Biomedical subjects

J W Said

Publications and source records attributed to J W Said.

At least 37 records · Page 2Linked to original sources

PubMed1999

Aberrant expression of CD27 and soluble CD27 (sCD27) in HIV infection and in AIDS-associated lymphoma.

CD27 is a member of the tumor necrosis factor receptor superfamily that is expressed primarily on T cells, as well as on subsets of B cells and NK cells. CD70, which is expressed on activated B and T cells, but not on resting lymphocytes, is a ligand for CD27. Cell surface CD27 can be proteolytically cleaved to produce a 32-kDa soluble CD27 (sCD27) molecule. Elevated levels of sCD27 are seen in a number of disease states and malignancies. Although it has been reported that cerebrospinal fluid sCD27 levels were elevated in people who had AIDS dementia, little is known about CD27 expression in HIV disease. To determine if sCD27 levels were elevated in those with HIV infection, and/or in those with AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL), sCD27 levels were measured in HIV-negative and HIV-positive subjects as well as in people who developed AIDS-NHL. Serum sCD27 levels were seen to be elevated in HIV+ subjects. Furthermore, sCD27 levels were particularly elevated in those subjects who went on to develop AIDS-NHL, with serum sCD27 levels in AIDS-NHL subjects being significantly higher than those in HIV+ subjects who did not develop lymphoma. Most AIDS-NHL cell lines and primary AIDS-NHL tumor specimens expressed both CD27 and its ligand, CD70. The proportion of circulating B cells that expressed cell surface CD27 was substantially reduced in those with HIV infection, and B cells from HIV-infected subjects produced decreased levels of sCD27 in culture. Together, these results indicate that CD27/sCD27 expression is abnormal in HIV infection and suggest that this molecule merits further examination as a potential marker for AIDS-NHL.

Antigens, CD↗

PubMed1999

Herpesvirus 8 inclusions in primary effusion lymphoma: report of a unique case with T-cell phenotype.

We describe a case of primary effusion lymphoma with T-cell phenotype, mixed genotype, and intranuclear herpesvirus inclusions visible with the light microscope. Cells were studied by immunohistochemical analysis, in situ hybridization, immunoglobulin and T-cell receptor gene rearrangement, and polymerase chain reaction. Primary effusion lymphoma cells with T-cell phenotype revealed herpesvirus 8 inclusions predominantly seen in apoptotic cells, suggesting that productive viral infection is associated with cell death. Clinical features were typical of primary effusion lymphoma. Cytologic, molecular genetic, and phenotypic features demonstrated a unique variant of primary effusion lymphoma.

Adult↗

PubMed1998

Allelotype analysis of adult T-cell leukemia.

Allelotype analysis of adult T-cell leukemia (ATL) was undertaken for the first time to identify chromosomal loci relevant to the development of acute/lymphomatous ATL. Loss of heterozygosity (LOH) was screened using 94 highly polymorphic microsatellite markers, distributed among all nonacrocentric, autosomal chromosomes. In each of the 22 cases, DNA obtained from their leukemic cells in acute/lymphomatous phase was compared with their constitutional DNA from mononuclear cells in chronic or remission phase. Allelic losses of at least on one chromosome arm occurred in 91% of the cases (20 individuals). Among 39 chromosome arms, allelic losses were observed on 31 arms at least for one sample. A high frequency of allelic loss (>30%) was seen on chromosome arms 6q (41%) and 17p (48%). The mean fractional allelic loss (FAL) was 0.109. These findings suggest that a novel tumor suppressor gene on chromosome arm 6q, as well as the p53 gene on chromosome arm 17p, probably have an important role in the development of acute/lymphomatous ATL.

Adult↗

PubMed1998

Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo.

Troglitazone, a thiazolidinedione derivative, is a widely used antidiabetic drug that binds and activates peroxisome proliferator-activated receptor gamma (PPARgamma) and enhances insulin sensitivity. It induces differentiation of adipocytes, which highly express PPARgamma. We report that human prostate cancer cells expressed PPARgamma at prominent levels and normal prostate tissues had very low expression. Dose-response clonogenic assays of the PC-3 prostate cancer cell line with troglitazone showed an antiproliferative effect (ED50, 3 x 10(-7) M) and other PPARgamma ligands (BRL49653: ED50, 8 x 10(-8) M; 15-deoxy-delta12,14-prostaglandin J2: ED50, 2 x 10(-6) M; ciglitizone: ED50, not reached; indomethacin: ED50, not reached) showed similar effects. Combinations of troglitazone and a ligand specific for either retinoid X receptor or retinoic acid receptor did not show a synergistic effect. Pulse-exposure to troglitazone (10(-5) M) for different durations showed that 4 days of pulse-exposure to the agent irreversibly inhibited 50% clonal growth of PC-3 cells. Interestingly, PC-3 cells cultured with troglitazone (10(-5) M) showed dramatic morphological changes both by light and electron microscopy, suggesting that the cells became less malignant. Nevertheless, troglitazone did not affect either the cell cycle or several markers of differentiation. LNCaP cells constitutively produced prostate-specific antigen, and levels were markedly enhanced by all-trans-retinoic acid. Troglitazone (10(-5) M, 4 days) decreased by 50% the levels of prostate-specific antigen produced by these cells. In vivo treatment of PC-3 tumors growing in male BNX triple immunodeficient mice with oral troglitazone (500 mg/kg/day) produced significant inhibition of tumor growth (P = 0.01). The only objective side effect of troglitazone in mice was the elevation of serum transaminases. Short-term culture of four surgically obtained human prostate cancer tumors with troglitazone (10(-5) M, 4 days) produced marked and selective necrosis of the cancer cells (about 60%) but not the adjacent normal prostate cells. Taken together, these results suggest that troglitazone may be a useful therapeutic agent for the treatment of prostate cancer, especially in the setting of low disease burden.

Animals↗

PubMed1998

Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice.

Induction of differentiation and apoptosis in cancer cells through ligands of nuclear hormone receptors (NHRs) is a novel and promising approach to cancer therapy. All-trans-retinoic acid (ATRA), an RA receptor-specific NHR ligand, is now used for selective cancers. The NHR, peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in breast cancer cells. Activation of PPARgamma through a synthetic ligand, troglitazone (TGZ), and other PPARgamma-activators cause inhibition of proliferation and lipid accumulation in cultured breast cancer cells. TGZ (10(-5) M, 4 days) reversibly inhibits clonal growth of MCF7 breast cancer cells and the combination of TGZ (10(-5) M) and ATRA (10(-6) M, 4 days) synergistically and irreversibly inhibits growth and induces apoptosis of MCF7 cells, associated with a dramatic decrease of their bcl-2 protein levels. Similar effects are noted with in vitro cultured breast cancer tissues from patients, but not with normal breast epithelial cells. The observed apoptosis mediated by TGZ and ATRA may be related to the striking down-regulation of bcl-2, because forced over-expression of bcl-2 in MCF7 cells cultured with TGZ and ATRA blocks their cell death. TGZ significantly inhibits MCF7 tumor growth in triple immunodeficient mice. Combined administration of TGZ and ATRA causes prominent apoptosis and fibrosis of these tumors without toxic effects on the mice. Taken together, this combination may provide a novel, nontoxic and selective therapy for human breast cancers.

Adenocarcinoma↗

PubMed1998

Detection and titration of human herpesvirus-8-specific antibodies in sera from blood donors, acquired immunodeficiency syndrome patients, and Kaposi's sarcoma patients using a whole virus enzyme-linked immunosorbent assay.

A human herpesvirus-8 (HHV-8) enzyme-linked immunosorbent assay (ELISA) with a whole virus lysate as antigen was developed and used to measure the seroprevalence rate and levels of IgG antibodies to HHV-8 in sera/plasma of various patient groups and blood donors. The virus antigen was prepared from the KS-1 cell line, which produces lytic virus, and therefore contains a broad array of viral proteins. Seroprevalence studies using this ELISA showed the following: 10 of 91 blood donors (11%) had an average HHV-8 antibody titer of 118; 67 of 72 (93%) classic Kaposi's sarcoma (KS) patients were positive with an average titer of 14,111; and 57 of 62 (92%) KS/human immunodeficiency virus (HIV) patients were positive with an average titer of 4,000. A study on a very limited number of serial serum samples from patients before and after diagnosis with KS showed highly elevated antibody titers to HHV-8 virus after KS lesions developed. Preliminary data show that 50% of the sera from HIV-1(+) homosexual patients contain IgG antibodies to HHV-8 suggesting that this population is at high risk for developing KS. Antibody results correlated well with the confirmatory immunofluorescent assays (IFA) using KS-1 cells as the substrate. This HHV-8 IgG antibody detection ELISA is sensitive and specific and does not cross-react with Epstein-Barr virus (EBV) or other human herpesviruses. The results of this HHV-8 antibody survey suggest that this rapid ELISA assay can be used to screen large numbers of sera to find those at risk for developing KS.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression.

The recently identified PTEN/MMAC1 gene is a candidate tumor suppressor implicated in multiple tumor types based on mutations or homozygous deletions of the gene in certain human cancers. No studies of PTEN/MMAC1 mRNA or protein expression in cancer cells have been reported, primarily because of significant numbers of normal cells contaminating most tumor samples and because of the lack of antibody reagents. We examined PTEN/MMAC1 in advanced prostate cancer for gene mutations or abnormalities in expression by using a series of recently derived xenografts free of normal human cells and a PTEN/MMAC1-specific antibody. Only 1 of 10 tumors contained a homozygous deletion of PTEN/MMAC1, and no mutations were detected in the entire coding region of the remaining nine xenografts. However, five of these showed reduced or absent PTEN/MMAC1 expression by Northern analysis and reverse transcription-PCR of mRNA. PTEN/MMAC1 mRNA expression was restored in nonexpressing prostate cancer cells by in vitro treatment with the demethylating agent 5-azadeoxycytidine. Alterations in PTEN/MMAC1 expression were confirmed at the protein level by immunoblot analysis, and immunohistochemical studies show that the endogenous wild-type PTEN/MMAC1 protein is localized exclusively in the cytoplasm. These results demonstrate that loss of PTEN/MMAC1 expression occurs frequently in advanced prostate cancer.

Azacitidine↗

PubMed1998

Mechanisms of growth control of Kaposi's sarcoma-associated herpes virus-associated primary effusion lymphoma cells.

Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity associated with Kaposi's sarcoma-associated herpes virus (KSHV). Several cytokines, including interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) may be important for survival of KS cells. However, little is known about the interaction of cytokines with KSHV-infected lymphocytes from PEL. Therefore, we investigated what cytokines were produced by KSHV-infected PEL cell lines (KS-1, BC-1, BC-2), what cytokine receptors were expressed by these cells, what response these cells had to selected cytokines, and what was the effect of IL-6 antisense phosphorothioated oligonucleotides. Reverse transcriptase-polymerase chain reaction (RT-PCR) and protein studies showed that these three cell lines produced IL-10, IL-6, and the receptors for IL-6. The granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1beta, IL-8, IL-12, bFGF, PDGF, and c-kit transcripts were not detected in the cell lines. High levels (0.7 to 5 ng/mL/10(6) cells/48 hours) of IL-6 protein were consistently detected in supernatants of the cell lines by enzyme-linked immunosorbent assay (ELISA) tests. In clonogenic assays, interferon-alpha (IFN-alpha) and IFN-gamma suppressed the clonal growth of the PEL cells, but GM-CSF, IL-4, IL-6, IL-8, IL-10, and oncostatin M did not change it. We examined for several autocrine loops that have been suggested to occur in KS. Experiments using antisense oligonucleotides showed that the clonal growth of KS-1 and BC-1 was nearly 100% inhibited by IL-6 antisense oligonucleotides (10 micromol/L), but not at all by either oligonucleotides (</=10 micromol/L) to IL-6 sense, IL-6 scrambled, viral IL-6 (vIL-6) antisense, or IL-10 antisense. Furthermore, the IL-6 antisense oligonucleotides had no effect on two B-cell lymphoma cell lines, which were not infected with KSHV. Addition of IL-6 antibody did not inhibit clonal growth of any of the cell lines. Taken together, we have defined the cytokines and their receptors expressed on PEL cells and have found that these cells synthesized IL-6 and IL-6 receptors; interruption of this pathway by IL-6 antisense oligonucleotides specifically prevented the growth of these cells. These findings will offer potential new therapeutic strategies for PEL.

Cell Division↗

PubMed1998

Infection of primary dermal microvascular endothelial cells by Kaposi's sarcoma-associated herpesvirus.

OBJECTIVE: To develop an in vitro model for infection of primary human cells with Kaposi's sarcoma (KS) herpesvirus (KSHV). DESIGN: The recent identification of a herpesvirus associated with KS, its successful isolation in vitro, and its complete DNA sequencing facilitates experiments on the pathogenesis of AIDS-related KS. Completed studies demonstrate that the endothelial cells lining the vascular slits in KS lesions are productively infected with KSHV and may be the principal site of virus replication. We have designed a model system to study the infection of primary human cells with KSHV. METHODS: A coculture technique was used with KS cells (KS-1) and primary dermal microvascular endothelial cells. RESULTS: We detected increasing viral DNA concentrations as well as viral mRNA suggesting that a productive virus infection occurs in the target cells. Infection of these cells is dose- and time-dependent and is inhibited by lobucavir, foscarnet and 9-(2-phosphomethoxyethyl) adenine. With a modification of the model, KSHV can be serially passaged in primary cells in excess of 16 passages. CONCLUSIONS: This novel model assay system makes new studies on the role of KSHV and KSHV-induced cellular products on the pathogenesis of KS possible. It also provides a high volume screening method to detect agents that inhibit KSHV infection of primary endothelial cells.

Animals↗

PubMed1998

Immunotherapy against murine leukemia.

The central hypothesis underlying specific anti-leukemia immunotherapy is that leukemic cells express antigenic determinants not expressed on their counterpart normal adult cells. We have developed a murine myeloid leukemia/tumor immunization model using the low-immunogenic WEHI3 leukemia in syngeneic mice. Mice preimmunized with irradiated, transduced IL-7-producing WEHI3 cells showed systemic protection and rejection of a lethal dose of intravenously (i.v.) injected parental WEHI3 cells (5 x 10(4)) with 40% long-term survival. When vaccinated with a mixture of parental WEHI3 cells and IL-2-producing NIH-3T3 fibroblasts (5 x 10(5)), 60% survival was observed. Vaccination with murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing WEHI3 cells resulted in only 20% survival of i.v. challenged mice, and the additional combination of IL-2- and IL-7-producing vaccine did not reveal any additive or synergistic effects. Immunizing mice with a pre-established leukemia burden (injected with 5 x 10(4) WEHI3 cells, i.v., 3 days prior to immunization) did not cure or result in a prolongation of survival, indicating that improved methods of immunization are needed. Taken together, we have identified IL-7 and IL-2 as effective cytokines in our leukemia/vaccination model with only marginal activity by GM-CSF.

3T3 Cells↗

PubMed1998

Microsatellite instability in adult T-cell leukaemia.

Microsatellite instability (MSI) is thought to represent a defect of the DNA mismatch repair system which has been implicated in the tumourigenesis of several human malignancies. We investigated MSI in acute/ lymphomatous adult T-cell leukaemia (ATL: n=22) using 54 highly polymorphic dinucleotide short-tandem repeat sequences. The corresponding control DNA from each individual was obtained from the peripheral blood in either chronic phase (n=5) or when complete remission was achieved (n=17). 10/22 (41%) patients had MSI, six of whom showed MSI in multiple loci; four loci had MSI in multiple samples. The incidence of MSI in ATL was found to be higher than in other haematological malignancies, indicating MSI as a feature of ATL, which may be involved in the progression of the disease.

Humans↗

PubMed1998

Methylation of the p16INK4A gene in multiple myeloma.

The p16INK4A (p16) binds to both cyclin D-CDK4 and cyclin D-CDK6 and inhibits the progression of the cell cycle from G1 to S phase. Loss of expression of this protein can occur by several mechanisms including structural alterations. Recent studies have suggested that the loss of expression of p16 can occur by hypermethylation of the gene. The methylation status of the p16 gene in multiple myeloma was examined in three myeloma cell lines (U266, RPMI8226 and IM9) and 16 primary myeloma samples using methylation-specific polymerase chain reaction (MSP). The U266 and RPMI8226 cell lines contained a completely methylated p16 gene and the IM9 line had a partially methylated p16 gene. Identical results were obtained by another polymerase chain reaction (PCR)-based methylation assay system as well as Southern blotting after using a methylation-sensitive restriction enzyme. The U266 cell line expressed no p16, and the IM9 had weak expression as determined by reverse transcript (RT-)PCR. The U266 cells began to express, and IM9 increased the accumulation of, the p16 RNA after treatment with the demethylating agent 5'-aza-2-deoxycytidine (10(-6)-10(-5) M). This suggested that the levels of methylation of the p16 gene detected by the MSP technique correlated with the regulation of transcription of this gene. Examination of the primary myeloma samples showed that eight of 16 (50%) contained a methylated p16 gene. We have previously found that alterations of the p16 gene, such as deletions and point mutations, are rare in primary multiple myeloma; none of the 16 samples included in this study had p16 gene alterations. Our results suggest that methylation of the p16 gene may contribute to the development and/or progression of multiple myeloma.

Aged↗

PubMed1998

Alterations in fascin-expressing germinal center dendritic cells in neoplastic follicles of B-cell lymphomas.

Germinal center dendritic cells (GCDCs) have essential functions in retention of immune complexes within secondary follicles, B-lymphocyte antigenic stimulation, B-cell activation, homing of B-cells via adhesion molecules such as ICAM-1 and VCAM-1, and B-cell survival via apoptosis. The neoplastic cells of follicular lymphomas (FLs) are thought to derive from follicular B lymphocytes, but their relationship to GCDCs remains unclear. This study used immunohistochemical staining for fascin, a 55-kDa actin-bundling protein strongly expressed in GCDCs and their processes, to evaluate their distribution in neoplastic follicles. Forty-two cases of B-cell FL were evaluated, and immunoreactive staining for fascin was compared with six cases of Castleman's disease (CD) and six cases of follicular hyperplasia. FLs generally revealed decreased or absent fascin-staining GCDCs, suggesting loss of fascin expression by dendritic cells in neoplastic follicles compared with hyperplastic follicular centers. In some follicles, there was partial retention of dendritic architecture with islands of residual syncytial network. Interdigitating reticulum cells in the parafollicular regions revealed normal fascin expression with intense staining of dendritic processes. In contrast with FLs, cases of follicular hyperplasia revealed normal or increased fascin-positive follicular dendritic cells, and in cases of hyaline vascular CD, follicular dendritic cells revealed tight syncytial networks. These results suggest that GCDCs are deficient in neoplastic follicles, compared with benign reactive or hyperplastic follicles. This alterations in the germinal center microenvironment might explain the inability of FL cells to present antigen to T lymphocytes and to mount an effective antitumor immune response.

Carrier Proteins↗

PubMed1998

Posttransplant lymphoproliferative disorder in pediatric bone marrow transplant recipients: disseminated disease of donor origin demonstrated by fluorescence in situ hybridization.

BACKGROUND: Posttransplant lymphoproliferative disorders in bone marrow transplantation are typically rapidly progressive and fatal B-cell lymphoid proliferations associated with Epstein-Barr virus, and are mostly of donor origin. We report three pediatric bone marrow transplant cases in which posttransplant lymphoproliferative disorder was diagnosed at postmortem examination. Epstein-Barr virus in these cases was identified by a combined in situ hybridization-immunoperoxidase technique and donor origin was identified by fluorescence in situ hybridization. METHODS: Tissues obtained from postmortem examination were evaluated by light microscopy, immunohistochemistry, combined in situ hybridization-immunoperoxidase technique with Epstein-Barr virus-encoded RNA probe, and fluorescence in situ hybridization with X and Y centromeric probes. RESULTS: Three pediatric patients underwent sex-mismatched, T-cell-depleted bone marrow transplants complicated by graft versus host disease, rapidly progressive multiple organ failure, and postmortem diagnosis of posttransplant lymphoproliferative disorder. Histologic examination and immunohistochemistry studies demonstrated immunoblastic lymphoma (one case) or polymorphic B-cell lymphoma (two cases). In all cases, Epstein-Barr virus-encoded RNA was detected by a combined in situ hybridization-immunoperoxidase technique. Fluorescence in situ hybridization for X and Y chromosomes in paraffin sections demonstrated donor origin in two cases (one case was indeterminate). CONCLUSION: Fluorescence in situ hybridization was used to prove donor derivation of Epstein-Barr virus-associated posttransplant lymphoproliferative disorders in pediatric bone marrow transplant recipients. Many features of posttransplant lymphoproliferative disorders in pediatric bone marrow transplant recipients are very similar to adult cases, although a higher proportion of children appear to be diagnosed postmortem and have a fatal outcome.

Bone Marrow Transplantation↗

PubMed1998

Isolated leptomeningeal Castleman's disease with viral particles in the follicular dendritic cells.

To our knowledge, five cases of Castleman's disease involving only the central nervous system have been reported previously. We report a sixth case, which occurred in a 47-year-old woman with a 3-month history of headaches and a large superior frontal lobe mass on neuroimaging. Excisional biopsy revealed confluent lymphoid nodular areas with multiple well-developed germinal centers surrounded by concentrically layered proliferations of small B lymphocytes typical of Castleman's disease. Ultrastructural study found 100-nm virallike particles within follicular dendritic cells as well as intercellular spaces. These particles were suggestive of a D-type retrovirus. The patient underwent postoperative radiotherapy and was neurologically normal 3 months after surgery.

Betaretrovirus↗

PubMed1998

Extension of useful reagent shelf life beyond manufacturers' recommendations. Cell Markers Committee of the College of American Pathologists.

OBJECTIVE: The College of American Pathologists Cell Markers Committee designed a study to evaluate the use of immunohistochemistry primary antibodies beyond manufacturers' recommended dates. METHODS: Pathologists were asked to save aliquots of primary antibodies during mid-1997 so that by spring 1998 the reagents would be "outdated" according to manufacturers' recommendations. Three tumors were immunostained both in mid-1997 and early 1998 (using outdated reagents in 1998). Two hundred twenty-one laboratories participated. PATIENT SAMPLES: Immunostained materials consisted of an angiomyolipoma immunostained for muscle-specific actin and HMB-45, a melanoma immunostained for S100 protein and HMB-45, and a large cell lymphoma immunostained for common leukocyte antigen and HMB-45. Blocks from the same tumor were used in each instance. MAIN OUTCOME MEASURE: We compared the immunostaining results as a percentage of laboratories indicating a positive or negative immunohistochemical result between the 1997 and 1998 time points. RESULTS: Only minor differences were identified for the 221 reporting laboratories in 1998 as compared with those in 1997. CONCLUSIONS: The data suggest review of the Health Care Financing Administration's ruling on extending the useful reagent shelf life beyond manufacturers recommendations. Similar studies using more inherently quantitative methodology are suggested.

Antibodies↗

PubMed1997

Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma.

We have recently demonstrated the presence of Kaposi's sarcoma-associated herpesvirus (KSHV) in cultured bone marrow (BM) stromal dendritic cells from all patients with myeloma studied. To show that these findings were not an artifact of tissue culture, we performed in situ hybridization (ISH) and polymerase chain reaction (PCR) to detect KSHV in BM core biopsies. Using ISH to open reading frame-72 (ORF 72), we localized KSHV to BM dendritic cells in 17 of 20 patients with myeloma, 2 patients with plasmacytosis associated with the acquired immunodeficiency syndrome, and 1 case of aplastic anemia. In contrast, BM from normal subjects (n = 4) and patients with lymphoma and leukemia (n = 21) did not contain KSHV. PCR amplification with KSHV primers demonstrated product in fresh BM biopsy samples from 6 of 7 myeloma patients, whereas three normal marrows contained no amplified product. These findings suggest that KSHV, possibly through alterations in the BM microenvironment and production of viral interleukin-6 (vIL-6), may stimulate and maintain abnormal plasma cell proliferation in myeloma and related disorders.

AIDS-Related Opportunistic Infections↗

PubMed1997

Kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8 encephalitis in HIV-positive and -negative individuals.

OBJECTIVE: Kaposi's sarcoma-associated herpesvirus (KSHV) human herpesvirus type 8 (HHV-8) has been associated with Kaposi's sarcoma and a variety of benign lymphoid proliferations including angioimmunoblastic lymphadenitis with dysproteinemia and Castleman's disease. KSHV/HHV-8 has also been associated with inflammatory conditions including interstitial pneumonitis. Although herpesviruses are commonly associated with encephalitis in immunosuppressed individuals, KSHV/HHV-8 has not previously been associated with central nervous system disease other than lymphoma. The first cases of KSHV/HHV-8 associated encephalitis have been described. METHODS AND DESIGN: KSVH/HHV-8 sequences were evaluated in brain biopsies from three cases of otherwise unexplained encephalitis from three patients, two of whom were positive for HIV. Amplification of the polymerase chain reaction product was confirmed with Southern blot hybridization on three separate occasions, and with appropriate positive and negative controls. RESULTS: All three cases of encephalitis were associated with KSHV/HHV-8 sequences. Characteristic lesions included endothelial cell swelling and perivascular cuffing by lymphocytes. CONCLUSIONS: KSHV/HHV-8 was associated with encephalitis in immunosuppressed individuals, and should have been considered in the differential diagnosis of unexplained viral encephalitis. KSHV/HHV-8 may have tropism for the central nervous system.

AIDS-Related Opportunistic Infections↗