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Biomedical subjects

A Bogdanov

Publications and source records attributed to A Bogdanov.

At least 19 recordsLinked to original sources
PubMed2005

Is there a place for interscalene block performed after induction of general anaesthesia?

BACKGROUND AND OBJECTIVE: The timing of interscalene block in relation to general anaesthesia remains a controversial subject. We believe that the results of our study demonstrate that this block may be performed safely on anaesthetized patients, providing that certain conditions are met. METHODS: Five hundred and forty-eight cases of arthroscopic shoulder surgery were analysed retrospectively in order to identify the results of interscalene block performed after induction of general anaesthesia, but before the start of surgery. Patients were kept in hospital for 24 h and assessed before being discharged from the hospital and again in the period from 4 to 8 weeks after surgery. Duration of the block, quality of postoperative pain relief and neurological complications were recorded. RESULTS: Our study failed to reveal any permanent or long-term neurological complications attributable to interscalene block performed after induction of general anaesthesia. CONCLUSION: It is our opinion that the primary factor for safe interscalene block is modification of the anaesthetic technique rather than the timing of regional block in relation to induction of general anaesthesia.

Amides↗
PubMed2004

Measurement of tumor interstitial volume fraction: method and implication for drug delivery.

It is important to evaluate the tumor interstitial volume fraction that is accessible for drug accumulation during the distribution phase in order to determine the potential efficacy of cancer chemotherapy. In this study, we performed simulations of magnetic resonance imaging (MRI) signal intensity using a two-compartment tissue model for quantitative analyses of absolute interstitial volume measurements while we experimentally characterized a mouse tumor model with a dual MR contrast-agent method. Previously, consecutive intravenous injections of a strictly intravascular T1 contrast agent followed by an extravasating agent were used as a strategy for the quantification of both relative blood volume (Rel_BV) and relative interstitial volume (Rel_ITST) (Weissleder et al. Eur J Cancer 1998;34:1448-1454; Bogdanov et al. Neoplasia 1991;1:438-435). In the current study, we demonstrate that this approach can be further improved, and that it enables one to accurately evaluate both relative and absolute interstitial volumes. The animal data indicated that a significant difference exists between the absolute interstitial volume fractions of subcutaneously implanted MDA PCa 2b tumor and skeletal muscle tissue (27.5 +/- 9.1% and 15.9 +/- 0.7%, respectively (P < 0.05)), while only a minor difference was found for the absolute blood volumes (Abs_BV) (Kim et al. Magn Reson Med 2002;47:1110-1120) of these tissues.

Animals↗
PubMed2002

Targeting of MPEG-protected polyamino acid carrier to human E-selectin in vitro.

Targeted diagnostic agents are expected to have a significant impact in molecular imaging of cell-surface associated markers of proliferation, inflammation and angiogenesis. In this communication, we describe a new class of targeted polyamino acid-based protected graft copolymers (PGC) of poly-(L-lysine) and methyl poly-(ethylene glycol) (PGC) covalently conjugated with a monoclonal antibody fragment, F(ab')(2). We utilized targeted PGC conjugates as carriers of near-infrared indocyanine fluorophores (Cy5.5) for optical imaging of endothelial cell populations expressing IL-1 beta inducible proinflammatory marker E-selectin. We compared two conjugation chemistries, involving either introduction of sulfhydryl group to F(ab')(2), or via direct attachment of the antibody fragment directly to the chemically activated PGC. Both PGC-based targeted agents demonstrated high binding specificity (20-30 fold over non-specific uptake) and were utilized for imaging E-selectin expression on human endothelial cells activated with IL-1 beta.

Amino Acids↗
PubMed2001

Direct localization by cryo-electron microscopy of secondary structural elements in Escherichia coli 23 S rRNA which differ from the corresponding regions in Haloarcula marismortui.

Insertions were introduced by a two-step mutagenesis procedure into each of five double-helical regions of Escherichia coli 23 S rRNA, so as to extend the helix concerned by 17 bp. The helices chosen were at sites within the 23 S molecule (h9, h25, h45, h63 and h98) where significant length variations between different species are known to occur. At each of these positions, with the exception of h45, there are also significant differences between the 23 S rRNAs of E. coli and Haloarcula marismortui. Plasmids carrying the insertions were introduced into an E. coli strain lacking all seven rrn operons. In four of the five cases the cells were viable and 50 S subunits could be isolated; only the insertion in h63 was lethal. The modified subunits were examined by cryo-electron microscopy (cryo-EM), with a view to locating extra electron density corresponding to the insertion elements. The results were compared both with the recently determined atomic structure of H. marismortui 23 S rRNA in the 50 S subunit, and with previous 23 S rRNA modelling studies based on cryo-EM reconstructions of E. coli ribosomes. The insertion element in h45 was located by cryo-EM at a position corresponding precisely to that of the equivalent helix in H. marismortui. The insertion in h98 (which is entirely absent in H. marismortui) was similarly located at a position corresponding precisely to that predicted from the E. coli modelling studies. In the region of h9, the difference between the E. coli and H. marismortui secondary structures is ambiguous, and the extra electron density corresponding to the insertion was seen at a location intermediate between the position of the nearest helix in the atomic structure and that in the modelled structure. In the case of h25 (which is about 50 nucleotides longer in H. marismortui), no clear extra cryo-EM density corresponding to the insertion could be observed.

Base Sequence↗
PubMed2001

DNA binding chelates for nonviral gene delivery imaging.

Noninvasive in vivo monitoring of gene delivery would provide a critically important information regarding the spatial distribution, local concentration, kinetics of removal and/or biodegradation of the expression vector. We developed a novel approach to noninvasive gene delivery imaging using heterobifunctional peptide-based chelates (PBC) bearing double-stranded DNA-binding groups and a technetium-binding amino acid motif. One of such chelates: Gly-Cys(Acm)-Gly-Cys(Acm)-Gly-Lys(4)-Lys-(N-epsilon-[4-(psoralen-8-yloxy)]butyrate)-NH(2) has been characterized and labeled with reduced (99m)Tc pertechnetate (oxotechnetate). The psoralen moiety (a DNA binding group of PBC) allowed linking to double-stranded DNA upon short-term irradiation with the near UV range light (>320 nm). Approximately 30-40% of added (99m)Tc-labeled PBC was nonextractable and co-eluted with a model pCMV-GFP vector during the gel-permeation chromatography. Nuclear imaging of "naked" DNA and DNA complexes with lipid-based transfection reagents ("lipoplexes") has been performed after systemic or local administration of (99m)Tc-PBC-labeled DNA in mice. Imaging results were corroborated with the biodistribution using (99m)Tc-PBC and (32)P-labeled DNA and lipoplexes. A markedly different biodistribution of (99m)Tc PBC-labeled DNA and lipoplexes was observed with the latter being rapidly trapped in the liver, spleen and lung. (99m)Tc PBC-DNA was used as an imaging tracer during in vivo transfection of B16 melanoma by local injection of "naked" (99m)Tc PBC-DNA and corresponding lipoplexes. As demonstrated by nuclear imaging, (99m)Tc PBC-DNA lipoplexes showed a slower elimination from the site of injection than (99m)Tc PBC-DNA alone. This result correlated with a higher expression of marker mRNA and green fluorescent protein as determined using RT-PCR and immunohistochemistry, respectively.

Animals↗
PubMed2000

Tyrosinase mutants are capable of prodrug activation in transfected nonmelanotic cells.

Tyrosinase has been suggested as a prodrug-converting enzyme for the treatment of melanoma. We hypothesized that tyrosinase expression in transfected nonmelanotic cells can be used in a gene therapy paradigm of prodrug activation. To verify our hypothesis, we used the following tyrosinase variants: (a) a full-length human tyrosinase clone (T); (b) a mutant lacking the COOH-terminal cytoplasmic domain (TdeltaC); (c) a mutant lacking the COOH-terminal transmembrane and cytoplasmic domains (TdeltaTC); and (d) a fusion with the eight COOH-terminal amino acids of lysosome-associated membrane protein-1 (TL). Expression of mutant and wild-type tyrosinases was induced by transfection in nontumorigenic human cells of epithelial origin (293HEK, MCF-10A adenoma, and NHDF-Ad human dermal fibroblasts) as well as in tumor cells (9L gliosarcoma, MCF7 adenocarcinoma, and HT-1080 fibrosarcoma). When compared with the wild-type tyrosinase transfectants, truncated mutant expression resulted in higher mRNA levels that paralleled higher enzyme activity of the truncated mutants. Two model tyrosinase prodrugs, hydroxyphenyl-propanol (HPP) and N-acetyl-4-S-cysteaminylphenol (NAcSCAP) inhibited proliferation and caused cell death of transfected cells in a dose-dependent manner. Effects of prodrug treatment were compared for tumorigenic cells and their nontumorigenic counterparts. Two truncated mutants (TdeltaC and TdeltaTC) showed low endogenous cytotoxicity and efficiently suppressed proliferation and induced cytotoxicity in transfected tumor cells in the presence of NAcSCAP. Overall, these results indicate that the developed tyrosinase mutants hold promise as prodrug activation systems for tumoral gene therapy.

Adenocarcinoma↗
PubMed2000

New approaches for imaging in gene therapy.

Gene therapy is increasingly used experimentally and clinically to replace defective genes and/or impart new functions to cells and tissues. With the recent advances in vector design, improvements in transgene and prodrug activation strategies, gene therapy has been applied to a wide variety of diseases, tissues and organ systems. It is now clear that our specialty will play a critical role in gene therapy research and its clinical applications. Three aspects of gene therapy are of particular interest to imaging. The first is in delivering genes and vector products by minimally invasive interventional techniques. The second is in quantitating gene and DNA deliveries, for example, by nuclear imaging. Finally, imaging can be used to monitor the levels of transgene expression in vivo. A variety of imaging techniques including PET imaging, nuclear imaging, MR imaging and optical imaging can potentially be used to achieve the latter. This brief introductory overview is intended to summarize current strategies and illustrate the role that radiology will play in this field.

Animals↗
PubMed2000

Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model.

PURPOSE: To investigate the accumulation and cellular uptake of long-circulating dextran-coated iron oxide (LCDIO) particles in malignant neoplasms in vivo. MATERIALS AND METHODS: A gliosarcoma rodent model was established to determine the distribution of a model LCDIO preparation in tumors. LCDIO accumulation in tissue sections was evaluated with multichannel fluorescence microscopy with rhodaminated LCDIO, green fluorescent protein as a tumor marker, and Hoechst 33258 dye as an intravital endothelial stain. Uptake into tumor cells was corroborated with results of immunohistochemical and cell culture uptake experiments. The effect of intratumoral LCDIO uptake on magnetic resonance (MR) imaging signal intensity was evaluated with a 1.5-T superconducting magnet. RESULTS: Tumoral accumulation of LCDIO was 0.11% +/- 0.06 of the injected dose per gram of tissue in brain tumors and was sufficient for detection at MR imaging. In tumor sections, LCDIO was preferentially localized in tumor cells (49.0% +/- 4.6) but was also taken up by macrophages in tumors (21.0% +/- 3.1) and by endothelial cells in the areas of active angiogenesis (6.5% +/- 1.4). In cell culture, LCDIO uptake was strongly correlated with growth rate of tumor cell lines. CONCLUSION: Tumoral LCDIO accumulation was not negligible and helped explain MR imaging signal intensity changes observed in clinical trials. Microscopically, LCDIO accumulated predominantly in tumor cells and tumor-associated macrophages. Uptake into tumor cells appeared to be directly proportional to cellular proliferation rates.

Animals↗
PubMed1999

In vivo assessment of vascular endothelial growth factor-induced angiogenesis.

To determine whether vascular endothelial growth factor (VEGF)-induced tumor microvascularity is detectable by in vivo NMR imaging, an experimental study was conducted in nude mice. Human breast cancer cells (MCF-7) and MCF-7 cells stably transfected with the cDNA for the VEGF165 isoform (MV165) were grown in nude mice and models were characterized by RT-PCR, Western blotting, ELISA, immunohistochemistry and NMR imaging using a novel synthetic protected graft copolymer (PGC) as a vascular probe. MV165 tumors showed a 1.6-fold higher microvascular density by histology. Both tumors showed identical MR signal intensities on non-contrast and Gd-DTPA enhanced images. PGC enhanced MR imaging of tumoral vascular volume fraction (VVF), however, revealed significant differences between the 2 tumor types (MV165: 8.9 +/- 2.1; MCF-7: 1.7 +/- 0.5; p < 0.003), as expected from histology. VVF changes were more heterogeneous in the MV165 model both among tumors as well as within tumors as determined 3-dimensionally at submillimeter resolutions. Our results have potential applications for non-invasive assessment of angiogenesis by in vivo imaging and for clinical monitoring during angiogenic therapies.

Animals↗
PubMed1999

Role of gastric microcirculation in the gastroprotection by glucocorticoids released during water-restraint stress in rats.

Our previous investigations demonstrated that glucocorticoids released in response to stress protect gastric mucosa against stress-induced ulceration. This study was designed to determine whether gastric microcirculation is involved in the mechanism of gastroprotective glucocorticoid action. For this we evaluated the effects of deficiency of glucocorticoid production during 3 hr water-restraint stress and corticosterone replacement on the stress-induced gastric erosions, gastric microcirculation and arterial pressure in rats. The stress was produced in awake rats and gastric microcirculation and arterial pressure were evaluated in animals anesthetized in 3 hr after the onset of water-restraint stress. An in vivo microscopy technique for the direct visualization of gastric microcirculation was employed. The gastric submucosal and the superficial mucosal microvessels were monitored on television screen through a microscope and the pictures were stored by microfilming for the analysis of red blood cell velocity and vessel diameter. Gastric microcirculation was estimated on the base of both the volume blood flow velocity in submucosal microvessels and the diameter of superficial mucosal venous microvessels. Gastric erosions were quantitated by measuring the area of damage. Plasma corticosterone levels were also measured after 3 hr stress by fluorometry. Water-restraint stress induced an increase in corticosterone level, an appearance of gastric erosions, a decrease in volume blood flow velocity of submucosal microvessels, a dilatation of superficial mucosal microvessels, a decrease in arterial pressure. The deficiency of glucocorticoid production during water-restraint stress promoted the stress-induced gastric ulceration, a dilatation of mucosal microvessels, a decrease of blood flow velocity in submucosal microvessels and of arterial pressure. Corticosterone replacement eliminated the effects of deficiency of glucocorticoid production on all of the parameters under study. Thus, the stress-induced corticosterone rise decreased gastric ulceration, restricted both the reduction of blood flow velocity in submucosal microvessels and a dilatation of superficial mucosal venous microvessels during water-restraint stress. These data suggest that the gastroprotective action of glucocorticoids during stress may be provided by the maintenance of gastric blood flow.

Animals↗
PubMed1999

Targeting of green fluorescent protein expression to the cell surface.

We have previously reported on GPI-anchored fusion proteins that bind radioactive isotopes. We targeted their expression to the cell surface to obtain a marker protein detectable by nuclear and optical imaging (1, 2). Here we suggest a novel approach for targeting a model protein (GFP) to the exoplasmic surface of the plasma membrane. An expression vector (pcPEP-GFP) was constructed containing GFP cDNA fused with the fragment encoding the N-terminal cytoplasmic domain and signal peptide/membrane anchoring domain of the rabbit neutral endopeptidase (PEP-GFP). Flow cytometry showed green fluorescence in 45% of cells transfected with GFP and in 34% of cells transfected with PEP-GFP (24 h after transfection). Fluorescence microscopy of fixed cells stained with rhodaminated anti-GFP antibodies showed positive reaction only in the case of PEP-GFP-transfected cells indicating cell-surface expression. The PEP-GFP fusion protein was identified as a component of the light microsomal and Golgi fractions by immunoblotting.

Animals↗
PubMed1999

Mechanism of gadophrin-2 accumulation in tumor necrosis.

The molecular mechanism by which gadophrin-2 targets necrotic tumor tissue was investigated. Biodistribution studies and magnetic resonance imaging (MRI) and histologic/autoradiographic correlation were performed in xenograft mouse models bearing human tumors (HT 29, WiDr, LX 1). Binding of gadophrin-2 to DNA, lipids, or proteins was determined by fluorescence spectrophotometry. Protein binding was determined by dialysis and gel electrophoresis. Accumulation of gadophrin-2 was low (<0.7% injected dose/g tissue at 24 hours after injection) in viable tumor but higher in necrotic tumor regions and was readily detectable by MRI. Within a given tumor, the agent preferentially localized in the periphery of necrotic areas. Within these regions gadophrin-2 was bound to interstitial albumin and not other proteins, lipids, or DNA. Tumoral accumulation of gadophrin-2 most likely occurs through its binding to plasma albumin and subsequent slow extravasation into the tumor interstitium.

Animals↗
PubMed1999

In vivo imaging of tumors with protease-activated near-infrared fluorescent probes.

We have developed a method to image tumor-associated lysosomal protease activity in a xenograft mouse model in vivo using autoquenched near-infrared fluorescence (NIRF) probes. NIRF probes were bound to a long circulating graft copolymer consisting of poly-L-lysine and methoxypolyethylene glycol succinate. Following intravenous injection, the NIRF probe carrier accumulated in solid tumors due to its long circulation time and leakage through tumor neovasculature. Intratumoral NIRF signal was generated by lysosomal proteases in tumor cells that cleave the macromolecule, thereby releasing previously quenched fluorochrome. In vivo imaging showed a 12-fold increase in NIRF signal, allowing the detection of tumors with submillimeter-sized diameters. This strategy can be used to detect such early stage tumors in vivo and to probe for specific enzyme activity.

Animals↗
PubMed1999

Treatment of experimental brain tumors with trombospondin-1 derived peptides: an in vivo imaging study.

Antiangiogenic and antiproliferative effects of synthetic D-reverse peptides derived from the type 1 repeats of thrombospondin (TSP1) were studied in rodent C6 glioma and 9L gliosarcomas. To directly measure tumor size and vascular parameters, we employed in vivo magnetic resonance (MR) imaging and corroborated results by traditional morphometric tissue analysis. Rats bearing either C6 or 9L tumors were treated with TSP1-derived peptide (D-reverse amKRFKQDGGWSHWSPWSSac, n=13) or a control peptide (D-reverse amKRAKQAGGASHASPASSac, n=12) at 10 mg/kg, administered either intravenously or through subcutaneous miniosmotic pumps starting 10 days after tumor implantation. Eleven days later, the effect of peptide treatment was evaluated. TSP1 peptide-treated 9L tumors (50.7+/-44.2 mm3, n=7) and C6 tumors (41.3+/-34.2 mm3, n=6) were significantly smaller than tumors treated with control peptide (9L: 215.7+/-67.8 mm3, n=6; C6: 184.2+/-105.2 mm3, n=6). In contrast, the in vivo vascular volume fraction, the mean vascular area (determined by microscopy), and the microvascular density of tumors were not significantly different in any of the experimental groups. In cell culture, TSP1, and the amKRFKQDGGWSHWSPWSSac peptide showed antiproliferative effects against C6 with an IC of 45 nM for TSP1. These results indicate that TSP1-derived peptides retard brain tumor growth presumably as a result of slower de novo blood vessel formation and synergistic direct antiproliferative effects on tumor cells. We also show that in vivo MR imaging can be used to assess treatment efficacy of novel antiangiogenic drugs non-invasively, which has obvious implications for clinical trials.

Animals↗
PubMed1999

Near-infrared optical imaging of protease activity for tumor detection.

PURPOSE: To build and test an optical imaging system that is sensitive to near-infrared fluorescent molecular probes activated by specific enzymes in tumor tissues in mice. MATERIALS AND METHODS: The imaging system consisted of a source that delivered 610-650-nm excitation light within a lighttight chamber, a 700-nm longpass filter for selecting near-infrared fluorescence emission photons from tissues, and a charge-coupled device (CCD) for recording images. The molecular probe was a biocompatible autoquenched near-infrared fluorescent compound that was activated by tumor-associated proteases for cathepsins B and H. Imaging experiments were performed 0-72 hours after intravenous injection of the probe in nude mice that bore human breast carcinoma (BT-20). RESULTS: The imaging system had a maximal spatial resolution of 60 microns, with a field of view of 14 cm2. The detection threshold of the nonquenched near-infrared fluorescent dye was subpicomolar in the imaging phantom experiments. In tissue, 250 pmol of fluorochrome was easily detected during the 10-second image acquisition. After intravenous injection of the probe into the tumor-bearing animals, tumors as small as 1 mm became detectable because of tumor-associated enzymatic activation of the quenched compound. CONCLUSION: Tumor proteases can be used as molecular targets, allowing visualization of millimeter-sized tumors. The development of this technology, probe design, and optical imaging systems hold promise for molecular imaging, cancer detection, and evaluation of treatment.

Adenocarcinoma↗
PubMed1998

Mapping the in vivo distribution of herpes simplex virions.

We describe a method for labeling enveloped viral particles with a radiotracer, indium-111, allowing labeled viruses to be traced in vivo by nuclear imaging. After initial optimization experiments, a labeling efficiency of 83% (incorporation yield) was achieved for herpes simplex virus (HSV), resulting in a specific activity of 30 microCi/10(9) PFU. The labeling procedure did not significantly reduce the infectivity of the labeled virus and the virus did not release any significant amounts of the radionuclide within 12 hr after labeling. Sequential imaging of animals after intravenous administration of the labeled virus showed fast accumulation in the liver and redistribution from the blood pool (immediately after injection) to liver and spleen (12-24 hr after injection). At 12 hr after injection 7% of the virus-associated (111)In had been eliminated from the body and the remaining organ distribution of the virus was as follows: spleen 2.87 +/- 0.54% ID/g; liver, 2.60 +/- 0.51% ID/g; kidney, 0.98 +/- 0.31% ID/g; lung, 0.57 +/- 0.10% ID/g; [corrected] and lower amounts in other organs. Our results indicate that the described method allows qualitative and quantitative assessment of viral biodistribution in vivo by nuclear imaging.

Animals↗