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Graft-versus-host disease (GVHD) after orthotopic liver transplantation (OLT) is a serious complication with mortality rates over 80%. Two patients with established GVHD after OLT were treated with Basiliximab, a chimeric murine human monoclonal antibody which binds to the alpha-chain of interleukin-2 receptor (IL-2R). Two males, aged 45 and 56 years, presented after OLT with a clinical picture consistent with GVHD. Quantitative measurements of recipient peripheral blood donor lymphocyte chimerism were carried out by flow cytometric analysis, and showed peak chimerism levels of 5% and 8%, respectively. Treatment comprised 3 doses of 1 g methyl prednisolone followed by 2 doses of 20 mg of Basiliximab. In both, treatment resulted in complete disappearance of macro-chimerism in blood. There was resolution of skin rash by day 7; however, diarrhea persisted. White cell scan showed increased uptake in the terminal ileum and small-bowel resection was performed in both patients. One patient is alive and well 36 months after OLT. The other patient had resolution of GVHD, but died of recurrent hepatitis C 1 year after OLT. The combination of immunological and surgical treatment for GVHD following solid organ transplantation has not previously been described.

The last 10 years has seen major improvements in our understanding of the g enetic anomalies that lie behind the development and progression of human astrocytic tumors. The least aggressive astrocytomas frequently show loss of wild type p53 as well as losses of alleles from a number of regions of the genome. The genes targeted have yet to be identified. The most aggressive tumors, the glioblastomas, show mutations affecting the cellular mechanisms controlling entry into the S–phase of the cell cycle. The picture has become more complex as regards the mechanisms targeted. The heterogeneous genetic abnormalities reported previously in individual tumors of the same type have become easier to understand with the realization that they represent the mutation of different genes that code for components of the same cellular control mechanisms. There remain many routes to explore before we understand in detail the molecular mechanisms behind the phenotype of these tumors.

Thirty-one patients with intracranial metastases were examined with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) as a tracer. The PET study was prompted by growth of the tumor in spite of therapy, or regrowth after an initially favorable response. Increased accumulation of FDG was seen in 14 patients (group 1) and decreased in 17 (group 2). Patients in group 1 had verified tumor growth in 9 of 14 cases. The median survival after radiosurgery was 12.3 months. One patient in this group is still alive after open surgery of a recurrent metastasis. Six patients in group 2 are still alive. The median survival after radiosurgery was 19.9 months. Verified radiation reaction/necrosis was found in 5/17 and viable tumor tissue in 2. The survival time in group 2 was significantly longer than in group 1. PET is superior to computed tomography and magnetic resonance imaging in the differentiation between recurrence and radiation reaction/necrosis. However, temporary radiation effects may mask remaining tumor tissue, and repeat PET studies may sometimes be necessary.

DiGeorge syndrome is a human developmental field defect with the pathological features of an abnormality of embryogenesis at 4 to 6 weeks of gestation. Cytogenetic analyses of patients have revealed a number of instances of monosomy 22q11-pter in this condition. We have analyzed 52 DNA markers that map to 22q11-pter and have found 27 that are deleted in DiGeorge syndrome patients with known monosomy for part of this region and that are duplicated in patients with the der22 syndrome. The set of clones mapping to the DiGeorge region was further assigned to a proximal or a distal location within the deletion.

Human glioma cells obtained from established cell lines (Tp-276MG, Tp-301MG, Tp-378MG, Tp-483MG and U-251MG) were analyzed for the presence of ion channels with the tight-seal voltage clamp technique. The current-voltage relation revealed a marked inward rectification at hyperpolarizing voltages, due to the presence of inward rectifying K-channels in cells from all studied cell lines. These channels were conducting when the membrane potential was more negative than the K-equilibrium potential. The slope conductance for the inward K-currents (gKi) was affected both by [K+]i and [K+]o. gKi was proportional to [K+]o raised to 0.35 or 0.50, of which the larger value was measured in the presence of low [K+]i (25 mM). The rectification was not significantly different in cells perfused with Mg-free EDTA-buffered internal solution. Tl+ was 3.5 times more permanent than K+. gKi was blocked by Cs+ (1 mM) in a voltage-dependent way (more effective in the hyperpolarized membrane), and by Na+ (154 mM) depending on voltage and time. From measurements of unitary current events in membrane patches (outside out or cell attached) the conductance of the single inward rectifying channel was estimated to be 27 +/- 7 pS. This type of ion channel may be important for K-uptake by glial cells and hence for the K-homeostasis in the brain.

Human malignant glioma cells from 5 different cell lines were voltage clamped and examined for the presence of depolarization-activated ion channels. Outward K-currents were elicited at membrane potentials greater than 40 mV, which had two main components, one which was delayed and blocked by externally applied tetraethylammonium (TEA, 10 mM), and another which was instantaneous and insensitive to TEA in the outside solution. The proportion of the two K-current components varied between cell lines. An increase in [Ca2+]o in the range 0-4 mM, decreased the leak conductance and shifted the activation of the instantaneous outward K-current towards more positive potentials. Mg2+, Zn2+ and Co2+ had qualitatively similar effects. Patch recordings with 150-160 mM K+-solution on both sides of the membrane revealed that the delayed outward K-current was carried through large conductance (250-300 pS) channels. Changes in free [Ca2+]i from 0 to 2 x 10(-8) M increased the activation of the large conductance K-channel. Small Na-currents were identified in cells from one cell line (Tp-378MG). The Na-conductance ranged from 0.5 to 7.5 nS in 25% of the cells, and was less than 0.5 nS in 75%. The Na-channels were activated and inactivated at 30-40 mV more positive potentials than in the mammalian peripheral nerve. Tetrodotoxin (100 nM) blocked gNa almost completely.

The mechanism for 201Tl+ uptake was studied in cultured human glioma cell lines. Ouabain (1 mM) decreased the uptake at steady-state to 60%, but the rate of uptake was faster in the presence of ouabain. Addition of non-radioactive Tl+ (to a K+-free medium) decreased the uptake, but much less than expected for a system limited by the number of transport sites. Changes in K+ concentration of incubation medium affected the 201Tl+ uptake as predicted by the electrochemical equilibrium (Nernst equation). Using the uptake in isotonic KCl as a reference for membrane potential (0 mV), the calculated membrane potential was -75 mV in a medium with 3.0 mM K+. The Tl+-flux constants and the membrane permeabilities for Tl+ and K+ were calculated from the rate of uptake and from wash-out experiments. This is a new method for membrane potential and permeability studies in cell populations. The mechanism for 201Tl+ uptake is relevant for the clinical interpretation of 201Tl+ scintigraphy.