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Biomedical subjects

R Blasberg

Publications and source records attributed to R Blasberg.

26 records · Page 2Linked to original sources
PubMed1983

Regional [14C]misonidazole distribution in experimental RT-9 brain tumors.

Regional [14C]misonidazole-derived radioactivity (MISO) was measured by quantitative autoradiography in experimental RT-9 brain tumors 0.5, 2, and 4 hr after an i.v. bolus (25 mg) and constant infusion (10 mg/hr). Misonidazole (MISO) concentration in plasma and brain was also measured by high-pressure liquid chromatography; the brain/plasma MISO ratio ranged between 0.5 and 0.7. MISO equivalents were calculated from tissue or plasma 14C radioactivity and [14C]MISO specific activity data. The MISO/MISO equivalents ratio, which represents the nonmetabolized fraction of [14C]MISO, fell gradually in plasma (0.89 at 4 hr) and more rapidly in brain (0.67 at 4 hr) and tumor (0.30 at 4 hr). MISO distributed uniformly throughout the brain at all three time periods. In contrast, MISO distribution in tumor was variable, and tumor concentrations relative to that in brain increased with time. The average tumor/brain MISO ratio was 1.3, 1.7, and 2.6 at 0.5, 2, and 4 hr, respectively, which suggests tumor uptake and binding of MISO or, more likely, MISO-derived 14C-labeled metabolites. In addition, MISO distribution in tumor tissue was strikingly heterogeneous at 4 hr, resulting in an average high/low tumor activity ratio of 4/1 and an average high tumor/brain ratio of 5/1. Tumor regions with high MISO activity correlated in part to viable-appearing cells around necrotic foci.

Animals↗
PubMed1981

Absorption resistance of cerebrospinal fluid after subarachnoid hemorrhage in the monkey; effects of heparin.

The morbidity and mortality of subarachnoid hemorrhage (SAH) is directly related to blood in the subarachnoid space. Blood was injected intracisternally in 10 monkeys, and the absorption resistance of cerebrospinal fluid (CSF) was studied. The monkeys given injections of nonheparinized blood maintained high absorptive resistances, whereas the resistances of the group that received heparinized blood returned to the original levels. If heparinization of the CSF can be achieved rapidly after SAH and the deposition of fibrin clots along the pathways of CSF drainage can be prevented, the resorption of blood through the arachnoid granulations might be facilitated.

Absorption↗
PubMedDate not supplied

Imaging transgene expression with radionuclide imaging technologies.

A variety of imaging technologies are being investigated as tools for studying gene expression in living subjects. Noninvasive, repetitive and quantitative imaging of gene expression will help both to facilitate human gene therapy trials and to allow for the study of animal models of molecular and cellular therapy. Radionuclide approaches using single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the most mature of the current imaging technologies and offer many advantages for imaging gene expression compared to optical and magnetic resonance imaging (MRI)-based approaches. These advantages include relatively high sensitivity, full quantitative capability (for PET), and the ability to extend small animal assays directly into clinical human applications. We describe a PET scanner (microPET) designed specifically for studies of small animals. We review "marker/reporter gene" imaging approaches using the herpes simplex type 1 virus thymidine kinase (HSV1-tk) and the dopamine type 2 receptor (D2R) genes. We describe and contrast several radiolabeled probes that can be used with the HSV1-tk reporter gene both for SPECT and for PET imaging. We also describe the advantages/disadvantages of each of the assays developed and discuss future animal and human applications.

Animals↗
PubMedDate not supplied

Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo.

A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, and could elucidate temporal dynamics and immune regulation at different stages of disease and following therapy. We developed and assessed a novel method for monitoring the T-cell receptor (TCR)-dependent nuclear factor of activated T cells (NFAT)-mediated activation of T cells by optical fluorescence imaging (OFI) and positron emission tomography (PET). The herpes simplex virus type 1 thymidine kinase/green fluorescent protein [HSV1-tk/GFP (TKGFP)] dual reporter gene was used to monitor NFAT-mediated transcriptional activation in human Jurkat cells. A recombinant retrovirus bearing the NFAT-TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting NFAT-specific enhancer. Transduced Jurkat cells were used to establish subcutaneous infiltrates in nude rats. We demonstrated that noninvasive OFI and nuclear imaging of T-cell activation is feasible using the NFAT-TKGFP reporter system. PET imaging with [(124)I]FIAU using the NFAT-TKGFP reporter system is sufficiently sensitive to detect T-cell activation in vivo. PET images were confirmed by independent measurements of T-cell activation (e.g., CD69) and induction of GFP fluorescence. PET imaging of TCR-induced NFAT-dependent transcriptional activity may be useful in the assessment of T cell responses, T-cell-based adoptive therapies, vaccination strategies and immunosuppressive drugs.

Animals↗
PubMedDate not supplied

Anti-neoplastic properties of human corticotropin releasing factor: involvement of the nitric oxide pathway.

We report a series of the in vivo and in vitro studies that evaluate the anti-neoplastic potential of hCRF in W256 rat mammary carcinoma. Using magnetic resonance imaging (MRI) and direct measurements of tumor and peritumoral brain water content we found that hCRF treatment (100 micrograms/kg subcutaneously twice a day for 3 days) caused significant inhibition of growth and vascular permeability of the i.c. W256 tumors. hCRF also exhibited antiproliferative and differentiation-inducing effects in W256 cells in vitro. The calculated IC50 values were 70 nM and 100 nM of hCRF, as measured by digital videomicroscopic quantitation of tumor cell population growth rate and by [3H]-thymidine incorporation assay, respectively. The observed effects in W256 cells were CRF receptor mediated. This was shown in two ways: by the presence of relatively high levels of CRF1 receptor mRNA in W256 cells, and by the fact that the tumor growth inhibitory and differentiation inducing effects of hCRF in vitro were abolished by the CRF receptor antagonist a-helical CRF (9-41). Antiproliferative and differentiation inducing effects of hCRF in W256 cells involve activation of nitric oxide synthase (NOS) and L-arginine-NO pathway. This was shown by using the inhibitor of NOS, the L-nitro-arginine methyl esther (L-NAME), which prevented the antiproliferative and differentiation inducing effects of hCRF in vitro. The cytotoxicity of NO in W256 cells was assessed by the addition of sodium nitroprusside (SNP) to the media. SPN exhibited dose-dependent cytotoxicity in W256 cells with IC50 of 100 muM SNP as measured by [3H]-thymidine incorporation assay. We conclude, that hCRF has substantial anti-neoplastic effects which include inhibition of proliferation and induction of differentiation of the tumor cells in vitro, and a decrease in tumor vascular permeability (and possibly neo-angiogenesis) in vivo.

Animals↗