{"title":"Constitutive activation of oncogenes by chromosomal translocations in B-cell derived tumors.","authors":"G Klein","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The mechanisms of chromosomal translocations and its role in Burkitt lymphoma (BL), mouse plasmacytoma (MPC) and rat immunocytoma (RIC) are discussed with particular emphasis on the following questions: 1) Does the cis-relationship between the c-myc oncogene and one of the 3 Ig-loci play a causative role in the genesis of these tumors? 2) How does the juxtaposition activate the myc-gene? 3) What is the functional role of the translocation in the tumorigenic process? Question 1) can be answered with some certainty. In BL, the translocation has been found in 100% of cases so far, with no difference between endemic or nonendemic, EBV-carrying or EBV-negative cases. One exceptional line, BJAB, can be disregarded, since it is not a typical BL. In RIC, all examined tumor had the translocations so far. Only 90% of the MPCs carry the translocations, but high resolution banding of some translocation negative MPCs has shown that they carry an interstitial deletion in the D2/D3 region of Chr. 15, corresponding to the myc locus. Molecular analysis showed a complex rearrangement that has led to the juxtaposition of c-myc and IgH-switch sequences. Sequencing data indicated that they must have arisen by at least two independent translocations and one inversion. A similarly complex rearrangement was found in the first RIC that has been examined. The regularity of the association between the translocation events and the tumors where they occur, together with the similarities between the human, mouse and rat systems can be interpreted by postulating that the activation of c-myc by the translocation represents an essential step in the genesis of these tumors. 2) The transposed myc gene becomes constitutively activated. In all probability, this renders the gene resistant to cell cycle and differentiation dependent regulations that govern its expression in the normal chromosomal location. 3) The hypothesis is advanced that the translocation affects B-cells at the point where an antigen activated cell is about to leave the proliferative process, upon the waning of the antigenic stimulus, and enters a program towards a long lived memory cell.</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S167-76"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14163478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y Zeng, J Fan, Q Zhang, P C Wang, D J Tang, S C Zhon, X W Zheng, D P Liu
{"title":"Detection of antibody to LAV/HTLV-III in sera from hemophiliacs in China.","authors":"Y Zeng, J Fan, Q Zhang, P C Wang, D J Tang, S C Zhon, X W Zheng, D P Liu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Using ELISA, Western blots and immunofluorescence techniques, we identified seropositivity for lymphadenopathy-associated virus/human lymphotropic virus-III (LAV/HTLV-III) in 4 of 18 hemophiliacs and 1 AIDS patient. The four seropositive patients had received factor VIII prepared by Armour Company. The hemophiliacs are all asymptomatic. Given this documentation of introduction of LAV/HTLV-III into China, a national surveillance program is underway.</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S147-9"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14235934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y Ishii, Y Kokai, A Yamaguchi, H Tsubota, K Kikuchi
{"title":"Surface marker expression of human B-cell lymphomas.","authors":"Y Ishii, Y Kokai, A Yamaguchi, H Tsubota, K Kikuchi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have generated a battery of monoclonal antibodies (MAbs) that distinguish different antigen molecules present in human B cells. Two antigen systems, termed L26 and L27, respectively, were expressed in most surface immunoglobulin-positive B cells and thus showed pan-B cell specificity. Two other antigens (L22 and L30) appeared to be expressed mainly on small resting B cells but not on large activated B cells. In contrast with L22 and L30, L29 and L4, the latter of which corresponds to OKT10, were not or little expressed on resting B cells, but were found on these B cells after activation either in-vivo or in-vitro with staphylococcal protein-A (SAC) plus interleukin-2 (IL-2) or with pokeweed mitogen (PWM). We also produced MAb (L10) that detected IL-2 receptors (IL-2R) consistently expressed on in-vitro activated B cells as described above. In contrast with L4, L10 and L29, L30 was lost from in-vitro-activated B cells, following the appearance of either L10 or L29 on these in-vitro-activated B cells. Then, we analyzed antigen profiles of B cell tumors using these MAbs as described above. Common acute lymphatic leukemia (CALL) expressed L4 and L30. B cell type chronic leukemia (B-CLL) and hairy cell leukemia (HCL) possessed most of the B cell antigens as described herein, and furthermore, HCL expressed IL-2R as detected by L10 MAb. In the case of B cell lymphomas, they were phenotypically divided into two groups, corresponding to either early or late activated B cells.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S87-93"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14616152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevention and treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative diseases in immune deficient patients.","authors":"D T Purtilo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prevention of EBV-associated lymphoproliferative diseases in immune deficient individuals is preferred; however, standard therapy for the B cell lymphomas has been successful. Chemotherapy must be given cautiously lest further immune compromise result in opportunistic infections. Recently, Acyclovir has decreased morbidity of patients with acute infectious mononucleosis in immune competent persons. In contrast, immunodeficient patients with X-linked lymphoproliferative (XLP) syndrome do not seem to respond favorably. Hence, a prospective study is underway using prophylactic immunoglobulin containing (EBV)-specific antibodies. The mortality rate is 85% following EBV infection in XLP due to fatal infectious mononucleosis associated with fulminant hepatitis and virus-associated hemophagocytic syndrome, acquired hypogammaglobulinemia or malignant B cell lymphoma. We can detect XLP by noting failure of switching from IgM to IgG antibody production on secondary challenge with bacteriophage phi X174. Also, linkage studies with the XLP locus using restriction fragment length polymorphisms are being done to detect affected males pre-EBV infection. Our rationale for prevention of phenotypes of XLP is based on observations that infants in tropical Africa and males with XLP do not develop EBV-induced diseases while neutralizing maternal antibodies are present. An EBV vaccine will be used, when available, in seronegative males with XLP. Prevention of acquired immune deficiency by screening blood for human immune deficiency virus, encouraging prudent life styles, development of specific immunosuppressive agents, development of new antiviral agents (i.e., DHPG), and identification of high risk seronegative patients offer possibilities for preventing life-threatening EBV-induced diseases.</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S177-81"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13581620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lymphotropic viruses, Epstein-Barr virus (EBV) and human T-cell lymphotropic virus-I (HTLV-I)/adult T-cell leukemia virus (ATLV), and HTLV-III/human immune deficiency virus (HIV) as etiological agents of malignant lymphoma and immune deficiency.","authors":"D T Purtilo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The ubiquitous, DNA herpesvirus, EBV, has B cell tropism and the geographically restricted RNA retrovirus, ATLV/HTLV-I has T cell tropism. Clinical descriptions by Burkitt and Takatsuki led to discovery of these viruses which infect silently early in life; however, ATLV is also transmitted to a spouse or by blood transfusion. In normal seropositive persons both viruses infect only 1 in about 10,000 B or T cells, respectively. EBV is associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and infectious mononucleosis. ATLV is associated with adult T cell leukemia/lymphoma and smoldering T cell lymphoma. EBV infects polyclonally and is controlled by multiple cellular and humoral control mechanisms. Escape from immune surveillance as in immune deficient African children with malaria, males with x-linked lymphoproliferative syndrome, organ transplant recipients, and AIDS patients permits conversion from polyclonal to oligoclonal and finally, monoclonal malignancy. T cell immune defects permit proliferation of cells which undergo molecular and/or cytogenetic alterations. In contrast to EBV, which is integrated and nonintegrated in B cells, ATLV is monoclonally integrated. Viral transforming proteins and immune suppressive substances are produced. Immune deficiency in silent carriers of ATLV and in those with smoldering ATL suggest that immune surveillance deters emergence of ATL. Prevention of primary infection by vaccination against these lymphotropic viruses, and use of immunotherapy and antiviral drugs may potentially retard conversion of infected B or T cells to monoclonal malignancy.</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S1-6"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14017949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Viruses, immunodeficiency, and human cancer. Proceedings of the sixth annual Sapporo Cancer Seminar. July 2-4, 1986, Sapporo, Japan.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S1-195"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14945418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical, immunological, and virological aspects in Japanese hemophiliacs and AIDS patients.","authors":"T Abe","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To date, 16 cases of AIDS have been officially reported in Japan: 8 of them were hemophiliacs and the others were male homosexuals. We had two hemophiliacs with AIDS, and describe these cases in this paper. One was a 48-year-old man with hemophilia B and the other was a 62-year-old man with hemophilia A. Both had ARC symptoms before developing overt and fatal opportunistic infections, candidiasis and a combination of atypical mycobacteriosis and aspergillosis. Impairment of cellular immunity such as lowered T4/T8 ratio, depressed lymphocyte response to mitogen and NK activity, and negative PPD skin reaction was evident in both patients. Anti-LAV/HTLV-III antibodies were detected in their sera, and the retrovirus was demonstrated in the lymph nodes and other organs on the postmortem electron microscopic examination. The assay for anti-LAV/HTLV-III on 70 other hemophiliacs in our clinic revealed seropositivity up to 50%. The seropositive group showed a significantly lower T4/T8 ratio on an average than the seronegative group. The prevalence of seropositivity for antibodies to other viruses including HBV, EBV, CMV, PV, and HTLV-I was markedly higher in the hemophiliacs. In LAV/HTLV-III seropositive hemophiliacs, however, no distinct correlation was found between T4/T8 ratio and the presence of antibodies to other viruses. There is a retrospective study to show that LAV/HTLV-III seropositive hemophiliacs appeared as early as 1980 in Japan. For prevention of LAV/HTLV-infection in hemophiliacs via blood products, heat-treated factor concentrates have recently become available. In a trial of the heat-treated products on 15 \"virgin\" hemophiliacs, no seroconversion has occurred thus far.</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S141-6"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14235933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Miwa, K Shimotohno, M Takano, H Shima, S Watanabe, M Tosu, T Sekiguchi, M Shimoyama, T Sugimura
{"title":"Structure of HTLV and its biological function in leukemogenesis of adult T-cell leukemia.","authors":"M Miwa, K Shimotohno, M Takano, H Shima, S Watanabe, M Tosu, T Sekiguchi, M Shimoyama, T Sugimura","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>There is a high homology of nucleotide sequence between 3' two-thirds of the X (or pX) regions of human T-cell leukemia virus (HTLV)-I, and of HTLV-II. Monoclonal antibody against p41 coded from X-IV, an open reading frame of X region of HTLV-I, was established. Two proteins coded by Xb, one of the open reading frames in X region of HTLV-II, were newly identified as p24 and p26. The expression of X protein of HTLV-II in the reconstituted mouse embryonal carcinoma cell line, which shows myoblastic morphology, reverted the morphology to that of the original embryonal carcinoma cells. This suggests that the function of X protein is to disturb the regulation of cell lineage determination. Leukemogenesis of adult T-cell leukemia (ATL) is also considered to consist of multisteps, in which HTLV-I constitutes one step, other factors also being involved. Even the role of HTLV-I factor could be similarly played by other factor(s). In agreement with this hypothesis, there are patients with ATL without associated HTLV-I.</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S61-70"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14019381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanism of the gene expression of HTLV-I and its association with ATL.","authors":"M Yoshida, J Fujisawa, J Inoue, M Seiki","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL) and a trans-acting viral function was proposed to be involved in ATL development because of the non-specific provirus integration in leukemic cells and the frequent immortalization of helper T-cells by in vitro infection. An extra sequence \"pX\" in the HTLV-1 genome codes for three proteins, p40x-, p27x- and p21x-, and the p40x- is trans-activator of transcription from the viral LTR. A sequence of 21 bp repeats in the LTR was found to be an enhancer and respond to the trans-activation by p40x-. The transient expression of p40x- also activates a cellular gene for interleukin 2 receptor (IL-2R) in helper T-cell lines. This induction of IL-2R may explain the mechanism of preferential growth of HTLV-1 infected cells and may be an early event of ATL development. For practical purposes, the env gene fragments was expressed in E. coli as fusion proteins with beta-galactosidase. Using these fusion proteins, a diagnostic system detecting anti-env antibodies was developed. Immunization of monkeys with these envelope-fusion proteins protected the monkeys from the viral infection, suggesting possible usage of envelope proteins as vaccine.</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S71-8"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14163483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevalence of antibodies to AIDS-associated retrovirus in in- and out-patients in Japan.","authors":"N Ikegami","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Serum specimens from 252 recipients of factor VIII and/or factor IX (237 hemophiliacs and 15 nonhemophiliacs), 99 blood transfusion recipients, 269 chronic diseases, and 366 healthy subjects (included blood donors, hospital personnel and family members of hemophiliacs) were tested for reactivity to lymphadenopathy-associated virus/T-lymphotropic retrovirus type III (LAV/HTLV-III) by ELISA test kit (Abbott), and the presence of the antibodies to LAV/HTLV-III was confirmed by indirect immunofluorescence assay (IFA). Seropositivity rates were 38.4% (91 of 237) in hemophiliacs, 13.3% (2 of 15) in nonhemophiliac recipients of factor VIII and/or factor IX, and 8% (2 of 27) in male homosexuals. None of the other patients and healthy individuals had antibodies to LAV/HTLV-III. In serological follow-up study on 40 seronegative and 10 seropositive hemophiliacs, 4 of the seronegative hemophiliacs converted to seropositive, and 7 of seropositive hemophiliacs had the antibody titers elevated by 2 to 4 fold within the period for 3.5 to 13 months after first blood samplings. Comparative analysis of the absolute numbers of T helper (T4) and T suppressor (T8) lymphocytes between the seropositive and seronegative hemophiliacs revealed that more than 50% of both seropositive and seronegative hemophiliacs had lower T4 lymphocyte numbers and higher T8 lymphocyte numbers than those of normal subjects. Particularly, over 80% of seropositive hemophiliacs had lower T4 lymphocyte numbers. Two Japanese AIDS cases (a hemophiliac B and a male homosexual) were found in the present study. Both died of pneumonia, and were confirmed officially as AIDS cases.</p>","PeriodicalId":77660,"journal":{"name":"AIDS research","volume":"2 Suppl 1 ","pages":"S29-34"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14235936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}