Summary of workshop findings for leukocyte antigens of cattle.
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Animals↗
Biomedical subjects
M Hadam
Publications and source records attributed to M Hadam.
Individual antigens of cattle. Bovine CD4 (BoCD4).
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Animals↗
Diminished expression of interleukin-2 receptors in vivo after prior chemotherapy in advanced cancer patients receiving recombinant interleukin-2.
In a phase I/II dose escalation study performed at our institution, a total of 14 advanced metastatic cancer patients received between 4 and 16 weeks of subcutaneous recombinant interleukin-2. Doses were escalated at weekly intervals, starting at 1.8 million IU/m2/day up to a maximum dose of 14.4 million U/m2 daily. When comparing patients with (n = 4) and without (n = 7) prior chemotherapy on day 0 (i.e., before rIL-2), both patient groups exhibited Tac IL-2 receptor (CD25) positive peripheral blood lymphocytes at equal levels of positivity (8%). In contrast, 4-week systemic treatment with subcutaneous rIL-2 at escalating dose levels revealed a significant difference in the up-regulation by interleukin-2 of CD25 cell surface receptor. Thus, after 4 consecutive weeks of treatment, patients without previous chemotherapy showed a mean CD25 positivity of peripheral blood lymphocytes at 38%, as compared with 22% in patients who did receive prior chemotherapy (p less than 0.05). These data suggest that chemotherapy pretreatment may have a significant effect on biological response to rIL-2 in vivo.
Antineoplastic Combined Chemotherapy Protocols↗
[LFA-1 defect: a rare granulocyte function disorders as a cause of therapy-resistant omphalitis in newborn infants].
A newborn infant suffered from severe omphalitis resistant to antibiotic therapy. The combination of the symptoms: delayed separation of the umbilical cord, omphalitis, impairment of wound-healing and extreme leukocytosis led to the diagnosis of LFA-1 (leukocyte function antigen)-deficiency, which was confirmed by monoclonal antibodies. The pathophysiology of this disorder is described shortly.
Anti-Bacterial Agents↗
[Differentiation and transplantation antigens on the surface of mononuclear cells of cattle, horses and dogs].
The determination of differentiation and transplantation antigens will be of growing importance in immune diagnosis for individual animals as well as for breeding purposes in populations. Differentiation antigens characterize subsets of cell populations and indicate their functional capacity while transplantation antigens represent markers of individuals of a species. Occurrence and significance of these antigenic systems are briefly reviewed.
Animals↗
Subcutaneous interleukin-2 and interferon-alpha 2b in patients with metastatic renal cell cancer: the German outpatient experience.
A phase II clinical trial was conducted using subcutaneous recombinant human interleukin-2 (rIL-2, EuroCetus) and subcutaneous interferon-alpha 2b (rIFN-alpha 2b, Essex) in patients with advanced cancer. Safety and tolerance of this outpatient regimen were assessed in 17 patients with progressive metastatic renal carcinoma, 14 of whom were evaluable for clinical response to combined rIL-2 and rIFN-alpha 2b. In this study, rIL-2 was administered every 12 hours, at 1.5 million (Cetus) U/m2 on days 1 and 2, followed by 0.3 million U/m2 5 days per week for 6 consecutive weeks. Concomitantly, rIFN-alpha 2b was given as 5 million U/m2 three times weekly for 6 consecutive weeks. Patients presenting with stable or regressive disease after 6 weeks of rIL-2 and rIFN-alpha 2b (11 of 14) were scheduled to repeat combination therapy. After one treatment cycle, five of 14 patients presented with partial remission; two of these patients achieved complete regression of metastatic lesions. After therapy, six patients have been in stable disease for up to 8 months. toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (World Health Organization criteria) fevers, chills, malaise, nausea and/or vomiting, and anorexia in 70% to 100% of patients treated. After 6 weeks of rIL-2 and rIFN-alpha 2b, laboratory evidence of treatment-related hypothyroidism and hyperthyroidism was obtained in one and four patients, respectively. Immunogenicity of sc rIL-2 was mostly limited to the development of nonneutralizing antibodies that occurred in approximately 40% of patients. None of the patients exhibited antibodies specific to rIFN-alpha 2b.
Ambulatory Care↗
Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy: a phase II outpatient study.
Recombinant interleukin-2 (rIL-2; EuroCetus, Amsterdam, Netherlands) was studied in an outpatient phase II trial in 14 patients with progressive metastatic renal carcinoma, malignant melanoma, and colorectal cancer. Escalating doses of rIL-2 were administered as subcutaneous bolus every 12 hours, starting at 0.3 million U/m2/d. A 100% dose increase occurred at weekly intervals, up to a maximum of 2.4 million U/m2/d. Responding patients or patients with stable disease after 4 weeks of rIL-2 (n = 9) were continued on maintenance therapy at 1.8 million U/m2 of rIL-2 administered once weekly. After 12 weeks of therapy, one renal cell cancer patient had a partial regression in lung metastases. Bolus injection of rIL-2 (1.2 million U/m2) resulted in peak serum levels of 25 to 30 U/ml. Toxicity of this regimen was moderate, with local inflammation at the injection sites, grade I-II (World Health Organization) malaise, nausea and/or vomiting, and fevers in 70% to 100% of patients treated. Thyroid dysfunction was observed in 10 patients receiving subcutaneous rIL-2; four of these patients had laboratory evidence of hyperthyroidism, and one had hypothyroidism. rIL-2-induced toxicity reversed spontaneously after cessation of treatment. In all patients receiving rIL-2, a dose-dependent increase in peripheral blood lymphocyte and eosinophil counts was noted, with a mean of 2.6 and 3.8 x 1,000/microliters after 4 weeks of therapy; mean lymphocyte and eosinophil counts were measured at 2.0 and 2.4 x 1,000/microliters in patients who received prior high-dose chemotherapy, compared with 3.2 and 5.1 x 1,000/microliters in those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)
Anorexia↗
Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia.
A 2-day-old girl developed a severe lactic acidosis with a normal lactate/pyruvate ratio and hyperammonaemia. Plasma arginine and citrulline levels were below the limit of detection. In muscle total pyruvate dehydrogenase complex (PDHC) and pyruvate decarboxylase (E1) activities were reduced to a fraction of lower control values. The acute neonatal period was bridged with peritoneal dialysis, dichloroacetate therapy, supplements of arginine and branched chain amino acids, a complete vitamin B complex and lipoic acid. Lactate homeostasis responded to pharmacological supplements of lipoic acid. At age 1 year the child was hypotonic, showed severe developmental retardation, optic atrophy and cranial dysmorphism. She died aged 1 year 8 months with signs of respiratory paralysis but with normal lactate levels under assisted breathing. Pathological findings at autopsy were suggestive of Leigh syndrome, interstitial pneumonia and extensive fatty infiltration of hepatocytes. Regression analysis of data from 187 plasma amino acid determinations from the patient over a period of 1 year 8 months revealed a persistent-imbalance involving alanine, glutamic acid, glutamine, proline, citrulline and branched chain amino acids. Aspects of acute and long-term therapy in this patient and some implications of the imbalances in plasma amino acids are discussed.
Acidosis, Lactic↗
Predominant immunoglobulin gene rearrangements in two patients with immunodeficiency: restricted use of V gene segments and DNA hypermethylation.
The majority of common variable immunodeficiencies (CVID) is caused by intrinsic B cell defects which impede distinct stages of B cell differentiation. B cell differentiation is accompanied by the rearrangement of immunoglobulin (Ig) genes. The first step in the rearrangement process is the assembly of IgH genes, and subsequently, IgL genes are rearranged. During B cell maturation, Ig genes are demethylated in a stepwise, locus-specific manner. Here, we examined the Ig gene rearrangements of four patients with classical CVID and of one child suffering from an unusual immunodeficiency associated with CD5+ B cell lymphocytosis. In one of the four adult patients with CVID, we observed a predominant type of VHDJH-gene rearrangement. In the child, different polyclonal VHDJH-gene rearrangements were found together with a predominant type of kappa light chain gene rearrangement. The rearranged kappa chain genes were methylated (as in the pre-B cell stage). These findings together with the cell phenotype analysis and the clinical course of the disease in the child suggests that in some patients with primary immunodeficiency a maturation arrest may occur in B cells leading to a predominant Ig V gene rearrangement.
Adolescent↗
Correlation of interleukin-2 receptor positive circulating lymphocytes and acute cardiac rejection.
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Acute Disease↗
TPA-induced differentiation and adhesion of U937 cells: changes in ultrastructure, cytoskeletal organization and expression of cell surface antigens.
Incubation of the human promonocytic cell line U937 with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 72 h resulted in differentiation into immature macrophage-like cells and was accompanied by marked morphological and functional changes. U937 cells which normally grow in suspension and show a smooth surface, extended pseudopodia and became adherent to each other and to the surface of the culture vessel. Concomitant with the TPA-induced adherence U937 cells ceased to proliferate. Our results show that phorbol ester-treated U937 cells exhibited markedly increased levels of fibronectin and of the cytoskeletal proteins actin, myosin and vimentin including a reorganization of actin and vimentin filaments. The induction of both cellular adherence and growth inhibition were accompanied by a significantly reduced level of cells expressing transferrin receptors and changes in cell surface antigen expression. Here, the expression of the leukocytefunction antigens (LFA-1), including CD11 and CD18 was markedly enhanced during phorbol ester-induced differentiation. TPA-treatment, however, failed to enhance the small amount of U937 cells expressing the monocyte/macrophage-specific CD14 antigen or expressing MHC class-II antigens. A detailed analysis of the CD14 cluster by 7 differential antibodies resulted in an induction of TM1, UCHM1, MEM15, My4, and 3C10, whereas the epitopes recognized by TM2 and Mo2 remained unaltered. Neither indomethacin nor interferon-gamma were capable of inducing a marked expression of these antigen epitopes in TPA-treated cells. Although these data demonstrate that during phorbol ester-induced differentiation U937 cells acquire many properties typically associated with macrophages, the failure to express marked levels of macrophage-specific cell surface antigens suggests a transition of U937 cells from a promonocytic to an immature macrophage intermediate state rather than into mature macrophage-like cells.
Antigens, Surface↗
Establishment and characterization of a permanent human IgA2/kappa myeloma cell line.
A human myeloma cell line designated LOPRA-1 has been established from ascites fluid containing malignant plasma cells of a patient with IgA2/kappa multiple myeloma. The cultured cells which are Epstein-Barr virus (EBV) negative have retained the morphological, cytochemical, ultrastructural and immunophenotypical features of well-differentiated plasma cells. They express the plasma cell antigen PCA-1, the antigens CD28 (Kolt-2) and CD38 (OKT10), the transferrin-receptor (OKT9), and some epitopes of the CD24 antigen (HB8, VIB E3), but are negative for surface immunoglobulins. HLA class II antigens (HLA-DP, -DQ, -DR) and other B-cell markers such as CD10 (CALLA), CD19 (B4), CD20 (B1), CD21 (B2), CD22 (HD39), CD23 (MHM6), CD37 (BL14) and CD39 (G28-8) as analysed by both flow cytometry and immunocytochemistry (PAP/APAAP). With respect to immunoglobulin synthesis, two stable clones were selected by single cell cloning: clone LOPRA-1/5 synthesizes large amounts of alpha 2 heavy and kappa light chains, but secretes only small amounts of these molecules, whereas clone LOPRA-1/4 is clearly devoid of intracellular immunoglobulin heavy and light chains and thus appears to be a chain loss variant. Cytogenetic analysis revealed a pseudotriploid phenotype with several structurally abnormal marker chromosomes: 3n + -, 70, XX, -X, -1, -4, -6, -8, -8, -13, -16, +7, +18, +21, +i(1q), +i(1q), +6q-, +3mar.
Cell Line↗
T-cell prolymphocytic leukemia (T-PLL) with unique surface phenotype.
Leukemic cells of a 19 year old patient with prolymphocytic leukemia of T-cell type (T-PLL) were characterized by surface markers and immunologic functions. Phenotypic analysis using a large panel of monoclonal antibodies corresponding to the clusters (CD) of differentiation antigens established on the Leukocyte Typing Workshops I and II revealed a unique T-cell phenotype not yet reported in the literature: CD1 (T6)-, CD2 (T11)+, CD3 (T3)+, CD4 (T4)-, CD5 (T1)-, CD6 (T411)+, CD7 (Leu9)+, CD8 (T811)-, CD10 (J5)-, CD11 (M22)+, CD12 (M67)-, CD13 (My7)-, CD14 (Mo2)-, CD16 (Vep13, 3G8, Leu11)+, CD18 (MHM23)+, CD19 (B4)-, CD20 (B1)-, CD25 (TAC)-, MHC-class II (HLA-DR, HLA-DQ)-, NKH1A+, Leu7-. Despite the expression of surface structures associated with natural killer (NK) function (CD16, CD18, NKH 1 A) the T-PLL cells were inactive in NK assays in vitro. Low in vitro ADCC activity was detectable. This unusual T-PLL phenotype might help to identify a new distinct T-cell differentiation stage.
Adult↗
Avidin-peroxidase. A new mast cell staining method.
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Animals↗
Macrophage cytotoxicity: interleukin 1 as a mediator of tumor cytostasis.
Purified macrophage interleukin 1 (IL 1) induced a concentration-dependent inhibition of the proliferation of two commonly used tumor cell target lines, the human myeloid K562 and the murine T lymphoma Eb. In contrast, mastocytoma-derived P815 cells were not inhibited. The cytostatic action of IL 1 was not associated with direct cytotoxicity and was only partially reversible. PGE or interferon did not appear to mediate these effects. IL 1 treatment of the multipotential K562 cells revealed no morphologic evidence for the induction of specific differentiation. FACS analysis of IL 1-treated K562 cells showed a rapid decrease in transferrin receptor density, and a more delayed, but highly significant, increase in HLA-A,B,C antigen density. These findings provide one explanation for the frequently reported macrophage cytostatic actions against tumor cells, and indicate as well that IL 1, like interferon, may enhance the expression of Class I MHC antigens. These observations further extend the range of IL 1 actions and underscore the fundamental and direct role of this monokine in macrophage antitumor activity.
Animals↗
Divergent expression of HLA-DC/MB, -DR, and -SB region products on normal and pathological tissues as detected by monoclonal antibodies.
A group of eight monoclonal antibodies directed against different monomorphic determinants of HLA-class II molecules was used to investigate the distribution of HLA-DC/DS/MB, -DR and -SB-like antigens on normal and pathological lymphoid and nonlymphoid tissues of human adult and fetal donors. HLA-MB/DC/DS-like molecules, as defined by the antibody TU 22, showed the most limited distribution as they were detected on B-lymphocytes, monocyte/macrophage subpopulations and distinct interstitial cells of various organs. HLA-DR and -SB-like antigens characterized by the other anti-HLA-class II reagents (TU34, TU35, TU37, TU39, TU43, TU58) were also present on these cell types. However, selective expression of HLA-DR and/or -SB like molecules was demonstrated with these antibodies on certain vascular endothelia, as well as different B-cell lymphomas and distinct epithelial cells in adults. Exclusive reactivity of the antibody TU39 shown on endothelial cells of fetal liver and kidney suggested specific functions of HLA-SB antigens during ontogeny. Furthermore, HLA-DR and/or -SB like molecules but not TU22+ HLA-DC/MB antigens were found to be inducible on normally Ia-like antigen negative epithelial cells of various diseased organs. Implications of this differential tissue distribution of HLA-DC/MB/DS, -DR and -SB like products in relation to organ transplantation, regulation of immune responses and cell differentiation are discussed.
Adult↗
[The GOX-anti-GOX(PAP) technic, a new method for the demonstration of adjacent antigens in the same section].
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Antigen-Antibody Complex↗
Effect of ASTA Z 7557 (INN mafosfamide) a precursor of 4-hydroxy-cyclophosphamide on human T-lymphocytes' Fc-receptors and immunoregulatory functions.
The precursor ASTA Z 7557 of the in vivo active metabolite 4-hydroxy-cyclophosphamide (4OH-Cy) of cyclophosphamide (Cy) was tested for selective effects on human T-lymphocytes' Fc gamma-receptor expression and certain immunoregulatory functions. It has been found that ASTA Z 7557 does not alter the expression of Fc gamma-F- or Fc gamma-I-receptors on the T-cell membrane nor does it exhibit differential toxicity for either T-cell subpopulation. PWM-induced B-cell proliferation is inhibited by ASTA Z 7557, whereas B-cells' Ig-synthesis as well as ConA-driven T-cell proliferation is only blocked with higher doses of the reagent. Final concentrations above 1 microgram/ml may therefore abrogate ConA-induction of suppressor T-lymphocytes. Already ConA-activated suppressor cells of PWM-driven B-cell cultures, however, are not inhibited even with high doses of ASTA Z 7557.
B-Lymphocytes↗