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

In an attempt to gain some insight into the many factors influencing antibody gene expression in human B cell lines, we have examined in detail the relationship between cell surface phenotype, cytokines, and the growth and antibody-producing capacity of a panel of immortalized human B cell lines. The cell panel comprised lines secreting either high or low titers of antibodies against Rhesus D, hepatitis B surface, and tetanus toxoid antigens. All the transformed cell lines exhibited a cell surface phenotype characteristic of well-differentiated peripheral blood cells strongly expressing CD23 and CD38 while weakly expressing CD10 and CD21. There was no obvious relationship between the antibody-body-secreting and proliferative capacity of the cell lines and their cell surface phenotype. Antibody secretion by the cells was rarely improved by the addition of a wide range of doses of recombinant IL-2, IL-4, or IL-6. In addition, such treatment frequently inhibited proliferation. Supernatants from some of the cell lines promoted the growth of unrelated cell lines but failed to influence antibody production. Such supernatants contained the highest concentration of IL-1, TNF beta, TGF beta, and soluble CD23. In contrast, the heterohybrid supernatant which inhibited cell growth secreted low levels of these cytokines. None of the cell lines secreted detectable amounts of IL-2, IL-4, INF gamma, or GCSF. There was no obvious relationship between cytokine production and antibody secretion. Finally, LPS had a slight but variable effect on antibody secretion but failed to influence cell growth.
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PMID:Cell surface phenotype, cytokines, and antibody gene expression in immortalized human B cell lines. 210 58

Fifty-four patients with acute lymphoblastic leukemia (ALL: 1 relapse, 21 high risk first complete remission (CR 1), 29 second CR (CR 2), and 3 third CR (CR 3) were treated by autologous bone marrow transplantation at three centers. Before storage, the marrows were purged ex vivo with appropriate MAbs RFAL3 (CD10), SB4 (CD19), and RFT2 (CD7), with rabbit serum as the source of complement. All patients received total body irradiation either 750 cGy (middose 15 cGy/min) as a single fraction or 6 x 200 cGy over 3 days (midline dose 16 cGy/min) with lung shielding from 1,100 cGy. The patients who received 750 cGy also received cyclophosphamide or the same drug combined with ara-C or prednisone, teniposide, vincristine, ara-C, and dauno-rubicin. Patients receiving 200 cGy x 6 also received either cyclophosphamide, melphalan, or ara-C and cyclophosphamide. Three patients died of post transplantation complications (interstitial pneumonia, hepatitis B liver necrosis, or encephalitis). This gives a procedure related mortality of 5%. Nonfatal complications were 10 cases of septicemia, 4 interstitial pneumonia, 2 interstitial nephritis, 1 veno-occlusive disease (VOD), and 1 case of hemolytic uremic syndrome. The patient autografted in relapse died of relapse within 2 months. In CR 1 6 or 21 patients have had a relapse, and the actuarial leukemia free survival from CR is 65% (median follow-up 16 months). In CR 2-3 18 of 32 patients have relapsed, and the actuarial leukemia free survival is 31% (median follow-up 18.5 months) from CR. Twelve patients have achieved an inversion, (i.e., present CR longer than previous CR), with a further seven with the potential to achieve inversion. We conclude that ABMT in high risk ALL has a low procedure related mortality (5%), and there are few other complications. The in vitro purging with MAbs had no adverse effect on bone marrow reconstitution, but this study was not designed to demonstrate its antileukemic efficacy. The actuarial leukemia free survival time in the present study for patients with high risk CR 1 and the inversions in CF 2-3 are promising and indicate a potential beneficial effect of ABMT.
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PMID:Autologous bone marrow transplantation with monoclonal antibody purged marrow for high risk acute lymphoblastic leukemia. 266 54

Pleural effusion presentation of posttransplant lymphoproliferative disorder (PTLD) is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement, and are associated with an aggressive clinical course. We report on a case of primary effusion PTLD in a 70-yr-old male liver transplant recipient with a history of hepatitis B infection. Cytomorphologically, the pleural fluid specimen showed a monomorphous population of intermediate to large-sized transformed lymphoid cells, with irregular multilobated nuclear contours and readily identifiable mitotic figures. Flow cytometric immunophenotypic studies revealed a CD5-negative, CD10-negative, lambda immunoglobulin light chain-positive, monoclonal B-lymphocyte (CD19-positive/CD20-positive) population. The immunocytochemical stain for CD30 antigen was negative. In situ hybridization study for Epstein-Barr virus (EBV) early RNA (EBER) and Southern blot analysis for EBV terminal repeat sequences were both positive. Southern blot analysis for human herpes virus-8 (HHV-8) was negative. No solid-organ PTLD was identified, and the cytologic results supported the diagnosis of primary effusion PTLD. Immunosuppression was decreased, and 8 mo following the diagnosis of pleural fluid PTLD, the patient was stable and his pleural effusion had markedly diminished. Recognition of primary effusion PTLD and its distinction from PTLD secondarily involving the body fluids and from other lymphomas is important, since the behavior and prognosis appear different.
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PMID:Primary pleural effusion posttransplant lymphoproliferative disorder: Distinction from secondary involvement and effusion lymphoma. 1146 13

Three types of recombinant pre-S antigens (i.e., pre-S1S2) of hepatitis B virus (HBV) were synthesized in Saccharomyces cerevisiae and secreted into extracellular medium: wild type (pre-S1S2) and two mutant antigens, pre-S1 degrees S2 (Asn15Gln) and pre-S1 degrees S2 degrees (Asn15Gln and Asn123Gln). An N-terminus sequence (Ser5-Ala28) of human interleukin 1 beta (hIL-1 beta) was used as synthetic prosequence of recombinant HBV surface antigen (pre-S), secreted from S. cerevisiae. The expression cassette comprised the signal peptide of the killer toxin of Kluyveromyces lactis, the synthetic prosequence above, KEX2 dibasic endopeptidase cleavage site (-Lys-Arg-), and the surface antigen. The recombinant pre-S1S2 and pre-S1 degrees S2 were secreted in the hyper-mannosylated form, while the recombinant pre-S1 degrees S2 degrees was produced without N-glycosylation. It has been demonstrated that the two particular N-linked glycans at Asn15 and Asn123 interfered with the B-cell response to the HBV-derived pre-S1S2, resulting in low titers of pre-S1S2-neutralizing antibodies. This problem was overcome by eliminating both of the N-glycosylation signals. Despite enhanced immunogenicity, the recombinant pre-S1 degrees S2 degrees showed two major problems: (1) inefficient Kex2 cleavage process in the secretory pathway and (2) the severe proteolytic degradation by yeast proteases. The efficiency of Kex2 cleavage increased dramatically by removing N-glycosylation signal in the synthetic prosequence, but the proteolysis of pre-S1 degrees S2 degrees was somewhat inevitable. Further systematic approaches including modulation of degree of N-glycosylation or relocation of N-glycosylation sites in the recombinant pre-S1S2 may make it possible to achieve both enhanced immunogenicity and resistance towards proteolytic degradation of the secreted pre-S antigen.
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PMID:The influence of glycosylation on secretion, stability, and immunogenicity of recombinant HBV pre-S antigen synthesized in Saccharomyces cerevisiae. 1265 34

Envelope protein precursors of many viruses are processed by a basic endopeptidase to generate two molecules, one for receptor binding and the other for membrane fusion. Such a cleavage event has not been demonstrated for the hepatitis B virus family. Two binding partners for duck hepatitis B virus (DHBV) pre-S envelope protein have been identified. Duck carboxypeptidase D (DCPD) interacts with the full-length pre-S protein and is the DHBV docking receptor, while duck glycine decarboxylase (DGD) has the potential to bind several deletion constructs of the pre-S protein in vitro. Interestingly, DGD but not DCPD expression was diminished following prolonged culture of primary duck hepatocytes (PDH), which impaired productive DHBV infection. Introduction of exogenous DGD promoted formation of protein-free viral genome, suggesting restoration of several early events in viral life cycle. Conversely, blocking DGD expression in fresh PDH by antisense RNA abolished DHBV infection. Moreover, addition of DGD antibodies soon after virus binding reduced endogenous DGD protein levels and impaired production of covalently closed circular DNA, the template for DHBV gene expression and genome replication. Our findings implicate this second pre-S binding protein as a critical cellular factor for productive DHBV infection. We hypothesize that DCPD, a molecule cycling between the cell surface and the trans-Golgi network, targets DHBV particles to the secretary pathway for proteolytic cleavage of viral envelope protein. DGD represents the functional equivalent of other virus receptors in its interaction with processed viral particles.
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PMID:Glycine decarboxylase mediates a postbinding step in duck hepatitis B virus infection. 1474 52

A rare variant of hepatocellular carcinoma (HCC) is encountered that produces small cirrhosis-like nodules diffusely throughout the liver (CL-HCC), instead of a larger evident mass. This pattern remains undetected as carcinoma clinically and radiographically and is unexpectedly discovered after liver transplantation in the explanted native liver. We studied 10 such cases (9 males and 1 female, age 35 to 80 y) from 4 medical centers. The pretransplant clinical, laboratory, and radiographical studies were reviewed to determine the cause and stage of liver disease, alpha-fetoprotein (AFP) levels, and detectability of a mass on imaging. All 10 cases had underlying cirrhosis of varying etiology [3 hepatitis C virus (HCV), 3 alcoholic hepatitis, 1 hepatitis B virus, 1 autoimmune, and 2 mixed HCV/alcoholic hepatitis and hemochromatosis/HCV] and underwent orthotopic liver transplantation with no preoperative clinical suspicion of HCC. Ultrasound and/or dynamic imaging showed cirrhosis and no definite HCC. AFP levels were only mildly elevated in only 3 of 10 cases (144, 150, and 252 ng/mL). Grossly, there were innumerable (from about 20 to >1000) small CL-HCC nodules (0.2 to 0.6 cm) scattered among cirrhotic nodules. Histologically, these were well or moderately differentiated HCC, often with pseudoglandular pattern, perinodular sclerotic rims, cholestasis, frequent Mallory bodies, and small vessel invasion. In addition to the usual HCC immunophenotype, CL-HCC showed frequent ubiquitin and cytoplasmic and membranous CD10 positivity, relatively low Ki-67 proliferative index and absence of AFP immunohistochemically. CL-HCC warrants recognition as a unique HCC variant that evades pretransplant detection despite massive tumor burden, mimics cirrhotic nodules, and shows some uncommon pathologic and immunophenotypical characteristics.
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PMID:Diffuse cirrhosis-like hepatocellular carcinoma: a clinically and radiographically undetected variant mimicking cirrhosis. 2046 69

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder, which has been characterized by the World Health Organization as a new entity. Although PBL is most commonly seen in the oral cavity of human immunodeficiency virus (HIV)-positive patients, it can also be seen in extra-oral sites in immunocompromised patients who are HIV-negative. Here we present a rare case of PBL of the small intestine in a 55-year-old HIV-negative male. Histopathological examination of the excisional lesion showed a large cell lymphoma with plasmacytic differentiation diffusely infiltrating the small intestine and involving the surrounding organs. The neoplastic cells were diffusely positive for CD79a, CD138 and CD10 and partly positive for CD38 and epithelial membrane antigen. Approximately 80% of the tumor cells were positive for Ki-67. A monoclonal rearrangement of the kappa light chain gene was demonstrated. The patient died approximately 1.5 mo after diagnosis in spite of receiving two courses of the CHOP chemotherapy regimen. In a review of the literature, this is the first case report of PBL with initial presentation in the small intestine without HIV and Epstein-Barr virus infection, and a history of hepatitis B virus infection and radiotherapy probably led to the iatrogenic immunocompromised state.
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PMID:Plasmablastic lymphoma of the small intestine: case report and literature review. 2323 45

Primary effusion lymphoma (PEL) is a rare subtype of non-Hodgkin lymphoma that proliferates in body cavities without detectable masses. PEL is universally associated with human herpes virus-8 (HHV-8) infection and has an aggressive prognosis. Recently, an HHV-8-unrelated PEL-like lymphoma that usually occurs in elderly individuals and follows a more indolent prognosis has been reported, and it is treated as a disease distinct from PEL. However, its pathogenesis and prognostic factors have not been sufficiently clarified. In PEL-like lymphoma accompanied by Epstein-Barr virus (EBV) infection, latent infection types are not mentioned in the literature. Herein, we report the case of an 85-year-old Japanese man with pericardial PEL-like lymphoma who showed good improvement in condition for 24 months after pericardiocentesis without chemotherapy. Serological test results were positive for EBV capsid antigen and EBV nuclear antigen 2 (EBNA2), but negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. The disease phenotype and EBV infection mechanism were immunohistochemically investigated by the cellblock prepared from pericardial effusion. Atypical cells were positive for CD20, CD30, CD45, BCL2, MUM1, EBNA2, latent membrane protein 1, and EBV-encoded RNA (on in situ hybridization), but negative for CD3, CD5, CD10, CD138, cytokeratin AE1/AE3, and HHV-8. Accordingly, this case was considered to be a B-cell activated phenotype with a type III latent EBV infection. Type III latent EBV infection is unusual in PEL.
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PMID:Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma in the pericardium: A case with latency type III Epstein-Barr virus infection showing good prognosis without chemotherapy. 2638 78

Hepatitis B virus (HBV) is the prototype of hepadnaviruses, which can be subgrouped into orthohepadnaviruses infecting mammals, avihehepadnaviruses of birds, metahepadnaviruses of fish, and herpetohepadnaviruses of amphibians and reptiles. The middle (M) envelope protein and e antigen are new additions in the evolution of hepadnaviruses. They are alternative translation products of the transcripts for small (S) envelope and core proteins, respectively. For HBV, e antigen is converted from precore/core protein by removal of N-terminal signal peptide followed by furin-mediated cleavage of the basic C-terminus. This study compared old and newly discovered hepadnaviruses for their envelope protein and e antigen expression or processing. The S protein of bat hepatitis B virus (BHBV) and two metahepadnaviruses is probably myristoylated, in addition to two avihepadnaviruses. While most orthohepadnaviruses express a functional M protein with N-linked glycosylation near the amino-terminus, most metahepadnaviruses and herpetohepadnaviruses probably do not. These viruses and one orthohepadnavirus, the shrew hepatitis B virus, lack an open precore region required for e antigen expression. Potential furin cleavage sites (RXXR sequence) can be found in e antigen precursors of orthohepadnaviruses and avihepadnaviruses. Despite much larger precore/core proteins of avihepadnaviruses and their limited sequence homology with those of orthohepadnaviruses, their proximal RXXR motif can be aligned with a distal RXXR motif for orthohepadnaviruses. Thus, furin or another basic endopeptidase is probably the shared enzyme for hepadnaviral e antigen maturation. A precore-derived cysteine residue is involved in forming intramolecular disulfide bond of HBV e antigen to prevent particle formation, and such a cysteine residue is conserved for both orthohepadnaviruses and avihepadnaviruses. All orthohepadnaviruses have an X gene, while all avihepadnaviruses can express the e antigen. M protein expression appears to be the most recent event in the evolution of hepadnaviruses.
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PMID:Tracing the evolutionary history of hepadnaviruses in terms of e antigen and middle envelope protein expression or processing. 3178 5

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. It has been hypothesized that chronic hepatitis C virus (HCV) infection stimulates IGH-BCL2 clone proliferation, leading to development of FL. Furthermore, regression of FL after antiviral treatment without chemotherapy has been reported in HCV-infected patients. To clarify the relationship between HCV and FL, we compared the prevalence of IGH-BCL2 translocation and other clinicopathologic characteristics between HCV-infected and HCV-uninfected FL patients and determined the impact of HCV eradication on the oncologic outcomes of HCV-infected FL patients. The study included HCV-infected patients (cases) with FL seen at our institution during 2004-2018. Cases were matched with HCV-uninfected FL patients (controls) according to year of lymphoma diagnosis, sex, and hepatitis B serology. We studied 19 cases and 57 controls. More cases than controls had splenic involvement of FL (26% vs 5%, P = 0.02), higher histologic grade (grade 3 in 56% vs 24%, P = 0.01), absent or weak CD10 expression (42% vs 11%, P = 0.005), and absent BCL2 expression (33% vs 4%, P = 0.004). Compared to controls, cases had a lower rate of detection of IGH-BCL2 translocation (31% vs 68%, P = 0.02). Finally, cases with a sustained virologic response (virologic cure of HCV) had a better 10-year overall survival rate than did cases not treated with antivirals or controls (P = 0.001). In conclusion, HCV-infected patients with FL have unique clinicopathologic characteristics including improved overall survival with HCV eradication. The pathogenesis of FL in HCV-infected patients seems unrelated to antiapoptotic effect of IGH-BCL2 rearrangement.
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PMID:Clinicopathologic characteristics of follicular lymphoma in hepatitis C virus-infected patients. 3219 14


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