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Biomedical subjects

M J Borowitz

Publications and source records attributed to M J Borowitz.

At least 109 records · Page 6Linked to original sources

Characterization of renal neoplasms with monoclonal antibodies to leukocyte differentiation antigens.

Several monoclonal antibodies against human leukocyte differentiation antigens have been shown to react with normal kidney. Four monoclonal antibodies with different patterns of reactivity on normal kidney were tested against 20 renal epithelial neoplasms and 5 Wilms' tumors. In general, the expression of these antigens on renal tumors was faithful to their presence on normal kidney; this finding suggested that most renal tumors may be derived from proximal tubule epithelium. There was, however, both intertumor and intratumor heterogeneity of expression of these antigens, but the different phenotypes encountered did not correlate in any simple way with histologic subclassification. In contrast, the five Wilms' tumors were phenotypically different from the epithelial neoplasms, consistent with an origin from a more primitive renal cell.

Antibodies, Monoclonal↗

The phenotypic diversity of peripheral T-cell lymphomas: the Southeastern Cancer Study Group experience.

Four member institutions of the Southeastern Cancer Study Group (SECSG) investigated 27 cases of malignant lymphoma proved to be of T-cell origin by a frozen section immunoperoxidase technique. The specimens were sent to one central laboratory in Michel's transport medium, where phenotyping studies were performed with a large number of monoclonal antibodies. The phenotypes encountered differed as a group from that reported for lymphoblastic lymphoma, but there was significant diversity within the peripheral T-cell lymphomas. Most tumors were of a mature helper/inducer phenotype (Leu-3+, Leu-2-), but nine of the 27 lymphomas expressed Leu-3 and Leu-2 in other combinations. Half of the lymphomas expressed abnormal T-cell phenotypes in that one or more pan-T-cell markers usually present in nonneoplastic T-cell proliferations were absent. Antibody 3A1 was the pan-T marker that was most frequently lacking in the peripheral T-cell lymphomas. The tumors were also studied for their expression of three markers associated with T-cell activation--HLA-DR, transferrin receptor, and interleukin 2 receptor. The majority of the lymphomas expressed one or more activation markers. However, these three markers appear to be expressed independently. In general, there was no simple correlation between the phenotype of the tumor and the histologic appearance, although neoplasms of morphologically higher grades were somewhat more likely to express T-cell activation markers.

Adult↗

Acute lymphoblastic leukemia of Burkitt's type (L3 ALL) with 8;22 and 14;18 translocations and absent surface immunoglobulins.

A 57-year-old woman presented with L3 acute lymphoblastic leukemia demonstrating typical Burkitt's type morphology. Cytogenetic analysis revealed one of the variant translocations seen in Burkitt's lymphoma [t(8;22)] and a 14;18 translocation. Surface marker data at presentation and at autopsy demonstrated several B-cell markers, but absent surface immunoglobulins. The case presented here reveals a possible cytogenetic link between Burkitt's lymphoma and follicular center-cell lymphoma, and illustrates a variant surface marker profile for Burkitt's lymphoma.

B-Lymphocytes↗

Clinicopathologic aspects of E rosette negative T cell acute lymphocytic leukemia: a Pediatric Oncology Group study.

The Pediatric Oncology Group has studied 1,367 patients with non-B cell acute lymphocytic leukemia (ALL) of whom 186 (14%) had blasts that reacted with previously well-characterized heteroantisera, recognizing a T-lymphocyte specific surface membrane antigen (PT+). In 87 of these T cell cases, the leukemic cells failed to form at least 20% of sheep erythrocytic rosettes at 4 degrees C. Comparison of clinicopathologic features among PT-, E-PT+, and E+ groups of patients revealed significant differences among them. E-PT+ patients were older than PT- patients, had higher white blood cell counts (WBCs) and were more likely to have a mediastinal mass, and thus contained a higher proportion of poor-risk patients. However, the E-PT+ patients were also significantly different from the more traditionally-defined E+ patients in that they had lower WBCs and hemoglobin levels, and less frequent lymphadenopathy or mediastinal mass. In many respects, then, E-PT+ patients were intermediate in character between PT- and E+ patients. Our findings support the notion that further subclassification of ALL using antibodies recognizing lineage-specific surface determinants will permit recognition of groups of patients with distinct clinicopathologic features that may differ in prognosis or response to therapy. Such classification also focuses future biological studies on the pathogenesis of leukemias to immunologically well-defined subgroups of lymphoid neoplasms.

Antibodies, Monoclonal↗

Gastrointestinal involvement and multiple lymphomatous polyposis in mantle-zone lymphoma.

The clinical, histologic, and immunologic features of three cases of lymphoma presenting with gastrointestinal symptoms and involving the gastrointestinal tract were studied. Two of the cases had involvement of long segments of the bowel with polypoid lesions, a rare presentation of gastrointestinal lymphoma referred to as multiple lymphomatous polyposis (MLP). All cases were classified as mantle-zone lymphoma (MZL), a follicular variant of intermediate lymphocytic lymphoma (ILL) characterized by the proliferation of small atypical lymphoid cells as wide mantles surrounding benign-appearing germinal centers. The patients were typical of other patients with MZL in that they were male, middle age or older, and their clinical courses were not aggressive despite the presence of disease at an advanced stage. Our review of the literature suggests that there is an inordinate number of cases of MZL with gastrointestinal involvement. We also note that most reports of cases of MLP have described histologic lesions remarkably similar to what we have observed. We conclude that MZL may have predilection for involvement of the gastrointestinal tract, that this involvement is often in the manner of MLP, and that most cases of MLP probably have MZL or ILL.

Aged↗

Cooperative effects of gamma interferon and 1-alpha,25-dihydroxyvitamin D3 in inducing differentiation of human promyelocytic leukemia (HL-60) cells.

Various agents induce differentiation of human leukemia cells in vitro. Most of these agents cause myeloid differentiation, but phorbol diesters, 1-alpha,25-dihydroxyvitamin D3 (1,25[OH2]D3), and certain lymphokines cause differentiation to monocyte-like cells. The purpose of this study was to determine the cooperative effects of 1,25(OH2)D3 and the lymphokine gamma interferon (IFN-gamma) on HL-60 cell differentiation. The recombinant human IFN-gamma or 1,25(OH2)D3 caused a slight reduction in the proliferation of the HL-60 cells (30%-40% reduction at doses of 100-200 U/ml [0.25-0.50 nM] IFN-gamma, or 5-25 nM 1,25[OH2]D3). HL-60 cells treated with 100 U/ml IFN-G had an eightfold increase in expression of nonspecific esterase (NSE) and a twofold increase in H2O2 production in response to phorbol myristate acetate (PMA). 1,25(OH2)D3 enhanced NSE expression eight- to 30-fold and H2O2 secretion twofold in response to PMA. There was also enhanced expression of HLA-DR and the receptor for C3bi. The 1,25(OH2)D3- and IFN-gamma-differentiating effects appeared to be additive or synergistic. Populations of IFN-gamma-treated HL-60 cells (but not the 1,25[OH2]D3-treated cells) had multinucleated giant cells. The polykaryons had NSE activity and had some properties of macrophage polykaryons or osteoclasts. 1,25(OH2)D3 did not augment the IFN-gamma-induced polykaryon formation.

Calcitriol↗

T-cell lymphoma mimicking granulocytic sarcoma.

A case of diffuse large cell lymphoma is described in which eosinophils and eosinophilic myelocytes were admixed with the neoplastic lymphoid cells. Because of the eosinophilic myelocytes, a diagnosis of granulocytic sarcoma was initially considered. No abnormalities of peripheral blood or bone marrow were found. Immunohistochemical studies of lymph node tissue demonstrated membrane antigens consistent with a lymphoma of helper T-cells. Small lymphoid cells with markedly irregular nuclei were present but rather inconspicuous among the larger lymphoid cells. Although a clinical remission was attained, the patient had a relapse with central nervous system involvement.

Antibodies, Monoclonal↗

Monoclonal antibody phenotyping of B-cell non-Hodgkin's lymphomas. The Southeastern Cancer Study Group experience.

This report describes the experience of the Southeastern Cancer Study Group (SECSG) with the frozen-section immunoperoxidase phenotyping of 162 cases of B-lineage non-Hodgkin's lymphomas. The authors used a panel of 13 different markers with varying degrees of specificity for B lymphocytes and B-cell neoplasms. All lymphomas were classified according to the International Working Formulation. Several antibodies, including anti-immunoglobulin, B1, Leu 12, and Leu 14 were B-cell-specific markers that were generally pan-reactive. Several other monoclonal antibodies, however, were selectively reactive with subpopulations of B-cell lymphomas. Three "selective-B" antigens (BA1, p24, CALLA) were found on about half of the B-cell lymphomas tested, while another three (HB31, transferrin receptor, C3d receptor) were found on about two-thirds of the lymphomas tested. Leu 1 reacted with 18% of the B-cell lymphomas, particularly the small lymphocytic lymphomas. When the reactivity of the monoclonal antibodies was compared with the histologic classification, two important points became apparent. First, with the large panel of antibodies, there was tremendous phenotypic diversity even among histologically similar tumors. Second, however, not all possible combinations of antibody phenotypes were encountered. That is, clusters of antigenic phenotypes were seen, and these phenotypes correlated to some degree with the histologic diagnosis of the tumor. Small lymphocytic and follicular lymphomas tended to be phenotypically distinct, although there was some overlap. Intermediate- and high-grade lymphomas were phenotypically more diverse. The more common phenotypes of lymphomas encountered could not be reconciled with any simple linear scheme of neoplastic B-cell differentiation.

Antibodies, Monoclonal↗

Glucocorticoid receptors in immunological subtypes of childhood acute lymphocytic leukemia cells: a Pediatric Oncology Group Study.

Glucocorticoid receptors were quantitated by a whole cell method in cells from 593 children with acute leukemia at the time of diagnosis. Leukemia cells were also immunologically typed and divided into early pre-B- (not reactive with antibodies to T-lymphocyte antigens, surface immunoglobulin-negative, cytoplasmic immunoglobulin-negative), pre-B- (not reactive with antibodies to T-lymphocyte antigens, surface immunoglobulin-negative, cytoplasmic immunoglobulin-positive), B- (not reactive with antibodies to T-lymphocyte antigens, surface immunoglobulin-positive), and T- (reactive with antibodies to T-lymphocyte antigens) subtypes. There was a median of 9.7 X 10(3) sites per cell in the 359 with early pre-B-acute lymphocytic leukemia, a median of 8.1 X 10(3) sites per cell from 103 patients with pre-B-cell leukemia, and a median of 4.0 X 10(3) sites per cell from 116 patients with T-cell leukemia. The distributions per cell were significantly different among these 3 groups (P less than 0.0001). The 15 patients with B-cell disease had a median of 3.2 X 10(3) sites per cell. At the time of analysis, remission induction data are available for most of these patients. Within the early pre-B- group 291 patients with a median receptor number of 9.9 X 10(3) achieved remission, while 13 with a median receptor number of 4.8 X 10(3) did not. These distributions were significantly different (P = 0.034). Within the pre-B- and T-cell groups the distributions of receptor numbers for responders and non-responders were not significantly different. We conclude that each immunological subtype has characteristic receptor distribution. High receptor number within the null group is associated with the ability of the patient to achieve remission; however, the range of values within each patient group is too broad to use this assay as a predictor of response for any individual patient.

Adolescent↗

Monoclonal antibody definition of T cell acute leukemia: a Pediatric Oncology Group study.

Leukemic blasts from 774 children with newly diagnosed acute lymphocytic leukemia (ALL) have been phenotyped by microcytotoxicity testing with a panel of monoclonal antibodies and heteroantisera as part of a Pediatric Oncology Group classification study of acute leukemia. One hundred twenty-two cases, or 16% were designated as T cell leukemia based on the reactivity of blast cells with previously well-characterized antisera (PT) against a T lymphocyte-associated antigen. Using this antisera-based definition as a standard, we looked for a monoclonal antibody combination that would be a suitable substitute. An algorithm calling for reactivity with either monoclonal antibody 3A1 or Leu-1 was a 92% sensitive and 97% specific predictor of PT reactivity. Only 27 of 755 cases of leukemia were incorrectly classified using this algorithm. Subsequently, Ficoll-Hypaque-separated bone marrow cells from 118 additional patients with ALL (21 of whom had T cell ALL) were stained by immunofluorescence using a combination of directly fluoresceinated 3A1 and Leu-1. Reactivity of 20% or more of the cells with this antibody combination was a 100% sensitive and 94% specific indicator of T cell ALL defined by PT positivity; with a higher cutoff value for positive values, or the use of supplemental tests, even this small number of false-positives could be eliminated. We conclude that this monoclonal antibody combination is a satisfactory replacement for our heteroantisera definition of T cell ALL.

Antibodies, Monoclonal↗

Expression of a melanoma-tumor-associated antigen as demonstrated by a monoclonal antibody (D6.1) in cytopathologic preparations of human tumor cells from effusions and needle aspirates.

Immunocytopathologic studies were performed on 79 fine needle aspiration biopsies (FNABs) and effusions from 13 melanomas and 57 other human neoplasms with the monoclonal antibody (MAb) D6.1 raised against a partially purified melanoma-tumor-associated antigen (MTAA). The purposes of these studies were (1) to evaluate the ability of MAb 6.1 to react with melanoma cells in cytopathologic preparations and (2) to define the spectrum of reactivity of MAb D6.1 in cytopathologic preparations of non-melanomas. Cytocentrifuge preparations of the cytopathologic specimens were permitted to react with the primary antibody and were then stained by the avidin-biotin-immunoperoxidase method. Thirteen of 13 FNABs of malignant melanomas exhibited staining reactivity with MAb D6.1. Among the nonmelanoma tumors tested, staining reactivity was observed in 30 of 57 specimens. Among specific neoplasms, staining was present in 5 of 11 adenocarcinomas of the breast, 2 of 7 ovarian adenocarcinomas and 5 of 6 metastatic adenocarcinomas from the colon. Among 17 lung cancers examined, staining was noted in 4 of 7 adenocarcinomas, 3 of 4 large-cell undifferentiated carcinomas and 2 of 3 poorly differentiated squamous-cell carcinomas. Two small-cell undifferentiated carcinomas and one carcinoid failed to stain. Three of three adenocarcinomas of the pancreas showed staining. Among the remaining neoplasms examined, one specimen each of carcinoma of the prostate and the cervix and one carcinoma of undetermined primary exhibited staining. Two malignant lymphomas did not stain. Staining of mesothelial cells was observed in three of nine benign effusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Extramedullary recurrence of acute lymphoblastic leukemia 15 years after initial diagnosis.

We describe a 19-year-old man with recurrence of a lymphoid malignancy involving the ethmoid sinus 15 years following diagnosis and 10 years after discontinuation of therapy for childhood acute lymphoblastic leukemia (ALL). The cytologic appearance and immunologic phenotype of the tumor cells suggest that this malignancy represents a recurrence of his original tumor. Initial relapse of ALL is unusual after 4 years of continuous remission off therapy. This case illustrates that late relapse can occur and may present with unusual sites of involvement.

Abdominal Neoplasms↗

Phylogenetic distribution of a 24,000 dalton human leukemia-associated antigen on platelets and kidney cells.

The distribution of a 24,000-dalton human leukemia-associated antigen, p24, was examined using the BA-2 and DU-ALL-1 monoclonal antibodies. BA-2 and DU-ALL-1 bound to human, gorilla, orangutan, macaque, and rabbit platelets but did not bind to mouse, rat, guinea pig, dog, horse, sheep, or goat platelets. Orangutan platelets demonstrated a decreased level of binding with BA-2 and DU-ALL-1. In addition, BA-2, but not DU-ALL-1, bound to chimpanzee platelets suggesting that the chimpanzee has lost the epitope of p24 detected by DU-ALL-1. Immunoperoxidase analysis of kidney tissue with BA-2 and DU-ALL-1 revealed staining of distal tubules and glomeruli, which occurred in a similar phylogenetic distribution to that of p24 on platelets. A monoclonal antibody to the high molecular weight common ALL antigen, J-5, reacted with glomeruli and proximal tubules from human, chimpanzee, orangutan, mangaby , rhesus, and rabbit kidneys but failed to react with rat or mouse kidney.

Animals↗

Differential diagnosis of undifferentiated malignant tumors with monoclonal antibody T29/33.

An immunoperoxidase method for distinguishing lymphomas from nonlymphoid neoplasms with monoclonal antibody T29/33 is described. This antibody recognizes a 200,000-dalton pan-hematopoietic glycoprotein antigen. Staining in nearly 200 hematopoietic tumors was positive for T29/33, although three of six plasmacytomas were negative for this antibody. Five undifferentiated tumors that were proved to be lymphomas by subsequent electron microscopic and immunohistologic studies were positive for T29/33. Conversely, 11 of 12 undifferentiated tumors with ultrastructural and clinical features of carcinoma or sarcoma were T29/33-negative. The only exception was one sarcoma that was T29/33-positive. Thus, monoclonal antibody T29/33 is a valuable tool for characterizing neoplasms that cannot be diagnosed by histopathologic examination alone.

Antibodies, Monoclonal↗

D6.1, a murine antimelanoma monoclonal antibody from congenitally athymic nude mice immunized with purified melanoma tumor-associated antigen.

An IgM monoclonal antibody, D6.1, has been obtained by fusion of P3 X 63Ag8.653 with spleen cells from congenitally athymic nu/nu mice immunized with partially purified human melanoma TAA bound to insolubilized lens culinaris lectin. The D6.1-defined antigen is present on the cell membrane of melanoma cells maintained in tissue culture but is not detected in spent culture media. Eighteen of twenty-three melanoma cell lines tested were found to react with D6.1, in contrast to only 17% of nonmelanoma tumor cell lines. Among those reactive nonmelanoma tumor lines were 3/3 colon adenocarcinomas tested. Melanoma cells, in general, express greater quantities of this antigen than do reactive nonmelanomas. Similar data were obtained using immunoperoxidase techniques on frozen sections of fresh tumor. All melanomas tested (8/8) stained intensely, although there was tumor cell heterogeneity. D6.1 reacted, but generally less intensely, with 42% (18/42) of the nonmelanoma tumors tested, including 7/8 colon carcinomas, but with smaller percentages of all other tumor types. D6.1 lightly stained normal stroma in many tissues and reacted strongly with macrophages but not with epithelial tissues. By HPLC filtration, the D6.1-defined TAA from detergent-solubilized melanoma cell membranes was determined to have an apparent molecular weight of 150,000 to 280,000 daltons. D6.1 does not precipitate TAA from exogenously (125I) or endogenously (35S-methionine, 33H-leucine, 33H-glucosamine) labeled melanoma cells.

Adenocarcinoma↗

Composite lymphoma: a unique case with two immunologically distinct B-cell neoplasms.

The authors recently have encountered a unique case of composite lymphoma arising in a 69-year-old man with severe long-standing rheumatoid arthritis. The neoplasm was composed of two B-cell lymphomas occurring within a single axillary lymph node: nodules of IgG-kappa nodular poorly differentiated lymphocytic lymphoma were surrounded by a diffuse growth of IgM-lambda well-differentiated lymphocytic lymphoma. It was the immunohistologic studies performed in this case that demonstrated the simultaneous occurrence of two separate monoclonal lymphocyte proliferations. Without the immunohistologic procedures, this composite lymphoma easily may have been overlooked. This unusual malignancy arose in the background of a long-standing autoimmune disease that may have played a role in its genesis.

Aged↗

Multiinstitution study of non-Hodgkin's lymphomas using frozen section immunoperoxidase: the Southeastern Cancer Study Group experience.

This report describes the experience of the Southeastern Cancer Study Group (SECSG) with a transport medium used for immunologic phenotyping of non-Hodgkin's lymphomas. In a 2-mo pilot study, portions of 53 specimens of non-Hodgkin's lymphoma from four member institutions of the SECSG and affiliated community hospitals were sent by regular mail to a central laboratory. Immunologic phenotyping was carried out using a frozen section immunoperoxidase technique. In 48 of the cases, a clear-cut immunologic phenotype was obtained. Thirty-four tumors were of B cell origin and 7 had T cell markers. Six of the remaining lymphomas had neither B nor T cell markers, and the seventh had both. In 12 cases, phenotyping was also carried out at the originating institution using conventional cell suspension techniques; agreement between the two methods was excellent. The immunologic results were correlated with histopathologic diagnosis standardized using the Working Formulation for non-Hodgkin's lymphomas. It was found that the low grade tumors were all B cell, but that the intermediate grade tumors were very heterogeneous immunologically. About one-fourth of the diffuse, intermediate grade or miscellaneous tumors had T cell markers. Our results indicate that immunologic phenotyping may be performed satisfactorily on transported material, making multiinstitution studies on the prognostic significance of immunologic phenotype in non-Hodgkin's lymphomas feasible.

B-Lymphocytes↗