Frequency of early occlusion and stenosis in bypass grafts after minimally invasive direct coronary arterial bypass surgery.
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Coronary Angiography↗
Biomedical subjects
V Subramanian
Publications and source records attributed to V Subramanian.
Integrated minimally invasive approaches for the treatment of atherosclerotic vascular diseases: Hybrid procedures.
Patients may develop simultaneous symptoms of atherosclerotic vascular disease from different arterial beds. A concurrent minimally invasive approach to the management of these clinical situations may be an advantage over conventional surgical procedures. This study describes two separate case series of patients undergoing coronary/peripheral (n = 38) and peripheral/peripheral procedures (n = 10). Technical and clinical success was achieved in all patients. There were two periprocedural complications (retroperitoneal bleed and septicemia) in the coronary/peripheral series and no complications in the peripheral/peripheral series. We also present five case reports to illustrate the utility of hybrid procedures in various clinical settings. This study suggests that the use of simultaneous or sequential minimally invasive procedures appears to be a safe and feasible strategy for the treatment of patients with symptoms from more than one vascular bed. Cathet Cardiovasc Intervent 2001;52:154-161.
Aged↗
Truncation of the Mll gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos.
The mixed lineage leukemia gene (MLL) was originally identified through its involvement in reciprocal translocations in leukemias. MLL codes for a large multidomain protein and bears homology to the Drosophila developmental control gene trithorax in two small domains in the amino terminal region, the central zinc finger domain and the carboxy SET domain. Like the Drosophila trx, MLL has also been shown to be a positive regulator of Hox gene expression. We have targeted Mll (the murine homologue of MLL) in exon 5 causing expression of three truncated in-frame Mll transcripts. These transcripts retain all or some of the AT hook motifs and the DMT domain. This mutant allele causes early in vivo preimplantation lethality of homozygous embryos prior to the 2-cell stage. Embryos cultured in vitro progress to the 2-cell stage, but further development is arrested. The heterozygotes exhibit mild skeletal defects as well as defects in some neuroectodermal derivatives.
Animals↗
Differentiation potential of intestinal mesenchyme and its interaction with epithelial cells: a study using beta-galactosidase-expressing fibroblast lines.
Rat intestinal fibroblast lines (F1:G9 and A1:F1) differing in their potential to support intestinal mucosal development were marked with reporter genes to investigate their differentiation potential. The fibroblasts were transfected with plasmids expressing either beta-galactosidase (with or without a nuclear localisation signal) or green fluorescent protein (GFP). Transfection using Tfx50 or Fugene was more efficient than electroporation. The expression of beta-galactosidase was more stable and stronger than GFP. Cells were optimally labelled using the plasmid pL27B-GAL, and sub-clones with a strong and uniform nuclear expression of beta-galactosidase were isolated. These clones expressed beta-galactosidase even after prolonged passage in the absence of selection. The beta-galactosidase tagged lines (F1:G9gal and A1:F1gal) retained the morphological characteristics, viability and differentiation properties of the parental non-transfected lines. In co-culture with a colorectal tumour cell line Caco-2, the F1:G9gal and A1:F1gal cells differed in their morphological organisation but this did not change their expression of smooth muscle alpha-actin.
Animals↗
High-level expression of three members of the murine angiogenin family in Escherichia coli and purification of the recombinant proteins.
Angiogenin (Ang) is a small basic protein which belongs to the pancreatic ribonuclease superfamily. It potently induces the formation of new blood vessels and has emerged as a promising anticancer target. Mice possess genes encoding one ortholog (mAng) and three homologs of Ang, designated angiogenin-related protein (mAngrp), angiogenin-3 (mAng-3), and angiogenin-4 (mAng-4). Structural and functional study of these homologs has been hampered by the low yield of protein from the existing heterologous expression system. In the experiments described, we used a pET expression vector to express these proteins in the cytoplasm of Escherichia coli BL21-CodonPlus(DE3)-RIL cells, whereupon substantial amounts of each accumulated in the form of insoluble aggregates. The proteins were renatured using an arginine-assisted procedure and subsequently purified by cation-exchange chromatography and reversed-phase HPLC; each purified protein was shown to be enzymatically active toward tRNA. The yields of pure mAngrp and mAng-3 were 7.6 and 12 mg/liter culture, respectively, representing substantial increases over previously reported experiments. This is also the first report of the expression and purification of mAng-4, obtained here in a yield of 30 mg/liter culture. The ready availability of milligram quantities of these proteins will enable further functional studies and high-resolution structural analyses to be conducted.
Angiogenesis Inducing Agents↗
Stem cells and the regulation of proliferation, differentiation and patterning in the intestinal epithelium: emerging insights from gene expression patterns, transgenic and gene ablation studies.
Tissues that undergo self-renewal such as the skin, the haematopoeitic system and the intestine are all maintained and renewed by a small group of multipotent stem cells. The stem cells of the intestinal epithelium are located in the crypts and give rise to its four main lineages located mainly in the finger like projections- the villi. An increasing number of genes are now being identified as either being necessary for or involved in the maintenance of intestinal stem cells and regulating differentiation along the crypt-villus axis. These developmental regulatory genes include among others, Tcf-4, Cdx-1 Fkh6, HFH11 and Nkx2-3. Other genes such as the integrins, and Indian hedgehog (Ihh) also affect function of the progenitor cells of the intestinal epithelium. This mini-review will focus on the more recent data on expression patterns of genes in the intestinal epithelium and the direct or indirect effects of their ablation on proliferation and differentiation.
Animals↗
Present status of asbestos mining and related health problems in India--a survey.
At present in India more than thirty mines are in operation. It produces 2800 tones of asbestos per month (mainly chrysotile and tremolite) and in recent years substantial quantity (-70%) is imported from Canada. The quality of asbestos produced in India is very poor. The mining and milling and other related processes expose the people to cancer and related diseases. Women are more affected by their exposure in processing unit compared to male who are generally working in mines. Direct and indirect employment in asbestos related industry and mine is around 100,000 workers. Latency period (length of the time between exposure and the onset of diseases) in India is estimated to be 20-37 yr. The causes for lung and breathing problem are mainly due to obsolete technology and direct contact with the asbestos products without proper precaution, because in India asbestos are sold without statutory warning. This paper reviews health effects (such as fibrosis, sequelae, bronchogenic cancer, and malignant mesothelioma) on the Indian mine workers caused due to asbestos mining related activities with respect to their present day condition.
Asbestos, Amphibole↗
Interaction of DNA with [Cr(Schiff base)(H(2)O)(2)]ClO(4).
The binding of Schiff base complexes of chromium(III) of the type [Cr(salen)(H(2)O)(2)](+) and [Cr(salprn)(H(2)O)(2)](+), where salen denotes 1,2-bis(salicylideneamino)ethane and salprn denotes 1,3-bis(salicylideneamino)propane to calf thymus DNA has been investigated by absorption, emission, circular dichroism, melting temperature and viscosity measurements. These chromium(III) complexes showed absorption hyperchromicity accompanied by red shift in charge transfer band, fluorescence enhancement, increase in melting temperature, some structural changes in CD spectra and changes in specific viscosity when bound to calf thymus DNA. The binding constant K(b) has been determined from absorption measurements for both the complexes and found to be (2.5+/-0. 4)x10(3) M(-1) for [Cr(salen)(H(2)O)(2)](+) and (1.7+/-0.3)x10(4) M(-1) for [Cr(salprn)(H(2)O)(2)](+). From the binding stoichiometry of DNA-[Cr(salprn)(H(2)O)(2)](+), the number of binding site size has been determined and found to be ten base pairs per bound complex molecule. The chromium(III) complexes also bring about single strand cleavage in plasmid DNA. The experimental results show that the chromium(III) complexes bind to DNA by non-intercalative mode. Major groove binding is the preferred mode of interaction for these Schiff base complexes of chromium(III).
Binding Sites↗
DNA cleavage by a Chromium(III) complex.
A new Cr(III) complex with the empirical formula [Cr(Schiff base) (H(2)O)(2)]ClO(4), where the Schiff base is 2, 3-bis¿[(2-hydroxy-4-diethylamino) (phenyl) (methylene)]amino¿2-butenedinitrile has been synthesized and characterized spectroscopically. Binding of this complex to DNA has been studied using UV-visible spectroscopy. The complex has been found to bind to the major groove of DNA with a binding constant, K = (1.3 +/- 0.2) x 10(3) M(-1). The induced CD spectrum of the complex in the presence of DNA is also indicative of major groove binding. Gel electrophoresis of plasmid DNA in the presence of the complex shows that the complex brings about nicking of the DNA.
Chromium Compounds↗
IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23.
End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.
Chromosome Mapping↗
Identification of DNA polymorphism in cultivated groundnut using random amplified polymorphic DNA (RAPD) assay.
Construction of a genetic linkage map is necessary to apply marker-assisted selection tools in a crop improvement program. Except for the recent studies from two laboratories, most of the previous studies have shown little or no DNA polymorphism in cultivated groundnut (Arachis hypogaea L.). In the present study, 70 selected genotypes, representing variability for several morphological, physiological, and other characters, were studied for polymorphism employing random amplified polymorphic DNA (RAPD) assay with 48 oligonucleotide primers. Of the 48 oligonucleotide primers only 7 (14.6%) yielded polymorphic amplification products. The total number of bands from the 7 primers was 408, of which 27 were polymorphic. Detection of polymorphism in cultivated groundnut opens up the possibility of development of its molecular map by judicious selection of genotypes that show DNA polymorphism. This approach will be useful for developing marker-assisted selection tools for genetic enhancement of groundnut for desirable traits.
Genes, Plant↗
Functional expression of a high affinity mammalian hepatic choline/organic cation transporter.
Uptake by the liver of the organic cation and essential nutrient choline is required for the hepatic synthesis of phosphatidylcholine. Uptake of other organic cations is also important for the metabolism and secretion of numerous endobiotics and drugs. Although a high affinity mammalian hepatic choline transporter has been kinetically defined, it has not been previously identified. We have developed stable transfectants of BALB/3T3 cells, using a murine member of the organic cation transporter gene family (mOct1/Slc22a1), and used these cells to characterize the transport of the organic cation choline and model organic cation tetraethylammonium (TEA). Functional expression of mOct1/Slc22a1 in BALB/3T3 cells confers the saturable, temperature-dependent uptake of choline with a K(m) of 42 micrometer, and uptake of TEA with a K(m) of 43 micrometer. We subsequently used our cell culture uptake system to kinetically define in HepG2 cells a high affinity choline uptake process, which transports choline with a K(m) similar to that of mOct1/Slc22a1 protein. We also demonstrated that organic cation transport by mOct1/Slc22a1 is inhibited by several organic cations, and that the gene is expressed in the perinatal period, at a time when phosphatidylcholine synthesis increases. We conclude that mOct1/Slc22a1 encodes a high affinity mammalian hepatic choline/organic cation transporter. This transporter may be important for hepatic phosphatidylcholine synthesis, and for the metabolism and secretion of many organic cationic drugs.
3T3 Cells↗
Chiral high-performance liquid chromatography of N-octyl bicycloheptene dicarboximide and confirmatory studies using liquid chromatography-tandem mass spectrometry and two-dimensional nuclear magnetic resonance spectroscopy.
N-Octyl bicycloheptene dicarboximide (MGK 264) has exo and endo diastereomers. Each structure has a chiral center at the nitrogen side chain. Enantioselective separation of MGK 264 was achieved by normal-phase high-performance liquid chromatography (HPLC) using cellulose-based Chiralcel OD column with diode-array and optical rotation detectors. Peaks were isolated with the purpose of identifying their stereochemical structures. Molecular mass of the HPLC peaks and their structural information was determined by liquid chromatography-electrospray tandem mass spectrometry (LC-ES-MS-MS). A two-dimensional nuclear magnetic resonance (NMR) spectroscopic technique was used to establish the structural features. Correlation of the data obtained from chiral separation and NMR facilitated in unambiguous assignment of the HPLC peaks.
Chromatography, High Pressure Liquid↗
Aluminum leaching from surrogate aluminum food containers under different pH and fluoride concentration.
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Acids, Acyclic↗
The angiogenins: an emerging family of ribonuclease related proteins with diverse cellular functions.
Angiogenin is a member of the ribonuclease superfamily, which shows an ever expanding collection of molecules being identified and cloned. It was initially isolated from the conditioned medium of cultured tumour cells. Its angiogenic activity appears to be critical for the maintenance and support of tumour growth. Angiogenin also plays a role in a number of non-malignant vasculoproliferative pathological conditions. Along with other related molecules, it has been identified in a wide variety of somatic tissues in adult and embryonic stages of vertebrate development. This suggests that angiogenin and related molecules are likely to play a vital role in normal physiology. Angiogenin is detectable in serum and to date has been implicated as a mitogen for vascular endothelial cells, an immune modulator with suppressive effects on polymorphonuclear leukocytes, an activator of certain protease cascades such as matrix metalloproteases and plasminogen-activated plasmin pathways, as well as an adhesion molecule. However, the role of the angiogenin family in both normal and abnormal physiology and in development will only fully be realised by genetic approaches involving gene deletion.
Journal Article↗
The murine Cdx1 gene product localises to the proliferative compartment in the developing and regenerating intestinal epithelium.
The mouse Cdx1 gene encodes a homeobox-containing transcription factor and is one of the few homeobox genes known to be expressed in endodermally derived tissues of the intestine in fetal and adult mice. A detailed and systematic study of the expression of the Cdx1 protein was carried out during embryonic intestinal development, postnatal cytodifferentiation and in the regenerating (after radiation-induced damage) intestine of the mouse. Using antibodies directed against Cdx1, we show for the first time that the Cdx1 protein is localised in the proliferating immature epithelium during intestinal development. It becomes restricted to the proliferative crypt compartment during postnatal differentiation, as well as in the adult intestine. The mesenchymal layer was completely negative both during embryonic development and in the postnatal intestine. The expression of the protein was first clearly detected throughout the simple columnar epithelium at day 15 of development. This expression progressively became restricted to the regions of epithelial proliferation in the crypts of the adult mouse by day 40 of post-natal development. There were occasional cells that were Cdx1 positive in the villi. During regeneration of the epithelium after radiation-induced damage, Cdx1 expression diminished during the initial phase of cellular regression. The expression was then very strong in the regenerating epithelial foci, but not in the quiescent sterilised crypts between day 4 and 6. The normal pattern was restored between day 6 and 7. The Paneth cells were negative. The physical segregation of Cdx1 with the proliferative compartment and the hierarchy of cell renewal in the intestinal epithelium is an important example of how regulatory genes function in the maintenance and in the dysfunction of renewing tissues.
Animals↗
Bioequivalence of two orally administered nicardipine products.
The relative bioavailabilities of orally administered nicardipine (Zenith Laboratories) and nicardipine (Cardene Syntex Laboratories) were compared following a single 30 mg dose under fasted conditions using a two-way crossover study with 34 healthy adult male subjects. In a separate study the effect of food on the relative bioavailabilities of these products was assessed following an identical dose by comparing the Zenith product under fasted conditions, the Zenith product under fed conditions, and the Syntex product under fed conditions using a three-way crossover study with 17 healthy adult male subjects. In the fasted study, 90% confidence intervals surrounding ratios (Zenith/Syntex) of least-squares means derived from 1n-transformed data were 0.84-1.02 for AUCt, 0.85-1.04 for AUCinfinity, and 0.86-1.05 for Cmax, clearly demonstrating bioequivalence of the two products. In the food-effect study ratios of least-squares means (Zenith under fed conditions/Zenith under fasted conditions) were 0.62 for AUCt, 0.65 for AUCinfinity, and 0.40 for Cmax, with tmax delayed from 0.906 +/- 0.337 h (Zenith under fasted conditions) to 2.33 +/- 0.717 h (Zenith under fed conditions) and 2.84 +/- 0.834 h (Syntex under fed conditions). Findings indicate that the presence of food in the gastrointestinal tract reduces the bioavailability of orally administered nicardipine. However, ratios under fed conditions (Zenith/Syntex) were very close to unity for each metric, suggesting that the observed food effect is independent of the product formulation. Findings further suggested that food effects on conventional pharmacokinetic metrics might be attributed to alteration of extent, rather than rate, of gastrointestinal absorption. Finally, these results question the applicability of the peak plasma concentration (Cmax) as an index of absorption rate in nicardipine studies.
Administration, Oral↗
Disruption of the murine homeobox gene Cdx1 affects axial skeletal identities by altering the mesodermal expression domains of Hox genes.
Cdx1 is expressed along the embryonic axis from day 7.5 postcoitum until day 12, by which time the anterior limit of expression has regressed from the hindbrain level to the forelimb bud region. To assign a functional role for Cdx1 in murine embryonic development, we have inactivated the gene via homologous recombination. Viable fertile homozygous mutant mice were obtained that show anterior homeotic transformations of vertebrae. These abnormalities were concomitant with posterior shifts of Hox gene expression domains in the somitic mesoderm. The presence of putative Cdx1-binding sites in Hox gene control regions as well as in vitro transactivation of Hoxa-7 indicates a direct regulation.
Animals↗