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A Bogdanova

Publications and source records attributed to A Bogdanova.

33 records · Page 2Linked to original sources
PubMed1997

A long-circulating co-polymer in "passive targeting" to solid tumors.

A co-polymer of O-methyl polyethylene(glycol)-O'-succinate (MPEGs, m.w. 5100) and poly-l-lysine (PL, median m.w. 32700, degree of polymerization 256) has been synthesized by covalent grafting. The resultant MPEGs-PL (30% modification degree of epsilon-amino groups) had a hydrodynamic diameter corresponding to a 690 kD protein. Free amino groups (180/mol of the co-polymer) were used for conjugation of diethylene pentaacetic or succinic acid residues to MPEGs-PL. The potential of the resultant compound as a carrier of therapeutic and diagnostic drugs was studied using a rodent carcinoma models. The co-polymer had a blood pool half-life of 36h in adenocarcinoma-bearing rats. Radioactively labeled preparations were resistant to trans-chelation with apotransferrin and stable in blood for 24 h. The co-polymer accumulated in solid tumors at the level of 1.5-2% injected dose/g of tumor in 24 h. At that time, 34-40% of the accumulated polymer was associated with tumor cell fraction. The co-polymer non-covalently associated with cis-diamminedichloroplatinum(II), showed a cytostatic effect against mouse F9 carcinoma, and induced a reversal in tumor growth after intravenous administration.

Animals↗
PubMed1996

Enhanced resolution of proton NMR spectra of malignant lymph nodes using magic-angle spinning.

Proton NMR spectroscopy has proven useful in the detection of cancer in lymph node tissue. However, due to the high fat content of this type of tissue, 2D 1H COSY measurements (requiring acquisition times of 4-5 h or longer) are necessary to obtain the spectral information necessary for diagnosis. T2-filtered proton magic-angle spinning (MAS) NMR spectroscopy provides 1D spectra of lymph nodes in approximately 20 min with sufficient spectral resolution allowing for identification of changes in cellular chemistry due to the presence of malignant cells. MAS data from lymph nodes of five control and six rats with mammary adenocarcinoma (R13762) demonstrated increases in the signal intensity of resonances associated primarily with lactate (delta = 4.12 ppm) P < 0.0004, creatines/lysine (delta = 3.04 ppm) P < 0.0032, and glutamate/ glutamine (delta = 2.36 ppm) P < 0.0002 in metastatic compared with normal lymph nodes. The infiltration of lymph nodes by malignant cells is an important prognostic factor for many cancers. The rapid assessment of node tissue without the introduction of sampling errors (inherent in currently employed histological procedures) would allow postoperative therapy decisions to be made more efficiently.

Adenocarcinoma↗
PubMed1996

Cytosolic distribution of villin in M cells from mouse Peyer's patches correlates with the absence of a brush border.

BACKGROUND & AIMS: The follicle-associated epithelium (FAE) of Peyer's patches mainly consists of two cell types: absorptive enterocytes with a brush border and M cells without this apical specialization. To study the controversial ontogeny of M cells (mesenchymal vs. epithelial origin), the expression pattern of tissue-specific cytoskeletal proteins, markers of cell origin that play a crucial role in the specific shape of epithelial cells and brush border assembly, was investigated. METHODS: The localization of cytokeratins, vimentin, and villin was determined on mouse FAE using immunocytochemistry and electron microscopy. RESULTS: Epithelial-specific cytokeratins were expressed in both absorptive enterocytes and M cells, whereas vimentin was not detected in mouse FAE. Villin, a tissue-specific, actin-binding protein of the brush border, was expressed in the two cell types. This protein had an unusual cytoplasmic distribution in FAE cells lacking a brush border and in cells having an intraepithelial pocket filled with lymphocytes. CONCLUSIONS: The presence of villin and the absence of vimentin in M cells support the intestinal origin of M cells. The cytoplasmic distribution of villin provides a new identification criteria for M cells and reflects the reorganization of the F-actin network, which correlates with the inability of M cells to assemble a brush border.

Animals↗
PubMed1996

Adhesion of Helicobacter pylori to polarized T84 human intestinal cell monolayers is pH dependent.

Epithelial cells, which form tight polarized monolayers on porous substrates, constitute ideal model systems to study bacterial adhesion and invasion. The binding of Helicobacter pylori to the apical membrane of T84 cells, an epithelial cell line derived from a human colon carcinoma, was assessed biochemically and morphologically. Attachment was rapid, and binding remained constant over time, with a significant (P < 0.01, Mann-Whitney U test) ca. fourfold increase at pH 5.4 (76% +/- 22%) compared with pH 7.4 (18% +/- 7%). In contrast, adhesion of enteropathogenic Escherichia coli was not enhanced at pH 5.4. The transepithelial electrical resistance of the T84 cell monolayers was not affected by pH or by H. pylori. Following binding, H. pylori induced a reorganization of the brush border as reflected by actin condensation, facilitating the intimate association of the bacteria with the apical plasma membrane. H.pylori was not internalized, as shown by confocal microscopy. Some bacteria, found in deep invaginations of the apical membrane, were probably inaccessible to gentamicin, thus accounting for the observed tolerance to the antibiotic. These data provide the first evidence that an acidic environment favors Helicobacter adhesion and that binding is followed by survival of the survival of the bacteria in pockets of the apical membrane.

Bacterial Adhesion↗
PubMed1996

Transimmortalized mouse intestinal cells (m-ICc12) that maintain a crypt phenotype.

This study describes the properties of a clone of immortalized cells (m-ICc12 cells) derived from the bases of small intestinal villi from 20-day-old fetuses of L-type pyruvate kinase (L-PK)/ TAg1 transgenic mice. The mice harbor the simian virus 40 large T antigen under the control of the 5' regulatory sequence from the L-PK gene. m-ICc12 cells expressed nuclear large T antigen, had a prolonged life span, and were nontumorigenic when injected into nude mice. They formed confluent monolayers of cuboid cells separated by tight junctions, developed dense, short apical microvilli, and formed domes. They also possessed cytokeratins, villin, aminopeptidase N, dipeptidyl-peptidase IV, and glucoamylase and retained crypt cell features, including intracellular sucrase isomaltase and alpha-L-fucose glycoconjugates accumulation and expression of the polymeric immunoglobulin receptor and the cystic fibrosis transmembrane conductance regulator gene. Thus the m-ICc12 cell line obtained by targeted oncogenesis in transgenic mice maintained in culture several important properties and differentiated functions of intestinal crypt cells.

Animals↗
PubMed1995

Cellular uptake and trafficking of a prototypical magnetic iron oxide label in vitro.

RATIONALE AND OBJECTIVES: Target-specific magnetic resonance (MR) contrast agents are being developed to improve the accuracy of MR imaging. The purpose of this study was to determine the mechanism of cell uptake, and modes of intracellular trafficking of a prototypical iron oxide label (RMA) used in the synthesis of some target-specific MR contrast agents. METHODS: The prototypical agent (RMA) consisted of a dextran-coated monocrystalline iron oxide that was modified with rhodamine (fluorescent label) and opsonized with albumin. Fluorescence microscopy was performed in a phagocytic C6 cell line and in murine bone marrow macrophages. Immunohistochemistry against lysosomal markers was used to confirm the intracellular location of the label. RESULTS: RMA was identified inside cells after incubation at concentrations as low as 4.0 x 10(-10) M Fe, typically observed with receptor mediated endocytosis and several orders of magnitude lower than that expected with fluid phase pinocytosis. Cell uptake could be inhibited by excess protein but not by dextran. RMA localized initially to tubular and to round intracellular organelles and co-localized with an antibody against a murine lysosomal glycoprotein antibodies (LGP-A) in macrophages. Three days after incubation, RMA was concentrated in perinuclear vesicles, which most likely represent terminal lysosomes where final breakdown appears to occur. CONCLUSIONS: The mechanism of cellular uptake of a prototypical opsonized iron oxide label is consistent with receptor-mediated endocytosis. Immediately after cell contact, RMA localizes to the lysosomal compartment and at long time points reside in vesicles that by morphology and distribution appear to be terminal lysosomes. Iron oxides therefore demonstrate metabolism via the lysosomal pathway.

Albumins↗
PubMed1995

MR imaging of phagocytosis in experimental gliomas.

PURPOSE: To determine whether phagocytosis can be observed in vivo in glioma cells. MATERIALS AND METHODS: Rat C6 glioma cells were studied in culture and after intracerebral implantation into 13 rats. Monocrystalline iron oxide nanoparticles (MION), a model marker of phagocytosis, was administered intravenously to tumor-bearing rats at 2-20 mg of iron per kilogram. Magnetic resonance (MR) imaging was performed at multiple time points. RESULTS: Glioma cells in culture showed uptake of MION in amounts of up to 10 ng of iron per 10(6) cells, corresponding to approximately 50,000 particles per cell. Fluorescently labeled MION was found to be located primarily in tubular lysosomes. Intracerebral gliomas showed characteristic changes in signal intensity at MR imaging that peaked 12 hours after administration of MION and lasted up to 5 days; these changes corresponded to uptake and subsequent biodegradation of MION by tumor cells. CONCLUSION: Phagocytosis of glioma cells can be detected in vivo with iron oxide-enhanced MR imaging, and this may permit accurate delineation of tumor margins.

Animals↗
PubMed1993

AUR Memorial Award 1993. A drug system (PDH) for interventional radiology. Synthesis, properties, and efficacy.

RATIONALE AND OBJECTIVES: The authors synthesized and tested a novel hydrogel system proposed for use in extra- and intravascular radiologic interventions, such as chemoembolizations and embolizations, and as a vehicle for sustained drug release. MATERIALS: The material was specifically designed to meet the prerequisites of biodegradation, biocompatibility, low immunogenicity, low toxicity, and easy use. The material consists of a protein backbone cross-linked with activated bifunctional polyethyleneglycol (PEG) derivatives (PEG-derivatized hydrogel, [PDH]) to which are attached therapeutic (e.g., doxorubicin, a chemotherapeutic agent = PDH-dx) or diagnostic labels (e.g. Gd-DTPA). RESULTS: PDH-dx effectively reduced the risk of local tumor recurrence in a rat model when implanted locally after surgical tumor removal. After administration, PDH is degraded by proteases release from macrophages; implantations of 1 mL samples into paraspinal muscles of rats were completely absorbed within 4 weeks and its constituents were metabolized. Antibody titers (total Ig response) against the PDH were not detectable 1 week after implantation, whereas protein control substances elicited a strong response. CONCLUSIONS: PDH and its derivatives are relatively nontoxic, biodegradable materials for use in radiologic interventions and as a vehicle for sustained drug release.

Animals↗
PubMed1993

[The dependence of fetal weight and fetal length at birth on the site of placental attachment].

The present study shows the connection between the location of the placenta in utero and the neonatal weight and length after delivery and also the relative part of abdominal delivery in relation to placental location. 289 pregnant women have been examined with ultrasonography in the III trimester of pregnancy. The results show that the neonatal length and the weight are normal when the placenta is anterior, posterior or fundal. The least neonatal weight and length have been measured in cases of placenta praevia. No correlation was found between maternal age and placental location.

Adult↗
PubMed1990

[Antibiotic prevention and treatment in cesarean section].

The aim of the authors ia to study the role of antibiotic prophylaxis in cesarean section for prevention of infectious complications during puerperium. 443 deliveries were studied, which took place by cesarean section at the obstetric clinic of the Higher Medical Institute in the town of Pleven for a 2-year period. One antibiotic was administered in 96 women (21.67%) up to the third day, but in 62 women--up to the sixth day (14.00%). Two antibiotics were used is 49 parturients (11.06%) up to the third day, but in 131 women (29.57%) up to the sixth day. The combination of 3 antibiotics, containing a preparation against anaerobic infection, was used in 43 women (9.7%). The most frequent complication--endometritis was observed in 17 of operated women (3.84%), but suppuration of the operative wound--in 8 women (1.81%). After a 6-day prophylaxis with penicillin and gentamycin the frequency of endometritis was higher than that with ampicillin and gentamycin (11.76% against 2.60%). An impression was created that there was not a single case with endometritis and only one case with suppuration among 62 (13.99%) women operated without usage of antibiotics as well as in 145 (32.73%) women with antibiotic therapy up to the third day. All these parturients were with low risk of puerperal infection. Our position is that they do not need antibiotic prophylaxis.

Anti-Bacterial Agents↗
PubMedDate not supplied

Magnetically labeled cells can be detected by MR imaging.

To determine the feasibility of MR imaging of magnetically labeled cells, different cell lines were labeled with monocrystalline iron oxide (MION) particles. Phantoms containing MION labeled cells were then assembled and imaged by MR at 1.5 T using T1-weighted and T2-weighted pulse sequences. MION uptake ranged from 8.5 x 10(4) to 2.9 x 10(5) particles/cell for tumor cells (9L and LX1, respectively) to 1.5 x 10(6) to 4.8 x 10(8) particles/cell for "professional phagocytes" (J774 and peritoneal macrophages, respectively). On the T1-weighted images, cell-internalized MION appeared hyperintense relative to agar and similar to MION in aqueous solution. On T2-weighted images, signal intensity varied according to concentration of MION within cells. Cell-internalized MION caused similar MR signal changes of cells as did free MION; however, at a dose that was an order of magnitude lower, depending on the pulse sequence used. The detectability of MION within cells was approximately 2 ng Fe, which corresponded to 10(5) tumor cells/well or 5 x 10(3) macrophages/well. We conclude that a variety of cells can be efficiently labeled with MION by simple incubation. Intracellular labeling may be used for MR imaging of in vivo cell tracking.

Contrast Media↗
PubMedDate not supplied

Magnetically labeled secretin retains receptor affinity to pancreas acinar cells.

Previously, we have developed a colloidal dextran-stabilized monocrystalline iron oxide nanocompound (MION-46) as a magnetic label for magnetic resonance imaging (MRI). In an effort to use this magnetic label to visualize pancreatic receptor function by MRI in vivo, we investigated the potential of secretin as a vector molecule. Secretin receptors, abundant on exocrine pancreas cells, recognize secretin through its amidated carboxyl terminal. In order to conjugate secretin to MION, we utilized the specific interaction between biotin and streptavidin, since direct conjugation of human secretin to MION has previously resulted in low yields and low affinity of the conjugate (unpublished results). Initially, we biotinylated the N-terminal primary amino group of secretin (60% yield). In a separate step, streptavidin (SA) was immobilized onto the surface dextran molecules of MION (79% yield) by reductive amination. Each secretin molecule was conjugated to one biotin molecule and each MION particle to an average of two SA molecules. The biotinylated secretin was then conjugated to MION through the biotin-streptavidin interaction (90% yield). The secretin-biotin-streptavidin-MION construct thus contained approximately two secretin molecules per MION. An in vitro competitive binding assay of pancreatic acinar cells demonstrated that the magnetically labeled secretin retained affinity to the secretin receptors. In vivo distribution studies in rats showed a significantly higher pancreatic accumulation of the secretin-biotin-streptavidin-MION construct as compared to the control group that had received unmodified MION. Our data indicate that bioactive peptides can be attached to dextran-coated iron oxide particles through the biotin-streptavidin interaction while retaining receptor affinity. Such target-specific agents have potential use in MR imaging to probe for a variety of receptor systems.

Animals↗
PubMedDate not supplied

Beta-adrenergic stimulation of volume-sensitive chloride transport in lamprey erythrocytes.

We measured the effects of a beta-adrenergic agonist, isoproterenol, on chloride transport and volume regulation of lamprey (Lampetra fluviatilis) erythrocytes in isotonic (288 mosm L(-1)) and hypotonic (192 mosm L(-1)) medium. Isoproterenol at a high concentration (10(-5) M) did not influence chloride transport in isotonic medium but markedly increased chloride fluxes in hypotonic conditions: unidirectional flux increased from 100 mmol kg dcw(-1) h(-1) in the absence to 350 mmol kg dcw(-1) h(-1) (dcw=dry cell weight) in the presence of isoproterenol. Simultaneously, the half-time for volume recovery decreased from 27 to 9 min. Isoproterenol caused an increase in cellular cyclic AMP (cAMP) concentration. The stimulation of chloride transport in hypotonic conditions could be induced by application of the permeable cAMP analogue, 8-bromo-cyclic AMP, suggesting that the effect of beta-adrenergic stimulation on chloride transport occurs downstream of cAMP production. As isoproterenol did not affect unidirectional rubidium fluxes in hypotonic conditions, the transport pathway influenced by beta-adrenergic stimulation is most likely the swelling-activated chloride channel. Because the beta-adrenergic agonist only influenced the transport in hypotonic conditions despite the fact that cAMP concentration also increased in isotonic conditions, the activation may involve a volume-dependent conformational change in the chloride channel.

Adrenergic beta-Agonists↗