Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the etiologic agent associated with Kawasaki disease (KD), we initially established a cocultivation system using concanavalin A (Con A)-stimulated lymphoblastoid cells obtained from each retrovirus-seronegative individual's peripheral blood mononuclear cells (MNCs) cocultivated with each of 1) 40 patients with KD, 2) 10 patients with other viral infection and skin rash, and 3) 10 age- and sex-matched normal controls. Five major findings suggested that virus-like particles with reverse transcriptase (RT) activity are associated with KD. First, RT activity appeared significantly higher on day 12 after the onset of fever in the KD patients than in those with other viral infections and normal controls (dTMP incorporation: 3,645 +/- 248 vs. 434 +/- 50 vs. 412 +/- 46 cpm, P < 0.0001). Second, the RT activity was not endogenous, because the Con A-stimulated lymphoblastoid cells were obtained from the individuals who were negative for retrovirus. Third, virus-like particles (80-100 nm in diameter) by electron microscopy were found in the concentrated pool supernatants of particulate fraction containing RT activity subjected to sucrose density gradient, obtained from KD patients. Fourth, the viral product, a 31.4 kilodalton molecule, was detected by SDS-PAGE after internal labelling (methionine-S35) and density gradient centrifugation. Fifth, using a "retrovirus universal pol gene region" as a primer and the RT-PCR method, a retrovirus-specific band was detected in the cocultivated supernatants obtained from four KD and one AIDS patients but not in patients with rubella or in healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Virus-like particles with reverse transcriptase activity associated with Kawasaki disease. 128 52

The particulate fractions of culture supernatants from peripheral blood mononuclear cells from 39 patients with Kawasaki disease (KD) were examined for the presence of particle-associated reverse transcriptase activity. The peak polymerase activity was significantly higher in cultures from KD patients compared to controls (mean = 6.4 versus 3.6 pmol of dTMP incorporated, p = 0.001). PBMC cultured between the 3rd and 9th wk after onset of fever were most likely to be associated with reverse transcriptase activity. Peak polymerase activity was positively associated with older age (r = 0.41, p = 0.01) and greater magnitude of the serum IgA response at 7-14 d after onset of fever (r = 0.45, p = 0.01) and IgM response at 6-9 wk after onset of fever (r = 0.46, p = 0.01). The appearance of enzyme activity was not associated with a decrease in viability of the cultured cells. A purified enzyme preparation showed radiolabel incorporation only with an RNA template with DNA primer. These data suggest that circulating mononuclear cells from KD patients may harbor a polymerase-associated agent and that these cells can be most readily detected in the early convalescent phase of KD from older patients who mount a marked humoral immune response.
 ...
PMID:Characterization of the polymerase activity associated with cultured peripheral blood mononuclear cells from patients with Kawasaki disease. 169 Mar 83

We and others previously reported DNA polymerase activity in culture supernatants of peripheral blood mononuclear cells from patients with acute Kawasaki syndrome (KS). In the present study, we further characterized the previously detected polymerase activity and attempted to confirm its presence in cultured peripheral blood mononuclear cells from additional patients with KS. Characterization experiments indicated that the polymerase activity was typical of a DNA-dependent DNA polymerase rather than viral reverse transcriptase. Peripheral blood mononuclear cell cultures from 17 additional KS patients were negative for reverse transcriptase activity in three laboratories. Our findings do not provide support for a retroviral etiology of KS. Further studies should continue to focus on infectious agents in efforts to elucidate the etiology of KS.
 ...
PMID:Failure to confirm the presence of a retrovirus in cultured lymphocytes from patients with Kawasaki syndrome. 171 54

In 18 consecutive children with Kawasaki disease of recent onset, reverse transcriptase (RT) activity was studied in co-cultivated peripheral-blood-mononuclear-cell/lymphoblastoid-cell supernatants. 8 of 18 children, but only 1 of 18 controls, showed RT activity in one or more sample (p = 0.009). RT activity was identified in 14 of 226 samples from patients, but in only 1 of 167 from controls (p less than 0.01). The findings suggest that a retroviral agent may be casually related to Kawasaki disease.
 ...
PMID:Does Kawasaki disease have a retroviral aetiology? 242

Kawasaki disease (KD) is an acute vasculitis of infancy and early childhood characterized by high fever, rash, mucositis, lymphadenopathy and coronary artery damage. Large epidemics have been described in Japan and the United States and the number of cases reported annually is steadily increasing. The aetiology of KD is unknown. During the acute phase of the disease marked immunologic alterations occur including generalized T-cell lymphocytopenia, activation of circulating T4+ helper T cells, decreased numbers of T8+ suppressor T cells and marked B-cell activation. We postulated that a lymphotropic virus with affinity for endothelial and lymphoid cells might explain the vasculitis and immunological abnormalities in KD. We report here our study of the particulate fraction from culture supernatants of peripheral blood mononuclear cells (PBMC) for evidence of retrovirus-associated reverse transcriptase (RT) activity. Activity was found in the supernatants from KD patients but not control cultures. This RT activity was transmitted to an established T-cell line (HUT-78) and thus may be due to an exogenous agent infecting KD lymphocytes.
 ...
PMID:Polymerase activity in lymphocyte culture supernatants from patients with Kawasaki disease. 243 Jan 87

Kawasaki syndrome, an acute febrile multisystem illness of young children, is a panvasculitis with prominent rheumatic features. Arthritis and pancarditis are frequent during the acute stage; coronary artery aneurysms occur in 20% of cases and the disease is now the leading cause of acquired heart disease in childhood. A microbial aetiology is suggested by the acute febrile self-limited character of the disease, the regular occurrence of epidemic outbreaks at intervals of 2-3 years, and the virtual restriction to young children, consistent with the early acquisition of immunity. Reports of elevated DNA polymerase activity (assumed to be RNA-dependent reverse transcriptase) in cultured lymphocytes from patients with acute Kawasaki syndrome suggest that a retrovirus might be the causative agent. We have measured supernatant DNA polymerase activity in lymphocyte cultures from 49 Hawaiian patients in acute and convalescent stages of Kawasaki syndrome and have been unable to demonstrate significant reverse transcriptase activity or other evidence of involvement of a retrovirus in the aetiology of the disease.
 ...
PMID:Absence of significant RNA-dependent DNA polymerase activity in lymphocytes from patients with Kawasaki syndrome. 246 87

Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us reverse transcriptase, oncogenes, and cloning vectors that may one day be exploited for human gene therapy. They have also given us leukaemia and the acquired immune deficiency syndrome (AIDS). Kawasaki disease and tropical spastic paraparesis are thought to be associated with retrovirus infection, and other diseases such as de Quervain's thyroiditis, multiple sclerosis, acquired hypogammaglobulinaemia, and certain forms of non-A, non-B hepatitis have come under passing suspicion of a retroviral aetiology. With AIDS threatening to become pandemic, and a second AIDS virus appearing in West Africa, human retroviruses are under intensive study for new antiviral drugs targeted to their unique mode of replication, and for the development of vaccines.
 ...
PMID:Retroviruses and human disease. 288 52

Kawasaki disease (KD) is an acute inflammatory disorder of children frequently associated with the development of coronary artery abnormalities. Although a great deal is known about inflammatory and immune responses in acute KD, the mechanisms linking the immune response to vascular changes are not known. To gain further insight into this process, we performed a microarray gene expression analysis on RNA isolated from the peripheral blood mononuclear cells of four patients with KD during both their acute and convalescent phases. Forty-seven genes of 7129 genes examined showed an increased expression in three or all four patients in the acute compared with the convalescent phase of KD. Fourteen of these genes were significantly (p < 0.05) up-regulated, including several inflammatory response genes (e.g. S-100 A9 protein) and also anti-inflammatory genes (e.g. TSG-6). Of greatest interest, the adrenomedullin (ADM) gene, known to be associated with coronary artery vasodilation, was up-regulated in the acute phase of KD (p = 0.024). Up-regulation of ADM in the acute phase of KD was confirmed in peripheral blood mononuclear cells of 11 additional KD patients by reverse transcriptase-PCR (p < 0.01). Isolated blood monocytes but not lymphocytes were demonstrated by real-time PCR to have increased ADM mRNA (p = 0.01). Plasma ADM protein level in 32 additional KD patients was also confirmed to be higher in acute KD compared with convalescent KD (p < 0.032). It is interesting that from microarray results, other molecules known to be associated with coronary dilation, including nitric oxide, prostacyclin, acetylcholine, bradykinin, substance P, and serotonin, were not elevated in acute KD. Our current study suggests that ADM-expressing monocytes that infiltrate the coronary vascular wall may be the cause of coronary dilation in the acute phase of KD.
 ...
PMID:Adrenomedullin is highly expressed in blood monocytes associated with acute Kawasaki disease: a microarray gene expression study. 1553 34