US and MRI of gastrointestinal graft-versus-host disease

Abdominal problems often complicate the clinical course after bone marrow transplantation. Graft-versus-host disease occurs as a complication of allogenic bone marrow transplantation. In this report, the findings of intestinal involvement are described and correlated with histopathological findings. Increased bowel-wall thickness and increased vascularity were shown by US. MRI demonstrated generalised increased bowel-wall thickness associated with bowel-wall enhancement after administration of i.v. gadolinium.     

Small-volume frequency-domain oximetry: phantom experiments and first in vivo results

We describe a new method to determine the oxygen saturation and the total hemoglobin content of tissue in vivo absolutely at small source-detector separations (<10 mm). Phase and mean intensity of modulated laser light of various wavelengths was measured at several predetermined source-detector separations in the frequency domain. From these measured quantities, the absorption coefficient was derived using the modified time-integrated microscopic Beer-Lambert law (MBL). In addition, the interaction volume of the photons was determined using a multi-layer Monte-Carlo model of human skin. To evaluate the method, we employed homogenous solid phantoms (consisting of TiO2 particles embedded in resin) with mean scattering and absorbing properties comparable to those of human skin. Furthermore, in vivo measurements were performed in a healthy volunteer to demonstrate that the technique is applicable for the determination of the oxygen saturation and the total hemoglobin content in the skin in vivo. The proposed technique is especially suited for the on-line determination of the oxygen saturation and total hemoglobin content in applications where small applicators are required (e.g., fetal oxygen monitoring sub partu).     

Cardiovascular risk factors do not predict clinically defined restenosis after percutaneous transluminal angioplasty for lower limb ischemia

The purpose of this study was to evaluate risk factors predicting restenosis and primary patency after percutaneous transluminal angioplasty. Follow-up data (including cardiovascular risk factor scores according to SCVIR criteria, preinterventional and postinterventional clinical data and patient history) of all patients who underwent successful percutaneous transluminal angioplasty for lower limb ischemia were analyzed retrospectively and patients, relatives, or referring physicians underwent a telephone interview. Patients with incomplete follow-up data were examined by means of a clinical examination, including Doppler measurements and treadmill test. Additionally all angiograms were evaluated to calculate lesion length, number of treated lesions, lesion type (SCVIR score), and runoff. The outcome was categorized into four groups: early recurrence (< 1 month, group I), mean recurrence (1-6 months, group II), late recurrence (>6 months, group III), and no recurrence (group IV). According to common concepts group I was defined as early (thrombotic) reocclusion, group II as clinically defined restenosis, and group III as progression of atherosclerosis. One hundred thirty-seven patients underwent percutaneous transluminal angioplasty of 148 extremities. The groups differ significantly only with respect to a higher diabetes score for group I in comparison to group IV (p=0.002, Kruskal-Wallis test), and a worse runoff of group I compared with group IV (p =0.008). There was a trend toward a higher diabetes score for group II in comparison to group IV (p = 0.014). There were no differences with regard to hyperlipemia, hypertension, and tobacco use between patient groups. Mean primary patency was 436 days. Predictors for lower patency rates were diabetes mellitus (p<0.001), runoff (p=0.005), and number of treated lesions (p=0.007) in a stepwise, multiple regression analysis. Patients with clinically defined restenosis showed no specific risk factor profile in this study. Predictors for lower primary patency were diabetes mellitus, number of treated lesions, and runoff.     

Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity

Transforming growth factor beta (TGF-beta), a pleiotropic cytokine that regulates cell growth and differentiation, is secreted by many human tumors and markedly inhibits tumor-specific cellular immunity. Tumors can avoid the differentiating and apoptotic effects of TGF-beta by expressing a nonfunctional TGF-beta receptor. We have determined whether this immune evasion strategy can be manipulated to shield tumor-specific cytotoxic T lymphocytes (CTLs) from the inhibitory effects of tumor-derived TGF-beta. As our model we used Epstein-Barr virus (EBV)-specific CTLs that are infused as treatment for EBV-positive Hodgkin disease but that are vulnerable to the TGF-beta produced by this tumor. CTLs were transduced with a retrovirus vector expressing the dominant-negative TGF-beta type II receptor HATGF-betaRII-Deltacyt. HATGF-betaRII-Deltacyt- but not green fluorescence protein (eGFP)-transduced CTLs was resistant to the antiproliferative and anticytotoxic effects of exogenous TGF-beta. Additionally, receptor-transduced cells continued to secrete cytokines in response to antigenic stimulation. TGF-beta receptor ligation results in phosphorylation of Smad2, and this pathway was disrupted in HATGF-betaRII-Deltacyt-transduced CTLs, confirming blockade of the signal transduction pathway. Long-term expression of TGF-betaRII-Deltacyt did not affect CTL function, phenotype, or growth characteristics. Tumor-specific CTLs expressing HATGF-betaRII-Deltacyt should have a selective functional and survival advantage over unmodified CTLs in the presence of TGF-beta-secreting tumors and may be of value in treatment of these diseases.     

Characterization of the levels of expression of retinoic acid receptors,galectin-3, macrophage migration inhibiting factor,and p53 in 51 adamantinomatous craniopharyngiomas

OBJECT: Craniopharyngiomas are histopathologically defined as benign tumors that can behave very aggressively at the clinical level. They can originate from different types of embryonal epithelial tissue in which correct spatiotemporal regulation has been disrupted at the effector production level. The goal of this study was to determine the efficacy of using selected biological markers to distinguish between recurring and nonrecurring craniopharyngiomas. METHODS: The authors used computer-assisted microscopy to determine quantitatively the immunohistochemical levels of expression of selected markers, including retinoic acid receptors (RARs), as response elements to retinoic acid in a series of 51 adamantinomatous craniopharyngiomas. These tumors may also originate as the result of physiological defects in the apoptosis-mediated elimination of embryological remnants of epithelial tissue. Galectin-3, p53, and the macrophage migration inhibiting factor (MIF) are known to play crucial roles in these processes. The authors quantitatively determined the levels of expression of these substances in this series of 51 craniopharyngiomas. The data show that all craniopharyngiomas were immunoreactive for RARalpha, whereas their immunoreactivity for RARbeta and RARgamma varied dramatically from one case to another. Craniopharyngiomas with low levels of RARbeta and high levels of RARgamma are more likely to recur than those with higher levels of RARbeta and lower levels of RARgamma. Rapidly recurring craniopharyngiomas also show significantly lower levels of expression of galectin-3 and MIF than nonrecurring or slowly recurring cases. Few tumors exhibited p53 immunopositivity. CONCLUSIONS: The data indicate that even in the so-called adamantinomatous group of craniopharyngiomas, several subgroups with different clinical behavior patterns can be identified on the basis of differentiation markers relating mainly to the presence or absence of RARbeta and RARgamma.     

Biomolecules linked to transition metal complexes--new chances for chemotherapy

From the synthetic point of view the fast developing fields of medicine and biology offer new opportunities for the design of very effective drugs with high selectivity. Especially in the field of anticancer therapy many efforts have been made to deliver drugs to specific tissues. Sugar substituted porphyrin compounds, bile acid conjugates, and pH-sensitive immunoliposomes are only some examples. Although there are many different approaches to exploit biomolecules as shuttles only a start has been made. Since the targeting of a drug is a very complex process, a successful design of a new compound has to consider chemical as well as biological aspects and requires a multidisciplinary cooperation with physicians and biologists. Three interesting concepts are evaluated exemplarily: antibodies, molecules with binding affinity to hormone receptors, and bile acids. The main issues are: selection of the drug and the carrier, ways of linking the pharmacological active compound to the biomolecule, the optimal way of linking the drug to the spacer, and cytotoxicity, apoptosis, and drug resistance.