In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans.

Human CD317 is an intrinsic immunity factor that restricts the release of enveloped viruses, including the major pathogens HIV and Lassa virus, from infected cells in culture. Its importance for infection control in humans is unclear, due in part to its incompletely defined in vivo expression pattern. CD317 also has been proposed as a selective target for immunotherapy of multiple myeloma. To provide a framework for studies of the biological functions, regulation, and therapeutic potential of CD317, we performed microarray-based expression profiling in 468 tissue samples from 25 healthy organs from more than 210 patients. We found that CD317 protein was expressed to varying degrees in all organs tested and detected in a number of specialized cell types, including hepatocytes, pneumocytes, ducts of major salivary glands, pancreas and kidney, Paneth cells, epithelia, Leydig cells, plasma cells, bone marrow stromal cells, monocytes, and vascular endothelium. Although many of these cell types are in vivo targets for pathogenic viruses, restriction by CD317 or virus-encoded antagonists has been documented in only some of them. Limited cell type-dependent coexpression of CD317 with the IFN biomarker MxA in vivo and lack of responsive stimulation in organ explants suggest that interferons may only partially regulate CD317. This in vivo expression profiling sheds light on the biology and species-specificity of CD317, identifies multiple thus far unknown interaction sites of viruses with this restriction factor, and refutes the concept of its restricted constitutive expression and primary IFN inducibility. CD317's widespread expression calls into question its suitability as a target for immunotherapy.

Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infarcted porcine heart.

Systemic delivery of bone marrow-derived mesenchymal stem cells (MSCs) is a noninvasive approach for myocardial repair. We aimed to test this strategy in a pig model of myocardial infarction. Pigs (n = 8) received autologous MSCs (1 x 10(6)/kg body weight) labeled with fluorescent dye 48 h post proximal left anterior descending artery (LAD) occlusion. Hemodyamics, infarct size, and myocardial function were assessed at baseline and after 1 month. Morphologic analysis revealed that labeled MSCs migrated in the peri-infarct region, resulting in smaller infarct size (32 +/- 7 vs. 19 +/- 7%, p = 0.01), higher fractional area shortening (23 +/- 3 vs. 34.0 +/- 7%, p = 0.001), lower left ventricular end diastolic pressure (18.7 +/- 5 vs. 10.2 +/- 4 mmHg, p = 0.02) and higher +dp/dt (4,570 +/- 540 vs. 6,742 +/- 700 mmHg/s, p = 0.03) during inotropic stimulation. Systemic intravenous delivery of MSCs to pigs limits myocardial infarct size and is an attractive approach for tissue repair.

Cytokine-induced killer cells against autologous CLL: direct cytotoxic effects and induction of immune accessory molecules by interferon-gamma.

Cytokine-induced killer cells (CIK cells), coexpressing CD3 and CD56, can be expanded from peripheral blood mononuclear cells by the timed addition of interferon-gamma (IFN-gamma), IL-2 and OKT3. The effects of CIK cells on primary, autologous CLL cells are described. We used MACS to separate CD3(+) cells for expansion of CIK cell effectors and CD19(+) targets from peripheral blood of 16 CLL patients. Apoptosis was assessed by measuring annexinV staining in CLL cells. After incubation of autologous CIK with CLL, specific apoptosis in CLL cells was 15%. Coincubation with irradiated CIK cells for 48 hr before adding vital CIK cells resulted in an increased ICAM-1 expression on CLL cells and an increase in apoptosis of CLL targets (30%). These effects were mediated by IFN-gamma secretion of CIK cells. In addition to their direct cytotoxic effect, CIK cells secrete IFN-gamma that modulates the expression of adhesion molecules on CLL cells, and this enhances apoptosis induction by cytotoxic effector cells.

Chlorhexidine and silver-sulfadiazine coated central venous catheters in haematological patients--a double-blind, randomised, prospective, controlled trial.

BACKGROUND: Central venous catheters (CVCs) are essential for the intensive care of patients with haematological illness. Catheter-related infections (CRI) are an important problem in modern medicine, which may lead to life-threatening situations, to prolonged hospitalisation and increased cost. In immunocompromised patients suffering from haemato-oncological diseases, CRI is a significant factor for adverse outcome. Several clinical studies have shown that CVCs coated with antiseptics such as chlorhexidine and silver-sulfadiazine (CHSS) reduce the risk of catheter-related bacteraemia. Most studies, however, were performed on intensive care patients not suffering from chemotherapy-induced immunosuppression. PATIENTS AND METHODS: A prospective double-blind, randomised, controlled trial was performed to investigate the effectiveness of CHSS-coated catheters in haemato-oncological patients. A total number of 184 catheters (median duration of placement, 11 days) were inserted into 184 patients (male 115, female 69), of which 90 were antiseptically coated. After removal, all catheters were investigated for bacterial growth. MAIN RESULTS: Catheters coated with CHSS were effective in reducing the rate of significant bacterial growth on either the tip or subcutaneous segment (26%) compared to control catheters (49%). The incidence of catheter colonisation was also significantly reduced (12% coated vs 33% uncoated). Data obtained show a significant reduction of catheter colonisation in CHSS catheters. There was no significant difference in the incidence of catheter-related bacteraemia (3% coated vs 7% uncoated). However, due to the overall low rate of CRI, we could not observe a significant reduction in the incidence of catheter-related bacteraemia. CONCLUSION: Our data show that the use of CHSS catheters in patients with haematological malignancy reduces the overall risk of catheter colonisation and CRI, although the incidence of catheter-related bacteremia was similar in both groups.

Catheter-related infection and thrombosis of the internal jugular vein in hematologic-oncologic patients undergoing chemotherapy: a prospective comparison of silver-coated and uncoated catheters.

BACKGROUND: Catheter-related venous thrombosis is one of the most frequent complications of central venous catheters (CVCs). This complication occurs in 4- 40% of patients with hematologic malignancies receiving conventional chemotherapy after placement of CVCs. METHODS: The objective of this prospective study was to assess whether a silver-coated CVC poses an additional risk in the development of catheter-related thrombosis in hematologic-oncologic patients. Patients were randomized to receive either silver-coated polyurethane catheters (BactiGuard; Metacot, Stockholm, Sweden) or uncoated standard polyurethane catheters (Cavatheter, Fresenius AG, Bad Homburg, Germany) for central venous access. Silver-coated catheters (n = 120) and standard catheters (n = 113) were inserted into the jugular vein in 233 consecutive patients. Variables that may be significant for the development of thrombosis were comparable in the two groups. After removal of the CVC, the patency of both jugularian veins internal as well as external was assessed with real-time ultrasound (Sonolayer-SAL-35A; Toshiba, Tokyo, Japan). RESULTS: Four of 233 patients (1.5%) were found to have venous thrombosis. Incomplete occlusion of the internal jugular vein occurred in 2 patients (0.75%, parietal thrombosis), and complete thrombosis, although clinically silent, was found in 2 patients (0.75%). There was no difference between patients with silver-coated and uncoated CVCs. CONCLUSIONS: The authors concluded that this novel silver-coated CVC does not cause a higher rate of central venous thrombosis compared with standard CVCs. The low overall incidence of central venous thrombosis might be attributed to the routine application of low-dose heparin in our patients during chemotherapeutic treatment.

Prophylactic treatment of known ifosfamide-induced encephalopathy for chemotherapy with high-dose ifosfamide?

We report about a case of advanced Ewing sarcoma in a 30-year-old woman. Initial treatment was started according to the Euro-Ewing 99 protocol. During the initial therapy, an ifosfamide-induced encephalopathy occurred as status epilepticus. Because of cerebral toxicity, the following chemotherapies went without ifosfamide. During final radiotherapy multiple lung metastasis were diagnosed. After two cycles of chemotherapy with cyclophosphamide and topotecan (no response), left thoracotomy, and palliative pneumectomy, the patient was transferred to our ward for further treatment. Undergoing two cycles of chemotherapy with ifosfamide 4 g/m(2) intravenously for 3 consecutive days followed by high-dose chemotherapy (HDCT) according to the ICE-regimen (ifosfamide 2 g/m(2), carboplatin 200 mg/m(2), and etoposide 2 x 100 mg/m(2) intravenously for 6 consecutive days), and peripheral blood stem cell transplantation (PBSCT), complete remission was achieved. Under preventive therapy with methylene blue, thiamin, and glucose 5% infusions, no encephalopathy occurred.