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Biomedical subjects

V Popov

Publications and source records attributed to V Popov.

At least 19 recordsLinked to original sources
PubMed2006

Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys: a corrosion cast study.

Autosomal-dominant polycystic kidney disease (ADPKD) accounts for about 10% of all cases of chronic renal failure requiring dialysis. The disease is characterized by proliferation of renal epithelial cells and formation of cysts that expand over years and replace the normal parenchyma of the kidney. As the cysts grow, the volume of the kidney can increase by more than 10-fold, implying that remodeling and expansion of the vasculature must occur to provide oxygenation and nutrition to the cyst cells. Our previous studies support the notion that there is angiogenesis in ADPKD. We report here results from resin casting of ADPKD kidneys vasculature. In this study, the corrosion-casting method was used in conjunction with scanning electron microscopy to study the vascular architecture and the evidence for angiogenesis in ADPKD kidneys. We found a well-defined vascular network around the cysts forming a 'vascular capsule' somewhat similar to that described in avascular leiomyomata. We also found that the normal vascular architecture is lost and replaced by an assortment of capillaries of larger size than those in the normal kidney, mixed with flattened and spiral arterioles, damaged glomeruli, and atresic venules, indicative of regression of the microvasculature. In the same areas, there was capillary sprouting, considered the hallmark of angiogenesis. The present study documents regression changes of the vasculature and confirms the existence of angiogenesis in ADPKD kidneys, and suggests the use of inhibitors of angiogenesis as a possible avenue for the treatment of the disease.

Adult↗
PubMed2006

High-gain lasing and polarization switch with a distributed optical-klystron free-electron laser.

This Letter reports the first experimental results from the world's first distributed optical-klystron (DOK) free-electron laser (FEL), the DOK-1 FEL, at Duke University. The DOK-1 FEL is a hybrid system, comprised of four wigglers: two horizontal and two helical. With the DOK-1 FEL, we have obtained the highest FEL gain among all storage ring based FELs at 47.8% (+/-2.7%) per pass. We have also demonstrated that the FEL gain can be enhanced by increasing electron bunching using wigglers with a different polarization. Furthermore, we have realized controlled polarization switches of the FEL beam by a nonoptical means through the manipulation of a buncher magnet.

Journal Article↗
PubMed2004

Blockade of N-methyl-D-aspartate receptors by phencyclidine causes the loss of corticostriatal neurons.

Perinatal administration of the N-methyl-Dd-aspartate (NMDA) receptor antagonist phencyclidine (PCP) has been reported to produce regionally selective apoptotic cell death in the frontal cortex. The development of certain behavioral abnormalities following PCP treatment suggested that extracortical regions such as the striatum also could be affected. In this study, perinatal PCP treatment caused a marked reduction in striatal, but not hippocampal, staining for polysialic acid-neural cell adhesion molecule (PSA-NCAM), an NMDA-regulated molecule important in synaptogenesis. In order to isolate striatal influences to the cortex, this investigation was continued in vitro using corticostriatal slices. For these experiments we cultured coronal corticostriatal slices from postnatal day 7 rats. After 4 days in vitro, PCP was added for 48 h and then washed out for 24 h before harvesting the tissue. Similar to what was observed in vivo, we found that PCP treatment results in a marked reduction in striatal staining for PSA-NCAM. No change was observed in the mature form of NCAM. In striatal synaptoneurosomes, immunoblot analysis confirmed that the levels of PSA-NCAM and synaptophysin, a molecule often used as a marker of synaptogenesis, were substantially down-regulated by PCP. These effects were prevented by M40403, a superoxide dismutase mimetic that also prevented the PCP-induced terminal dUTP nick-end labeling of DNA fragments that was observed selectively in the cortex. These data suggest that PCP causes cell death by apoptosis selectively in the cortex, but not in the striatum, following either in vivo treatment of perinatal rat pups or in vitro treatment of corticostriatal slices. Further, cortical apoptosis induced by PCP negatively impacts striatal synaptogenesis, a process important in normal neural development. This deficit is probably caused by a reduction in corticostriatal neurotransmission. It is possible that the dysregulation of striatal synaptogenesis contributes to the behavioral abnormalities observed following perinatal PCP administration in vivo.

Analysis of Variance↗
PubMed2001

Origins and divergence of the Roma (gypsies).

The identification of a growing number of novel Mendelian disorders and private mutations in the Roma (Gypsies) points to their unique genetic heritage. Linguistic evidence suggests that they are of diverse Indian origins. Their social structure within Europe resembles that of the jatis of India, where the endogamous group, often defined by profession, is the primary unit. Genetic studies have reported dramatic differences in the frequencies of mutations and neutral polymorphisms in different Romani populations. However, these studies have not resolved ambiguities regarding the origins and relatedness of Romani populations. In this study, we examine the genetic structure of 14 well-defined Romani populations. Y-chromosome and mtDNA markers of different mutability were analyzed in a total of 275 individuals. Asian Y-chromosome haplogroup VI-68, defined by a mutation at the M82 locus, was present in all 14 populations and accounted for 44.8% of Romani Y chromosomes. Asian mtDNA-haplogroup M was also identified in all Romani populations and accounted for 26.5% of female lineages in the sample. Limited diversity within these two haplogroups, measured by the variation at eight short-tandem-repeat loci for the Y chromosome, and sequencing of the HVS1 for the mtDNA are consistent with a small group of founders splitting from a single ethnic population in the Indian subcontinent. Principal-components analysis and analysis of molecular variance indicate that genetic structure in extant endogamous Romani populations has been shaped by genetic drift and differential admixture and correlates with the migrational history of the Roma in Europe. By contrast, social organization and professional group divisions appear to be the product of a more recent restitution of the caste system of India.

DNA, Mitochondrial↗
PubMed2001

Leishmania amazonensis-dendritic cell interactions in vitro and the priming of parasite-specific CD4(+) T cells in vivo.

The progressive disease following Leishmania amazonensis infection in mice requires functional CD4(+) T cells, which are primed to a disease-promoting phenotype during the infection. To understand how these pathogenic T cells are generated and the role of dendritic cells (DCs) in this process, we use DCs of susceptible BALB/c and resistant C3H/HeJ mice to examine parasite-DC interactions in vitro as well as the effector phenotype of T cells primed by parasite-exposed DCs in vivo. Our results demonstrate that amastigotes and metacyclics efficiently enter and activate DCs of both genetic backgrounds. Infection with amastigotes fails to induce CD40-dependent IL-12 production, but rather potentiates IL-4 production in BALB/c DCs. Upon transfer into syngeneic recipients, amastigote-exposed BALB/c DCs prime parasite-specific Th cells to produce significantly higher levels of IL-4 and IL-10 than their C3H/HeJ counterparts. Transfer studies with IL-4(-/-) DCs indicate that this enhanced Th2 priming seen in BALB/c mice is partially due to the IL-4 production by amastigote-carrying DCs. These results suggest that L. amazonensis amastigotes may condition DCs of a susceptible host to a state that favors activation of pathogenic CD4(+) T cells, and thereby provide a new perspective on the pathogenesis of cutaneous leishmaniasis and protozoan parasite-host interactions in general.

Animals↗
PubMed2001

Anomalous acoustoelectric effect in La0.67Ca0.33MnO3 films.

We have studied the acoustoelectric (AE) effect produced by surface acoustic waves (SAW) in a monolithic layered structure, composed of a piezodielectric LiNbO3 substrate and a La0.67Ca0.33MnO3 film. The experiments unexpectedly revealed in the longitudinal AE effect an anomalous contribution, invariant upon reversal of SAW propagation, which coexists with the ordinary (odd in wave vector) effect. The anomalous effect dominates near the metal-insulator transition, while the ordinary effect prevails at high and low temperatures. We show that the anomalous effect is caused by strong modulation of the film conductivity produced by the SAW elastic deformations.

Journal Article↗
PubMed2001

De novo design of fibrils made of short alpha-helical coiled coil peptides.

BACKGROUND: The alpha-helical coiled coil structures formed by 25-50 residues long peptides are recognized as one of Nature's favorite ways of creating an oligomerization motif. Known de novo designed and natural coiled coils use the lateral dimension for oligomerization but not the axial one. Previous attempts to design alpha-helical peptides with a potential for axial growth led to fibrous aggregates which have an unexpectedly big and irregular thickness. These facts encouraged us to design a coiled coil peptide which self-assembles into soluble oligomers with a fixed lateral dimension and whose alpha-helices associate in a staggered manner and trigger axial growth of the coiled coil. Designing the coiled coil with a large number of subunits, we also pursue the practical goal of obtaining a valuable scaffold for the construction of multivalent fusion proteins. RESULTS: The designed 34-residue peptide self-assembles into long fibrils at slightly acid pH and into spherical aggregates at neutral pH. The fibrillogenesis is completely reversible upon pH change. The fibrils were characterized using circular dichroism spectroscopy, sedimentation diffusion, electron microscopy, differential scanning calorimetry and X-ray fiber diffraction. The peptide was deliberately engineered to adopt the structure of a five-stranded coiled coil rope with adjacent alpha-helices, staggered along the fibril axis. As shown experimentally, the most likely structure matches the predicted five-stranded arrangement. CONCLUSIONS: The fact that the peptide assembles in an expected fibril arrangement demonstrates the credibility of our conception of design. The discovery of a short peptide with fibril-forming ability and stimulus-sensitive behavior opens new opportunities for a number of applications.

Amino Acid Motifs↗
PubMed2001

Patterns of inter- and intra-group genetic diversity in the Vlax Roma as revealed by Y chromosome and mitochondrial DNA lineages.

Previous genetic studies, supported by linguistic and historical data, suggest that the European Roma, comprising a large number of socially divergent endogamous groups, may be a complex conglomerate of founder populations. The boundaries and characteristics of such founder populations and their relationship to the currently existing social stratification of the Roma have not been investigated. This study is an attempt to address the issues of common vs independent origins and the history of population fissioning in three Romani groups that are well defined and strictly endogamous relative to each other. According to linguistic classifications, these groups belong to the Vlax Roma, who account for a large proportion of the European Romani population. The analysis of mtDNA sequence variation has shown that a large proportion of maternal lineages are common to the three groups. The study of a set of Y chromosome markers of different mutability has revealed that over 70% of males belong to a single lineage that appears unique to the Roma and presents with closely related microsatellite haplotypes and MSY1 codes. The study unambiguously points to the common origins of the three Vlax groups and the recent nature of the population fissions, and provides preliminary evidence of limited genetic diversity in this young founder population.

Base Sequence↗
PubMed2001

Positron emission mammography-guided breast biopsy.

UNLABELLED: Positron emission mammography (PEM) is a technique to obtain planar images of the breast for detection of potentially cancerous, radiotracer-avid tumors. To increase the diagnostic accuracy of this method, use of minimally invasive methods (e.g., core biopsy) may be desirable for obtaining tissue samples from lesions detected with PEM. The purpose of this study was to test the capabilities of a novel method for performing PEM-guided stereotactic breast biopsies. METHODS: The PEM system consisted of 2 square (10 x 10 cm) arrays of discrete scintillator crystals. The detectors were mounted on a stereotactic biopsy table. The stereotactic technique used 2 PEM images acquired at +/-15 degrees and a new trigonometric algorithm. The accuracy and precision of the guidance method was tested by placement of small point sources of (18)F at known locations within the field of view of the imager. The calculated positions of the sources were compared with the known locations. In addition, simulated stereotactic biopsies of a breast phantom consisting of a 10-mm-diameter gelatin sphere containing a concentration of (18)F-FDG consistent with that reported for breast cancer were performed. The simulated lesion was embedded in a 4-cm-thick slab of gelatin containing a commonly reported concentration of FDG, simulating a compressed breast (target-to-background ratio, approximately 8.5:1). An anthropomorphic torso phantom was used to simulate tracer uptake in the organs of a patient 1 h after a 370-MBq injection of FDG. Five trials of the biopsy procedure were performed to assess repeatability. Finally, a method for verifying needle positioning was tested. RESULTS: The positions of the point sources were successfully calculated to within 0.6 mm of their true positions with a mean error of +/-0.4 mm. The biopsy procedures, including the method for verification of needle position, were successful in all 5 trials in acquiring samples from the simulated lesions. CONCLUSION: The success of this new technique shows its potential for guiding the biopsy of breast lesions optimally detected with PEM.

Biopsy, Needle↗
PubMed2000

The potential role of positron emission mammography for detection of breast cancer. A phantom study.

Positron emission mammography (PEM) is a new, specialized imaging modality utilizing PET radiopharmaceuticals to detect breast cancer. The capabilities and limitations of PEM in detecting breast tumors were investigated with a series of phantom experiments. The PEM imager was mounted on a standard Lorad biopsy table (separated by 18 cm). In the initial phase of the investigation, basic scanner parameters (resolution, sensitivity, and scatter fraction) were measured. The effects of a number of breast imaging parameters (length of acquisition, breast thickness, and breast density) on detection of breast lesions were then explored utilizing special phantoms. Moderately compressed breasts were simulated with a block of gelatin containing amounts of FDG consistent with 370 MBq injections. Lesions were simulated with four hollow spheres (inner diameters=5 mm, 8 mm, 12 mm, and 15 mm) filled with amounts of FDG representative of uptake in malignant breast tumors (target-to-background concentration ratio=8.5:1). Resolution at the center of the imager was 3.9 mm, sensitivity was 0.059 kcps/kBq/ml and the Compton scatter fraction was approximately 12%. Objects as small as 8 mm in diameter could be detected after 30 s of data acquisition; 5 mm spheres were detectable after 300 s. Object detection capabilities were reduced with increasing breast thickness. In thin compressed breasts (2 cm) even the smallest sphere (5 mm in diameter) could be detected; increasing breast thickness increased the minimum detectable sphere diameter to 8 mm. Increased background activity caused by FDG uptake in metabolically active normal tissue more prevalent in radiodense breasts compared to "fatty" breasts was simulated and shown to reduce the minimum detectable lesion size to 12 mm for the densest breasts. These results demonstrate the potential of PEM for the detection of breast lesions. The addition of the system to a standard biopsy apparatus indicates its potential for use to guide some core biopsies of breast cancers.

Breast Neoplasms↗
PubMed2000

Role of decay-accelerating factor domains and anchorage in internalization of Dr-fimbriated Escherichia coli.

Dr-fimbriated Escherichia coli capable of invading epithelial cells recognizes human decay-accelerating factor (DAF) as its cellular receptor. The role of extracellular domains and the glycosylphosphatidylinositol anchor of DAF in the process of internalization of Dr(+) E. coli was characterized in a cell-cell interaction model. Binding of Dr(+) E. coli to the short consensus repeat 3 domain of DAF expressed by Chinese hamster ovary cells was critical for internalization to occur. Deletion of short consensus repeat 3 domain or replacement of Ser(165) by Leu in this domain, or the use of a monoclonal antibody to this region abolished internalization. Replacing the glycosylphosphatidylinositol anchor of DAF with the transmembrane anchor of membrane cofactor protein or HLA-B44 resulted in abolition or reduction of internalization respectively. Cells expressing glycosylphosphatidylinositol-anchored DAF but not the transmembrane-anchored DAF internalized Dr(+) E. coli through a glycolipid pathway, since the former cells were more sensitive to inhibition by methyl-beta-cyclodextrin, a sterol-chelating agent. Electron microscopic studies revealed that the intracellular vacuoles containing the internalized Dr(+) E. coli were morphologically distinct between the anchor variants of DAF. The cells expressing glycosylphosphatidylinositol-anchored DAF contained a single bacterium in tight-fitting vacuoles, while the cells expressing transmembrane-anchored DAF contained multiple (two or three) bacteria in spacious phagosomes. This finding suggests that distinct postendocytic events operate in the cells expressing anchor variants of DAF. We provide direct evidence for the DAF-mediated internalization of Dr(+) E. coli and demonstrate the significance of the glycosylphosphatidylinositol anchor, which determines the ability and efficiency of the internalization event.

Adhesins, Escherichia coli↗
PubMed1999

Decay-accelerating factor and cytoskeleton redistribution pattern in HeLa cells infected with recombinant Escherichia coli strains expressing Dr family of adhesins.

Escherichia coli strains expressing Dr fimbriae are able to enter epithelial cells by interacting with a complement-regulatory protein, decay-accelerating factor. This model of bacterial internalization, with a well-characterized bacterial ligand and host receptor, provides a unique opportunity to investigate the early stages of invasion. We used immunofluorescence staining techniques to examine the distribution of receptor and cytoskeletal proteins in HeLa cells infected with E. coli recombinant strains that expressed Dr family of adhesins: Dr, Dr-II, F1845, AFA-I, and AFA-III. A major rearrangement of decay-accelerating factor was found at the adherence sites of recombinant strains expressing Dr, Dr-II, and F1845 adhesins. The changes in the distribution of receptor were significantly smaller on HeLa cells infected with E. coli bearing AFA-I or AFA-III afimbrial adhesins. Receptor aggregation was associated with the redistribution of cytoskeleton-associated proteins such as actin, alpha-actinin, ezrin, and occasionally tropomyosin. Purified Dr fimbriae coated on polystyrene beads were capable of triggering clustering of receptor and accumulating actin at the adhesion sites of beads to HeLa cells. Using scanning and transmission electron microscopic techniques, we have shown that beads coated with Dr fimbriae, as opposed to beads coated with bovine serum albumin, were enwrapped by cellular microvilli and ultimately internalized into HeLa cells. This indicates that interaction of Dr fimbriae with decay-accelerating factor is associated with redistribution of receptor and is sufficient to promote bacterial internalization.

Actins↗
PubMed1998

Synaptogenesis via dendritic filopodia in developing hippocampal area CA1.

To determine the role of dendritic filopodia in the genesis of excitatory synaptic contacts and dendritic spines in hippocampal area CA1, serial section electron microscopy and three-dimensional analysis of 16 volumes of neuropil from nine male rat pups, aged postnatal day 1 (P1) through P12, were performed. The analysis revealed that numerous dendritic filopodia formed asymmetric synaptic contacts with axons and with filopodia extending from axons, especially during the first postnatal week. At P1, 22 +/- 5.5% of synapses occurred on dendritic filopodia, with 19 +/- 5.9% on filopodia at P4, 20 +/- 8.0% at P6, decreasing to 7.2 +/- 4.7% at P12 (p < 0.02). Synapses were found at the base and along the entire length of filopodia, with many filopodia exhibiting multiple synaptic contacts. In all, 162 completely traceable dendritic filopodia received 255 asymmetric synaptic contacts. These synapses were found at all parts of filopodia with equal frequency, usually occurring on fusiform swellings of the diameter. Most synaptic contacts (53 +/- 11%) occurred directly on dendritic shafts during the first postnatal week. A smaller but still substantial portion (32 +/- 12%) of synapses were on shafts at P12 (p < 0.036). There was a highly significant (p < 0.0002) increase in the proportion of dendritic spine synapses with age, rising from just 4.9 +/- 4.3% at P1 to 37 +/- 14% at P12. The concurrence of primarily shaft and filopodial synapses in the first postnatal week suggests that filopodia recruit shaft synapses that later give rise to spines through a process of outgrowth.

Aging↗
PubMed1997

Dr fimbriae operon of uropathogenic Escherichia coli mediate microtubule-dependent invasion to the HeLa epithelial cell line.

Escherichia coli Dr adhesin and decay-accelerating factor (DAF) receptor-mediated interaction was proposed as the mechanism of ascending urinary tract infection (UTI) and chronic interstitial nephritis. This report provides novel evidence for Dr fimbriae operon-mediated invasive capacity of Dr+ E. coli. Insertional mutants draE, draC, and draB, and adherent draD and UV-inactivated BN406 were unable to enter HeLa cells. Complementation of the dra mutation restored invasiveness. Internalization was inhibited by anti-Dr fimbriae IgG (100%), anti-SCR-3 domain of DAF (75%), and nocodazole (95%). Increased receptor-ligand density occurred at the site of internalization. Internalized Dr+ E. coli did not significantly multiply in the HeLa cell line. Accordingly, the dra operon and DAF were required for microtubule-dependent internalization of E. coli to HeLa cells. The relatively low invasion and multiplication rates of Dr+ E. coli may hypothetically contribute to the postattachment steps of ascending UTI and chronic renal infection.

Adhesins, Escherichia coli↗
PubMed1997

Molecular cloning and characterization of Dr-II, a nonfimbrial adhesin-I-like adhesin isolated from gestational pyelonephritis-associated Escherichia coli that binds to decay-accelerating factor.

Bacterial adhesins play an important role in the colonization of the human urogenital tract. Escherichia coli Dr family adhesins have been found to be frequently expressed in strains associated with pyelonephritis in pregnant females. The tissue receptor for known Dr adhesins has been localized to the short consensus repeat-3 (SCR-3) domain of decay accelerating factor (DAF), a complement regulatory protein. In this report, we identified and cloned draE2, a gene encoding a novel 17-kDa DAF-binding adhesin, Dr-II, from a strain of E. coli associated with acute gestational pyelonephritis. Despite the significant sequence diversity between Dr-II and Dr family adhesins, the receptor of Dr-II was found to be the SCR-3 domain of DAF. Sequence analysis of the 186-amino-acid Dr-II open reading frame revealed significant diversity from other members of the Dr adhesin family, including Dr, AFA-I, AFA-III, and F1845, but only an 8-amino-acid difference in sequence from that of the 17-kDa nonfimbrial adhesin NFA-I of unknown receptor specificity. N-terminal peptide sequencing of the purified adhesin confirmed the identity of the open reading frame and indicated cleavage of a 28-amino-acid signal peptide. Antibodies raised against purified Dr-II adhesin exhibited little or no cross-reactivity to Dr adhesin. Characterization of the biological properties demonstrated that like the Dr adhesins, Dr-II was associated with the ability of E. coli to bind to tubular basement membranes and Bowman's capsule and to be internalized into HeLa cells.

Adhesins, Escherichia coli↗
PubMed1997

Phenotypic characterization of an intestinal subepithelial myofibroblast cell line.

Subepithelial myofibroblasts are located at the interface between the epithelium and lamina propria in most mucosal tissues. Their biological functions are largely unknown because a long-term cell culture model for these cells has not been available. In this report, we define the phenotypic properties of a human colonic cell line (18Co) that exhibits most of the known characteristics of intestinal subepithelial myofibroblasts in situ. These characteristics include 1) a cell shape that can be reversibly interconverted between a flattened discoid and stellate morphology, 2) intracellular organelles reminiscent of myofibroblasts and smooth muscle cells in situ, 3) expression of alpha-smooth muscle actin, 4) plasma membrane receptors for endothelins and natriuretic peptides, and 5) regulation of epithelial sensitivity to calcium-dependent secretagogues by paracrine secretion of prostaglandins. 18Co cells provide an exploitable model to begin defining the physiological and pathophysiological functions of intestinal subepithelial myofibroblasts at the molecular level.

Actins↗