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Biomedical subjects

A J Fishleder

Publications and source records attributed to A J Fishleder.

35 records · Page 2Linked to original sources

Systemic vasculitis in association with human immunodeficiency virus infection.

Fourteen cases of vasculitis associated with human immunodeficiency virus infection have thus far been described. Five of these cases may be classified as angiocentric immunoproliferative disorders, including benign lymphocytic angiitis, lymphomatoid granulomatosis, and angiocentric lymphoma. We report a case of benign lymphocytic angiitis of T cell lineage. Extensive studies found no evidence of viral antigens in the inflammatory infiltrates, and immunologic evaluation of the pathologic lesions revealed the infiltrating cells to be predominantly CD3+, CD8+, CD4-. A significant number of these lymphocytes demonstrated a deletion of T cell antigen receptor determinants. We believe that in certain cases of human immunodeficiency virus disease, there occurs a spectrum of lymphoproliferative disorders with angiocentric features that lead to the clinical picture of systemic necrotizing vasculitis. Clinicians should be aware of this association.

Acquired Immunodeficiency Syndrome↗

Investigation of the clonality of lymphocytes in Hashimoto's thyroiditis using immunoglobulin and T-cell receptor gene probes.

Southern blotting and DNA hybridization were used for the detection of immunoglobulin and T-cell receptor gene rearrangements in thyroid tissue from six patients with Hashimoto's thyroiditis, three patients with B-cell lymphoma complicating Hashimoto's thyroiditis, and two patients with nonspecific lymphocytic thyroiditis. Immunoglobulin gene rearrangements were detected only in patients with histologic evidence of lymphoma. A single T-cell receptor beta-chain gene rearrangement was detected in one of the patients with uncomplicated Hashimoto's thyroiditis. Based on our knowledge of primary thyroid lymphomas, it is highly unlikely that this case represents an early, histologically occult T-cell lymphoma. The uniform lack of immunoglobulin gene rearrangements in Hashimoto's thyroiditis supports the use of genotypic analysis in differentiating between uncomplicated Hashimoto's thyroiditis and non-Hodgkin's lymphoma. The finding of a T-cell receptor gene rearrangement in a case of Hashimoto's thyroiditis suggests that the immune response in this disease occasionally may be clonally restricted.

Adult↗

Immunoglobulin and T-cell receptor gene rearrangement. Implications for the diagnosis of lymphoproliferative disorders.

Recent studies have significantly broadened understanding of immunoglobulin production and T-cell receptor formation at the gene level. A limited number of genes can be rearranged during the course of B-cell or T-cell development to yield unique DNA sequences that will code for specific antibodies and T-cell receptor proteins. Southern blot hybridization analysis allows sensitive examination of lymphocyte DNA for the presence or absence of gene rearrangements. General mechanisms that underlie immunoglobulin and T-cell receptor rearrangement are reviewed, along with the diagnostic applications of detection of gene rearrangement by Southern blot hybridization technique.

Blotting, Southern↗

bcr rearrangement: potential false positive secondary to an Eco RI restriction fragment length polymorphism.

Molecular studies have demonstrated that the Philadelphia chromosome (Ph) translocation characteristic of chronic granulocytic leukemia (CGL) and 50% of the cases of Ph positive acute lymphocytic leukemia (ALL) involves a limited 5.8 Kb region on chromosome 22 termed the breakpoint cluster region (bcr). Detection of bcr rearrangement by Southern blot analysis has proven to be a sensitive diagnostic method and can identify this translocation in some cases which appear cytogenetically negative. Restriction fragment length polymorphisms (RFLP) which involve bcr have the potential to be misinterpreted as gene rearrangements since they result in alteration of the DNA fragment size detected by Southern blot hybridization. We have identified a RFLP involving bcr that is detectable with Eco RI digestion but not with Bam HI, BgI II, or Xba I. The polymorphic fragments generated indicate that this RFLP is the result of an Eco RI restriction site sequence polymorphism.

Adult↗

Immunophenotypic and genotypic characterization of diffuse mixed non-Hodgkin's lymphomas.

Diffuse, mixed small and large cell lymphomas (DML) are a heterogeneous group of non-Hodgkin's lymphomas. There are only a few published immunophenotypic and/or genotypic studies of DML, and they include a small number of cases. It is unclear whether these neoplasms are monoclonal, oligoclonal, or perhaps of dual lineage. Using monoclonal antibodies (UCHL1, MB2, MT1, LN1, LN2, and L26) that are effective in paraffin-embedded, B5-fixed tissue, 13 cases of DML were studied. This method allowed for improved correlation between cell morphology and immunophenotype compared with frozen section immunohistology. In addition, Southern blotting/DNA hybridization was used to identify directly the lineage of the neoplastic cell population. In each case a population of large B lymphocytes was demonstrated by immunohistology. In six of the cases, a single class of immunoglobulin light chains was detected by frozen section immunohistology, cytospin immunocytology, or both supporting the hypothesis that the B lymphocytes are monoclonal. In almost all the cases (12 of 13), the small cell population consisted predominantly of T lymphocytes. Immunoglobulin gene rearrangements were detected in seven cases, but no T cell receptor gene rearrangements were detected. It was concluded that DML are monoclonal lymphomas of B cell lineage with a non-neoplastic T cell component.

Blotting, Southern↗

Absence of B-cell or T-cell clonal expansion in nodular, lymphocyte predominant Hodgkin's disease.

Recent studies based upon immunophenotypic data have provided strong evidence that nodular lymphocyte predominant Hodgkin's disease (NLPHD) represents an entity that is distinct from other subtypes of Hodgkin's disease (HD). In contract to other forms of HD, the predominance of B-lymphocytes in NLPHD has prompted the thesis that this lesion is actually an atypical B-cell hyperplasia or follicular center cell lymphoma. Three cases of NLPHD by restriction endonuclease analysis were studied in an attempt to identify a clonal B-cell or T-cell expansion in this disorder. DNA was extracted from these tumors and hybridized to probes for the immunoglobulin genes (C kappa, C lambda, JH) and the T-cell receptor beta chain gene. Gene rearrangements were not detectable in any of the cases. The results provide genotypic evidence that there is not a monoclonal or oligoclonal proliferation of small B-lymphocytes or T-lymphocytes in NLPHD. The possibility that the L&H Reed-Sternberg cells are monoclonal cannot be excluded because their small number is below the level of sensitivity of this technique.

Antigens, Differentiation, T-Lymphocyte↗

Immunoglobulin and T-cell receptor genes in thymomas: genotypic evidence supporting the nonneoplastic nature of the lymphocytic component.

On the basis of morphologic and immunophenotypic studies, it is generally accepted that the lymphocyte population in thymomas is not neoplastic. We studied 10 thymomas with restriction endonuclease and Southern blot/DNA hybridization methods in an attempt to provide genotypic evidence in support of this hypothesis. The clinical, gross, and microscopic features of each case were reviewed and found to be entirely consistent with the diagnosis of thymoma. In addition to conventional histologic methods, we also studied each tumor by immunohistologic techniques. The lymphocytes generally had an immunotype characteristic of immature cortical thymocytes, and the epithelial cells were uniformly stained by antikeratin antibodies. DNA probes for the T-cell receptor beta-chain gene and immunoglobulin genes (C kappa, C lambda, and JH) were used in the genotypic studies. No gene rearrangements were detected in any of the thymomas. This study provides additional evidence that clonal proliferations of T or B lymphocytes are not present in thymomas; therefore, these cells are almost certainly not neoplastic. The results also provide a basis for the effective use of restriction endonuclease and Southern blot/DNA hybridization analysis in the differential diagnosis of non-Hodgkin's lymphoma and thymoma.

Adult↗

Immunotypic and genotypic characterization of non-Hodgkin's lymphomas of the ovary.

Ovarian non-Hodgkin's lymphomas (NHLs) are rare, and accurate diagnosis is frequently problematic. Previous studies have not provided either complete immunotypic or genotypic analyses. The authors report immunotyping and genotyping of three cases of ovarian NHL, including both primary and secondary types. Immunotyping disclosed all three were B-cell lymphomas composed of secretory blast stage lymphocytes showing kappa immunoglobulin (Ig) light chain clonal excess. DNA extracted from frozen tissue of each tumor was subjected to restriction endonuclease digestion and hybridized to probes for Ig genes, C kappa, C lambda, JH, and the T-cell receptor beta-chain gene. Rearrangements of the heavy chain and light chain Ig genes were observed in all three cases, confirming the monoclonal B-cell origin of the neoplastic population. No detectable rearrangements were observed in DNA extracted from three nonlymphoid ovarian tumors (dysgerminoma, granulosa cell tumor, and fibrothecoma). This study documents the potential value of immunotyping and genotypic analysis in the study of ovarian tumors.

Adult↗

Immunoregulatory Leu-7+ and T8+ lymphocytes in B-cell follicular lymphomas.

Lymphocyte subpopulations were profiled in lymph nodes and tonsils showing follicular hyperplasia and in follicular lymphomas with monoclonal antibodies on frozen tissue sections. Immunoregulatory lymphocyte subsets identified with T8 and Leu-7 monoclonal antibodies were quantified within the follicular centers (FC) of the nonneoplastic tissue and neoplastic follicles of the lymphomas with an optical grid defining a unit surface area (USA) of 0.04 mm2. T8+ cells were essentially confined to the interfollicular areas, with a few cells occupying the FC of the nonneoplastic specimens (mean, two and five cells/USA for tonsils and benign lymph nodes, respectively). Although lymphomas exhibited a similar pattern of distribution of T8+ cells, 17 T8+ cells/USA were observed in the follicular small cleaved cell (FSCL) group and eight T8+ cells/USA within the follicular mixed small cleaved and large cell (FML) group. Leu-7+ cells were almost entirely confined to the FC of the nonneoplastic tissues and increased (mean, 17 and 19 cells/USA for tonsils and benign lymph nodes, respectively) compared with the T8+ population. Variable distributions of Leu-7+ cells were found in the FSCL group, with a mean of 16 cells/USA. Very few Leu-7+ cells were present in the FML group. Natural killer cells and/or cytotoxic/suppressor T lymphocytes may play an immunoregulatory role in modulating the growth of follicular lymphomas.

Antibodies, Monoclonal↗

Immunophenotypic characterization of acute leukemia by immunocytology.

The potential for specific immunophenotypic characterization of the acute leukemias has been enhanced greatly by the development of monoclonal antibodies. Currently, this immunologic data is obtained most commonly by flow cytometric analysis or cellular cytotoxicity assays. The former is an expensive technic that lacks morphologic evaluation unless cell sorting is performed. The latter precludes morphologic assessment by the nature of the assay. The authors have developed an immunostaining procedure utilizing cytospin preparations and immunoperoxidase methods that are relatively inexpensive and allow simultaneous assessment of the immunologic markers and cellular morphology. Although a comparison of flow cytometry and immunocytology revealed quantitative differences for individual cell surface markers, the "qualitative" immunologic phenotype of the leukemic population was virtually identical by the two technics.

Acute Disease↗

Oncogenes and cancer: clinical applications.

Oncogenes are aberrant forms of proto-oncogenes, which are normal cellular genes that participate in cell growth and development; proto-oncogenes contribute to tumor formation when mutations or chromosomal translocation cause them to escape normal controls. Anti-oncogenes, also involved in neoplasm development, normally participate in inhibition of cell growth and proliferation; they become tumorigenic when mutations alter their function. Oncogene or anti-oncogene abnormalities have been characterized for a variety of tumors, with resulting clinical applications. In some forms of leukemia, for example, determining the presence or absence of the bcr-abl gene rearrangement has both diagnostic and prognostic value. The best-studied anti-oncogene is that found in retinoblastoma. Molecular techniques can differentiate the hereditary from the nonhereditary form of this disease and, with hereditary retinoblastoma, predict disease likelihood in family members.

Breast Neoplasms↗

Lambda light chain myeloma with pleural involvement.

A case is reported of lambda light chain multiple myeloma complicated by a myelomatous pleural effusion. Pleural effusions are uncommon in multiple myeloma, and most are secondary to nonmalignant causes. The clinical characteristics, natural history and pathophysiology of myelomatous pleural effusions are reviewed.

Aged↗