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J W Said

Publications and source records attributed to J W Said.

At least 55 records · Page 3Linked to original sources
PubMed1997

Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients.

Kaposi's sarcoma-associated herpesvirus (KSHV) was found in the bone marrow dendritic cells of multiple myeloma patients but not in malignant plasma cells or bone marrow dendritic cells from normal individuals or patients with other malignancies. In addition the virus was detected in the bone marrow dendritic cells from two out of eight patients with monoclonal gammopathy of undetermined significance (MGUS), a precursor to myeloma. Viral interleukin-6, the human homolog of which is a growth factor for myeloma, was found to be transcribed in the myeloma bone marrow dendritic cells. KSHV may be required for transformation from MGUS to myeloma and perpetuate the growth of malignant plasma cells.

Blotting, Southern↗
PubMed1997

Is Kaposi's sarcoma--associated herpesvirus ubiquitous in urogenital and prostate tissues?

Controversy exists as to whether Kaposi's sarcoma-associated herpesvirus (KSHV) is more widespread than originally reported. Recently, Monini et al reported that KSHV is ubiquitous in urogenital and prostate tissues and sperm of healthy Italian adults using nested polymerase chain reaction (PCR). We have examined for the presence of KSHV in 10 normal prostates from Italian men and 10 from men from the United States, as well as 32 prostatic, 30 vulvar, 24 ovarian, 20 cervical, and 30 testicular cancer specimens from patients from the United States. None of the patients had a history of human immunodeficiency virus infection. The samples were tested by nested PCR. The sensitivity of this assay was determined by a dilution study performed by diluting KSHV DNA from the KS-1 cells (a primary effusion lymphoma cell line which is estimated to have 16 copies of KSHV per cell) in DNA from a K562 myeloid cell line. The nested PCR that we used can detect 2.4 copies of KSHV sequences on a background of K562 DNA. All the samples were negative for KSHV sequences. Therefore, we cannot confirm the finding that KSHV sequences are ubiquitous in urogenital and prostate tissues. Furthermore, because our samples were from both the United States and Italy, the discrepancy between results is unlikely to be explained by either ethnic or environmental factors. False-positive results easily occur using nested primer PCR because of contamination. Our data argue that KSHV is not widely disseminated in urogenital tissues from nonimmunosuppressed individuals.

Adult↗
PubMed1997

Synergistic decrease of clonal proliferation, induction of differentiation, and apoptosis of acute promyelocytic leukemia cells after combined treatment with novel 20-epi vitamin D3 analogs and 9-cis retinoic acid.

Patients with acute promyelocytic leukemia (APL) usually relapse after all-trans retinoic acid (RA) treatment because this therapy fails to eradicate the malignant clone. Our data showed that KH 1060 and other 20-epi vitamin D3 analogs alone were potent inhibitors of clonal growth of NB4 cells, an APL cell line (ED50, approximately 5 x 10(-11) M). The combination of KH 1060 and 9-cis-RA synergistically and irreversibly enhanced this effect. Neither KH 1060 nor 9-cis-RA (10(-6) M, 3 d) were strong inducers of differentiation of NB4 cells. However, 98% of the cells underwent differentiation to a mature phenotype with features of both granulocytes and monocytes after exposure to a combination of both compounds. Apoptosis only increased after incubation of NB4 cells with 9-cis-RA alone (28%) or with a combination of 9-cis-RA plus KH1060 (32%). Immunohistochemistry showed that the bcl-2 protein decreased from nearly 100% of the wild-type NB4 cells to 2% after incubation with a combination of KH 1060 and 9-cis-RA, and the bax protein increased from 50% of wild-type NB4 cells to 92% after culture with both analogs (5 x 10(-7) M, 3 d). Western blot analysis paralleled these results. Studies of APL cells from one untreated individual paralleled our results with NB4 cells. Taken together, the data demonstrated that nearly all of the NB4 cells can be irreversibly induced to differentiate terminally when exposed to the combination of KH 1060 and 9-cis-RA.

Antigens, Differentiation↗
PubMed1997

Ultrastructural characterization of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) in Kaposi's sarcoma lesions: electron microscopy permits distinction from cytomegalovirus (CMV).

Kaposi's sarcoma (KS) has been shown by molecular techniques to be associated with infection with human herpesvirus 8 (HHV8/KSHV), but specific ultrastructural characterization of the virus has been impaired by the frequent presence in these lesions of other herpesviruses, particularly cytomegalovirus (CMV). Since the ultrastructural appearance of HHV8/KSHV has been studied in the cell line KS-1 uninfected with other viruses including CMV, it was possible to undertake a comparative study of CMV and HHV8/KSHV in KS lesions. HHV8/KSHV was sparsely present and lytic infection was restricted to endothelial cells. The following specific ultrastructural features allowed distinction between HHV8/KSHV and CMV: the viral particles were more delicate and less numerous in cases of HHV8/KSHV infection; the viral tegument was more electron-dense in CMV than in HHV8/KSHV; dense bodies characteristic of CMV were absent in HHV/KSHV; complete CMV viral particles were more variable in size and generally larger (150-200 nm) than HHV8/KSHV (120-150 nm); and finally, the viral envelope was more pleomorphic in CMV than in KSHV/HHV8. Similarities between CMV and HHV8/KSHV included the basic structure of the nucleocapsids and the presence of capsids lacking central DNA cores (so-called non-infectious enveloped particles). These observations show that electron microscopy can be used to identify HHV8/KSHV and confirm the relationship between HHV8/KSHV and KS.

Cytomegalovirus↗
PubMed1997

Analysis of p18INK4C in adult T-cell leukaemia and non-Hodgkin's lymphoma.

p18INK4C, a cyclin-dependent kinase inhibitor, is a homologue of p15INK4B and p16INK4A which are frequently altered in a variety of malignancies. We searched for structural alterations of the p18INK4C gene in 44 adult T-cell leukaemias (ATLs), 101 non-Hodgkin's lymphomas (NHLs), two polyclonal B-cell proliferations, seven ATL cell lines and seven leukaemia/lymphoma cell lines, by Southern blot and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analyses. No genomic alterations of the p18INK4C gene were found in any of the samples. By RT-PCR, p18INK4C was not expressed in three of five ATL cell lines, whereas it was expressed in all the non-ATL leukaemia/lymphoma cell lines. Tax did not inhibit the expression of p18INK4C in tax-expressing Jurkat cells.

Adult↗
PubMed1997

Kaposi's sarcoma-associated herpesvirus and human herpesvirus 8 (KSHV/HHV8)-associated lymphoma of the bowel. Report of two cases in HIV-positive men with secondary effusion lymphomas.

This report describes two cases of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/HHV8)-associated lymphomas that primarily involved the large bowel and that secondarily caused malignant effusions. Involvement of the gastrointestinal tract is of interest because epidemiologic evidence suggests that KSHV/HHV-8 may be transmitted via the fecal-oral route, and KSHV/HHV8 DNA has been detected in rectal samples from HIV-positive patients. This report describes two HIV-positive men who developed primary KSHV/ HHV8-associated lymphomas of the bowel. Despite similar morphology and immunophenotype, these cases differ from most KSHV/HHV8-associated primary effusion lymphomas, which present with malignant effusions in the absence of a solid tumor mass. The spectrum of KSHV/HHV8-associated lymphomas is expanded to include a subset of primary bowel lymphomas in individuals infected with human immunodeficiency virus.

AIDS-Related Opportunistic Infections↗
PubMed1997

Fascin, a sensitive new marker for Reed-Sternberg cells of hodgkin's disease. Evidence for a dendritic or B cell derivation?

Immunohistochemical localization of human fascin, a distinct 55-kd actin-bundling protein, was determined for a wide variety of lymphoid tissues (364 specimens total). In non-neoplastic tissues, reactivity was highly selective and localized predominantly in dendritic cells. In the thymus, this protein was distinctly localized to medullary dendritic cells. In reactive nodes, interdigitating reticulum cells of T zones, cells in subcapsular areas, and cells of the reticular network were reactive, with variable reactivity observed for follicular dendritic cells. Splenic dendritic cells of the white pulp and sinus-lining cells of the red pulp were reactive. Endothelial cells of all tissues exhibited variable reactivity. Lymphoid cells, myeloid cells, and plasma cells were uniformly nonreactive. In the peripheral blood, only dendritic (veiled) cells were reactive for fascin. A striking finding was observed for cases of Hodgkin's disease (total 187 cases). In all cases of nodular sclerosis (132), mixed cellularity (34), lymphocyte depletion (2), and unclassified types (5), all or nearly all Reed-Sternberg cells and variants were immunoreactive for fascin. Neoplastic cells exhibited strong diffuse cytoplasmic staining and frequently assumed dendritic shapes, particularly in the nodular sclerosis type, producing an interdigitating meshwork or syncytial network of cells. In cases of mixed cellularity type, neoplastic cells generally appeared more discrete. In all 14 cases of nodular lymphocyte predominance type, L&H variants were nonreactive. By contrast, neoplastic lymphoid cells of only 24 of 156 (15%) other lymphoid neoplasms (127 B cell, 27 T cell, and two null cell evaluated) were reactive for fascin. Fascin represents a highly effective marker for detection of certain dendritic cells in normal and neoplastic tissues, is an extremely consistent marker for Reed-Sternberg cells and variants of Hodgkin's disease (except L&H types), and may be helpful to distinguish between Hodgkin's disease and non-Hodgkin's lymphoma in difficult cases. The staining profile for fascin raises the possibility of a dendritic cell derivation, particularly an interdigitating reticulum cell, for the neoplastic cells of Hodgkin's disease, notably in nodular sclerosis type. However, as fascin expression may be induced by Epstein-Barr virus infection of B cells, the possibility that viral induction of fascin in lymphoid or other cell types must also be considered in Epstein-Barr virus-positive cases.

B-Lymphocytes↗
PubMed1997

Human immunodeficiency virus-related lymphoid proliferations.

Human immunodeficiency virus (HIV) infection is associated with a range of lymphoid alterations from generalized lymphadenopathy to abnormal lymphoid proliferations and malignant lymphomas. Special characteristics of lymphoid proliferation are seen in the lungs and thymus of children infected with HIV. HIV-related lymphoid proliferations may be associated with other infectious agents including pneumocystis carinii, mycobacteria, rickettsial-like organisms, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). The histological features of the spectrum of lymphoid proliferations associated with HIV infection are described.

HIV Infections↗
PubMed1997

The role of follicular and interdigitating dendritic cells in HIV-related lymphoid hyperplasia: localization of fascin.

Fascin is a 55-kDa, actin-bundling protein expressed in follicular and interdigitating dendritic cells (DCs). Because these cells play a pivotal role in the pathogenesis of human immunodeficiency virus-related lymphoid hyperplasias (HLP), we evaluated them in 49 cases by immunohistochemical localization of fascin, and we related the findings to the histologic stage of disease. Fifteen cases of early HLP revealed strong localization of fascin within DCs of hyperplastic follicles and intense staining in interdigitating DCs and their processes in the interfollicular zones. Some follicles revealed focal disruption of the fascin-positive dendritic framework. DCs were also aligned beneath the peripheral sinuses of the node. In 15 cases of progressive HLP with partial follicular involution, 3 cases revealed findings similar to those described above. Twelve cases revealed loss of follicular dendritic staining, which was moderate in five cases and marked in seven. Residual clusters of DCs remained after partial dissolution. Interfollicular dendritic staining was reduced in 13 cases, and perisinusoidal staining was reduced in 7. In late-stage HLP, staining of both follicular and interdigitating DCs was reduced or absent. Nine cases of diffuse immunoblastic or angioimmunoblastic lymphadenopathy-like proliferation had markedly reduced or absent follicular DCs, but prominent staining was present in interfollicular DCs, which formed a meshwork throughout the node in eight cases. Two cases of hyaline-vascular lymphoid hyperplasia had increased follicular DCs forming a tight syncytial network. In most cases, there was reduction of dendritic fascin-expressing cells with advanced disease and destruction of the dendritic framework of the node. Diffuse hyperplasia of fascin-positive interdigitating cells occurred in cases with angioimmunoblastic morphologic features, and cases of hyaline-vascular lymphoid hyperplasia had increased follicular dendritic histiocytes forming a tight syncytial network. Destruction of DCs and, in some cases, interdigitating cell hyperplasia might be associated with the variable clinical course of HLP.

Biopsy↗
PubMed1997

Donor origin of posttransplant lymphoproliferative disorder localized to a liver allograft: demonstration by fluorescence in situ hybridization.

SETTING: Posttransplant lymphoproliferative disorders in solid organ transplantation are mostly of recipient origin. We report an unusual case of posttransplant lymphoproliferative disorder following liver transplantation with localized limited involvement of the solid organ allograft. DESIGN: Tissues were obtained at the time of surgery and evaluated by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization with chromosome X and Y centromeric probes. PATIENT: A 53-year-old Hispanic man with hepatic failure due to hepatitis C virus who underwent orthotopic liver transplant from a female donor and developed posttransplant lymphoma in the transplanted liver. INTERVENTION: Withdrawal of immunosuppression, resection of liver allograft, and second transplant. RESULTS: This posttransplant lymphoproliferative disorder was clearly shown to be derived from Epstein-Barr virus-infected donor lymphoid cells. This was demonstrated by fluorescence in situ hybridization for X and Y chromosomes in paraffin sections in a sex-mismatched transplant. Despite aggressive histology (monoclonal B-cell immunoblastic lymphoma) and lack of response to withdrawal of immunosuppression, the posttransplant lymphoproliferative disorder was successfully managed by repeat liver transplantation without recurrence. CONCLUSION: Fluorescence in situ hybridization was used to prove donor derivation in a posttransplant lymphoma of the liver. Allograft-localized donor posttransplant lymphoproliferative disorder may represent a unique category with more favorable prognosis requiring different clinical management from other cases.

Female↗
PubMed1996

Primary effusion lymphoma in women: report of two cases of Kaposi's sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women.

Recent molecular evidence suggests an association with a new herpes virus, Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8), and primary effusion lymphomas (PEL). PELs have a characteristic morphology, phenotype, and clinical presentation with malignant effusions in the absence of a contiguous solid tumor mass. Most cases of PEL have occurred in human immunodeficiency virus (HIV)-positive male patients who are coinfected with Epstein-Barr virus (EBV). This report describes two cases of PEL in HIV- and EBV-negative women. In one patient, a pleural cavity PEL was preceded by classic Kaposi's Sarcoma (KS) of the lower extremities. In the second patient, PEL developed in an artificial cavity related to the capsule of a breast implant. Both cases had the characteristic morphologic appearance of high-grade anaplastic/B-cell immunoblastic lymphomas, with loss of B-cell differentiation antigens, clonal immunoglobulin heavy chain gene rearrangements, and expression of activation antigen CD30. Both cases were negative for EBV, herpes virus simplex, and cytomegalovirus (CMV). DNA extracted from both lymphomas and skin KS specimen showed KSHV sequences by molecular analysis. This report expands the spectrum of KSHV-associated disease to include PEL in HIV-negative women.

Aged↗
PubMed1996

Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein-Barr virus.

The recently identified Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), has been found to be consistently associated with an unusual subset of acquired immunodeficiency syndrome-related lymphomas, the so-called body cavity-based lymphomas (BCBL) or primary effusion lymphomas (PEL). These lymphomas are characterized by a unique spectrum of morphologic and molecular characteristics, and grow as lymphomatous effusions without an identifiable contiguous tumor mass. Until now, efforts to delineate the role of KSHV in the pathogenesis of PELs have been hampered by the lack of appropriate model systems and the concomitant presence of Epstein-Barr virus (EBV) in nearly all cases examined, and in all previously established cell lines. We now report the establishment and characterization of a novel PEL cell line, BC-3, which is KSHV+ by polymerase chain reaction (PCR) but EBV- as assessed by a variety of methods including PCR for EBER, EBNA-2, and EBNA-3C. This cell line was established from a lymphomatous effusion obtained from an HIV- patient, and has immunophenotypic and molecular features consistent with the diagnosis of PEL, including an indeterminate immunophenotype with a B-cell immunogenotype and lack of c-myc proto-oncogene rearrangements. Pulsed-field gel electrophoresis shows an intact KSHV genome of about 170 kb both in the cell line and in the viral isolate, whereas herpesvirus-like capsids are visible by electron microscopy. Consequently, the BC-3 cell line represents an invaluable tool as a source of KSHV, for both the evaluation of the pathogenic potential of this virus and the mechanistic characterization of its role in the development of Kaposi's sarcoma and malignant lymphoma.

Electrophoresis, Gel, Pulsed-Field↗
PubMed1996

mdm-2 oncogene expression in non-Hodgkin's lymphomas.

The mdm-2 protein is a 90-kD protein that forms a complex with the p53 protein, enabling cells from some human neoplasms to overcome the growth-suppressing activity of p53. Most non-Hodgkin's lymphomas lack p53 mutations, and the mechanism of inactivation of tumor suppressive function remains obscure. To assess the role of mdm-2 in lymphomagenesis, 22 cases were evaluated for mdm-2 gene amplification or rearrangement in Southern blots. Localization of the mdm-2 protein was performed on cryostat sections and compared with expression of the p53 gene product. No case exhibited mdm-2 gene amplification or rearrangement, but overexpression of nuclear mdm-2 gene protein product was found in three of six diffuse large cell (B-cell immunoblastic) lymphomas (30-70% of the tumor cells stained). The mdm-2 protein was absent from low- and intermediate-grade lymphomas with the exception of a few cells (5% or less) in four cases. The mdm-2-positive cases stained negative for p53. Southern blot analysis showed that samples overexpressing mdm-2 did not have amplification or rearrangement of the gene. In summary, amplification of the mdm-2 gene does not appear to play a prominent role in the pathogenesis of non-Hodgkin's lymphomas, although overexpression of the protein gene product occurs, particularly in high-grade neoplasms.

Blotting, Southern↗
PubMed1996

Remission of acromegaly caused by pituitary carcinoma after surgical excision of growth hormone-secreting metastasis detected by 111-indium pentetreotide scan.

GH-secreting carcinomas of the pituitary are extremely rare. We describe a 37-yr-old woman with refractory acromegaly 15 yr after transphenoidal surgery and radiotherapy, with no evidence of a recurrent pituitary mass. Scanning with 111-indium pentetreotide revealed an area of intense activity in the left neck. A 3.5 x 2.5-cm mass was excised from the neck after demonstrating an arterio-venous GH gradient of 7:1. GH levels (50 ng/mL) dropped to 0.8 ng/mL 3 h after surgery and remained normal. GH gene expression was demonstrated in the metastasis by Northern and Western blot analyses and by positive immunocytochemistry and immunoelectron microscopy. In vitro cultured cells responded to GHRH and TRH by increasing GH levels (P < 0.01). Medium GH was identical to authentic pituitary GH, as demonstrated by high pressure liquid chromatography. RT-PCR of hypothalamic hormone receptor messenger RNA in the mass revealed somatostatin receptor subtypes 2, 3, and 5 and GHRH, TRH, and dopamine receptor expression. No GH gene amplification, rearrangement, or gsp mutation was found. RB gene deletion and H-ras mutations, previously reported in PRL- and ACTH-secreting carcinomas, were not detected. In conclusion, clinical and molecular features of a GH-secreting pituitary carcinoma are presented. This metastatic lesion synthesized GH and expressed functional hypothalamic hormone receptors.

Acromegaly↗
PubMed1996

p53 in lymphomas of mucosal-associated lymphoid tissues.

Lymphomas of mucosal-associated lymphoid tissues (MALT) constitute a distinct clinicopathologic entity comprised of centrocyte-like cells with a characteristic morphologic appearance and immunophenotype. The origin of these cells is still undetermined, although evidence suggests that they might derive from marginal zone lymphocytes present in normal lymph nodes and spleens. Recently, marginal zone lymphomas have been shown to have a high rate of p53 mutation. To determine whether p53 mutations were also present in MALT lymphoma, we evaluated specimens from eight patients (six gastric specimens, one parotid, and one from the small bowel) for p53 mutations using polymerase chain reaction and single strand conformational polymorphism analysis. Exon-4 through exon-8 were evaluated, because these are common sites of p53 mutation. In addition, tissues from 15 patients with MALT (including seven studied by single strand conformational polymorphism analysis) were examined for expression of p53 gene protein product by immunohistochemical techniques. All specimens were negative for p53 mutations, suggesting that mechanisms of lymphomagenesis are different for MALT than for splenic marginal zone lymphomas. Despite the absence of p53 point mutations, p53 gene product was localized in tissues from three of 15 patients with MALT. Staining was restricted to nuclei of neoplastic cells and was present in less than 10% of the cells. In summary, low-grade MALT lymphomas differ from marginal zone lymphomas in lacking p53 point mutations, although some patients express low levels of p53 gene product.

Base Sequence↗
PubMed1996

Kaposi's sarcoma-associated herpesvirus in non-AIDS related lymphomas occurring in body cavities.

DNA sequences belonging to the recently discovered Kaposi's sarcoma-associated herpesvirus (KSHV), now provisionally designated human herpesvirus 8, have been previously identified in an uncommonly occurring subset of AIDS-related lymphomas, referred to as body-cavity-based lymphomas (BCBLs), which present as lymphomatous effusions. Pyothorax-associated lymphomas (PALS) are non-Hodgkin's lymphomas that arise in the pleural cavity after long-standing pleural inflammation resulting from therapeutic artificial pneumothorax or from tuberculosis pleuritis. Although PALs present as solid tumor masses, they are otherwise similar to BCBLs in that they also are B cell lymphomas, usually exhibit immunoblastic morphology, and contain Epstein-Barr virus. We investigated whether KSHV sequences are present in 2 BCBLs in patients without AIDS and 12 in Japanese and 2 French PALs. The 2 BCBLs were positive for KSHV sequences, whereaas all 14 PALs were KSHV negative. This finding strongly suggests that BCBLs and PALs are distinct clinicopathological entities and further strengthens the association between the presence of KSHV and an effusion phenotype. Based on these findings, we propose replacing the term body-cavity-based lymphoma with the term primary effusion lymphoma, which describes these non-Hodgkin's lymphomas more accurately and avoids confusion with other lymphomas that may occur in the body cavities, such as the PALs.

Aged↗
PubMed1996

Alterations of the cyclin-dependent kinase inhibitor p19 (INK4D) is rare in hematopoietic malignancies.

Cyclin-dependent kinase inhibitors (CDKIs) can be classified into two groups based on the structure of the proteins. One group includes the p21 (CIP1, WAF1, CAP20), p27 (Kip1), and p57 (Kip2) CDKIs, which contain a homologous amino-terminal cyclin-dependent kinase (cdk) inhibitory domain. The p16 (INK4A), p15 (INK4B), and p18 (INK4C) CDKIs, which have an ankyrin repeat motifs, belong to the other group. The p16 and p15 CDKI genes are very frequently altered in a variety of cancers including hematopoietic malignancies. The p19 (INK4D) gene is a newly cloned CDKI which belongs to the latter group. To determine if p19 genetic alterations play a role in hematopoietic malignancies, we examined DNA from 45 childhood newly diagnosed acute lymphocytic leukemias (ALLs), 30 acute myeloblastic leukemias (AMLs), 10 chronic myelocytic leukemias (CMLs), 45 adult T cell leukemias (ATLs), 70 non-Hodgkin's lymphomas (NHLs), and 20 multiple myelomas (MM) as well as 14 ALL, 20 AML, two ATL, and five lymphoma cell lines. Using Southern blot analysis, one homozygous deletion of the p19 gene was detected in a human immunodeficiency virus (HIV)-related Burkitt-like lymphoma sample. No point mutations in any of the samples were found by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Our investigation suggests that alterations of p19 do not play an important role in the development of most hematopoietic malignancies.

Base Sequence↗