correlated with the number of infected cells that were estimated by the integrated HTLV-1 DNA. These results suggest that HTLV-1-infected cells are expressing the PTHrP gene. This concept was further supported by the finding that the HTLV-1 trans-activator, the tax gene product, caused trans-activation of the PTHrP gene promoter linked to the CAT gene. These observations might explain the general expression of the PTHrP gene in ATL patients and the high incidence of hypercalcemia in ATL.
 ...
PMID:Constitutive expression of parathyroid hormone-related protein gene in human T cell leukemia virus type 1 (HTLV-1) carriers and adult T cell leukemia patients that can be trans-activated by HTLV-1 tax gene. 238 34

We have established an interleukin 2-dependent, OKT4-positive T-cell line, named HCT-1, from cells in the cerebrospinal fluid obtained from a patient with human T-cell lymphotropic virus type I (HTLV-1)-associated myelopathy. Antigens for HTLV-I were detected in HCT-1 cells by indirect immunofluorescence and Western blot testing, and type C virus particles were detected by electron microscopy. Southern blot analysis of HCT-1 cellular DNA, using an HTLV-I probe, revealed that the integrated provirus genome could not be distinguished from the HTLV-I genome in adult patients with T-cell leukemia.
 ...
PMID:Characterization of HTLV-I in a T-cell line established from a patient with myelopathy. 264 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>