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B Shiramizu

Publications and source records attributed to B Shiramizu.

16 recordsLinked to original sources
PubMed2001

Mitochondrial DNA decrease in subcutaneous adipose tissue of HIV-infected individuals with peripheral lipoatrophy.

OBJECTIVE: To determine whether the peripheral fat wasting (lipodystrophy), which is seen in association with highly active antiretroviral therapy (HAART) that includes a nucleoside reverse transcriptase inhibitor (NRTI), is associated with a decrease in subcutaneous adipose tissue mitochondrial DNA (mtDNA) content or with large mtDNA deletions or insertions. DESIGN: A four cohort cross-sectional study. METHODS: The mtDNA content of subcutaneous fat tissue from the neck, abdomen and thigh was determined by polymerase chain reaction utilizing the amplification of three different mtDNA fragments. The results from HIV-infected patients with peripheral fat wasting following more than 6 months of NRTI-containing HAART were compared with the results from three different control cohorts: HIV-infected patients with a similar treatment history without lipodystrophy; HIV-infected patients naive to antiretroviral therapy and HIV sero-negative participants. RESULTS: A decrease in mtDNA content was found in HAART-treated HIV-infected patients with peripheral fat wasting in comparison with subjects in the control cohorts. No large mitochondrial deletions or insertions were found. CONCLUSIONS: Lipodystrophy with peripheral fat wasting following treatment with NRTI-containing HAART is associated with a decrease in subcutaneous adipose tissue mtDNA content.

Adipose Tissue↗
PubMed1995

Influence of molecular characteristics on clinical outcome in human immunodeficiency virus-associated non-Hodgkin's lymphoma: identification of a subgroup with favorable clinical outcome.

The relationship between clinical and molecular characteristics of 45 treated individuals with histologically-documented human immunodeficiency virus (HIV)-associated B-cell non-Hodgkin's lymphoma was examined to determine whether differences in molecular features of lymphoma were associated with differences in clinical outcome. Tissue specimens from these tumors were evaluated for evidence of Ig heavy-chain gene rearrangements using both Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Lymphomas were also evaluated for the presence of Epstein-Barr virus (EBV) DNA sequences and c-myc gene rearrangements. Twenty-five lymphomas were characterized as polyclonal and 20 as monoclonal. PCR amplification of expressed Ig variable (V)-region genes confirmed polyclonality in three extensively studied polyclonal lymphomas. The median CD4 count was significantly higher in the group with polyclonal disease (277/microL) than in the group with monoclonal disease (123/microL), P = .04. The complete response rate to therapy was significantly higher in patients with polyclonal disease (78%) and CD4 greater than 200/microL (81%) than in those with monoclonal disease (31%) and CD4 less than 200/microL (33%). CD4 count, clonality, and presence of EBV DNA sequences were the most important predictors of survival. Both Kaplan-Meier and Cox proportional hazards analyses showed a markedly prolonged survival in those patients with both CD4 > or = 200/microL and polyclonal disease. Histologically the polyclonal lymphomas were high grade in appearance and contained prominent macrophages. All seven surviving patients were in this group. Median survival for those individuals whose tumors contained EBV sequences was only 3.2 months (range, 0.4 to 19.5), whereas those with EBV- tumors survived for a median of 9.0 months (range, 0.7 to 65.2), P = .0007. These data indicate that molecular features of HIV-associated lymphomas may be important predictors of clinical outcome. These characteristics define a distinct subset of patients with polyclonal EBV- tumors and CD4 counts greater than 200/microL that appear to have a less aggressive clinical course.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Cytokine expression in large cell lymphoma associated with acquired immunodeficiency syndrome.

Cytokine expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) in a retrospective sampling of 16 AIDS-associated large cell lymphomas (LCL). IL-6 receptor (IL-6R) and IL-10 expression was detected in a majority of the tumor specimens tested, IL-6 expression was detected in 5 of 16 lymphomas that also expressed IL-6R, suggestive of an autocrine mechanism of disease. A subset of tumor samples described as mixed immunophenotype contained large numbers of infiltrating T lymphocytes and macrophages. Immunoperoxidase staining of a representative tumor of mixed immunophenotype demonstrated the presence of HIV-infected macrophages that also stained with anti-IL-6. This finding suggests that IL-6 produced by nonlymphoid cells may act as a paracrine growth factor for tumor cells that express IL-6R. Although earlier studies of AIDs burkitt's lymphoma cell lines suggested that IL-10 expression required EBV infection, 7 of 12 AIDS LCLs that expressed IL-10 did so in the absence of EBV by EBER in situ hybridization. Because AIDS LCLs frequently express cell surface CD5, we speculate that IL-10 may act as an autocrine or paracrine growth factor for this class of lymphoma. These studies suggest that IL-6 and IL-10 are involved in the pathogenesis of AIDS-associated large cell and mixed immunophenotype lymphoma.

Base Sequence↗
PubMed1994

Identification of a common clonal human immunodeficiency virus integration site in human immunodeficiency virus-associated lymphomas.

Infection with human immunodeficiency virus type 1 (HIV-1) is associated with a high incidence of lymphoma. Typically, the lymphomas are B-cell in origin, and although they occur in the setting of HIV-1 infection, historical studies have found no evidence for the presence of HIV-1 within the transformed B-cells. We describe a new class of large cell lymphoma wherein HIV p24 expression within the tumor specimens was found to be extremely high. In the first case, HIV was expressed in the tumor-associated transformed T-cells. In three other cases, HIV was found to be highly expressed in tumor-associated macrophages. These tumors exhibited a mixed immunophenotype histologically. Analysis by inverse polymerase chain reaction, using HIV long terminal repeat primers, demonstrated monoclonal HIV integration sites for all four tumors. Direct sequencing of the T-cell lymphoma inverse polymerase chain reaction products identified the HIV integration site within the fur gene, just upstream from the c-fes/fps protooncogene. Using segments of the fur gene as a probe, the other three monoclonal integration sites mapped to the same region. Although the integration and up-regulation of c-fes/fps was localized to the tumor cells within the T-cell lymphoma, the cells containing the monoclonal HIV in the other mixed immunophenotype lymphomas are currently unknown. These observations suggest that HIV may contribute directly to lymphomagenesis and identify a common site of HIV integration within a subset of acquired immunodeficiency syndrome lymphoma.

Base Sequence↗
PubMed1994

Evaluation of lymphadenopathy in children.

This chapter provides an approach to the evaluation of lymphadenopathy in children. Malignant etiologies, including HIV-associated malignancies are reviewed. In discussing infectious agents or causes of lymphadenopathy, particular emphasis is placed on chronic regional lymphadenopathy with a focus on new advances in cat-scratch disease and tuberculous and non-tuberculous mycobacterial lymphadenitis. After a suggested preliminary set of laboratory tests, biopsy is often necessary both for histologic and cultural investigation. Therapy must be specific and must follow an accurate diagnosis.

AIDS-Related Complex↗
PubMed1992

Molecular and immunophenotypic characterization of AIDS-associated, Epstein-Barr virus-negative, polyclonal lymphoma.

PURPOSE: A molecular analysis of non-Hodgkin's lymphomas (NHLs) from patients with AIDS was undertaken to determine the prevalence and immunophenotype of polyclonal B-cell lymphoma. MATERIALS AND METHODS: DNA was extracted from 40 diagnostic biopsy specimens obtained from patients seen at University of California, San Francisco (UCSF) between 1986 and 1990. Clonality, infection with Epstein-Barr virus (EBV), and presence of a rearranged c-myc gene were determined by Southern blot analysis. Lymphoma immunophenotypes were determined by frozen-section immunohistochemical analysis. RESULTS: The most prevalent genotype of lymphoma in this study was that of polyclonal, EBV-negative tumors with no evidence of c-myc rearrangement (14 of 40; 35%). Monoclonal, EBV-positive tumors with no evidence of c-myc rearrangement comprised the second most prevalent class (10 of 40; 25%), and polyclonal, EBV-positive tumors similar to those seen in transplant patients were observed in only a small subset (three of 40; 8%) of specimens analyzed. The immunophenotype of B cells in the polyclonal EBV-negative subset was equally divided into B-cell-predominant and mixed-phenotype lymphomas, with the latter category containing numerous infiltrating T cells. The B cells in each category were immunoglobulin M-positive (IgM+), CD20+, CD21-. All but one of the polyclonal NHLs had large-cell histology. CONCLUSIONS: EBV-negative, AIDS-associated, polyclonal B-cell lymphoma appears to be a new class of human immunodeficiency virus (HIV)-associated disease more prevalent in the current study than any other molecular subclass. The absence of CD21, the EBV receptor, may explain in part the absence of EBV within this polyclonal B-cell population.

Blotting, Southern↗
PubMed1991

Patterns of chromosomal breakpoint locations in Burkitt's lymphoma: relevance to geography and Epstein-Barr virus association.

We have examined, by Southern blotting, the patterns of chromosomal breakpoint locations in 55 cases of Burkitt's lymphoma (BL) with respect to geography and Epstein-Barr virus (EBV) association. We have confirmed the association between chromosome 8 breakpoint and geography: 74% of endemic (eBL) but only 9% of sporadic BL (sBL) had breakpoints outside the HindIII fragment encompassing the c-myc gene (P2 less than .00001). Conversely, not only did 91% of sBL manifest a rearranged HindIII fragment, but at least 56% of these cases, in contrast to 17% of eBL cases, had a breakpoint within the first exon or intron of c-myc (P2 less than .004). Breakpoints outside the switch mu (S mu) region (ie, the HindIII fragment encompassing S mu) on chromosome 14 were twice as common overall (73%) as those within S mu (27%), but in the 15 tumors with S mu breakpoints, 13 (87%) had a rearranged c-myc gene. Breakpoints outside the HindIII fragment encompassing c-myc on chromosome 8 were predominantly associated with non-S mu breakpoints on chromosome 14 (85%) and this was the combination most frequently associated with eBL (65%; 6% of sBL, P2 less than .00001). In sBL, the most frequent breakpoint combination was a rearranged c-myc gene with a non-S mu breakpoint (63%; 13% of eBL). Twenty-eight percent of sBL and 13% of eBL had breakpoints both within c-myc and within S mu. EBV DNA was present in 19 of 20 tumors with breakpoints outside c-myc, in none of 7 with a breakpoint in the immediate 5' region of c-myc, in 4 of 5 tumors with breakpoints in the first exon, and in 7 of 12 tumors with breakpoints in the first intron. These data suggest that the pathogeneses of eBL and sBL differ with regard to the mechanism of c-myc deregulation, and probably also with regard to the state of differentiation of the target cell for malignant transformation. We have formulated a testable hypothesis regarding the potential role of EBV in pathogenesis: that it is required to contribute to the deregulation of c-myc in the presence of some, but not all, types of c-myc damage arising from the chromosomal translocations.

Blotting, Southern↗
PubMed1991

Evidence for molecular subtypes of HIV-associated lymphoma: division into peripheral monoclonal, polyclonal and central nervous system lymphoma.

The pathogenesis of the HIV-associated lymphomas is not well understood. In order to begin characterizing this class of lymphoma, we initiated a molecular genetic study of DNA extracted from 31 diagnostic biopsy specimens from patients diagnosed with AIDS-associated non-Hodgkin's lymphoma. Analysis of 25 peripheral lymphomas showed that 14 were monoclonal B-cell processes, while 11 appeared to be of polyclonal origin. Five of the 14 monoclonal lymphomas were found to have rearrangements of the c-myc gene. Epstein-Barr virus (EBV) genomes were found in seven out of 14 monoclonal samples, but only two out of nine polyclonal samples. The six primary central nervous system (CNS) lymphoma samples were more homogeneous than the peripheral samples and all were monoclonal, positive for EBV and lacked detectable c-myc gene rearrangements. This study allows us to subdivide the HIV-associated lymphomas into three major molecular subtypes: (1) monoclonal B-cell process frequently associated with c-myc rearrangement or detectable EBV genomes, (2) polyclonal B-cell process typically without evidence of EBV, and (3) monoclonal primary CNS process associated with EBV genomes and lacking detectable c-myc rearrangement.

Acquired Immunodeficiency Syndrome↗
PubMed1991

AIDS-associated polyclonal lymphoma: identification of a new HIV-associated disease process.

High-grade non-Hodgkins B-cell lymphoma is one of the principle malignancies that occurs in individuals infected with the human immunodeficiency virus (HIV-1). Immunoblastic lymphomas that arise in immunosuppressed transplant patients have been described as both monoclonal and polyclonal, and occur in association with Epstein-Barr virus (EBV) infection. To test whether polyclonal lymphoma occurred in patients with AIDS we studied tumors from multiple sites in three patients who died with widespread AIDS-associated large cell or large cell immunoblastic lymphoma. All biopsy specimens contained invasive lymphoma. Tumor cells were mature IgM-positive immunoblasts by immunohistochemical analysis, with the same B-cell phenotype observed in all tumor sites. Only a minority of sites from all patients analyzed were monoclonal as measured by immunoglobulin gene rearrangements, with one case having several foci of monoclonal disease with other histologically identical metastases showing no evidence of monoclonal proliferation. Similar to the transplant-associated polyclonal B-cell proliferations. EBV gene sequences were present in multiple sites from one autopsy. In the other two autopsies, polyclonal B-cell proliferations occurred in the absence of EBV involvement except at one site, where a minor clone of EBV-infected cells was found. In contrast to HIV-associated Burkitt's lymphoma, no c-myc rearrangements were found at any site. These studies describe the occurrence of polyclonal lymphoma in AIDS and suggest that EBV-negative polyclonal lymphoma may be a distinct disease entity unique to HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Molecular pathogenesis of AIDS-associated non-Hodgkin's lymphoma.

The pathogenesis of non-Hodgkin's lymphoma (NHL) in HIV-infected individuals is currently poorly understood; however, recent molecular studies have subdivided these lymphomas into distinct molecular pathologic entities. Similar to endemic and sporadic Burkitt's lymphoma, monoclonal B-lymphoma subsets were found to be infected with Epstein-Barr virus (EBV) or have c-myc gene rearrangements, suggesting a role for EBV infection or chromosomal translocation in a subset of AIDS NHLs. Similar to lymphomas that occur in immunosuppressed transplant patients, EBV-positive polyclonal lymphomas also have been described. Unique to HIV-infected patients, however, is the subset of polyclonal B-cell lymphoma with no evidence for EBV infection. Based on these molecular studies, it is apparent that the AIDS NHLs represent a heterogeneous set of diseases with a number of pathogenic processes involved in lymphomagenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Localization of breakpoints by polymerase chain reactions in Burkitt's lymphoma with 8;14 translocations.

Translocations involving chromosomes 8 and 14 in Burkitt's lymphoma (BL) often involve the switch mu (Smu) region on chromosome 14, which contains multiple repeats. This has enabled us to use the polymerase chain reaction (PCR) to detect breakpoints that involve this region on chromosome 14 and the c-myc gene on chromosome 8. Using pairs of flanking primers, each pair including one annealing to repeat sequences within the switch region and one of three primers from the c-myc region (first intron, 3', or 5' flanking sequence of the first exon of c-myc), we have been able to amplify DNA fragments containing the corresponding breakpoint regions from chromosome 14 in both cell lines and biopsied tumor samples. The definitive demonstration of sequences from both chromosomes in these fragments permitted the confirmation of the presence of a translocation. Because of the sensitivity of PCR, we were able to localize breakpoints in samples containing as few as 1 neoplastic cell in 10(8) cells. PCR provides a valuable tool for the detection of 8;14 chromosomal translocations, which should prove to be of value in diagnosis and molecular epidemiologic studies, as well as providing a means of detecting minimal disease.

Burkitt Lymphoma↗
PubMed1989

Biology and treatment of small non-cleaved cell lymphoma.

Small non-cleaved cell lymphoma occurs predominantly in the first two decades of life, and in this age group can be divided into two major types, both of which are associated with non-random chromosomal translocations. The endemic form occurs at high frequency in equatorial Africa, and the sporadic form occurs at low frequency throughout the world. Treatment consists primarily of chemotherapy; surgery has an important role in resectable abdominal disease, but radiation is of limited value. Prophylactic treatment of the central nervous system is recommended in nearly all patients. The most effective regimens result in cure in almost all patients who have limited disease, and in a high proportion of patients with extensive disease. Patients with bone marrow or central nervous system involvement have a poor prognosis with most regimens. Therapy for recurrent disease continues to be a challenge, and remains largely experimental.

Biology↗
PubMed1988

The molecular analysis of chromosomal translocations as a diagnostic, epidemiological and potentially prognostic tool in lymphoid neoplasia.

Neoplasms have been shown to be associated with specific non-random chromosomal abnormalities. The present paper summarizes molecular consequences of chromosomal translocations in lymphoid malignancies, especially in Burkitt's lymphoma. Among such consequences are derangements of the regulation of oncogene transcription. Besides their possible importance for lymphoma pathogenesis, chromosomal translocations are associated in some lymphoid neoplasms with a worse prognosis.

Burkitt Lymphoma↗
PubMedDate not supplied

Absence of human herpesvirus-6 genome by polymerase chain reaction in children with Hodgkin disease: a Children's Cancer Group Lymphoma Biology Study.

BACKGROUND: Human herpesvirus-6 (HHV6) has been implicated in adult lymphomas but the role that HHV6 has in lymphomagenesis is unclear. Because primary infection occurs in children, a prospective study was undertaken to detect HHV6 in those with pediatric Hodgkin disease (HD). OBSERVATIONS: Tumor was obtained from children with HD entered on a Children's Cancer Group Biology Study. Polymerase chain reaction (PCR) was performed using HHV6 primers. All 47 specimens (40 nodular sclerosing; 3 lymphocyte predominant; 3 mixed cellularity; and 1 unclassified) were negative for HHV6. CONCLUSIONS: The results demonstrate no HHV6 sequence in childhood HD.

Child↗