Background-Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular functionafter experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs. Methods and Results-Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [ 111 In]indium oxine. EPCs (10 6 ) were injected in athymic nude rats 24 hours after myocardial infarction (nϭ8) or sham operation (nϭ8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, Ϸ70% of the radioactivity was localized in the spleen and liver, with only Ϸ1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02Ϯ0.19 in sham-operated animals to 2.03Ϯ0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69Ϯ1.54 in sham-operated animals to 4.70Ϯ1.55 (PϽ0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone. Conclusions-Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy. (Circulation.

Regulatory macrophages (M regs) were administered to two living-donor renal transplant recipients. Both patients were minimized to low-dose tacrolimus monotherapy within 24 wk of transplantation and subsequently maintained excellent graft function. After central venous administration, most M regs remained viable and were seen to traffic from the pulmonary vasculature via the blood to liver, spleen, and bone marrow. By 1 y posttransplantation, both patients displayed patterns of peripheral blood gene expression converging upon the IOT-RISET signature. Furthermore, both patients maintained levels of peripheral blood FOXP3 and TOAG-1 mRNA expression within the range consistent with nonrejection. It is concluded that M regs warrant further study as a potential immune-conditioning therapy for use in solid-organ transplantation. The results of this work are being used to inform the design of The ONE Study, a multinational clinical trial of immunomodulatory cell therapy in renal transplantation.

The serum detection of S100B, a new melanoma marker, has shown clinical significance in early studies. The aim of our study of 1,339 serum samples from 412 different melanoma patients and 107 control patients was to prove the prognostic value of serum S100B levels in melanoma patients at different stages of disease and at follow-up (median: 30 months). Using a cutoff level of 0.2 μg/l S100B, 5 of 286 patients (1.7%) with primary tumors (stage I/II), 14/73 (19.2%) patients with locoregional metastasis (stage III) and 57/84 (67.9%) patients with advanced disease (stage IV) were S100B positive (statistically significant differences for stage I/II vs. III, I/II vs. IV, and III vs. IV, p < 0.001). The estimated overall survival time was significantly longer (p < 0.001) for patients with S100B values below 0.2 μg/l compared to patients with elevated S100B levels (≥0.2 μg/l), which was independent of the stage of disease (I–IV). Regarding prognosis, we were furthermore able to distinguish different subgroups among stage III and IV patients using S100B serum levels (p < 0.01). Patients with different cutaneous non-melanoma diseases served as S100B-negative controls. S100B serum evaluations using the Sangtec^®100 IRMA are highly specific and sensitive for the detection of metastatic melanoma. S100B has been shown to be a relevant prognostic factor for survival in a study with a large sample size of melanoma patients including close follow-up evaluations.

In the immunohistology of malignant melanoma the use of polyclonal antibodies against protein S100 is well established. Recently, it was shown that S100B, a subunit of the S100 protein family, is detectable in the serum of melanoma patients and correlates with the stage of the disease in patients with metastatic melanoma. In the present study, the first evaluation of a large number of treatment observations (n = 77) in 64 different patients during chemotherapy and/or immunotherapy for advanced metastatic melanoma (stage IV) is presented. All patients received treatment according to standardized protocols comprising 8 weeks of treatment followed by routine staging procedures to evaluate therapeutic outcome. In 13 patients with tumour enlargement after first-line therapy, a second-line treatment was subsequently given. S100B immunoradiometric assay (IRMA) tests were performed before, during and after treatment at scheduled time points. In the interim analysis at 4 weeks 29 of 37 (78%) patients with tumour progression during treatment showed a raised S100B level. In the final analysis at 8 weeks, 31 of these 37 patients (84%) demonstrated rising S100B values (P < 0.001). Patients who responded to treatment (stable or regressing metastatic disease) showed constant or declining S100B levels in 38 of 40 patients (95%) at the interim analysis, at 8 weeks this was further increased to 39 of 40 patients (98%; P < 0.001). Thus, the use of S100B for monitoring treatment is adequate in the majority of cases. Our observations are of great interest for therapeutic trials of adjuvant and palliative therapies as the rise of S100B levels might indicate that re-staging and/or changes in therapy strategies should be chosen.

No abstract

SUMMARY Studies have shown that the extraction of glucose per unit flow is increased in moderately ischemic myocardium primarily due to anaerobic glucose metabolism manifested as lactate production, whereas myocardial infarction is characterized by the loss of metabolically active myocardium. To determine the feasibility of demonstrating these metabolic abnormalities reflecting both ischemia and infarction, we used positron computed tomography (PCT) to evaluate relative regional myocardial exogenous glucose utilization and perfusion in 15 patients with recent myocardial infarction. The positron-emitting tracers of glucose metabolism and perfusion, 18F-2-fluoro-2-deoxyglucose (FDG) and N-13 ammonia, respectively, were used. Fourteen of 19 documented infarctions were demonstrated by PCT to have concordantly decreased glucose utilization and perfusion. However, in an additional 11 regions, glucose utilization was disproportionately increased relative to perfusion, consistent with ischemic glucose consumption. These findings correlated with the presence of postinfarction angina, the site of ischemic electrocardiographic changes during chest pain, and the presence of regional left ventricular dysfunction and severe coronary artery disease. Because three ECG infarct zones not detected by PCT demonstrated ischemic glucose utilization, only two of 19 electrocardiographically defined infarctions had no detectable metabolic abnormality.We conclude that the changes in regional FDG and N-13 ammonia concentrations detected with PCT in patients who had had a recent myocardial infarction are consistent with regional exogenous glucose utilization and perfusion in moderately ischemic and irreversibly infarcted myocardium. This approach has the potential to identify and differentiate resting myocardial ischemia from infarction and to assess tissue viability after an ischemic event.POSITRON computed tomography (PCT)' has made possible noninvasive evaluation of in vivo regional biochemical processes. The information obtained by PCT is analogous to that obtained by in vitro autoradiography.2 Use of the positron-emitting radionuclides 13N, 150 "C and 'F allows labeling of a variety of biologically important compounds whose physiologic fate is either identical to that of their naturally occurring analogs or altered in a predictable fashion. PCT can be used to measure exogenous glucose utilization quantitatively in brain and myocardium using '5F-2-fluoro-2-deoxyglucose (FDG) and relative regional perfusion can be evaluated accurately with N-13 ammonia.3 12 Clinically and experimentally, the glycolytic flux that is maintained or accelerated and manifested as lactate production in moderately ischemic myocardium is absent in infarcted myocardium.'3-16 This observation suggests that the increased extraction of glucose per unit flow in ischemic myocardium with modest flow reductions will result in increased myocardial FDG accumulation relative to N-13 ammonia, 17 whereas the reduced glucose metabolism and perfusion in infarcted myocardium w...

Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.

No abstract