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Biomedical subjects

A Bogdanov

Publications and source records attributed to A Bogdanov.

At least 55 records · Page 3Linked to original sources
PubMed1994

MR lymphography: study of a high-efficiency lymphotrophic agent.

PURPOSE: To investigate the utility of a monocrystalline iron oxide nanoparticle (MION) as a contrast agent in magnetic resonance (MR) imaging of lymph nodes. MATERIALS AND METHODS: Pharmacokinetic data were obtained in rats after intravenous, subcutaneous, and intraarterial injection of indium-111-MION-46. MR imaging was performed to determine optimal dosages and pulse sequences in rats. Models of lymph node metastasis in rabbits and lymph node hyperplasia in rats were used to demonstrate the efficacy of MION in differentiation of malignant and benign adenopathies. RESULTS: Biokinetic data indicate that nodal accumulation occurs primarily after extravasation of agent into the interstitial space (slow component) and subsequent trapping by lymph node macrophages (fast component). Relatively low concentrations (15-25 mumol Fe per kilogram for peripheral nodes after intraarterial injection) decrease signal intensity of nodes at MR imaging. CONCLUSIONS: Lymph node accumulation of MION-46 is high. Modification of injection techniques that alter capillary permeability allows use of systemically administered agent at doses as low as 15-25 mumol Fe per kilogram.

Animals↗
PubMed1994

Determinants of in vivo MR imaging of slow axonal transport.

PURPOSE: To investigate specific surface characteristics of magnetic contrast agents based on a monocrystalline iron oxide nanoparticle (MION) that may determine their uptake and/or transport by axons. MATERIALS AND METHODS: MION were modified to have a range of surface charges or were covalently linked to wheat germ agglutinin (WGA), a neurotropic protein. Each agent was injected directly into the sciatic nerves or femoral arteries of rats (n = 22), and magnetic resonance (MR) images were obtained several days later. The imaging results then were correlated with results at postmortem histologic examination. RESULTS: Substantial uptake and/or transport by axons occurred only after intraneural injection and only if the agent had a strong surface charge or was covalently linked to WGA. The sciatic nerves appeared as uniformly hypointense structures having lengths proportional to the time from injection to imaging, and the calculated transport rates (4-7 mm/d) were consistent with slow axonal transport. Numerous Schwann cells and macrophages acquired large fractions of the injected agents and contributed substantially to the imaging results. CONCLUSION: Those characteristics of MION-based contrast agents that promote efficacy after intraneural injection may impede delivery to the nerve after intraarterial injection.

Animals↗
PubMed1993

Site-directed cross-linking of mRNA analogues to 16S ribosomal RNA; a complete scan of cross-links from all positions between '+1' and '+16' on the mRNA, downstream from the decoding site.

mRNA analogues containing 4-thiouridine residues at selected sites were used to extend our analysis of photo-induced cross-links between mRNA and 16S RNA to cover the entire downstream range between positions +1 and +16 on the mRNA (position +1 is the 5'-base of the P-site codon). No tRNA-dependent cross-links were observed from positions +1, +2, +3 or +5. Position +4 on the mRNA was cross-linked in a tRNA-dependent manner to 16S RNA at a site between nucleotides ca 1402-1415 (most probably to the modified residue 1402), and this was absolutely specific for the +4 position. Similarly, the previously observed cross-link to nucleotide 1052 was absolutely specific for the +6 position. The previously observed cross-links from +7 to nucleotide 1395 and from +11 to 532 were however seen to a lesser extent with certain types of mRNA sequence from neighbouring positions (+6 to +10, and +10 to +13, respectively); no tRNA-dependent cross-links to other sites on 16S RNA were found from these positions, and no cross-linking was seen from positions +14 to +16. In each case the effect of a second cognate tRNA (at the ribosomal A-site) on the level of cross-linking was studied, and the specificity of each cross-link was confirmed by translocation experiments with elongation factor G, using appropriate mRNA analogues.

Base Sequence↗
PubMed1993

Monocrystalline iron oxide nanocompounds (MION): physicochemical properties.

We have previously described a novel monocrystalline iron oxide nanocompound (MION), a stable colloid that enables target specific MR imaging. In this study, the physicochemical properties of MION are reported using a variety of analytical techniques. High resolution electron microscopy indicates that a MION consists of hexagonal shaped electron-dense cores of 4.6 +/- 1.2 nm in diameter. This iron oxide core has an inverse spinel crystal structure which was confirmed by x-ray powder diffraction. Chemical analysis showed that each core has 25 +/- 6 dextran molecules (10 kD) attached, resulting in a unimodal hydrodynamic radius of 20 nm by laser light scattering. Because of the flexibility of the dextran layer, the radius is only 8 nm in nonaqueous reverse micelles. At room temperature, MION exhibit superparamagnetic behavior with an induced magnetization of 68 emu/g Fe at 1.5 T. Mössbauer studies show that the saturation internal magnetic field is 505 KOe, and blocking temperature is at 100 K. The R1 relaxivity of MION is 16.5 (mM.sec)-1 and the R2 relaxivity is 34.8 (mM.sec)-1 in aqueous solution at 37 degrees C and 0.47 T. In vitro phantom studies show that the detectability of MION in liver tissue is less than 50 nmol Fe/g tissue using gradient echo imaging techniques.

Ferric Compounds↗
PubMed1993

MR imaging of slow axonal transport in vivo.

Three magnetopharmaceuticals based on a monocrystalline iron oxide nanocompound (MION) are evaluated as potential contrast agents for demonstrating axonal transport in vivo by magnetic resonance (MR) imaging. One agent has a strong positive charge, one has a strong negative charge, and the third is covalently linked to wheat germ agglutinin, a plant lectin with a high affinity for axon terminals. All three agents were tagged with rhodamine, and fluorescence microscopy was used to determine their fate after administration and to validate the imaging results. Following injection into or near various neural structures in the motor and visual systems of rats, MR images were obtained at multiple times up to 11 days later, and the imaged tissues were processed for subsequent histological examination. Similar results were obtained with all three agents. Axonal transport was not seen by MR imaging or fluorescence microscopy when the agents were injected into the calf muscles, the vitreous of the eye, or the superior colliculus. However, bidirectional axonal transport was shown unequivocally by both methods after injection directly into the site of a focal crush injury to the sciatic nerve. The nerve, which otherwise is isointense with surrounding tissues on MR images, appeared as a uniformly hypointense structure having a length approximately in proportion to the time from injection to imaging. By 11 days, the course of the nerve was traceable from its component roots in the cauda equina to its bifurcation into the tibial and common peroneal nerves in the leg. A transport rate of about 5 mm/day was calculated, which is consistent with the mechanism of slow transport. MION-based magnetopharmaceuticals thus can be used to demonstrate slow axonal transport, and thereby visualize peripheral nerves, in vivo by MR imaging.

Animals↗
PubMed1993

Stimulating effect of DEODAN (an oral preparation from Lactobacillus bulgaricus "LB51") on monocytes/macrophages and host resistance to experimental infections.

DEODAN is a lysozyme lysate from Lactobacillus bulgaricus for oral administration which has shown antitumor activity in mice and humans. The effects of this preparation on some functions of monocytes/macrophages and on host resistance to experimental infections were examined. The oral administration to mice of DEODAN-150 mg/kg daily (the recommended dose in humans) caused an increase of the spreading ability and phagocytic activity of peritoneal macrophages, which showed morphological signs of cell activation. The level of Interleukin-1 (IL-1) secreted in the culture supernatant of peritoneal macrophages of DEODAN-treated mice was found to be slightly increased only when the mice were treated with 150 mg/kg DEODAN for 10 days. However, the in vitro incubation of human blood monocytes with DEODAN resulted in induction of membrane-bound and cytoplasmic IL-1 and Tumor Necrosis Factor (TNF)-alpha. The oral treatment of mice with DEODAN also caused a decrease in mortality after experimental infections with Klebsiella pneumoniae and Listeria monocytogenes. These results indicate that DEODAN activates the phagocytic and secretory functions of mononuclear cells and increases host resistance to bacterial infections.

Adjuvants, Immunologic↗
PubMed1993

MION-ASF: biokinetics of an MR receptor agent.

Receptor-directed MR contrast agents are currently being designed to improve sensitivity and specificity of MR imaging and to provide for functional MR imaging. In the current study we have synthesized a conjugate of asialofetuin (ASF), a bovine plasma protein with a known, high affinity for the hepatic asialoglycoprotein receptor, and a well defined, single crystal superparamagnetic label (monocrystalline iron oxide nanoparticle, MION). MION-ASF is cleared from the circulation more than 300 times faster than MION, has a 3.7 times higher hepatic accumulation, increases liver R2 relaxivity 2.8-fold compared to MION, and accumulates in hepatocytes unlike MION, which accumulates only in macrophages. Competition assays indicate that receptor-mediated hepatocyte uptake can be competitively blocked and that this effect can be demonstrated by imaging. These studies indicate that sensitive iron oxide based probes can be developed for functional MR imaging.

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↗
PubMed1992

Segments of Escherichia coli genome similar to the exons of human prothymosin alpha gene.

Identification of the putative prothymosin alpha homolog in Escherichia coli cells prompted the search for a prothymosin alpha-coding gene in the E. coli genome. A set of interspersed DNA segments was identified, which match various parts of the human prothymosin alpha molecule. Their location in the E. coli genome and high degree of similarity with the appropriate regions of the human prothymosin alpha gene suggest that some kind of trans-splicing should exist in E. coli, which could be responsible for bringing these putative bacterial prothymosin alpha-coding exons together.

Amino Acid Sequence↗
PubMed1992

Three widely separated positions in the 16S RNA lie in or close to the ribosomal decoding region; a site-directed cross-linking study with mRNA analogues.

Synthetic mRNA analogues were prepared by T7 transcription, each containing several thio-uridine residues at selected positions. After binding to the ribosome in the presence of cognate tRNA, the thio-U residues were activated by UV irradiation and the resulting sites of cross-linking to 16S RNA analysed. Three distinct cross-links were consistently observed: (i) from position '+6' of the mRNA (the 3'-base of the A-site codon) to base 1052 of 16S RNA; (ii) from position '+7' of the mRNA to base 1395; and (iii) from '+11' to base 532. Individual yields of the cross-links were strongly dependent on the particular mRNA sequence in each case. The '+11/532' and '+6/1052' cross-links were always entirely tRNA-dependent, whereas the '+7/1395' cross-link was observed at lower intensity in the absence of tRNA. In the presence of a second (A-site bound) tRNA the +6/1052 cross-link was markedly reduced. A cross-link to the 1050 region was again observed when a message carrying a thio-U at position '+9' was translocated on the ribosome so as to bring the thio-U to position +6. Taken together, the data are incompatible with some current models both for the three-dimensional arrangement of 16S RNA and for the orientation of the tRNA-mRNA complex in the ribosome.

Base Sequence↗
PubMed1992

Endogenous production of tumor necrosis factor in normal mice orally treated with Deodan--a preparation from Lactobacillus bulgaricus "LB51".

The ability of orally administered Deodan, a product from the cell wall of Lactobacillus bulgaricus strain "I. Bogdanov patent strain tumoronecroticance B51" ATCC #21815, shortly called "LB51", to induce endogenous tumor necrosis factor-alpha (TNF alpha) production in normal mice was evaluated. The priming and triggering activities of the preparation were investigated in combination with lipopolysaccharide (LPS) and live BCG vaccine. Deodan was applied at a dose of 150 mg/kg and various treatment schedules were employed. The serum levels of TNF alpha in treated mice were quantified by ELISA. Oral administration of Deodan at a dose of 150 mg/kg for 1, 3, 10 or 20 consecutive days only enhanced serum TNF alpha levels in treated mice. Maximal TNF alpha levels were reached 6 h after the last application of Deodan. Deodan was effective in priming TNF alpha in mice triggered intravenously (i.v.) with LPS. Deodan triggered the production of TNF alpha in BCG-primed mice. The preparation, however, was not an effective trigger of mice primed intradermally (i.d.) with 1 microgram/mouse LPS. These findings suggest that Deodan is both a primer and trigger of endogenous TNF alpha. The advantages of treatment of neoplastic disease with agents which induce endogenous TNF alpha is discussed.

Adjuvants, Immunologic↗
PubMed1992

Determination of cytokine release after in vivo and in vitro administration of Deodan (a preparation from Lactobacillus bulgaricus "LB51") by the rabbit pyrogen test.

We investigated the in vivo and in vitro cytokine inducing effects of Deodan, an oral preparation from Lactobacillus bulgaricus "LB-51", using the rabbit pyrogen test. In the first experimental approach we administered Deodan, or its chromatographically purified fraction, via the i.m. or i.v. routes. Low doses of Deodan i.m. caused the formation of a single temperature peak, whereas large doses produced a biphasic temperature curve. Intravenous injection of Deodan produced a monophasic fever in all tested doses. Chromatographically purified Deodan injected i.v. to rabbits caused a febrile response with a dose-dependent pattern, strikingly similar to that of lipopolysaccharide. LAL-testing of Deodan, however, showed that the preparation does not contain endotoxin. In in vivo neutralization studies we demonstrated that IL-1, TNF alpha, and IL-6 mediate the rabbit febrile response to Deodan. Interestingly, the effects of Deodan on the production of TNF alpha and IL-6 were more pronounced than its IL-1 inducing activity. In the second approach, we injected supernatants from mononuclear cells incubated with nonpyrogenic doses of Deodan, intravenously to rabbits ("monocyte type" of pyrogen test). Rapid-onset monophasic fevers were observed, typical for the rabbit pyrogen reaction to i.v. administration of exogenous IL-1 and TNF. Finally, we demonstrated the presence of pyrogenic cytokines in the supernatants from macrophages of Deodan-treated mice. Together, these results indicate that Deodan induces the production of cytokines with endogenous pyrogenic activity.

Adjuvants, Immunologic↗
PubMed1992

Drug targeting in magnetic resonance imaging.

This review summarizes the attempts of drug targeting in the field of magnetic resonance imaging. Although the field is young and most work is performed in nonspecific lanthanide chelates, it is obvious that target selectivity and receptor and/or antigen specificity is the most important issue if functional magnetic resonance imaging is to establish itself in the next decade. Recent advances in biochemical engineering and magnetic resonance research have made targeting of diagnostic drugs a credible alternative to conventional drug use in magnetic resonance imaging.

Animals↗
PubMed1991

30S ribosomal subunits with fragmented 16S RNA: a new approach for structure and function study of ribosomes.

A new approach for function and structure study of ribosomes based on oligodeoxyribonucleotide-directed cleavage of rRNA with RNase H and subsequent reconstitution of ribosomal subunits from fragmented RNA has been developed. The E coli 16S rRNA was cleaved at 9 regions belonging to different RNA domains. The deletion of 2 large regions was also produced by cleaving 16S rRNA in the presence of 2 or 3 oligonucleotides complementary to different RNA sites. Fragmented and deleted RNA were shown to be efficiently assembled with total ribosomal protein into 30S-like particles. The capacity to form 70S ribosomes and translate both synthetic and natural mRNA of 30S subunits reconstituted from intact and fragmented 16S mRNA was compared. All 30S subunits assembled with fragmented 16S rRNA revealed very different activity: the fragmentation of RNA at the 781-800 and 1392-1408 regions led to the complete inactivation of ribosomes, whereas the RNA fragmentation at the regions 296-305, 913-925, 990-998, 1043-1049, 1207-1215, 1499-1506, 1530-1539 did not significantly influence the ribosome protein synthesis activity, although it was also reduced. These findings are mainly in accordance with the data on the functional activity of some 16S rRNA sites obtained by other methods. The relations between different 16S RNA functional sites are discussed.

Base Sequence↗
PubMed1991

Misoprostol and dalargin for the inpatient treatment of duodenal ulcer in the USSR.

In the USSR, uncomplicated duodenal ulcer is usually managed in an inpatient setting. A double-blind, randomized, double-dummy, multiclinic, comparative trial examined the safety and efficacy of oral misoprostol (200 micrograms qid) and intramuscular dalargin (1 mg bid) in duodenal ulcer healing. Dalargin, an enkephalin peptide with gastric antisecretory and cytoprotective properties, is commonly used in the USSR for treating peptic ulcer. The trial characteristics and monitoring were performed in accordance with US standards. Consenting patients of either sex, aged 18 to 70 years, who had a duodenal ulcer of 0.3 to 2.5 cm in diameter were enrolled. Endoscopy, physical examination, and laboratory assessments were performed on entry and after 4 weeks of treatment. The effects of the treatments on complete ulcer healing, dyspeptic symptoms, antacid consumption, adverse drug reactions, and safety were determined. Both treatment groups were well matched for demographic characteristics. The majority of patients were smokers and alcohol users and had a history of recurrent peptic ulcers. Misoprostol was significantly more effective than dalargin in inducing duodenal ulcer healing, both in the intent-to-treat cohort (P = .001) and in the evaluable cohort (P = .0001). Both regimens were well tolerated, and no patients were withdrawn from the study because of adverse reactions. Mild, self-limiting diarrhea was reported more frequently in patients receiving misoprotol (9.4% incidence) than those receiving dalargin (1.9%). The disparity in ulcer healing between the two groups suggests that hospitalization alone is not an optimum treatment in this high-risk patient population.

Adolescent↗
PubMed1990

Transition of the mRNA sequence downstream from the initiation codon into a single-stranded conformation is strongly promoted by binding of the initiator tRNA.

Using an RNA footprinting technique, accessible sites on the mRNA initiation region bound to the ribosome have been determined. Chemical probing experiments have been done both in the presence and absence of the initiator tRNA with dimethyl sulfate, kethoxal and carbodiimide as reagent probes. As an mRNA, a mini-mRNA containing the initiation region of bacteriophage lambda gene cro has been used. This region is characterized by a long single-stranded Shine-Dalgarno (SD) sequence followed by two hairpin structures of which the first one comprises in its loop the initiation codon. As compared to a free mRNA, the only nucleotides additionally protected in the binary mRNA-ribosome complex have been those which belong to the S-D sequence and the initiation codon. The protection of other nucleotides has not changed. Addition of the initiator RNA results in the modification of nucleotides in the stems of the downstream hairpin structures of the initiation region. This reflects their transition into a single-stranded conformation promoted by tRNA. A possible implication of these findings for the decoding process is discussed.

Base Sequence↗