Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas

OBJECTIVE: This study used quantitative radiological imaging to determine the effect of surgical resection on postoperative survival of patients with malignant astrocytomas. Previous studies relied on the surgeons' impressions of the amount of tumor removed, which is a less reliable measure of the extent of resection. METHODS: Information concerning possible prognostic factors was collected for 75 patients undergoing magnetic resonance imaging or computed tomography preoperatively and within 10 days postoperatively. Image analysis of the neuroradiological studies was conducted to quantify pre- and postoperative total tumor volumes and enhancing volumes. Univariate and multivariate proportional hazards models were used to analyze the regression of survival regarding 22 covariates that might affect survival. The covariates that were entered included age, gender, tumor grade, cumulative radiation dose, chemotherapy, seizures as a first symptom, Karnofsky performance status at presentation, pre- and postoperative total and enhancing tumor volumes, ratio of pre- to postoperative total and enhancing tumor volumes, tumor location, surgeon's impression of the degree of resection, and subsequent surgery. RESULTS: There were 23 patients with anaplastic astrocytomas and 52 with glioblastomas multiforme. The estimated mean survival time was 27 months for patients undergoing gross total resection, 33 months for subtotal resection, and 13 months for open or stereotactic biopsy. Five factors that were significant predictors of survival in multivariate analysis were tumor grade, age, Karnofsky performance status, radiation dose, and postoperative complications (P < 0.05). In univariate analysis, tumor grade, radiation dose, age, Karnofsky status, complications, presence of enhancing tumor in postoperative imaging, and postoperative volume of enhancing tumor were significantly associated with survival (P < 0.05). CONCLUSION: We conclude that the most important prognostic factors affecting survival of patients with anaplastic astrocytomas and glioblastomas multiforme are tumor grade, age, preoperative performance status, and radiation therapy. Postoperative complications adversely affect survival. Aggressive surgical resection did not impart a significant increase in survival time. Surgical resection may improve survival, but its importance is less than that of other factors and may be demonstrable only by larger studies.     

2-[125I]Iodomelatonin binding sites in the quail heart: characteristics, distribution and modulation by guanine nucleotides and cations

To investigate whether melatonin has a direct action on the cardiovascular system, putative melatonin receptors were studied in quail heart membrane preparations using the specific melatonin agonist 2-[125I]iodomelatonin (125I]Mel, as the radioligand. The [125I]mel binding demonstrated in the mature quail heart was saturable, highly 5.2 pM; Bmax = 1.32 +/- 0.25 fmol/mg protein; n = 8). The linear Scatchard plots and the close to unity Hill coefficient indicated a single class of binding sites. The pharmacological profile was in the affinity order of 2-iodomelatonin = 2-phenylmelatonin > melatonin > 6-chloromelatonin > 6-hydroxymelatonin > 6-sulphatoxymelatonin > N-acetylserotonin>5-hydroxytryptamine. Guanosine 5'-triphosphate and guanosine 5'-O-(3-thiotriphosphate) (GTP gammaS) dose dependently inhibited the binding. Ten microM GTPgammaS lowered the binding affinity by 50% in saturation studies. The order of potency of inhibition by cations was: Ca2+ > Mg2+ > Li+ > Na+ > K+ > choline chloride. Contrary to most other melatonin binding sites, millimolar concentrations of Ca2+ and Mg2+ did not promote binding in the quail heart membranes. In vitro autoradiography indicated homogenous labeling in the heart. Our results demonstrated [125I]Mel binding sites in the quail heart. That guanine nucleotides and Na+ inhibited the binding indicated that these putative melatonin receptors are coupled to guanine nucleotide-binding proteins (G-proteins).     

Expression of the myxoma virus tumor necrosis factor receptor homologue and M11L genes is required to prevent virus-induced apoptosis in infected rabbit T lymphocytes

Myxoma virus is a leporipoxvirus that causes a highly lethal virulent disease known as myxomatosis in the European rabbit. An important aspect of myxoma virus pathogenesis is the ability of the virus to productively infect lymphocytes and spread to secondary sites via lymphatic channels. We investigated the infection of the CD4+ T lymphoma cell line RL-5 with myxoma virus and Shope fibroma virus, a related but benign leporipoxvirus, and observed that myxoma virus, but not Shope fibroma virus, was able to productively infect RL-5 cells. We also discovered that infection of RL-5 cells with Shope fibroma virus or attenuated myxoma virus mutants containing disruptions in either the T2 or the M11L gene resulted in the rapid induction of DNA fragmentation, followed by morphological changes and loss in cell integrity characteristic of cell death by apoptosis. Purified exogenous T2 protein was unable to prevent apoptosis, suggesting that T2 functions intracellularly. Thus, myxoma virus T2, originally described as a secreted homologue of the tumor necrosis factor receptor, and M11L, a novel transmembrane species with no known cellular homologue, function to extend virus host range for replication in rabbit T lymphocytes through the inhibition of apoptosis in infected T lymphocytes.     

Depletion of striatal dopamine transporter does not affect psychostimulant-induced locomotor activity

The effect of neurotoxin-induced depletion of striatal dopamine transporter (DAT) binding sites on animals' responses to psychostimulants was investigated. Multiple 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or methamphetamine (METH) injections but not a single METH injection to Swiss Webster mice resulted in > 60% depletion of striatal DAT. MPTP-induced depletion of DAT did not affect METH- and cocaine-stimulated locomotor activity compared with the response of control mice. Pre-exposure to either the neurotoxic or the single non-neurotoxic dose of METH resulted in a marked locomotor sensitization in response to METH or cocaine challenge injections. The present results indicate that > 60% loss in striatal DAT binding sites has no effect on animals' responses to psychostimulants, and suggest that neural systems other than striatal DAT may contribute to the induction of locomotor sensitization to METH and cocaine.     

Acute and chronic phases of Toxoplasma gondii infection in mice modulate the host immune responses

Murine antibody responses to soluble proteins are generally restricted to the immunoglobulin G1 (IgG1) isotype. When mice were infected with Toxoplasma gondii Beverley and concomitantly immunized with a soluble unrelated protein antigen, a modification in the isotypic distribution of antibodies directed against this nonparasite antigen was observed, with a preferential production of IgG2a. Interestingly, when mice were immunized with a soluble protein antigen during the chronic phase (day 40) of infection with T. gondii Beverley, a similar modification in the isotypic distribution of antiprotein antibodies was observed.