(211)At-antiCD33 in NMRI nu/nu mice. Biodistribution, in vivo stability and radiotoxicity.

UNLABELLED: The aim of this study is to verify the in vivo stability, to determine the biodistribution and to estimate the unspecific radiotoxicity of an (211)At-labelled CD33-antibody ((211)At-antiCD33) in mice with a view to therapeutic application in treating leukaemia. ANIMALS, METHODS: (211)At was produced via the (209)Bi(a,2n)(211)At reaction and was linked via 3-(211)At-succinimidyl-benzoate to the antiCD33-antibody. The biodistribution and the in vivo stability in serum were determined after i.v.-injection in NMRI nu/nu-mice. For toxicity experiments, mice received either three times 315-650 kBq (211)At-antiCD33 or unlabelled antibody and NaCl-solution respectively. RESULTS: (211)At-antiCD33 showed a characteristic biodistribution complying with the unspecific antibody retention in the reticular endothelial system. The largest proportion of radioactivity remained in blood and blood-rich tissues with a minor accumulation in the thyroid and stomach. After 21 h, >85% of activity in serum still represented intact antibody. Mice showed no difference in unspecific toxicity of (211)At-labelled antibodies over six months compared to those treated with unlabelled antibody and NaCl-solution respectively, with regard to histopathologic lesions, survival time, behaviour and haemograms. CONCLUSION: The radiolabelling method yielded adequate in vivo stability of (211)At-antiCD33. Biodistribution with rapid elimination of free (211)At via kidneys and urine complies with requirements for targeted therapy. Activity doses potentially required for treatment do not elicit radiotoxicity to normal organs in mice. Further development is required to enhance the apparent specific activity and to verify the efficacy in an adequate animal model before phase I clinical studies in leukaemia can be envisaged.

T cell stimulation via the erythrocyte receptor. Synergism between monoclonal antibodies and phorbol myristate acetate without changes of free cytoplasmic Ca++ levels.

We observed that certain E-receptor antibodies (CD2 antibodies) can induce proliferation of resting human T cells in the presence of PMA, while other CD2 antibodies fail to have such an effect. The same CD2 antibodies that were mitogenic in the presence of PMA (9.6, X11, VIT13), but not the nonreactive ones, were also able to induce T cell proliferation via the so-called alternative pathway of T cell activation, i.e., when added pairwise in certain combinations to T cells in the absence of PMA. While the simultaneous addition of two comitogenic CD2 antibodies (9.6 or X11 plus VIT13) or the addition of a single nonmitogenic CD3 antibody (VIT3) led to a clearcut elevation of intracellular Ca++ levels, no such effect could be observed after the addition of one CD2 antibody alone. Even in the presence of PMA, one comitogenic CD2 antibody alone was unable to trigger a significant Ca++ response, although this combination induced a proliferative response. These data indicate that, distinguishable by their influence on free cytoplasmic Ca++, there are two different mechanisms of T cell activation via CD2. While simultaneous triggering with two antibodies leads to cell proliferation preceded by an increase of Ca++ levels, stimulation with one antibody plus PMA results in proliferation without a measurable early Ca++ response. We conclude that T cells treated by certain CD2 antibodies alone already recognize an activation signal probably unrelated to Ca++ homeostasis, a signal that can further be developed by PMA to result in a completely developed proliferative response.

Leukosialin (CD43)-major histocompatibility class I molecule interactions involved in spontaneous T cell conjugate formation.

Resting T cells spontaneously adhere in a selective manner to potent accessory cells, such as dendritic cells (DC) and lymphoblastoid B blasts (LCL). Here we demonstrate that leukosialin (CD43) and major histocompatibility complex class I molecules (MHC-I) might play a critical role in this process. T cell conjugate formation with monocyte-derived DC (md-DC) and LCL could be strongly inhibited by either preincubating T cells with Fab fragments of CD43 monoclonal antibody (mAb) 6F5 or by preincubating md-DC or LCL with MHC-I mAb W6/32. Intact CD43 mAb 6F5, in contrast to monovalent Fab fragments, enhanced T cell adhesiveness by transactivating CD2 binding to CD58 molecules. Interestingly, induction of this proadhesive signal via CD43 with intact 6F5 mAb was found to revert mAb W6/32-mediated inhibition of T cell conjugate formation. These observations indicated that CD43 cross-linkage mimics and monovalent mAb 6F5 inhibits interaction of T cell CD43 with a stimulatory ligand on opposing cells, presumably MHC-I. For the demonstration of direct physical interaction between CD43 on T cells and MHC-I-coated beads it was necessary, however, to ligate CD2 on T cells with a stimulatory pair of CD2 mAbs (VIT13 plus TS2/18). This suggests that CD2 ligation crosswise upregulates CD43 binding avidity for MHC-I and that both adhesion molecule pairs (CD43/MHC-I and CD2/CD58) act in concert to induce and mediate T cell conjugate formation with certain cell types.

Interaction of CD31 with a heterophilic counterreceptor involved in downregulation of human T cell responses.

CD31 is a 130-kD glycoprotein of the immunoglobulin (Ig) superfamily expressed on the surface of endothelial cells, platelets, and several leukocyte subsets. Previous reports indicated that CD31 can mediate intercellular adhesion via both homophilic and heterophilic interaction mechanisms. Using a soluble recombinant CD31-Ig fusion protein (CD31 receptor globulin [Rg]), we demonstrate here that human CD31- T lymphocytes and CD4+CD31- T cell clones express a heterophilic CD31 ligand that is upregulated 18 h after activation. Interaction of CD31Rg with CD31- T helper cell (Th) clones was divalent cation independent but could be blocked by heparin, thus indicating that the CD31 counterreceptor on T cells can be distinguished from the ligands identified on other cell types. Moreover, a single chain protein of 120 kD was precipitated by CD31Rg from the lysates of CD31- Th clones. CD31Rg completely downregulated the proliferative response and cytokine production (interleukin-4, interferon-gamma, and tumor necrosis factor-alpha) of CD31- Th clones when the cells were maximally stimulated via immobilized CD3 monoclonal antibody. These results suggest that interaction of CD31 with a heterophilic counterreceptor on T lymphocytes can interfere with a positive regulatory pathway of T cell activation, or directly signal T cells to downregulate immune function.

Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells.

Urokinase plasminogen activator receptor, beta 2-integrins, and Src-kinases within a single receptor complex of human monocytes.

The glycosylphosphatidylinositol (GPI)-anchored membrane protein urokinase plasminogen activator-receptor (uPA-R; CD87) is one of the key molecules involved in migration of leukocytes and tumor cells. uPA bound to uPA-R provides the cell proteolytic potential used for degradation of extracellular matrix. uPA-R is also involved in induction of cell adhesion and chemotaxis. Here, we provide a molecular explanation for these uPA-R-related cellular events. By size fractionation of monocyte lysate and affinity isolation on its natural ligand uPA, we demonstrate uPA-R as a component of a receptor complex of relatively large size. Reprecipitation and immunoblotting techniques allowed us to detect the protein tyrosine kinases (PTKs) p60fyn, p53/56lyn, p58/64hck, and p59fgr as components of this "uPA-R complex". Activation of monocytes even with enzymatically inactivated uPA resulted in induction of tyrosine phosphorylation, suggesting modulation of uPA-R-associated PTKs upon ligand binding. In spite of their presence in large complexes, we did not find the GPI-linked proteins CD14, CD58, and CD59 in the uPA-R complex, which indicates the presence of different receptor domains containing GPI-linked proteins in monocytes. However, we identified the leukocyte integrins LFA-1 and CR3 as components of the uPA-R complex as indicated by coisolation of these molecules, as well as by cocapping and comodulation of uPA-R and leukocyte integrins on the monocyte surface. The assemblage of uPA-R, PTKs and membrane spanning beta 2-integrins in one receptor complex indicates functional cooperation. In regard to the involvement of these molecules in pericellular proteolysis, signal transduction, as well as adhesion and chemotactic movement, we suggest uPA-R complex as a potential cellular device for cell migration.

Neutrophil granulocyte-committed cells can be driven to acquire dendritic cell characteristics.

Polymorphonuclear granulocytes (PMNs) are thought to fulfill their role in host defense primarily via phagocytosis and release of cytotoxic compounds and to be inefficient in antigen presentation and stimulation of specific T cells. Dendritic cells (DCs), in contrast, are potent antigen-presenting cells with the unique capacity to initiate primary immune responses. We demonstrate here that highly purified lactoferrin-positive immediate precursors of end-stage neutrophilic PMN (PMNp) can be reverted in their functional maturation program and driven to acquire characteristic DC features. Upon culture with the cytokine combination granulocyte/macrophage colony-stimulating factor plus interleukin 4 plus tumor necrosis factor alpha, they develop DC morphology and acquire molecular features characteristic for DCs. These molecular changes include neo-expression of the DC-associated surface molecules cluster of differentiation (CD)1a, CD1b, CD1c, human leukocyte antigen (HLA)-DR, HLA-DQ, CD80, CD86, CD40, CD54, and CD5, and downregulation of CD15 and CD65s. Additional stimulation with CD40 ligand induces also expression of CD83 and upregulates CD80, CD86, and HLA-DR. The neutrophil-derived DCs are potent T cell stimulators in allogeneic, as well as autologous, mixed lymphocyte reactions (MLRs), whereas freshly isolated neutrophils are completely unable to do so. In addition, neutrophil-derived DCs are at least 10,000 times more efficient in presenting soluble antigen to autologous T cells when compared to freshly isolated monocytes. Also, in functional terms, these neutrophil-derived DCs thus closely resemble "classical" DC populations.

Activated human T lymphocytes express MHC class I heavy chains not associated with beta 2-microglobulin.

We present here the molecular characterization of a new activation-induced surface structure on human T lymphocytes, termed LA45, with high homology (93% at protein level) to MHC class I molecules. Antigen modulation and sequential immunoprecipitation experiments revealed that LA45 and HLA class I proteins do not crossreact with the corresponding antibodies. Furthermore, LA45 is not associated with beta 2-m. On the other hand, we could show that the separation of HLA-A,B,C and beta 2m molecules, induced by SDS-denaturation, leads to a conformational change in the heavy chain in such a way that it becomes reactive with LA45. The 90/45 kD LA45 proteins thus appear to be non-beta 2m-associated MHC class I alpha chains that are selectively expressed by activated but not by resting human T lymphocytes.

GPI-anchored cell-surface molecules complexed to protein tyrosine kinases.

Binding of ligand or antibody to certain cell-surface proteins that are anchored to the membrane by glycophosphatidylinositol (GPI) can cause activation of leukocytes. However, it is not known how these molecules, which lack intracellular domains, can transduce signals. The GPI-linked human molecules CD59, CD55, CD48, CD24, and CD14 as well as the mouse molecules Thy-1 and Ly-6 were found to associate with protein tyrosine kinases, key regulators of cell activation and signal transduction. A protein tyrosine kinase associated with the GPI-linked proteins CD59, CD55, and CD48 in human T cells, and with Thy-1 in mouse T cells was identified as p56lck, a protein tyrosine kinase related to Src. This interaction of GPI-linked molecules with protein tyrosine kinases suggests a potential mechanism of signal transduction in cells.

[Guideline for radioimmunotherapy of CD20+ follicular B-cell non-Hodgkin's lymphoma]. / Leitlinie für die Radioimmuntherapie des CD20-positiven follikulären B-Zell-Non-Hodgkin-Lymphoms.

This guideline is a prerequisite for the quality management in the treatment of non-Hodgkon-lymphomas in patients with relapsed or refractory follicular lymphoma after rituximab therapy and as consolidation therapy after first remission following CHOP like treatment using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (hemato-oncologists) who propose, in general, radioimmunotherapy under consideration of the development of the disease.

Human major group rhinoviruses downmodulate the accessory function of monocytes by inducing IL-10.

Human rhinoviruses (HRVs) are the predominant cause of the common cold. Although this disease is per se rather harmless, HRV infection is considered to set the stage for more dangerous pathogens in vivo. Here we demonstrate that HRV-14, a member of the major group HRV family, can efficiently inhibit antigen-induced T-cell proliferation and T-cell responses to allogeneic monocytes. HRV-14 triggered a significant downregulation of MHC class II molecules on monocytes. Moreover, supernatants from monocytes cultured in the presence of HRV-14 strongly reduced the allogeneic T-cell stimulatory property of untreated monocytes and monocyte-derived dendritic cells (md-DCs), whereas Epstein Barr virus-transformed B-lymphoblastoid cells were not sensitive. Analysis of the supernatant revealed that HRV-14 induced the production of significant amounts of the immunosuppressive cytokine IL-10. The important T-cell stimulatory cytokine IL-12 or the proinflammatory cytokines IL-1beta or TNF-alpha were not detected or were only minimally detected. Finally, monocytes pretreated with HRV-14 were greatly inhibited in their production of IL-12 upon stimulation with IFN-gamma/LPS. These observations suggest that altered cytokine production in mononuclear phagocytes upon interaction with HRV downmodulates appropriate immune responses during the viral infection.

Deficiency of the autologous mixed lymphocyte reaction in patients with classic hemophilia treated with commercial factor VIII concentrate. Correlation with T cell subset distribution, antibodies to lymphadenopathy-associated or human T lymphotropic virus, and analysis of the cellular basis of the deficiency.

14 patients with hemophilia were studied for the distribution of T cell subsets, the presence of antibody to lymphadenopathy-associated or human T lymphotropic virus type III (LAV/HTLV-III), and their responsiveness in autologous mixed lymphocyte reactions. In addition, mitogen and alloantigen responsiveness and Interleukin-2 production were investigated. Seven patients were found to have low Leu 3a/Leu 2a (T4/T8) ratios; eight patients had antibody to LAV/HTLV-III; and an additional patient had acquired immunodeficiency syndrome. Responsiveness to mitogens and alloantigens as well as Interleukin-2 production were comparable with those of healthy individuals. However, patients with low ratio, many of whom had antibodies to LAV/HTLV-III, had a highly deficient autologous mixed lymphocyte reaction. This reduced response of T cells to autologous non-T cells could not be corrected by elimination of Leu 2a/T8 cells, which indicated that there was a preferential loss of the Leu 3a cell subset(s) which responded to autologous non-T cells. Thus, these patients have a deficiency of intercellular communication within their immune system.

Post transplant lymphoproliferative disease in pediatric solid organ transplant patients: a possible role for [18F]-FDG-PET(/CT) in initial staging and therapy monitoring.

Post transplant lymphoproliferative disease (PTLD) is a severe complication after solid organ or bone marrow transplantation. In pediatric transplant recipients PTLD is the most common malignancy. The aim of this study was to evaluate a possible role for positron emission tomography with [18F]-2-fluoro-2-desoxy-glucose (FDG) in the initial staging and in therapy monitoring of pediatric patients suffering from biopsy-proven CD20-positive PTLD after solid organ transplantation. Seven pediatric patients were included. All available imaging studies - CT (n=15), MRI (n=16) and PET/PETCT (n=16) - were reviewed on a lesion by lesion base. The performance of FDG-PET in the initial staging and during therapy with a chimeric anti-CD20 antibody was compared to conventional cross sectional imaging and correlated with the clinical outcome. FDG-PET identified all sites of disease as shown by CT/MRI and helped to clarify the significance of equivocal findings. The initial stage of disease was correctly identified by FDG-PET alone when compared to CT/MRI. During therapy, FDG-PET was superior to conventional cross-sectional imaging in the early evaluation of response.

Psychosocial interventions for cocaine and psychostimulant amphetamines related disorders.

BACKGROUND: The consumption of psychostimulants for non-medical reasons probably occurs because of their euphoriant and psychomotor-stimulating properties. Chronic consumption of these agents results in development of stereotyped behaviour, paranoia, and possibly aggressive behaviour. Psychosocial treatments for psychostimulant use disorder are supposed to improve compliance, and to promote abstinence. Evidence from randomised controlled trials in this subject needs to be summarised. OBJECTIVES: To conduct a systematic review of all RCTs on psychosocial interventions for treating psychostimulant use disorder. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, and LILACS (to may 2006); reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of psychostimulants abuse/ dependence. SELECTION CRITERIA: All randomised-controlled trials focusing on psychosocial interventions for treating psychostimulants abuse/ dependence. DATA COLLECTION AND ANALYSIS: Three authors extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated, when possible. The reviewers assumed that people who died or dropped out had no improvement (intention to treat analysis) and tested the sensitivity of the final results to this assumption. MAIN RESULTS: Twenty-seven randomised controlled studies (3663 participants) fulfilled inclusion criteria and had data that could be used for at least one of the main comparisons. There was a wide heterogeneity in the interventions evaluated: this did not allow to provide a summary estimate of effect and results cannot be summarised in a clear cut way. The comparisons between different type of Behavioural Interventions showed results in favour of treatments with some form of Contingency management in respect to both reducing drop outs and lowering cocaine use.. AUTHORS' CONCLUSIONS: Overall this review reports little significant behavioural changes with reductions in rates of drug consumption following an intervention. Moreover, with the evidence currently available, there are no data supporting a single treatment approach that is able to comprise the multidimensional facets of addiction patterns and to significantly yield better outcomes to resolve the chronic, relapsing nature of addiction, with all its correlates and consequences.

Exposure by desialylation of myeloid antigens on acute lymphoblastic leukemia cells.

The 3-fucosyl-N-acetyllactosamine structure, a sugar sequence contained in the human milk oligosaccharide lacto-N-fucopentaose III, is recognized by most of the granulocyte-specific monoclonal antibodies (MoAb) reported in the literature, including the six MoAb from our laboratory. Blast cells from patients with acute myeloblastic leukemia (AML) displayed a heterogeneous reaction pattern when they were exposed to MoAb against this moiety, and the proportion of reactive cells in individual cell samples was highly variable. The intensity of the reaction was strongly enhanced by neuraminidase treatment of AML blasts, and reactive structures were exposed on previously negative AML blast cells. Surprisingly, this granulocyte-associated antigen was exposed by desialylation not only on malignant myeloid precursor cells but also on common acute lymphoblastic leukemia cells. No such effect was seen when normal peripheral blood lymphocytes, lymphocytes from patients with chronic lymphatic leukemia, or blast cells from patients with B-cell acute lymphoblastic leukemia, acute erythroid leukemia, and acute megakaryoblastic leukemia were treated with neuraminidase.

Synthesis and preliminary biological evaluation of [123I]Me2Pyr, a new potential ligand for imaging of central cannabinoid CB1 receptors.

A synthesis of 1-(2,4-dichlorophenyl)-5-(4-[123I]iodophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid N',N'-dimethyl-hydrazide ([123I]Me2Pyr), a new radioiodinated analogue of the high-affinity cannabinoid CB1 receptor antagonist SR141716A, is described. Labelling was achieved by radioiododestannylation of the tributylstannyl precursor with [123I]iodide in the presence of chloramine T. HPLC purification afforded the labelled product in 48% radiochemical yield. Preliminary rat brain biodistribution studies with the 125I labelled compound revealed high uptake in the substantia nigra, the globus pallidus externus and the cerebellum, which is consistent with the known distribution of CB1 receptors.

Increased thermal response to ultrasound in the Walker carcinosarcoma treated with vasoactive drugs.

In order to evaluate the potential of a highly selective Ca2+ entry blocker (nisoldipine) and of 5-hydroxytryptamine (5-HT) as adjuvant in hyperthermia treatment, we studied the differential flow response and time-course of tumor and normal tissue temperature following the administration of the two substances and during ultrasound heating. In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2-0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 +/- 1.9 (SD) to 1.74 +/- 0.86 as determined by intraarterial 133Xe injection; i.p. injection of 2-8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 +/- 2.67 to 1.3 +/- 1.59. During a 20-min period of 41 degrees C normal tissue temperature-controlled ultrasound heating without drugs, tumor temperature attained 40.8 +/- 0.9 degrees C (N = 16). Nisoldipine or 5-HT injection at continuing 41 degrees C normal tissue temperature controlled energy delivery produced an instantaneous further increment of tumor temperature, eventually to 44.0 +/- 1.14 degrees C or 44.2 +/- 1.26 degrees C, respectively, after a period of 20 min. Injection of 0.9% NaCl (N = 4) solution caused only insignificant changes. Blood pressure and muscle perfusion were distinctly influenced by nisoldipine, but not by 5-HT. Since both drugs instantaneously increased the temperature differential between tumor and normal tissue, though by different vasoaction, they should be considered as adjuvants in hyperthermia.

Glycosphingolipid carriers of carbohydrate antigens of human myeloid cells recognized by monoclonal antibodies.

Six monoclonal antibodies with known specificities for the carbohydrate antigens i, X or Y, and seven anti-myeloid antibodies (determinants unknown) selected for their differing reaction patterns with human leucocytes were tested in chromatogram binding assays for reactions with myeloid cell glycolipids derived from normal human granulocytes and chronic myelogenous leukemia cells. Antigenicities were found exclusively on minor glycolipids which were barely or not at all detectable with orcinol-sulphuric acid stain. Among these, a neutral glycosphingolipid bound the anti-i antibody Den and chromatographed as the ceramide octasaccharide, Gal beta 1----4GlcNac beta 1----3Gal beta 1----4GlcNac beta 1----3Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4Glc-Cer. Several species of neutral glycosphingolipids with six to more than ten monosaccharides were detected which carry the X antigen and others the Y antigen: Gal beta 1----4(Fuc alpha 1----3)GlcNAc and Fuc alpha 1----2Gal beta 1----4(Fuc alpha 1----3)GlcNAc, respectively. In addition, three new types of carbohydrate specificities were detected among the myeloid cell glycolipids. Two were associated with neutral glycolipids: the first, recognised by anti-myeloid antibodies VIM-1 and VIM-10, was expressed on a distinct set of glycolipids with six or more monosaccharides, and the second, recognized by VIM-8, was expressed on glycolipids with more than ten monosaccharides. The third specificity, recognised by the anti-myeloid antibody VIM-2, was expressed on slow migrating sialoglycolipids with backbone structures of the poly-N-acetyllactosamine type that are susceptible to degradation with endo-beta-galactosidase. Thus, we conclude that the i and Y antigens occur among the glycolipids of normal myeloid and chronic myelogenous leukemia cells and that a high proportion of hybridoma antibodies raised against differentiation antigens of myeloid cells are directed at carbohydrate structures.

Prognostic significance of surface marker expression on blasts of patients with de novo acute myeloblastic leukemia.

The prognostic significance of the expression of surface membrane antigens on the blasts of 123 consecutive patients with de novo acute myeloblastic leukemia (AML) was evaluated. For this purpose, reactivity of monoclonal antibodies (mAbs) CLB-ERY3 (antiblood-group H antigen), VIM-D5 (CD15), WT1 (CD7), MY7 (CD13), MY9 (CD33), VID-1 (antihuman leukocyte antigen locus DR [anti-HLA DR]), VIM-2 (CDw65L), VIM-13 (CD14), 63D3 (CD14) and anti-TdT with leukemic blast cell populations was prospectively analyzed with respect to the rates of complete remission (CR), continuous complete remission (CCR), and survival. The overall rate of CR was 65%, the 6-year rates of overall CCR and survival were 23% and 13%, respectively (median period of patient observation, 30 months). Of all Abs tested, four (CLB-ERY3, MY7, anti-TdT, and VIM-D5) were found to be of prognostic value. Reactivity of CLB-ERY3, MY7, and anti-TdT was predictive for CR (CLB-ERY3+, 43% v CLB-ERY3-, 73%, P less than .02; MY7+, 59% v MY7-, 91%, P less than .003; TdT+, 28% v TdT-, 71%, P less than .001, respectively) and probability of survival (significantly lower survival rates: CLB-ERY3+, P less than .02; MY7+, P less than .03; and TdT+ cases, P less than .001, respectively). Reactivity of VIM-D5 was significantly associated with a higher probability of CCR (P less than .01). Our results confirm earlier reports on the prognostic significance of expression of CD13 and TdT in AML and indicate CLB-ERY3 (antiblood-group H antibody) and VIM-D5 (CD15) as further markers predictive for the clinical outcome in patients with de novo AML.

Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia.

The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium.