Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of a pasteurization step (heating in solution to 60 degrees C for 10 h) makes it possible to inactivate viruses, thus increasing the safety of the preparations. Using Factor XIII concentrate solution, it can be shown that hepatitis B virus and 10 other virus species are inactivated. Pasteurized Factor XIII was produced from starting material containing a total of 10(5.7) CID50 hepatitis-B virus (10(3.5) CID50/ml; CID = chimpanzee infectious dose). This Factor XIII preparation was injected in 4 chimpanzees; they remained healthy over an observation period of 37 weeks, whereas the 2 chimpanzees that received nonheated starting material developed hepatitis B. Furthermore, Rous-sarcoma, Epstein-Barr, cytomegalo, herpes simplex, measles, and rubella virus added to Factor XIII solution are inactivated by pasteurization within 2 h, mumps virus within 8 h, and adeno, polio, and vaccinia virus within 10 h. Pasteurizing of clotting factor preparations during the manufacturing process is a suitable for inactivating viruses and thereby increasing the safety of the preparations.
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PMID:[Inactivation of viruses in Factor XIII concentrate by pasteurization]. 654 27

Liver cancer is an uncommon indication for liver transplantation in children. Between 1986 and 1995, five children with hepatocellular cancer (HCC), three with hepatoblastoma (HEP), and one with sarcoma were referred to the transplant service. All nine tumors were considered unresectable. Four of the five children with HCC had underlying predisposing conditions (2 hepatitis B, 1 biliary atresia, 1 tyrosinemia). Preoperative evaluation of all patients included careful radiological screening and pretransplantation laparotomy for staging. Two patients with HCC were excluded from further consideration because of intraabdominal spread. Three patients had transplantation (mean age, 6.0 +/- 7.1 years), and all have survived for 1 to 5 years with no evidence of recurrence. Three patients with HEP were assessed (mean age 2.0 +/- 1 years); two had stage 4 disease and one had stage 3. All three received preoperative chemotherapy. The two with stage 4 had thoracotomies as part of their assessment. Two of three patients had a significant decrease in the size of the primary tumor during the waiting period. These two patients and one with stage 4 disease have survived more than 2 years since transplantation, with no recurrence. The third patient had recurrence within 2 months of transplantation. In summary, liver transplantation should be considered for all children who have unresectable hepatic malignancies, given the 83% survival rate and no evidence of tumor recurrence. Stage 4 disease in HEP does not necessarily exclude patients from transplantation. Early referral is encouraged so that tumor spread beyond the liver is minimized.
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PMID:Results of liver transplantation in children with unresectable liver tumors. 878 17

2',3'-Dideoxyadenosine (ddA), 2',3'-didehydro-2',3'-dideoxyadenosine (d4A) and their lipophilic 5'-monophosphate triester (aryloxyphosphoramidate) prodrugs were evaluated for their anti-retrovirus and anti-hepatitis B virus activity in various cell culture models. The aryloxyphosphoramidate derivatives of ddA (Cf 1093) and d4A (Cf 1001) showed markedly superior (100-1000-fold) efficacies than the parent drugs against human immunodeficiency virus type 1 (HIV-1), HIV-2, simian immunodeficiency virus (SIV), Moloney murine sarcoma virus (MSV) and human hepatitis B virus (HBV) replication regardless of the cell type in which the virus replication was studied (i.e., human T-lymphocyte CEM, MT-4, Molt/4 and C8166 cells, peripheral blood lymphocytes (PBL), monocyte/macrophages (M/M), murine embryo fibroblasts and human hepatocyte cells). Also the selectivity index (ratio of cytotoxic concentration/antivirally effective concentration) of both aryloxyphosphoramidate prodrugs was markedly increased. In particular the d4A prodrug Cf 1001 showed a selectivity index of 300-3000 as compared with 2-3 for the parental d4A in established laboratory cell lines. Also Cf 1001 had a selectivity index of 400-650 in HIV-1-infected PBL and M/M, respectively. Both Cf 1001 and Cf 1093 were equally efficient as 3TC (lamivudine) in inhibiting HBV replication in hepatocytes, and rank among the most potent HIV and HBV inhibitors reported so far in cell culture.
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PMID:Conversion of 2',3'-dideoxyadenosine (ddA) and 2',3'-didehydro-2',3'-dideoxyadenosine (d4A) to their corresponding aryloxyphosphoramidate derivatives markedly potentiates their activity against human immunodeficiency virus and hepatitis B virus. 923 55

To overcome the low oral bioavailability of the highly potent and selective antiretroviral agent (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA), a new lipophilic ester derivative, i.e., the bis(isopropyloxycarbonyloxymethyl)-ester [bis(POC)-PMPA], was prepared. The usefulness of bis(POC)-PMPA as an oral prodrug for PMPA was investigated in the intestinal mucosa Caco-2 cell monolayer model. The total transport of bis(POC)-PMPA was 2.7%, whereas it was less than 0.1% for PMPA. Bis(POC)-PMPA was considerably metabolized inside the epithelial cells, since the majority of the compound was recovered after transport in the form of the monoester metabolite [mono(POC)-PMPA]. In contrast, bis(POC)-PMPA was relatively resistant to degradation at the luminal side of the Caco-2 cells. Pharmacokinetic studies with mice showed that the oral bioavailability of bis(POC)-PMPA (calculated from the curves of the concentration of free PMPA in plasma) was 20%. Neither bis(POC)-PMPA nor mono(POC)-PMPA could be recovered in plasma, suggesting the efficient release of the active drug PMPA after oral administration of bis(POC)-PMPA. Severe combined immunodeficient (SCID) mice infected with Moloney murine sarcoma virus (MSV) and treated orally with bis(POC)-PMPA for 5 or 10 days (dosages, 50, 100, or 200 mg of PMPA equivalent per kg of body weight per day) showed a significant delay in MSV-induced tumor appearance and tumor-associated death. The antiviral efficacy of oral bis(POC)-PMPA was related to the dosage and treatment period and was not significantly different from that of subcutaneous PMPA given at an equivalent dose. The favorable pharmacokinetic profile, marked antiviral efficacy, and low toxicity make bis(POC)-PMPA an attractive oral prodrug of PMPA that should be further pursued in clinical studies with patients infected with human immunodeficiency virus or hepatitis B virus.
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PMID:Antiretroviral efficacy and pharmacokinetics of oral bis(isopropyloxycarbonyloxymethyl)-9-(2-phosphonylmethoxypropyl)adenine in mice. 966 Sep 84

Chronic infection with hepatitis B virus (HBV) in humans is strongly linked to the development of hepatocellular carcinoma (HCC). Activation of growth-regulatory genes may play a crucial role in carcinogenesis. Proto-oncogene expression has been shown to be higher in HCC tissue with integrated HBV DNA than in the normal liver. Earlier, we showed that the 3' end of the HBV major surface gene (S) (426-855 nucleotides of the S region) is a transactivator of the X promoter-enhancer regulatory element in co-transfection experiments. This region expresses a truncated carboxy terminal S protein extending from amino acid residues 102 to 226. In this study, the truncated S protein (trc-S) was examined for its enhancing activity on several viral and cellular regulatory elements. The results indicate that trc-S activates rous sarcoma virus long terminal repeat (LTR), human T-lymphotropic virus 2 LTR, human immunodeficiency virus 1 LTR, and the c-jun and c-fos promoters. Electrophoretic mobility shift assays carried out to investigate its DNA-binding properties established that trc-S binds to HBV X promoter and oligonucleotides representing binding sites for the AP1 and TFIID transcription factors. The specificity of this interaction was confirmed by using competition experiments and supershift assays. These experiments suggest that trc-S is a transactivator of several cellular and viral promoters and that this activity is mediated by direct interaction with DNA.
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PMID:Hepatitis B virus surface (S) transactivator with DNA-binding properties. 1074 25

A patient with cervical non-Hodgkin lymphoma was treated with chemotherapy. Fourteen months after the diagnosis of the lymphoma, an endometrial adenocarcinoma was detected as a secondary malignant tumor. The patient was treated with surgery followed by radiotherapy. Approximately 7 years after the diagnosis of endometrial cancer, vaginal invasive squamous cell carcinoma was diagnosed as the third primary malignancy, and a second-line palliative radiotherapy was applied. Seven months after the last radiotherapy, postradiational sarcoma in the vagina was diagnosed. Congenital and acquired immune system disorders, viral oncogenes, and various human leukocyte antigen (HLA) types were investigated. Total blood count and lymphocyte subset analysis were performed, and CD4+ lymphopenia was detected. Serologic tests were carried out for human immunodeficiency virus, hepatitis B virus, human papillomavirus, Epstein-Barr virus, and herpes simplex virus infection. Epstein-Barr virus viral capsid antigen IgG was found positive. Low-risk human papillomavirus panel was detected by Hybrid Capture method in the cervical smear. The HLA investigation revealed HLA-A2, HLA-A3, HLA-B57, HLA-B35, HLA-B4, HLA-B6, HLA-DR3, HLA-DR1, HLA-DR51, HLA-DR52, HLA-DQ6(1), and HLA-DQ7(3). The patient died because of the disease.
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PMID:A case with multiple gynecological malignancies. 1582 28

Cancer therapy and supportive measures entail the risk of infection with hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV). The objective of this analysis was to establish the incidence of infections with these viruses during antineoplastic treatment in our paediatric sarcoma patients, who are being followed-up within the Late Effects Surveillance System (LESS), which prospectively registers sequelae of therapy for Ewing's-, soft tissue- and osteosarcoma in patients treated in Germany, Austria and Switzerland within the trials EICESS-92/EURO-E.W.I.N.G.-99, CWS-96/CWS-2002P and COSS-96. We studied 264 eligible relapse-free paediatric patients [median age at diagnosis 14.3 (IQR 11.1-16.4) years], treated from January 7, 1998 until April 24, 2004. According to the LESS protocol, serological examinations for HBV, HCV and HIV were scheduled 4 weeks and 6 months after cessation of antineoplastic treatment. The median follow-up was 20.6 (IQR 12.4-26) months. None of the patients was reported to have acquired HBV, HCV or HIV during antineoplastic treatment. Blood donor screening and prophylactic measures employed in Germany, Austria and Switzerland to prevent infections of cancer patients with HBV, HCV and HIV seem to be very effective, having fully prevented new infections in this large cohort of paediatric sarcoma patients.
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PMID:Prospective evaluation of hepatitis B, C and HIV infections as possible sequelae of antineoplastic treatment in paediatric sarcoma patients: a report from the Late Effects Surveillance System. 1646 31

A line of research beginning in the early 1960s with the observation that West Nile virus and, later, several strains of rabies virus could inhibit the development of the Rous sarcoma virus-induced tumor in the wing-web of chicken (a "sarcoma-blockade") eventually culminated in the characterization of a 14-kDa circulating anti-sarcoma and anti-viral activity christened "plasma factor" (PF) which, unlike the interferons, inhibited the replication of diverse RNA-containing viruses, but not of any DNA-containing viruses. The possibility that this 14 kDa protein represented a novel antiviral cytokine has been strengthened by analysis of partial amino acid sequencing data which suggest that this 14-kDa cytokine may correspond to the 127-amino acid-long chicken YB2-like protein (Locus: XP_423576) deduced very recently from the genomic sequencing of chicken. Biologically, proteins of the Y-box family (such as chicken YB1 and YB2) not only bind DNA and thus regulate transcription but also bind single-stranded RNA in a sequence-specific and reversible manner, repress viral RNA translation, inhibit retroviral transformation of chicken fibroblasts, and are known to regulate transcription of human immunodeficiency virus and hepatitis B virus. Taken together, the available data point to a novel anti-viral cytokine with a novel mechanism of action.
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PMID:Is the anti-sarcoma and anti-viral cytokine "plasma factor" a novel chicken Y-box protein? 1713 7

A middle aged chronic alcoholic presented with deep jaundice, markedly enlarged and tender spleen with leukoerythroblastic blood picture and bone marrow biopsy showing mild fibrosis. He was tested negative for HIV, hepatitis B and C viruses. Besides very high serum bilirubin, alkaline phosphatase was raised four times the normal value. Contrast enhanced CT showed enlarged spleen and liver with multiple heterogenous lesions in spleen and tiny hypo-dense lesions in liver. In hospital, he developed haemolytic uraemic syndrome and succumed to his illness. At autopsy spleen weighed 5200 gms and variegated in appearance due to large areas of necrosis and whitish tumour nodules. Histology revealed morphology of an angiosarcoma. Liver was also infiltrated by the tumour mainly in and around portal tract areas.
Sarcoma 2003
PMID:Splenic angiosarcoma presenting with jaundice, ascites and bone marrow fibrosis. 1852 85

A 32-year-old G6P5 (hepatitis B carrier, of African origin) with a spontaneous twin pregnancy gave birth at the 37th gestational week. Four hours later she collapsed. Upon an emergency laparotomy, right liver lobe rupture and later massive liver necrosis were diagnosed. Four days later, a liver transplantation was performed. She was discharged from the hospital 38 days after her delivery, four laparotomies, and having received 179 units of red blood cells, 221 units of fresh frozen plasma, 144 units of platelets, and various separate clotting concentrates. As a result of immune suppression medication, she later developed diabetes, sarcoma Kaposi, a Pneumocystis carinii pneumonia, and coenurosis. Four years later, she is, however, in a relatively good condition.
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PMID:Long-term survival after postpartum liver rupture and necrosis requiring liver transplantation in a twin pregnancy. 1884 88


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