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)

We studied a series of 18 patients with CD3- lymphoproliferative disease of granular lymphocytes (LDGL) for evidence of chronic viral infection, including Epstein-Barr (EBV), hepatitis B (HBV), hepatitis C (HCV), human T lymphotropic virus (HTLV), and human immunodeficiency virus (HIV). Although all patients tested had serologic evidence for past infection with EBV, polymerase chain reaction (PCR) analysis of peripheral blood mononuclear cell (PBMC) DNA utilizing specific EBV primers demonstrated the presence of EBV-DNA in only six of 17 CD3- LDGL cases. A previous history of HBV infection, as defined by the presence of circulating IgG anti-HBc antibodies associated with either HBsAg positivity or negativity, was documented in seven cases; however, viral DNA was not detected in PBMC of these patients using PCR with specific HBV primers. Specific anti-HCV antibodies, confirmed by recombinant immunoblot assay, were detected in five CD3- LDGL patients; PCR analysis demonstrated the presence of viral RNA in PBMC of two of these cases. No patient had antibodies to HTLV-I/II or HIV-1/2. Five patients were infected by more than one virus (two with HBV and EBV and three with HBV and HCV). Our results provide serologic evidence for past viral infection in the large majority of CD3- NK-type LDGL patients. These data suggest that viral infection may have played a role early in disease pathogenesis and may no longer be necessary in sustaining GL proliferation in CD3- NK-type LDGL.
Leukemia 1995 Jul
PMID:Serologic and molecular evidence for a possible pathogenetic role of viral infection in CD3-negative natural killer-type lymphoproliferative disease of granular lymphocytes. 763 Jan 96

In the 35 years since the discovery of interferon, significant biological activity has been described for interferon-alpha (IFN alpha) in various cancers, particularly haematological malignancies such as hairy cell leukaemia and chronic myelogenous leukaemia. Except for localised therapy in bladder and ovarian cancer, activity against most solid tumours has been disappointing. Other notable exceptions include Kaposi's sarcoma, renal cell carcinoma and malignant melanoma, tumours known to be susceptible to immunological attack. More recently, broad spectrum antiviral activity has been demonstrated for both recombinant and naturally occurring IFN alpha. Hepatitis C is responsive to IFN alpha in about 40% of patients, but long term remissions are rare. In contrast, long term suppression of hepatitis B is common following IFN alpha therapy. Both diseases respond in a dose proportional fashion, with daily doses of 5 million units (MU) significantly more effective than lower doses. The mechanism of action in viral diseases involves the expression of unique antiviral proteins such as endonuclease and 2'-5'-oligoadenylate synthetase which enhance the destruction of viral RNA. General cellular protein synthesis is also inhibited, including cytochrome P450 enzymes. This forms the basis for potential drug interactions, with IFN alpha slowing the clearance of highly metabolised drugs such as theophylline. As an antitumour agent, the mechanism of action of IFN alpha is unclear, particularly in haematological cancers. In melanoma and renal cell carcinoma, antitumour effects may be mediated by augmented immune responses including activation of natural killer lymphocytes and enhanced expression of cell surface antigens (e.g. MHC I and II). Conversely, antibody formation to recombinant IFN alpha may result in a loss of activity. This has been observed in both renal cell cancer and hepatitis B and C. The elimination half-life of IFN alpha is short, 4 to 5 hours, but biological activity extends for 2 to 3 days after administration, which facilitates daily or thrice weekly administration. Clearance of IFN alpha is mediated by catabolism in the renal tubules; no intact drug is excreted in the urine. It is probable that the antiviral indications of IFN alpha will expand as the agent is more clearly recognised as a primary endogenous defence against various viral conditions.
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PMID:Interferon-alpha in malignant and viral diseases. A review. 768 71

A total of 203 paediatric cancer treatment survivors were tested for serum antibodies against hepatitis-C virus (anti-HCV). Anti-HCV was detected in 41 patients (20.2%) with first generation anti-HCV ELISA. Positive results were confirmed in all samples retested with a second generation ELISA (n = 35) and in all but two cases re-analysed by immunoblotting (n = 23). Anti-HCV positive children had received significantly more blood product transfusions compared to seronegative patients. In 75 children (32%) chronic liver disease was found. It was defined as an elevation of serum alanine aminotransferase values to a least 2.5 times the upper limit of normal persisting for 6 months or longer. Hepatitis A was never detected, and in 58 children the chronic hepatopathy was unexplained by hepatitis B (non-A non-B chronic liver disease). Of these patients 29 (50%) were seropositive for anti-HCV. Surprisingly, non-A/non-B chronic liver disease was associated with anti-HCV in 14 of 19 solid tumour patients (78.9%), but in no more than 14 of 39 leukaemia and lymphoma patients (35.9%). This phenomenon was not explained by different rates of cytomegalovirus disease and drug toxicity related hepatopathies between the two groups. It may be related to differences of leukaemia/lymphoma compared to solid tumour therapy schedules (differential immunosuppression and liver toxicity).
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PMID:Association of hepatitis C virus infection with chronic liver disease in paediatric cancer patients. 768 44

The epidemiological situation regarding blood-borne infections in Sweden is favourable and under very good control. The prevalence of infectious markers in the blood-donor population is low. In 1993 the frequencies of confirmed positive tests were three in 1,000,000 for human immunodeficiency virus type-1 (HIV-1), one in 100,000 for hepatitis B virus (HBV) and three in 100,000 for hepatitis C virus (HCV). The safety of the blood supply is high and relies on strict donor selection, information on risky behaviour, and screening for syphilis, HBV and antibodies to hepatitis B core antigen, HCV, HIV-1, HIV-2 and human T-cell leukaemia virus type I and II (HTLV-I/-II). No donors with syphilis have been identified for many years. Screening for anti-HTLV-I/-II was introduced in February 1994 and no results have been reported yet. Donation is usually not permitted at the first visit, as the risk of transfusion-transmitted infections is greater in first-time donors. The risk of acquiring a transfusion-transmitted infection is low, but still a few cases of HBV and HCV infection occur each year among about 150,000 patients receiving transfusions. As far as we know, HIV infection has not been transmitted by blood components in Sweden since 1985.
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PMID:Epidemiology of viral infections in the Swedish blood-donor population. 774 44

The selection of blood donors and the introduction of tests identifying virus-infected donors has led to a permanent increase in the safety of blood transfusion. In most European countries, there is a low risk of infection from viruses such as hepatitis B virus, hepatitis C virus and human immunodeficiency virus. Examples of viruses that pose a risk to children but not adults following transfusion-transmitted infection are parvovirus B19 and cytomegalovirus. Other viruses may be transmitted in the blood but, because of their low pathogenicity and high prevalence, they are not relevant for transfusion. Further work is required to determine the relevance of hepatitis A virus as a blood-borne viral infection. Human T-cell leukaemia virus is seldom transmitted during transfusion but may be an important risk factor in the future in some countries.
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PMID:Blood-borne viral infections. 774 48

We studied the serologic status, with respect to hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus type-I (HTLV-I) of blood donors in an area endemic for adult T-cell leukemia (ATL). Similarly, we studied the serologic status of hepatocellular carcinoma (HCC) patients from the same district. In the donors, the incidence of serological positivity for these viruses was 0.95, 1.23, and 3.75%, respectively. There was a positive correlation between the presence of anti-HCV and serological HTLV-I positive status in these subjects (1.9 vs. 1.1%) for those with HTLV-I negative status, implying high susceptibility for HCV infection among HTLV-I carriers. Fifty-nine percent of HCC patients were positive for anti-HCV and twenty-six percent of those were simultaneously positive for the antibody to HTLV-I. HCC patients infected with HTLV-I were younger than patients not so infected (61.5 +/- 8.8 vs. 64.8 +/- 8.4 years, p < 0.05). These observations suggest the possibility that HTLV-I could be one of the factors that promote the development of HCC caused by hepatotropic viruses.
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PMID:Human T-lymphotropic virus type-I influence on hepatotropic virus infections and the subsequent development of hepatocellular carcinoma. 781 78

Pursuing their chief work--gathering, processing and distributing blood--the blood donor centres of the Canadian Red Cross Society follow standard operating procedures like those in place at the Ottawa centre. Here, recruitment staff and volunteers work to recruit donors to meet needs at a time when the number of donors is falling. When they register, donors must show proof of identity. Each receives a permanent identification number that is linked to the numbers assigned to the units of blood each donates and to the date the unit was collected and the centre that collected it. Donors must answer questions about health and high-risk activity, and the blood of those who report high-risk activity is not accepted. Units are screened by automated instruments for syphilis, hepatitis B and C, HIV types 1 and 2, and human T-cell leukemia virus. Units with a negative test result are broken down into components for use in hospitals. A reactive test result prompts quarantining of the unit and a second screening test. If this test result is also reactive, a sample of the unit is sent to the National Testing Laboratory for confirmatory testing, and the unit is discarded. Once it has the results of the confirmatory test, the centre contacts the donor. Blood is now considered a drug. Red Cross practices in Canada and around the world have been changing since 1989 to reflect this.
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PMID:What happens to donated blood? 785

In Taiwan, a country with 21 million people, 388 bone marrow transplants (BMTs), 308 allografts and 80 autografts, were performed in 5 BMT centers from November 1983 to October 1993. The commonest indications were leukemia, aplastic anemia, lymphoma and thalassemia. Campaigns promoting an unrelated marrow donor registry were started in August 1993 and recruited approximately 26,000 volunteers. A peripheral stem cell program is just beginning. The overall results of BMT in Taiwan are comparable to other countries. The complications of BMT are similar to Western series, except that acute GVHD was rarer in one large series; this observation needs further study. A particular indication for allogeneic BMT in Taiwan is thalassemia, accounting for 10% of all patients. Disease-free survival after BMT for thalassemia is 44%; graft rejection is the major cause of treatment failure. Another important issue is the role of hepatitis B virus (HBV) in BMT, since the prevalence of HBV infection in Taiwan is very high (> 90%). Abnormal liver function is currently the most common complication and might be related to HBV. Among nearly 100 allogeneic BMTs with HBV carriers as either donor or recipient, 2 patients (approximately 2%) died of HBV-related hepatic failure. Whether the HBV status of the donor and recipient is an important prognostic factor remains to be defined.
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PMID:Bone marrow transplantation in Taiwan: an overview. 792 Feb 98

Hepatitis B virus (HBV) infection and replication have been linked to the development of hepatocellular carcinoma. Bone marrow-derived cells, as well as mesenchymal and epithelial cells, were recently shown to support HBV replication. We hypothesize that the mechanism that links HBV infection and liver tumors might also promote tumor development in tissues permissive for HBV replication. Between 1980 and 1993 we retrospectively identified 22 patients who were hepatitis B surface antigen (HBsAg) carriers and had extra-hepatic malignancies. These patients had 25 tumors, of which 22 were bone marrow derived. HBsAg was detected by immunohistochemistry in bone marrow cells of leukemia patient and of 3 of 10 lymphoma patients. In addition, in 4 of 10 patients with lymphoma, including 2 patients in which HBsAg stained bone marrow cells, HBsAg was also detected in the endothelial cells of blood vessels of the tumor tissue. These results suggest that the identification of an HBV gene product in endothelial cells might point to a role of HBV infection in the development of certain hematopoietic tumors, possibly through activation of cytokines or growth factors, which may eventually lead to bone marrow cell proliferation.
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PMID:Hepatitis B virus infection associated with hematopoietic tumors. 760 82

For pathogenic viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human influenza A virus, and human T-cell leukemia virus type I (HTLV-I), the evolutionary features were briefly reviewed with special reference to the rates of synonymous and nonsynonymous substitutions. In particular, these rates were discussed in connection with the neutral theory of molecular evolution. It was common to all the five pathogenic viruses that the rate of synonymous substitution was higher than that of nonsynonymous substitution particularly when the entire gene regions were compared between different isolates. This suggests that the viral proteins are quite conservative to functional and structural changes even though most of these viral genomes are evolving at a speed extraordinarily higher than their host genomes. Thus, this feature is consistent with the neutral theory. However, it is also pointed out that positive selection may be operating on some specific sites such as antigenic sites in order for the pathogenic viruses to escape from the host immune system.
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PMID:Evolution of pathogenic viruses with special reference to the rates of synonymous and nonsynonymous substitutions. 799 69


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