Biomedical subjects

A Bogdanov

Publications and source records attributed to A Bogdanov.

63 records · Page 4Linked to original sources

PubMed1989

Prothymosin alpha is an evolutionary conserved protein covalently linked to a small RNA.

A 13 kDa protein, covalently linked to a small RNA from the cytoplasm of mouse cells, was studied. Sequence analysis of its tryptic peptides revealed that the RNA-linked protein is identical to prothymosin alpha. Very similar RNA-protein complexes were identified in human, bovine and yeast cells. Tryptic peptide maps of 125I-labelled RNA-linked proteins of diverse origin demonstrated their marked similarity, thus indicating high evolutionary conservation of prothymosin alpha from yeast to man.

Amino Acid Sequence↗

PubMedDate not supplied

Polymeric contrast agents for MR imaging of adrenal glands.

A variety of adrenal imaging agents have been used in nuclear medicine, but no agent has been developed for magnetic resonance (MR) imaging. The authors have previously observed accumulation of aminated macromolecules in adrenal glands. They now report the synthesis of a model polymeric aminated contrast agent for enhanced MR imaging of the adrenal glands. The model agent consisted of a poly-L-lysine conjugate (molecular weight, 245 kd) that had 70% free epsilon amino groups and 30% diethylenetriaminepentaacetic acid (DTPA)-derivatized amino groups to bind indium-111 or gadolinium. One hour after intravenous administration of this compound, adrenal uptake was 10.1% +/- 0.7 of injected dose per gram of tissue. When all free epsilon amino groups of the polylysine were completely substituted with DTPA, adrenal uptake was 3.4 times lower, indicating the importance of free amino groups for adrenal uptake. MR imaging in rats showed that a dose of 0.08 mmol of gadolinium per kilogram of the agent was sufficient to enhance the signal intensity of adrenal glands. There hours after intravenous administration of the agent, signal intensity of the adrenal glands was 186% of precontrast values (liver, 165%; kidney, 91%). Fluorescence microscopy showed that the agent accumulated primarily in the cortical zona glomerulosa and in the adrenal medulla. These initial studies demonstrate the feasibility of designing contrast agents for MR imaging of the adrenal glands.

Adrenal Glands↗

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

Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages.

Although several dextran-coated iron oxide preparations are in preclinical and clinical use, little is known about the mechanism of uptake into cells. As these particles have been shown to accumulate in macrophages and tumor cells, we performed cellular uptake and inhibition studies with a prototypical monocrystalline iron oxide nanoparticle (MION). MION particles were labeled with fluorescein isothiocyanate or radioiodinated and purified by gel permeation chromatography. Two preparations of MION particles were used in cell experiments: nontreated MION and plasma-opsonized MION purified by gradient density purification. As determined by immunoblotting, opsonization resulted in C3, vitronectin, and fibronectin association with MION. Incubation of cells with fluorescent MION showed active uptake of particles in macrophages both before and after opsonization. In C6 tumor cells, however, intracellular MION was only detectable in dividing cells. Quantitatively, 125I-labeled MION was internalized into cells with uptake values ranging from 17 ng (in 9L gliosarcoma) to 970 ng iron per million cells for peritoneal macrophages. Opsonization increased MION uptake into macrophages sixfold, whereas it increased the uptake in C6 tumor cells only twofold. Results from uptake inhibition assay suggest that cellular uptake of nonopsonized (dextran-coated) MION particles is mediated by fluid-phase endocytosis, whereas receptor-mediated endocytosis is presumably responsible for the uptake of opsonized (protein-coated) particles.

Animals↗

PubMedDate not supplied

Clinical study of the effect of the preparation DEODAN on leukopenia, induced by cytostatics.

The aim of the study is to establish the effect of the preparation DEODAN on leukopenia induced by chemotherapeutics in oncological patients. DEODAN is an oral preparation, obtained from lyzozyme lysates of Lactobacillus bulgaricus strain "I. Bogdanov patent strain tumoronecroticance B-51" ATCC 21815, called shortly LB51. In the study there are included two groups of patients--from National Oncological Centre, Sofia, the other from Clinic of Medicine, Bertha Academic Hospital, Clinics of Duisburg, Duisburg. All the patients, (78) have undergone combined chemotherapy. In all patients, leukopenia has been established in moderate and medium levels. The scheme of the application of DEODAN has been 3 g, three times a day before meals, from the first day of establishing the disturbances of the haemopoesis. The treatment lasted until the restoration of the haematological values. Only DEODAN was applied. The results obtained show that the recovery of the WBC count (values above 3000) took place in all of the patients between days 3 and 5. None of the patients displayed any infectious or febrile complications, as a result of the applied chemotherapy and the treatment with the preparation. DEODAN also improves the general condition of the patients.

Administration, Oral↗

PubMedDate not supplied

Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging.

Angiogenesis is a critical step in tumor development and more than 25 angiogenesis inhibitors are currently in clinical trials. Noninvasive in vivo imaging of angiogenesis represents a unique opportunity of repeatedly quantitating microvascular parameters prior to and during anti-angiogenic treatments. While several imaging tracers have been proposed for MR and nuclear imaging, there does not exist any consensus of what constitutes an ideal size of an imaging agent. A series of synthetic pegylated DOTA derivatized graft copolymers (30, 60, 120 kDa) were synthesized and their in vivo behavior tested in two breast cancer models differing in vascular endothelial growth factor (VEGF) expression. Polymers were labeled with different lanthanides (Eu, Gd, Dy) and absolute blood and tumor concentrations were determined by ICP-AES measurements. DOTA and the 30 kDa polymers underwent renal clearance resulting in low plasma levels. Slow leakage across neovasculature into tumor interstitium was clearly dependent on the molecular mass of all tested agents in MCF-7 tumors. However, a cutoff was observed with minimal extravasation occurring at and above 120 kDa in well differentiated MCF-7 tumors. VEGF overexpression caused detectable differences in extravasation of all polymers, including the 120 kDa compound. We conclude that large molecular weight contrast agents with a molecular mass of <120 kDa extravasate from experimental tumor neovasculature and may not be an accurate marker for measuring true blood volume fractions when in vivo imaging is performed in the steady state.

Animals↗

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

Antibody-mediated versus nontargeted delivery in a human small cell lung carcinoma model.

The uptake of macromolecular agents in tumor cells (LX-1, human small cell lung carcinoma) and in corresponding tumor xenografts was compared in a parallel study utilizing a long-circulating biocompatible graft copolymer, MPEGs-PL-DTPA [Bogdanov, A., Jr., et al. (1995) Adv. Drug Delivery Rev. 16, 335-348; Bogdanov, A., Jr., et al. (1996) Bioconjugate Chem. 7, 144-149] and a tumor-specific chimeric monoclonal antibody, BR96 [Hellstrom, I., et al. (1990) Cancer Res. 50, 2183-2190; Garrigues, J., et al. (1993) Am. J. Pathol. 142, 607-622]. Covalent grafted conjugates of methoxy-(polyethylene glycol)succinate and polylysine and BR96 were modified with DTPA, biotinyl, or rhodamine-X-residues. Using radionuclide and fluorescent labeled derivatives of the copolymer and the antibody, we established that (1) the copolymer does not associate with the plasma membrane in N-ethylmaleimide-treated cells and is slowly internalized by live cells at 37 degrees C; (2) the antibody binds rapidly to the surface of LX-1 cells and shows active internalization in vesicles with a subsequent slow decrease in the cell-associated antibody concentration; (3) LX-1 cells bear more than 1 million BR96 binding sites/cell (with an apparent Kd of 4.5 x 10[-7] M); and (4) intravesicular fluorescence intensity in LX-1 cells was linearly dependent on copolymer concentration, suggesting fluid phase endocytosis. Tumor localization by nuclear imaging, biodistribution, microdistribution by histology, and determination of tumor cell fraction uptake was performed in LX-1 tumor xenografts. In vivo study showed that MPEGs-PL-DTPA progressively accumulates in the tumor, yielding from 2.8+/-1.5% injected dose per gram of tissue (ID/g) at 24 h to 5.2+/-1.7% ID/g of tissue at 48 h. The antibody accumulation peaked at 24 h (6.0+/-3.2% ID/g) and decreased thereafter. We determined that at 24 h 43.9+/-11.29% of the polymer accumulated in the tumor was associated with tumor cell fraction with the remainder of the accumulated dose localized in the interstitium. Accumulation of the biotinylated graft copolymer and the antibody in LX-1 xenografts and their uptake in cells were confirmed by histology using avidin-peroxidase staining. Our study demonstrates that, although BR96 is highly specific in vitro, tumoral drug delivery in vivo can be equally high with long-circulating graft copolymers because of slow extravasation at the tumor site.

Animals↗

PubMedDate not supplied

[The use of 3rd-generation antacid preparations for the treatment of patients with nonulcerous dyspepsia and peptic ulcer complicated by reflux esophagitis].

In the present investigation on the treatment of patients with nonulcerous dyspepsia and peptic ulcer, hiatus hernia complicated with reflux esophagitis, a mechanism has been studied of the action of topalkan, a 3rd generation aluminium-magnesium antacid, that involves not only its antacid properties but in an even greater degree the availability of alginic acid in its formula which has antipeptic and protective effect with respect of the mucous membrane of the stomach and esophagus, and provides, together with the magnesium salts, a floating layer of the preparation in the stomach. In grave course of nonulcerous dyspepsia (preulcerous condition) and peptic ulcer complicated by reflux disease of the esophagus topalkan was used in combination with present-day antisecretory preparations pyrenzepine or H2-blockaders of histamine receptors capable of enhancing the antisecretory effect of topalkan as well as endowed with cytoprotective properties with respect of the mucous membrane of the stomach and duodenum promoting healing of erosions and healing and scarring of ulcerous defects.

Aluminum Hydroxide↗