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Hepatitis B transmitted via urine?
Literature
The
MOLECULAR MEDICINE TODAY, APRIL 2000 (VOL. 6)
Reversal of leukaemia Cancer is generally the end result of multiple genetic events that cause irreversible malignancy. However, this might not be the case in some leukaemias that are associated with balanced translocations. Transgenic animals provide an ideal system in which to study the effects of gene fusion products that are generated by translocations. Huettner and colleagues1 have created a transgenic mouse in which expression of a BCR-ABL1 oncogene, which is a causative agent in 90% of chronic myelogenous leukaemia (CML) and up to 15% of adults with de novo acute lymphoblastic leukaemia (ALL), can be turned on or off in a specific cell type in the adult animal. Expression of this oncogene resulted in acute B-cell leukaemia in 100% of animals from four different transgenic lines. However, when the gene was switched off, all animals exhibited reversal of the phenotype, including those with advanced disease. Remission was permanent in 100% of animals from three of the lines, but all animals from the fourth line developed a rapidly progressing B-cell leukaemia that was independent of BCR-ABL1 expression. This line had taken much longer than the others to develop the initial B-cell leukaemia, perhaps implying that there had been more time for secondary mutations to accumulate. This work is important, as it shows both that continued expression of this oncogene is necessary for the maintenance of cancer in vivo and that the phenotype can be completely reversed, even at an advanced stage. The results suggest that drugs that inhibit leukaemic oncogenes should provide very effective therapy in this disease, and that this model is an excellent system for the testing of such drugs. Finally, it will be interesting to see whether this mechanism applies to other translocation associated leukaemias. 01 Huettner, C.S. et al. (2000) Reversibility of acute Bcell leukaemia induced by BCR-ABL1. Nat. Genet. 24, 57–60
Hepatitis B transmitted via urine? Hepatitis B virus (HBV) is a serious health threat, causing acute and chronic hepatitis. The number of virus carriers is estimated to exceed 300 million worldwide. The acute disease is often self-limiting, but 5–10% of infections progress into chronic hepatitis, which is associated with a high risk of liver cirrhosis and, eventually, liver carcinoma. The only treatments currently available for chronic HBV infection are interferon therapy and liver transplantation. Unfortunately, the former is expensive and the latter has serious medical consequences; at best, both are only partially successful. Because of its role as a major human pathogen, HBV has been the subject of intensive study, and many features of its structure and replication are understood. This is particularly striking in light of the difficulties in culturing HBV in vitro; consequently, much of our current knowledge comes from modern techniques of molecular biology. HBV is the prototype member of the recently defined family of viruses called the Hepadnaviridae, which replicate their DNA genomes by reverse transcription of an RNA intermediate. Although immunization against HBV is possible, it is unfortunate that an effective worldwide vaccination programme will be prohibitively expensive. Thus, limiting infections by understanding the risks associated with infectious individuals is important. Classically, there has been much documentation of vertical, sexual and parenteral transmission of HBV. However,
among young and pre-adolescent children, horizontal transmission without apparent parenteral exposure is a common mode of acquisition, and the basis of this route of infection has been unresolved. This problem has been addressed by Knutsson and Kidd-Ljunggren1, who have used a sensitive polymerase chain reaction (PCR) assay to identify HBV DNA in the urine of HBV carriers. Results show the detection of HBV DNA in urine, which raises the possibility that infectious virus particles are present. Earlier research has shown that, during HBV virus assembly, a quality control mechanism ensures that only replication competent particles are secreted from infected cells. Thus, it seems plausible that urine is a potential source of HBV infection. These results indicate that a high proportion of patients infected with HBV have HBV DNA detectable by PCR in their urine. Thus, urine from all HBV carriers could harbour infectious HBV. These findings might explain the horizontal transmission of HBV among young children, and must be considered seriously in matters of hospital hygiene and the risk of nosocomial transmission. 1 Knutsson, M. and Kidd-Ljunggren, K. (2000) Urine from chronic hepatitis B virus carriers: Implications for infectivity. J. Med. Virol. 60, 17–20 Roger Hewson PhD [email protected]
The literature page is designed to alert readers to recent primary papers that are important to biomedical researchers, particularly innovative, likely to have significant clinical impact, or controversial. A panel of senior active researchers is commissioned to select one or two papers published in the last six weeks that is within their area of expertise. If you are interested in joining this panel, send an e-mail message to the Editor at:
Kathryn L. Evans PhD [email protected]
1357-4310/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
[email protected]
141
The
MOLECULAR MEDICINE TODAY, APRIL 2000 (VOL. 6)
Reversal of leukaemia Cancer is generally the end result of multiple genetic events that cause irreversible malignancy. However, this might not be the case in some leukaemias that are associated with balanced translocations. Transgenic animals provide an ideal system in which to study the effects of gene fusion products that are generated by translocations. Huettner and colleagues1 have created a transgenic mouse in which expression of a BCR-ABL1 oncogene, which is a causative agent in 90% of chronic myelogenous leukaemia (CML) and up to 15% of adults with de novo acute lymphoblastic leukaemia (ALL), can be turned on or off in a specific cell type in the adult animal. Expression of this oncogene resulted in acute B-cell leukaemia in 100% of animals from four different transgenic lines. However, when the gene was switched off, all animals exhibited reversal of the phenotype, including those with advanced disease. Remission was permanent in 100% of animals from three of the lines, but all animals from the fourth line developed a rapidly progressing B-cell leukaemia that was independent of BCR-ABL1 expression. This line had taken much longer than the others to develop the initial B-cell leukaemia, perhaps implying that there had been more time for secondary mutations to accumulate. This work is important, as it shows both that continued expression of this oncogene is necessary for the maintenance of cancer in vivo and that the phenotype can be completely reversed, even at an advanced stage. The results suggest that drugs that inhibit leukaemic oncogenes should provide very effective therapy in this disease, and that this model is an excellent system for the testing of such drugs. Finally, it will be interesting to see whether this mechanism applies to other translocation associated leukaemias. 01 Huettner, C.S. et al. (2000) Reversibility of acute Bcell leukaemia induced by BCR-ABL1. Nat. Genet. 24, 57–60
Hepatitis B transmitted via urine? Hepatitis B virus (HBV) is a serious health threat, causing acute and chronic hepatitis. The number of virus carriers is estimated to exceed 300 million worldwide. The acute disease is often self-limiting, but 5–10% of infections progress into chronic hepatitis, which is associated with a high risk of liver cirrhosis and, eventually, liver carcinoma. The only treatments currently available for chronic HBV infection are interferon therapy and liver transplantation. Unfortunately, the former is expensive and the latter has serious medical consequences; at best, both are only partially successful. Because of its role as a major human pathogen, HBV has been the subject of intensive study, and many features of its structure and replication are understood. This is particularly striking in light of the difficulties in culturing HBV in vitro; consequently, much of our current knowledge comes from modern techniques of molecular biology. HBV is the prototype member of the recently defined family of viruses called the Hepadnaviridae, which replicate their DNA genomes by reverse transcription of an RNA intermediate. Although immunization against HBV is possible, it is unfortunate that an effective worldwide vaccination programme will be prohibitively expensive. Thus, limiting infections by understanding the risks associated with infectious individuals is important. Classically, there has been much documentation of vertical, sexual and parenteral transmission of HBV. However,
among young and pre-adolescent children, horizontal transmission without apparent parenteral exposure is a common mode of acquisition, and the basis of this route of infection has been unresolved. This problem has been addressed by Knutsson and Kidd-Ljunggren1, who have used a sensitive polymerase chain reaction (PCR) assay to identify HBV DNA in the urine of HBV carriers. Results show the detection of HBV DNA in urine, which raises the possibility that infectious virus particles are present. Earlier research has shown that, during HBV virus assembly, a quality control mechanism ensures that only replication competent particles are secreted from infected cells. Thus, it seems plausible that urine is a potential source of HBV infection. These results indicate that a high proportion of patients infected with HBV have HBV DNA detectable by PCR in their urine. Thus, urine from all HBV carriers could harbour infectious HBV. These findings might explain the horizontal transmission of HBV among young children, and must be considered seriously in matters of hospital hygiene and the risk of nosocomial transmission. 1 Knutsson, M. and Kidd-Ljunggren, K. (2000) Urine from chronic hepatitis B virus carriers: Implications for infectivity. J. Med. Virol. 60, 17–20 Roger Hewson PhD [email protected]
The literature page is designed to alert readers to recent primary papers that are important to biomedical researchers, particularly innovative, likely to have significant clinical impact, or controversial. A panel of senior active researchers is commissioned to select one or two papers published in the last six weeks that is within their area of expertise. If you are interested in joining this panel, send an e-mail message to the Editor at:
Kathryn L. Evans PhD [email protected]
1357-4310/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
[email protected]
141