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Biomedical subjects

J W Said

Publications and source records attributed to J W Said.

At least 91 records · Page 5Linked to original sources

Absence of bcl-2 major breakpoint region and JH gene rearrangement in lymphocyte predominance Hodgkin's disease. Results of Southern blot analysis and polymerase chain reaction.

Recent evidence suggests that nodular lymphocyte predominance Hodgkin's disease (NLPHD) is a distinct entity that may be related to progressively transformed germinal centers, abnormal B-lymphoid hyperplasia, and low-grade B-cell lymphoma. bcl-2 is a marker for the translocation t(14;18)(q32;q21), which occurs in most follicular-derived B-cell lymphomas. Eleven cases of NLPHD and 19 cases of Hodgkin's disease of nodular sclerosis (NSHD) and mixed cellularity (MCHD) type were analyzed for immunoglobulin JH gene rearrangement. bcl-2 translocation was determined with Southern blot analysis and the polymerase chain reaction using biotin labeled probes to the major breakpoint region and the alkaline phosphatase reaction. All cases of NLPHD were negative for JH gene rearrangement and bcl-2 translocation. Cases of NSHD and MCHD were similarly negative for bcl-2, although three cases exhibited clonal JH gene rearrangements. These results confirm that a clonal B-cell population is not detected in NLPHD. Cases of NLPHD differ from most low-grade follicular B-cell lymphomas in that they lack bcl-2 gene rearrangement and t(14;18) translocation at the major breakpoint region.

Amino Acid Sequence↗

Immunohistochemical localization of human immunodeficiency virus (HIV) in central nervous system lymphoproliferative disorders of patients with AIDS.

Immunohistochemical localization of human immunodeficiency virus type 1. (HIV-1) in central nervous system lymphoma lesions and uninvolved regions of the brain in seven patients with AIDS revealed evidence of frequent association of HIV-labeled macrophages and multinucleated giant cells with the lesions. Five of seven cases displayed a higher density of labeled cells within and at the periphery of mass lesions and angiocentric infiltrates than in brain parenchyma farther than 1 cm from such lesions. In addition, no label was detected within the neoplastic lymphoid cells in any patient. HIV could not be localized within similarly appearing macrophages associated with destructive lesions (e.g. related to cytomegalovirus encephalitis) or small thrombotic infarcts in brain tissue from the same patients. All lymphomas studied were of a high-grade B-cell type with similar histology in multiple sites. Leptomeningeal spread of the tumor was found in all cases. Facilitation of the development of malignant B-cell clonal proliferation might occur in foci of HIV replication. Alternatively, the development of lymphoma may be due to the generalized immunosuppression; in this case, local activation of macrophages in proximity to the malignant lymphocytes might lead to preferential concentration of disseminated virus by these cells.

Acquired Immunodeficiency Syndrome↗

Peripheral/post-thymic T-cell lymphomas: a spectrum of disease. Clinical, pathologic, and immunologic features of 78 cases.

The clinical, pathologic, and immunologic features of 78 cases of peripheral/post-thymic T-cell lymphomas are described. These neoplasms were extremely heterogeneous and were classified as small lymphocytic, mixed small and large cell, large cell, lymphoepithelioid cell, angiocentric, and adult T-cell leukemia/lymphoma type. Some cases revealed angioimmunoblastic or Hodgkin's-like features. These neoplasms mainly affected older adults (mean age, 57 years; median age, 60 years). Lymphadenopathy represented the most frequent clinical presentation, although most patients demonstrated both nodal (87%) and extranodal involvement (77%) during the course of disease. Sites of extranodal disease included skin/soft tissue, spleen, lung, liver, bone, gastrointestinal tract, central nervous system, peripheral blood, nasopharynx, and retrovaginal tissue. Splenomegaly at presentation was most frequently observed in lymphoepithelioid cell lymphomas. Angiocentric lymphomas involved lung. A mediastinal presentation was typically observed in young adults and associated with a poor prognosis. Patients with gastrointestinal lymphomas presented with bleeding and/or malabsorption. B symptoms were present in most cases (65%). Hypercalcemia occurred in four patients. Phenotypic studies of T-cell antigens demonstrated the loss of one or more pan-T-cell markers in eight of 47 cases evaluated. Assessment of T-cell subsets revealed a helper/inducer phenotype for nearly all immunoreactive cases. For the overall series, 32 patients died of disease (median survival time, 11.5 mo). There was a statistical difference between the combined groups of small lymphocytic and lymphoepithelioid cell types as compared with mixed and large cell types, with a poorer survival for the latter group. Angiocentric and adult T-cell leukemia/lymphoma were associated with poor survival. This series of T-cell lymphomas further documents the marked heterogeneity of this group of neoplasms as well as the poor prognosis observed for certain histologic types.

Adolescent↗

Specific phenotyping of T-cell proliferations in formalin-fixed paraffin-embedded tissues. Use of antibodies to the T-cell receptor beta F1.

Antibody beta F1 to a common framework determinant of the beta subunit of the T-cell receptor (TCR) was used as a specific phenotypic marker for T-cell differentiation in malignant lymphomas. Sensitivity of immunoperoxidase staining in paraffin sections was enhanced by pronase pretreatment, overnight incubation of primary antibody in Tween 20, and use of streptavidin horseradish peroxidase complexes to amplify the reaction. All 43 cases of B-cell lymphoma were negative for TCR. Reed Sternberg (RS) cells in 3 of 20 cases of Hodgkin's disease exhibited cell membrane staining for TCR (all nodular sclerosis type), further evidence that some RS cells may be T-cell derived. Twenty-nine of 44 cases of T-cell lymphoma expressed TCR (66%). These included 11 of 12 cases of peripheral T-cell lymphoma (PTCL) of small and mixed cell type, 8 of 9 cases of lymphoepithelioid cell (Lennert's) lymphoma, and 2 of 4 cases of T-cell lymphoblastic lymphoma. Loss of immunoreactivity for TCR occurred in lymphomas of large or activated T-cell type, including 7 of 9 cases of T-cell immunoblastic lymphoma and 3 of 4 cases of large cell PTCL. Antibody beta F1 is a specific and relatively sensitive marker of T-cell phenotype in formalin-fixed paraffin sections of malignant lymphomas.

Antibody Specificity↗

Diagnosis of malignant lymphoma in effusions from patients with AIDS by gene rearrangement.

Patients infected with human immunodeficiency virus are prone to a wide variety of lymphoproliferative disorders. In these patients the clinical presentation of malignant lymphoma often overlaps with that of benign lymphoid proliferations. Both may include lymphadenopathy, splenomegaly, blood and bone marrow dyscrasias, and lymphocyte-rich effusions. Because benign and malignant lymphocyte-rich effusions, as well as effusions from other malignancies, may contain large cells that resemble immunoblasts or Burkitt's cells, cytomorphologic characteristics alone are unreliable for definitive diagnosis of malignant lymphoma. Usual immunotyping panels using antibodies to B- and T-cell markers frequently fail to demonstrate cell lineage in lymphoma cells of patients with acquired immune deficiency syndrome (AIDS). The authors used gene rearrangement to confirm the diagnosis of malignant lymphoma in effusions from three patients with AIDS when routine cell marker studies failed to demonstrate cell lineage or clonality. Use of biotinylated probes eliminated the need for handling radioactive material and enabled performance of studies in a routine immunohistochemistry laboratory.

Acquired Immunodeficiency Syndrome↗

Polymerase chain reaction for bcl-2 in diagnostic lymph node biopsies.

bcl-2 is a marker for the translocation t(14;18)(q32;q21) indicative of follicular B-cell lymphoma. We studied 115 cases of lymphoproliferative disease with the polymerase chain reaction for bcl-2 oncogene using biotin and radiolabeled probes to the major breakpoint and minor cluster regions. Twenty-three percent of B-cell lymphomas were positive for bcl-2. These included 12 of 20 cases of nodular follicular center cell lymphoma (nine small cleaved cell, one mixed small and large cell, and two large cell types). bcl-2 translocation was detected in only three of 45 cases of diffuse B-cell lymphoma, and cases of AIDS-related malignant lymphoma, monocytoid B-cell lymphoma, and mantle zone lymphoma were all negative. Nonneoplastic lymphoid proliferations were negative for bcl-2 including nine cases of abnormal follicular hyperplasia from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Cases of T-cell lymphoma and five cases of Hodgkin's disease were also negative. The polymerase chain reaction for bcl-2 is a rapid, sensitive technique in the evaluation of follicular B-cell proliferations, and the use of biotinylated probes and the alkaline phosphatase reaction eliminates the requirement for radioactive reagents.

AIDS-Related Complex↗

Leu-22: a preferential marker for T-lymphocytes in paraffin sections. Staining profile in T- and B-cell lymphomas, Hodgkin's disease, other lymphoproliferative disorders, myeloproliferative diseases, and various neoplastic processes.

Monoclonal antibody Leu-22 represents an effective reagent for detection of neoplastic and nonneoplastic T-cells in paraffin sections of routinely processed tissues (242 specimens evaluated). In nonneoplastic tissues, immunoreactivity was localized mainly to lymphoid cells corresponding to a T-cell distribution. Immunoreactivity in lymphoid neoplasms, however, was preferentially, but not exclusively, limited to T-cell populations. Fifty-four of 60 T-cell neoplasms (90%) of various histologic types were Leu-22 positive. The pattern of immunoreactivity consisted mainly of membrane staining, with focal weak cytoplasmic positivity. Twenty-five of 67 B-cell neoplasms (37%) were also Leu-22 positive, with low-grade lymphomas (well/moderately well-differentiated lymphocytic types) representing most immunoreactive cases. In Hodgkin's disease, although most small lymphoid cells were Leu-22 positive, only rare Reed-Sternberg cells were immunoreactive. In all cases, histiocytes and myeloid cells exhibited variable immunoreactivity. The epitope identified by Leu-22 was detectable in formalin- and B5-fixed tissues but apparently was denatured after fixation in Zenker's-acetic acid solution used for bone marrow biopsies. Evaluation of a wide variety of nonhematopoietic neoplasms (64 total) revealed diffuse cytoplasmic staining in a few cases. However, membrane staining, typically noted for lymphoid cells, was not observed. Leu-22 potentially represents a useful marker for lymphoid cells, preferentially of T-cell origin, with optimal applicability as part of a panel that includes an effective pan-B-cell marker.

Antibodies, Monoclonal↗

Identification of growth hormone at the myocardial cell surface.

Growth hormone immunoreactivity has been demonstrated in a variety of normal human tissues, and ectopic production has been documented in a number of malignant tumors. However, myocardium has not previously been reported to contain growth hormone. Monkey anti-rat growth hormone antiserum was used in a sensitive immunoperoxidase staining method to histologically localize growth hormone in myocardium obtained from normal rats and rats harboring growth hormone-secreting tumors. Immunoreactive growth hormone was localized to the myocardial cell surface and was not seen in vascular endothelial cells of small arteries, veins, or capillaries. No intracellular staining of myocytes was evident. Specific staining was abolished by neutralization with purified growth hormone. Specific staining was abolished by neutralization with purified growth hormone. Myocardial cells did not stain with anti-triiodothyronine or anti-thyroxine immune serum. The cell surface staining is consistent with the binding of growth hormone to the myocardial cell surface, as it is unlikely that the myocardium synthesizes growth hormone polypeptide. These findings suggest that growth hormone may have a direct growth promoting or metabolic effect on cardiac tissue.

Animals↗

Immunopathology of interstitial cystitis.

This study describes histologic, ultrastructural, and immunofluorescence microscopy findings of cystoscopically directed biopsies of lesional tissue and uninvolved bladder from 308 patients with chronic interstitial cystitis (IC) and no evidence of infection, collagen vascular, or other systemic disease. The majority of cases exhibited strong urothelial cell staining for immunoglobulin A (IgA), which was focal or diffusely involved all layers of the epithelium. Electron microscopy revealed widening of the interstitium between urothelial cells, which may explain leakage of IgA into the urine in cystitis patients. Staining for fibrinogen and IgA was present both in lesional biopsies and uninvolved bladder tissue, suggesting a response to injury affecting the entire bladder urothelium. A minor patient population with idiopathic IC revealed granular IgM (with or without C3) in vessel walls of the lamina propria, suggesting immune complex disease. Ultrastructural evidence of vascular damage included necrosis of endothelial cells, fibrin deposition, and reduplication of basement membranes. Staining for IgE correlated with presence of mast cells and was present in less than 2% of cases, indicating that these cells do not play a prominent role in the pathogenesis of the disease. In the majority of patients with IC mucosal staining for IgA and fibrinogen was a characteristic pattern representing increased IgA secretion and a reaction pattern to injury of unknown cause. A subgroup of patients had evidence of vascular damage and immune complex disease. This study therefore defines two main reaction patterns in interstitial cystitis, which may have implications on prognosis and therapy of the disorder.

Adult↗

Immunohistochemical staining for terminal deoxynucleotidyl transferase (TDT). An enhanced method in routinely processed formalin-fixed tissue sections.

This report describes an improved technique for sensitive and specific localization of terminal deoxynucleotidyl transferase (TdT) in routinely processed paraffin-embedded, formalin-fixed tissue sections using DNAse pretreatment and the avidin-biotin complex (ABC) technique. This method is useful in identifying lymphoblastic lymphomas (14/15 cases positive), with all other B- and T-cell lymphomas tested negative for the reaction. Used in conjunction with monoclonal antibodies immunoreactive for T- and B-cells in paraffin sections this technique should prove helpful in immunophenotyping malignant lymphomas where fresh tissue is unavailable for study.

B-Lymphocytes↗

Cytodiagnosis of malignant melanoma. Immunoperoxidase staining with HMB-45 antibody as an aid to diagnosis.

The specificity and sensitivity of HMB-45, an antimelanoma monoclonal antibody, was evaluated in cytologic specimens from extracutaneous melanomas. Melanoma cells in 23 of 25 (92%) cases stained with this antibody. Staining was intense and diffuse in 22 of these melanomas and focal in 1. Amelanotic tumors and tumors with scanty pigment were included. Neither degree of pigmentation, site of primary, cytologic characteristics of tumor, nor source of specimen predicted the immunostaining pattern. Cytopreparations containing benign (6 cases) and malignant (16 cases) cells with which melanoma may be confused constituted the nonmelanoma group. None of the 22 cases in this group stained. Undifferentiated carcinomas, adenocarcinomas, large cell lymphomas, sarcomas, mesothelial hyperplasias, and a benign nerve sheath tumor were included. Effusions, fine-needle aspirates, bronchial material, and imprints were studied. All smears had been fixed and stained by Papanicolaou's method before immunostaining. Excellent cytomorphologic characteristics were preserved, and immunostaining was not affected. HMB-45 antibody is a highly specific and sensitive marker for malignant melanoma in cytologic material.

Antibodies, Monoclonal↗

Human chorionic gonadotropin expression in lung, breast, and renal carcinomas.

Conflicting results have emerged from studies that have examined nontrophoblastic tumor tissue for the presence of human chorionic gonadotropin (hCG) by immunoperoxidase techniques. We evaluated 11 lung carcinomas, ten breast carcinomas, and ten renal cell carcinomas for the presence of immunoreactive hCG by the avidin-biotin-horseradish peroxidase method. The hCG was found in 36% (4/11) of lung tissues, 10% (1/10) of breast tumors, and none of renal tumors. These values are lower than earlier reports for the frequency of detected hCG in the tumor tissue, but they are similar to several more recent studies. The possible reason for these discrepancies are discussed.

Adenocarcinoma↗

AIDS-related lymphadenopathies.

Lymphoid proliferations in the acquired immunodeficiency syndrome reflect the profound immunologic imbalances induced by the lymphotropic human immunodeficiency virus, and comprise a range of lymphoproliferative disorders from benign lymphadenopathy to malignant lymphoma. Persistent generalized lymphadenopathy (PGL) is associated with a frequently debilitating complex of clinical symptoms and waxing and waning lymphadenopathy. Biopsies of lymph nodes, bone marrow, and other involved tissues show a spectrum of abnormal lymphoid proliferations, with eventual lymphoid depletion, lymphadenopathic Kaposi's sarcoma, and malignant lymphoma. Although individual features of AIDS-related lymphadenopathy may not be specific, the constellation of histologic, immunologic, and ultrastructural findings is highly characteristic of the disorder and useful as a predictor of clinical course. Malignant lymphomas that develop within this setting of multicloncal B cell expansion and impaired immune surveillance have distinctive clinical, histologic, and molecular biologic parameters.

AIDS-Related Complex↗

DNA content of T-cell lymphomas. A flow-cytometric analysis.

Paraffin-embedded archival tissue from 29 cases of malignant non-Hodgkin's lymphoma of T-cell type and 9 control lymph nodes were examined by flow cytometry for DNA aneuploidy and cell-cycle kinetics. DNA aneuploidy was detected in 4 cases (13%) and was not related to histologic grade. Proliferative activity, as measured by proliferative index and S-phase fraction, was significantly increased in lymphomas, compared with controls, and was significantly higher in morphologically high-grade lymphomas, compared with low-grade lymphomas and control lymph nodes (P less than 0.05). Different morphologic types of T-cell lymphoma were also significantly different in their proliferative activity P less than 0.05). Moreover, within the category of peripheral T-cell lymphoma, different proliferative rates occurred in tumors in which small cells predominated, compared with intermediate- and large-cell tumors, suggesting biologic differences within this group.

Aneuploidy↗

Hodgkin's disease, lymphocyte predominance type, nodular--further evidence for a B cell derivation. L & H variants of Reed-Sternberg cells express L26, a pan B cell marker.

Immunoreactivity for L26, a highly effective pan B cell marker that can be detected in paraffin sections, was evaluated in 72 cases of Hodgkin's disease of various histologic types. In all cases of nodular lymphocyte predominance type of Hodgkin's disease, L & H variants of Reed-Sternberg cells uniformly exhibited strong immunoreactivity for L26. Other variants of Reed-Sternberg cells, eg, lacunar, mononuclear, and diagnostic forms, present in nodular sclerosis, mixed cellularity, and lymphocyte depletion types of Hodgkin's disease, infrequently expressed L26 reactivity. In 55 of 63 cases (87%) of these combined types, less than 5% of Reed-Sternberg cells or variants were L26 positive. In the remaining cases, a larger proportion of these cells expressed L26. Topographic patterns of immunoreactivity for small lymphocytes in these different types of Hodgkin's disease also varied. In nodular lymphocyte predominance type, L26 positive lymphocytes (presumptive B cells) were mainly localized to nodular areas of the proliferation. In other types of Hodgkin's disease, L26 positive cells occurred in small or large aggregates and generally represented a minor proportion of the population of lymphoid cells. These studies further support a B cell derivation for L & H variants of Reed-Sternberg cells and provide additional evidence that nodular lymphocyte predominance type Hodgkin's disease may represent a distinct entity, possibly an unusual low grade B cell lymphoma. These data also suggest that some Reed-Sternberg cells and variants present in other histologic types of Hodgkin's disease may be of B cell derivation, and precludes the use of L26 as a diagnostic discriminant in cases in which the distinction between Hodgkin's disease and non-Hodgkin's lymphoma is unclear.

Antigens, Surface↗

Epithelial membrane antigen in the cytodiagnosis of effusions and aspirates: immunocytochemical and ultrastructural localization in benign and malignant cells.

Immunoreactivity for epithelial membrane antigen (EMA) was evaluated in exfoliated benign and malignant cells using immunoperoxidase and immunogold techniques. In addition, protein A-colloidal gold was used for ultrastructural localization of EMA. Our results suggest that EMA is useful in distinguishing adenocarcinoma cells (strongly positive) from reactive mesothelial cells (negative or weakly positive), lymphoid cells (negative), and a variety of nonepithelial neoplasms (negative) with which they may be confused. Exfoliated cells from two mesotheliomas were also strongly positive for EMA. Ultrastructurally, EMA was distributed in a dense, even, linear pattern along the cell membrane and microvillous surface processes of adenocarcinoma cells. A similar but sparse distribution pattern was observed in reactive mesothelial cells. These observations reflect the increased sensitivity and higher resolution of the immunogold technique.

Adenocarcinoma↗

Ultrastructural localization of Leu M1 in Reed-Sternberg cells and normal myeloid cells.

An antigen Leu M1 has been localized to myelomonocytic cells and Reed-Sternberg cells by light microscopic immunocytochemical studies. We used both pre- and post-embedding immunoelectron microscopy to define the ultrastructural distribution of this antigen. Post-embedding techniques heavily labeled the granules of polymorphonuclear leukocytes and the nonspecific granules of eosinophils. At high concentrations there was labeling of the specific granules of the eosinophil. The antibody consistently labeled the perinuclear granules and vesicles of Reed-Sternberg cells. Some Reed-Sternberg cells also exhibited labeling of the endoplasmic reticulum, suggesting that these cells have the capacity to synthesize this antigen. Although plasma membranes were labeled with the post-embedding technique, these structures were most heavily labeled with the pre-embedding method. These results indicate that Leu M1 is synthesized and packaged by Reed-Sternberg cells and represents an integral structural component of these cells.

Antibodies, Monoclonal↗