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Biomedical subjects

A J Fishleder

Publications and source records attributed to A J Fishleder.

18 recordsLinked to original sources
PubMed1992

Precursor Langerhans cell histiocytosis. An unusual histiocytic proliferation in a patient with persistent non-Hodgkin lymphoma and terminal acute monocytic leukemia.

BACKGROUND: Langerhans cell precursors are considered to be identical to their mature counterparts except for the lack of Birbeck granules. Proliferations composed of such histiocytes appear to be uncommon. METHODS: Standard immunophenotypic, molecular genetic, and DNA content studies were used to characterize various hematopoietic disorders, including a proliferation of precursor Langerhans cells, which arose sequentially in a patient. RESULTS: The patient studied initially had a low-grade, B-cell, non-Hodgkin lymphoma and subsequently had an unusual histiocytic proliferation (precursor Langerhans cell histiocytosis) in cutaneous and lymph node sites. The patient eventually died of acute myelogenous leukemia (FAB, M5). CONCLUSIONS: A larger series is required to determine the significance of the precursor Langerhans cell phenotype, particularly with respect to the development of acute myelogenous leukemia.

Adult↗
PubMed1992

Comparison of cisternal and lumbar CSF examination in leptomeningeal metastasis.

We compared cisternal and lumbar CSF examination in 14 patients suspected of having leptomeningeal metastasis from cancer. Malignant cells were present in 12 patients--in both cisternal and lumbar CSF in nine patients and only in cisternal CSF in three. Cisternal CSF cytologic examination should be considered in patients suspected of having leptomeningeal metastasis if lumbar CSF is nondiagnostic.

Adult↗
PubMed1992

Incidence of mixed chimerism using busulfan/cyclophosphamide containing regimens in allogeneic bone marrow transplantation.

The incidence of mixed chimerism (MC) following allogeneic bone marrow transplantation (allo-BMT) is in part a measure of the marrow ablative effect of preparative regimens. Although the incidence of MC has been reported for many patients treated with total body irradiation (TBI), limited data for busulfan/cyclophosphamide (BU/CY) recipients have been examined. We performed restriction fragment length polymorphism (RFLP) analysis on 68 peripheral blood samples from 26 patients treated with BU/CY prior to allo-BMT for chronic myelogenous leukemia or acute myeloid leukemia. MC was detected in four of 26 patients for an overall incidence of 15.4%. Three of four MC patients are alive with no evidence of disease at 263 to 795 days post-transplantation. A fourth patient is alive at day 501 but developed CNS relapse at day 274. The level of recipient origin cells was less than 10% in all samples and detectable MC was transitory with an RFLP pattern that reverted to full chimerism. These results are comparable to those reported for TBI-containing regimens in patients receiving non-T cell-depleted bone marrow. The efficacy of BU/CY in conjunction with a T cell depletion still requires exploration.

Adult↗
PubMed1992

Identification of monoclonal B-cell populations by rapid cycle polymerase chain reaction. A practical screening method for the detection of immunoglobulin gene rearrangements.

Alternatives to Southern blot hybridization for gene rearrangement analysis are being studied because of the time, labor, cost, and radioisotopes required for this technique. We have utilized a rapid, hot air, thermocycling polymerase chain reaction (PCR) system to examine various lymphoproliferative disorders for immunoglobulin heavy chain (IgH) gene rearrangements. This unique system amplifies DNA from 10 microliters samples placed in glass capillary tubes, over a total cycle time of about 30 minutes. Amplified bands are easily visualized on ethidium bromide-stained agarose gels. Forty-one monoclonal B-cell proliferations, 27 reactive lymphoid hyperplasias, 17 T-cell lymphomas and 3 cases of Hodgkin's disease were studied. All 88 cases were fully characterized by morphologic, immunophenotypic, and genotypic (Southern blot) analyses. Each case was separately evaluated by PCR with two primer pairs: 1) IgH variable region (VH) and IgH joining region (JH) and 2) bcl-2 and JH. Thirty-four of 41 monoclonal B-cell proliferations revealed a distinct band (within an expected base pair range) with 1 or both primer combinations supporting B-cell monoclonality; the other 7 cases were considered false negatives. The 47 entities without IgH gene rearrangements detectable by Southern analysis demonstrated no amplified product or a smear of amplified DNA with no distinct band. The overall specificity of PCR was 100%, and the sensitivity was 83% when directly compared with Southern blot analysis. Although its sensitivity is currently less than optimal, PCR is a rapid and practical screening method for the detection of IgH gene rearrangements. If a positive result is obtained no further analysis is required; however, if there is a negative result, standard Southern blot analysis should be performed to definitively exclude the presence of a monoclonal B-cell population in the sample.

B-Lymphocytes↗
PubMed1992

Pseudo-gamma heavy chain (IgG4 lambda) deposition disease.

Two patients with Ig deposition disease presented with acute renal failure, moderate proteinuria, and hematuria. A plasmacytoid lymphocytic infiltrate was identified in bone marrow that produced IgG4 lambda and free lambda light chains. One patient developed an anaplastic plasmacytoma (secreting only lambda light chains) 1 yr after renal biopsy. Renal biopsy in both patients demonstrated a nodular intercapillary glomerulopathy and electron dense granular deposits, associated with a linear pattern of IgG4 heavy chain deposition in vascular, tubular, and glomerular basement membranes (VBM, TBM, and GBM). In one patient this entrapped IgG4 was unassociated with detectable kappa or lambda light chains. In the second patient, lambda light chains (1+) were detected only in the GBM, but IgG4 (4+) was identified in GBM/TBM. Neither circulating (peripheral blood and bone marrow serum) nor cellular free gamma chains were present. We propose the term "pseudo-gamma heavy chain deposition disease" for the process.

Aged↗
PubMed1991

Concomitant delineation of surface Ig, B-cell differentiation antigens, and HLADR on lymphoid proliferations using three-color immunocytometry.

Accurate and consistent enumeration of B-cell subpopulations in lymphoid tissue was achieved through multiparameter three-color immunofluorescence and flow cytometric analysis (FCM). Phycoerythrin (PE)-anti-CD19 (Leu12) and biotinylated anti-HLADr/streptavidin-Duochrome (PE/Texas Red), used in conjunction with polyclonal fluorescein isothiocyanate (FITC) conjugated anti-surface immunoglobulin (SIg) antibodies, effectively separated non-specific binding and background fluorescence from true B-cell surface FITC immunofluorescence, while concomitantly analyzing for HLADr and CD19 phenotypic expression/deletion. Autofluorescence was measured to establish a fluorescence threshold. A second control measured non-specific binding of isotypic control mouse Ig and non-immune rabbit IgG. Cell suspensions from 128 samples of various lymphoid proliferations were studied. In 116 of the 128 samples, kappa/lambda ratios determined by flow cytometry correlated well with immunocytology results obtained using cytospins from the same cell suspension and with histopathologically established diagnosis. Clonality and lineage as defined immunotypically by flow cytometry was concordant with genotypic results in 64 of the 67 cases evaluated. SIg, HLADr, and CD19 deletions were demonstrated by flow cytometry in 8, 4, and 1 case(s), respectively. Discordance was usually attributable to selective loss of large neoplastic cells in flow cytometry specimens or absent expression of SIg by some cytoplasmic Ig (CIg+) lymphomas.

Antigens, CD↗
PubMed1991

The expression of CD22 (Leu 14) and CD11c (LeuM5) in chronic lymphoproliferative disorders using two-color flow cytometric analysis.

The monoclonal antibodies (MoAbs) CD22 and CD11c recognize B-lymphocyte- and monocyte-associated antigens, respectively. Reports indicate that when these two MoAbs co-express, they represent a unique marker for hairy cell leukemia (HCL) although neither is specific for that disease. The authors evaluated the expression and diagnostic utility of CD22 and CD11C in specimens from 26 normal subjects, 29 patients, with various nonlymphoproliferative disorders (NLPDs), and 75 patients with different types of chronic lymphoproliferative disorders (CLDs) using two-color flow cytometric analysis of peripheral blood lymphocytes. Lymphocytes co-expressed CD22 and CD11c in less than or equal to 3% of the normal subjects and in less than or equal to 6% of the patients with NLPDs. These markers were expressed in greater than 10% of the lymphocytes of 46% (32/69) of the patients with B-cell CLDs: B-cell chronic-lymphocytic leukemia, 9/41; B-cell non-Hodgkin's lymphoma, 8/14; HCL, 11/11; B-cell lymphoproliferative disorder (NOS), 1/2; and B-cell prolymphocytic leukemia, 1/1. None (0/6) of the lymphocytes of patients with T-cell CLDs expressed greater than 10% CD22-positive (CD22+) or CD11c-positive (CD11c+) cells. The HCL cases demonstrated a unique CD22+CD11c+ fluorescence histogram pattern, distinct from other lymphoproliferative disorders, that was characterized by uniformly intense CD11c and CD22 fluorescence. Differences in the expression of the CD22+CD11C- and CD22+CD11C+ phenotypes between diagnostic groups were found, most notable was a paucity of CD22+CD11c+ cells in lymphocytes of patients with HCL. CD22 also had more variable expression than CD19 and HLA-DR in the cases of B-cell CLD. This study demonstrates that the CD22+CD11c+ phenotype is not unique to HCL but is a consistent feature of that disorder and that the immunofluorescence pattern of co-expression in HCL is diagnostically useful.

Antigens, CD↗
PubMed1991

Frozen sections of cellular lymphoid proliferations provide adequate DNA for routine gene rearrangement analysis.

Optimal use of frozen tissue procured as part of a thorough diagnostic workup of suspected lymphoma is important, and conservation of similar samples is a prerequisite for maintaining a large and varied frozen archive repository. The authors have evaluated a simple tissue-conserving method for the preparation of cellular lymphoid specimens for immunoglobulin and T-cell receptor gene rearrangement analysis. Initially, 16-microns-thick frozen tonsil sections were examined to determine adequacy for DNA extraction. Specimens containing three, six, and nine sections each were evaluated separately. DNA quantitation disclosed yields ranging from 84 to 204 micrograms (mean, 156 micrograms). The authors have used this technique on 24 cellular lymphoid proliferations from their frozen archives. Six to ten 16-microns sections were used, depending on tissue size. DNA quantitation ranged from 0 to 520 micrograms (mean, 135 micrograms). Twenty-one of 24 cases yielded adequate DNA for analysis; each showed appropriate germline or rear-ranged bands with respect to the particular morphologic diagnosis. Attempts to obtain adequate DNA with the use of this technique on skin biopsy specimens with lymphoid infiltrates resulted in overall poor yields; this may be because of dermal collagen or small sample size. This method of sample preparation provides adequate DNA for routine Southern blot hybridization analysis of cellular lymphoid tissues and offers the additional advantage of allowing preservation of frozen tissue for future study.

Blotting, Southern↗
PubMed1991

Reliable and cost-effective paraffin section immunohistology of lymphoproliferative disorders.

We studied 110 neoplastic and reactive lymphoid proliferations with three monoclonal antibodies--CD20 (L26), CD43 (Leu22), and CD45RO (UCHL1)--on B5-fixed, paraffin-embedded tissue to evaluate the utility of this panel as an immunotypic screen of such lesions. All cases were initially immunotyped by conventional methods. Genotyping by Southern blot hybridization was also done in 54 cases. Seventy-four of 79 malignant lymphomas and both of two hairy cell leukemias were of B-cell origin; and five lymphomas were defined as T-cell lineage. Lineage assignment was identical for paraffin section immunohistology and conventional immunotyping in 73 of 76 B cell and all of five T-cell tumors. CD20 was reactive with 73 of 76 B-cell tumors. CD43 was reactive with 12 of 74 B-cell lymphomas, and CD20/CD43 coexpression was seen in 11 of these cases. CD43 and CD45RO marked all of five and three of five T-cell lymphomas, respectively. Lineage assignment was identical for paraffin immunohistology and genotyping in 48 of 50 cases with identifiable gene rearrangements. Twenty-four nonneoplastic and five Hodgkin's disease cases that were studied also showed similar immunoreactivity patterns by both paraffin and conventional immunotypic methods. This panel of three monoclonal antibodies is an efficient, cost-effective approach for immunotyping most lymphoid proliferations in paraffin sections. Nevertheless, the pathologist should always try to obtain fresh or frozen tissue to aid in resolving occasional discrepant cases, to establish clonality in morphologically ambiguous ones, and to profile prognostically important phenotypic deletions.

Antibodies, Monoclonal↗
PubMed1990

Induction by interleukin-2 of oligoclonal expansion of cultured tumor-infiltrating lymphocytes.

To better understand the modulatory effects of interleukin-2 (IL-2) on lymphocyte proliferation, we examined the clonality of the in vitro T-cell response by Southern blot hybridization. Tumor-infiltrating lymphocytes (TILs) grown in the presence of IL-2 for 15-26 days had detectable T-cell receptor beta-chain gene rearrangements, which indicated oligoclonal enhancement in culture in four of nine TIL samples. In contrast, none of 11 uncultured TIL samples had detectable gene rearrangements. Lack of detection in at least three of the five negative, cultured TIL samples could be explained by increased numbers of natural killer cells. We hypothesize that the oligoclonal expansion noted results from the enhanced response of immune-primed T cells to IL-2.

Blotting, Southern↗
PubMed1990

Lymphocytic alveolitis in primary HIV infection.

Primary infection with the human immunodeficiency virus (HIV-1) has been associated with a self-limited illness resembling acute infectious mononucleosis. Pulmonary manifestations have been notably absent in published reports. The authors describe a 28-year-old homosexual male who presented with primary HIV-1 infection associated with CD8+ lymphocytic alveolitis. Diagnosis was delayed because HIV antibody was not detected by the Abbott ELISA, although the same and subsequent specimens were later found to be positive by Genetic Systems' ELISA and Western blot analysis. Lymphocytic alveolitis must be added to the expanding clinical spectrum of acute HIV-1 infection. The time to detection of seroconversion may vary with different immunoassays.

Adult↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗