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Biomedical subjects

D Roy

Publications and source records attributed to D Roy.

At least 91 records · Page 5Linked to original sources
PubMed1999

Healing of experimental aneurysms. II: Platelet extracts can increase the thickness of the neointima at the neck of treated aneurysms.

PURPOSE: To assess the effect of platelet extracts (PE) on neointima formation following gelfoam packing of experimental porcine aneurysms. A strategy involving the local delivery of platelet growth factors may potentially improve long term results of endovascular treatment of aneurysms. METHODS: Bilateral lateral wall common carotid aneurysms were constructed on 30 pigs. A collagen sponge containing a PE rich in growth factors was used to pack one aneurysm with the controlateral lesion being embolized with a sponge containing NaCl 0.9% (22 animals). In 8 animals, a control sponge was used on both sides. Animals were sacrificed at 1, 2, 3, 4 and 9 weeks and the thickness of the neointima covering the neck of PE-treated aneurysms was measured in 5 locations for each lesion at 2 and 3 weeks and compared with the control aneurysm of the same animal. Morphometric data was analysed using the paired Student's t-test. RESULTS: The thickness of the neointima was significantly increased in lesions treated with PE as compared to control lesions at 2 weeks (p = 0.008, n = 9). There was no significant difference at 3 weeks (p = 0.99, n = 9). There was no significant difference between lesions of control animals (p = 0.95, n = 8). CONCLUSION: PE rich in growth factors can increase the thickness of the neointima at the neck of treated experimental porcine aneurysms at 2 weeks, but had no effect at 3 weeks. This accelerated neointimal formation may have some value in improving healing following endovascular treatment. This hypothesis could not be supported with this experimental model which has a spontaneous tendency to heal. Further studies using an animal model which reproduces the clinical problem of recurrences may help to define the role of the local delivery of growth factors in combination with coils in a strategy designed to improve results of endovascular treatment.

Aneurysm↗
PubMed1998

Concentration dependence of prooxidant and antioxidant properties of catecholestrogens.

Estradiol is an established antioxidant in vitro and in vivo. In contrast, prooxidant effects such as 8-hydroxylation of guanine bases of DNA have been induced by various estrogens in hamsters and by 4-hydroxyestradiol or -estrone and a microsomal activating system in vitro. As part of an examination of these conflicting reports, we studied the enhancement or inhibition of lipid peroxidation (conjugated diene formation monitored at 240 nm) by catecholestrogens in human low-density lipoprotein (LDL) incubated with cupric sulfate in phosphate buffer. Addition of 2- or 4-hydroxyestradiol, 2- or 4-methoxyestradiol, or estradiol or estriol (0.5-50 microM) increased lag times for diene formation by 30 to <300% over control values in the absence of estrogens (lag time, 1.6 h). In contrast, low concentrations (5 pM-100 nM) of catecholestrogens decreased lag times by about 40-50%, demonstrating their prooxidant activities. The prooxidant capabilities of catecholestrogens were examined by assaying the reduction by estrogens of Cu(II) to Cu(I) and of Fe(III) to Fe(II). Both 2- and 4-hydroxyestradiol and 2- and 4-methoxyestradiol reduced Cu(II) and Fe(III) ions to their lower oxidation state. In conclusion, the reduction of Cu(II) to Cu(I) by catecholestrogens is proposed to initiate lipid peroxidation and thus oxidation of LDL. In contrast, at high concentrations of catecholestrogens, the scavenging of oxygen radicals may predominate over lipid peroxidation and free radical generation by analogy to the action of similar phenolic antioxidants. With estradiol, estriol, and the methoxyestrogen metabolites, only antioxidant effects were observed.

Animals↗
PubMed1998

Characterization of bifidobacteria by random DNA amplification.

RAPD conditions were optimized to generate reproducible banding patterns by testing primers, thermocyclers and overall reproducibility in repeat DNA analysis and separate DNA extractions. Five primers were chosen on the basis of band intensity and distribution (between 2 and 10 bands) which clearly distinguished among strains of Bifidobacterium adolescentis, B. animalis, B. bifidum, B. breve, B. infantis and B. longum. The use of five single-primer reactions under optimized conditions improved the resolution and accuracy of the RAPD method for the characterization of dairy-related bifidobacteria. The results indicated that this method was highly reproducible in repeated analysis. Similarity between bifidobacteria strains was evaluated based on their RAPD profiles. Using a set of five primers, it was demonstrated that it may be possible to distinguish three different species of Bifidobacterium (B. breve, B. bifidum and B. adolescentis), based on similarity of the RAPD profiles to known reference strains. Furthermore, application of the RAPD technique may also be useful and faster, than traditional systematics for placement of industrial strains into specific clusters (either B. longum/infantis or B. animalis/lactis).

Animals↗
PubMed1998

Is exposure to environmental or industrial endocrine disrupting estrogen-like chemicals able to cause genomic instability?

Human and wild life populations are continually exposed to a wide variety of environmental estrogen-like chemicals. Most research to date on environmental endocrine disrupting estrogen-like chemicals has focussed on screening of estrogenic activity of environmental or industrial chemicals, their bioaccumulative properties and toxicokinetics, and developing the structure-activity relationship between environmental or industrial chemicals and estrogen-receptor. Whether estrogen-like chemicals also possess the ability to alter the stability of the genome is not clear. It is very important to understand the effects of estrogen-like chemicals at the genome level. This article evaluates the current status of knowledge of the potential of producing genomic instability in response to the exposure of estrogen-like chemicals, which might help in understanding the mechanisms of some of the adverse effects. We and others have shown several structural, numerical, and functional changes at the cellular levels in response to DES exposure. Some other phenolic estrogen-like chemicals, such as, bisphenol A, phenylphenol and nonylphenol, also follow some of the pattern of effects similar to DES. These compounds also alter cell cycle kinetics, induce DNA damages, and produce telomeric associations and chromosomal aberrations. Whether weak or strong, the estrogenic response of a chemical, if not overcome, will add extra estrogenic burden to the system, and particularly those endocrine disrupting environmental and industrial estrogen-like chemicals capable of producing genomic instability will induce additional burden of genomic instability. Though, estrogenically some of these compounds may be weak, however, they may have different activities in generation of genomic instability. For example, nonylphenol is weak in estrogen-like action compared to DES, however, it is equal or more potent in producing telomeric associations in MCF-7 cells compared to DES. Additive or synergistic extra-burden of estrogenicity and genomic instability could produce detrimental effects compare to estrogenic action alone. Screening of endocrine disrupting environmental estrogen-like chemicals for their ability to produce genomic instability and analysis of molecular basis of some of the adverse human health outcomes as a result of exposure of these types of chemicals should lead to a better understanding of how these environmental estrogen-like chemicals may influence the development of some adverse effects in humans and wildlife.

Animals↗
PubMed1998

In vitro transformation of ampicillin to cephalexin by free and immobilized cells of Streptomyces sp.

In vitro transformation of ampicillin to cephalexin was studied using calcium alginate-immobilized and free Streptomyces sp. strain DRS-1 packed in glass columns. Tris-HCl buffer containing ampicillin was continuously circulated through the columns for four cycles, each cycle (with fresh ampicillin) being continued for 5 h. The pattern of product formation was identical in both cases, i.e. in each cycle, after reaching a certain concentration, its formation did not increase. Product formation was always higher with immobilized cells. Conversion of ampicillin to cephalexin by the strain was affected by cell and substrate concentration.

Alginates↗
PubMed1998

Legg-Perthes disease in three siblings, two heterozygous and one homozygous for the factor V Leiden mutation.

A family is described with three-generation transmission of factor V Leiden (a thrombophilic mutation that causes resistance to activated protein C). Legg-Perthes disease developed in three siblings in this family. The male proband and his sister were heterozygous for the mutation and had unilateral hip disease at age 2 years. The brother, who had bilateral hip disease, was homozygous. This novel family provides compelling evidence for the pathoetiologic role of familial thrombophilia in Legg-Perthes disease.

Adult↗
PubMed1998

A slipped replication intermediate model is stabilized by the syn orientation of N-2-aminofluorene- and N-2-(acetyl)aminofluorene-modified guanine at a mutational hotspot.

The Escherichia coli NarI restriction enzyme recognition site 5'G1G2C3G4C5C63' is a mutational hotspot for -2 deletions in E. coli plasmid pBR322, resulting in the sequence 5'GGCC3' when G4 is modified by the aromatic amine N-2-(acetyl)aminofluorene (AAF) [Burnouf, D., Koehl, P., and Fuchs, R. P. P. (1995) Proc. Natl. Acad. Sci. U.S.A. 86, 4147-4151] even though each G shows similar reactivity [Fuchs, R. P. P. (1984) J. Mol. Biol. 177, 173-180]. Modification at G4 by the related aromatic amine 2-aminofluorene (AF), which lacks the acetyl group of AAF, can also cause -2 deletions, but at a lower frequency [Bichara, M., and Fuchs, R. P. P. (1985) J. Mol. Biol. 183, 341-351]. A specific mechanism has been proposed to explain the double-base frameshifts in the NarI sequence in which the GC deletion results from a slipped mutagenic intermediate formed during replication [Schaaper, B. M., Koffel-Schwartz, N., and Fuchs, R. P. P. (1990) Carcinogenesis 11, 1087-1095]. We address the following key questions in this study. Why does AAF modification dramatically increase the mutagenicity at the NarI G4 position, and why does AAF enhance the mutagenicity more than AF? We studied two intermediates which model replication at one arm of a fork, using a fragment of DNA modified by AF or AAF at G4 in the NarI sequence: Intermediate I can be converted into intermediate II by misalignment. Elongation of intermediate I leads to error-free translesion synthesis, while elongation of intermediate II leads to a -2 frameshift mutation. Minimized potential energy calculations were carried out using the molecular mechanics program DUPLEX to investigate the conformations of the AF and AAF adducts at G4 in these two intermediates. We find that the slipped mutagenic intermediate is quite stable relative to its normally extended counterpart in the presence of AF and AAF in an abnormal syn orientation of the damaged base. An enhanced probability of elongation from a stable slipped structure rather than a properly aligned one would favor increased -2 frameshift mutations. Furthermore, AAF-modified DNA has a greater tendency to adopt the syn orientation than AF because of its greater bulk, which could explain its greater propensity to cause -2 deletions in the NarI sequence.

2-Acetylaminofluorene↗
PubMed1998

Feasibility of cardiac cryoablation using a transvenous steerable electrode catheter.

We investigated the feasibility of using cryogenic technology in an electrode catheter for percutaneous ablation of cardiac tissue. Despite its high success rate, radiofrequency catheter ablation has important limitations especially with regards to the treatment of ventricular arrhythmias associated with a chronic scar. Arrhythmia surgery experience has shown that freezing with a hand held probe can permanently ablate the arrhythmogenic substrate of ventricular tachycardia associated with an old scar. Moreover, cryosurgery also allows for reversible "ice mapping," in which the area likely responsible for the arrhythmia can be evaluated by suppressing its electrophysiologic properties prior to the creation of an irreversible state. A new steerable cryoablation catheter using Halocarbon 502 as a refrigerant was utilized in six dogs. Serial cryoapplications were performed in the right and left ventricles. In two dogs, we attempted reversible ice mapping of the AV node. Pathological evaluation of the lesions was done acutely in all the animals. Forty-two cryoapplications were delivered at a mean temperature of -45 +/- 9.8 degrees C. No lesion was found at pathological evaluation for 16 cryoapplications which did not achieve a temperature of less (colder) than -30 degrees C. The remaining applications resulted in 26 lesions which were hemorrhagic and sharply demarcated from normal myocardium. Histological evaluation revealed contraction band necrosis. Reversible ice mapping of the AV node was successfully achieved in two animals. Cryoablation is feasible using an electrode catheter with multiple electrodes. This technology has the potential to allow for reversible ice mapping to confirm a successful ablation target before definitive ablation.

Animals↗
PubMed1998

One-to-two atrioventricular conduction causing nonreentrant tachycardia: successful treatment with radiofrequency ablation.

The anatomical substrate for AV nodal reentrant tachycardia (AVNRT) is well known and is due to anterograde conduction through a slow conducting pathway and retrograde conduction using a fast conducting pathway. In this report, we describe a patient with AVNRT who also presented with frequent episodes of paroxysmal nonreentrant tachycardia due to the occurrence of two conducted ventricular beats for each sinus depolarization. Palpitations and arrhythmias were abolished after radiofrequency ablation of the slow pathway.

Adult↗
PubMed1998

Insulin stimulation of glucose uptake in skeletal muscles and adipose tissues in vivo is NO dependent.

The purpose of this study was to investigate whether in vivo nitric oxide synthase (NOS) inhibition influences insulin-mediated glucose disposal in rat peripheral tissues. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or saline was infused constantly during a hyperinsulinemic-euglycemic clamp in normal rats. Glucose utilization rates of insulin-sensitive tissues (individual muscles, heart, and adipose tissues) were simultaneously determined using tracer infusion of 2-deoxy-D-[3H]glucose (2-[3H]DG). NOS blockade with L-NAME resulted in significant (P < 0.05) reduction in both whole body glucose disposal (-16%, P < 0.01) and plasma 2-[3H]DG disappearance rate (-30%, P < 0.05) during hyper-insulinemic-euglycemic clamp. L-NAME significantly decreased insulin-stimulated glucose uptake in heart (-62%, P = 0.01), soleus (-42%, P = 0.05), red (-53%, P < 0.001) and white (-62%, P < 0.001) gastrocnemius, tibialis (-57%, P < 0.01), and quadriceps (-33%, P < 0.05) muscles. The NOS inhibitor also decreased insulin action in brown interscapular (-47%, P < 0.01), retroperitoneal (-52%, P = 0.07), and gonadal (-66%, P = 0.06) adipose tissues. In contrast to in vivo NOS blockade, L-NAME failed to affect basal or insulin-stimulated 2-[3H]DG transport in isolated soleus or extensor digitorum longus muscles in vitro. These results support the hypothesis that the action of insulin to augment glucose uptake by skeletal muscles and other peripheral insulin-sensitive tissues in vivo is NO dependent.

Adipose Tissue↗
PubMed1998

Regulation of gonadotropin-releasing hormone (GnRH) gene expression by 5alpha-dihydrotestosterone in GnRH-secreting GT1-7 hypothalamic neurons.

Hypothalamic GnRH secretory neurons are precisely regulated by circulating gonadal steroids. However, the question of whether these cells are directly responsive to steroid hormones remains a central and controversial issue in reproductive science. In the present study, we demonstrate the expression of androgen receptor (AR) in a mouse hypothalamic GnRH-secreting cell line, GT1-7. AR messenger RNA was detected by Northern blot analysis of 10 microg total cellular RNA. Western blot analysis revealed a 110K AR immunoreactive band, and saturation binding analysis confirmed the presence of a high affinity low capacity androgen binding entity (Kd = 0.06 nM; Bmax = 12.4 fmol/mg protein). In addition, GT1-7 cells were found to express ARA70, an AR-specific coactivator that has been reported to enhance transactivational activity of the AR. GT1-7 cells transiently transfected with an androgen responsive MMTV-luciferase reporter construct displayed a 4.2-fold induction of luciferase reporter gene activity by 1 nM 5alpha-dihydrotestosterone (DHT), further demonstrating the presence of a functional AR. Treatment of GT1-7 cells with 1 or 10 nM DHT resulted in approximately 55% reduction in GnRH messenger RNA measured at 24 and 36 h after treatment. This repression was completely blocked by hydroxyflutamide, an AR antagonist. These results provide the first demonstration that androgen acts directly through an AR-mediated pathway to repress GnRH gene expression in hypothalamic GnRH-secreting neurons.

Animals↗
PubMed1998

Is there a future for antiarrhythmic drug therapy?

Drug therapy has traditionally been the mainstay of treatment for both ventricular and supraventricular arrhythmias. However, increasing knowledge about the potentially significant adverse effects of these medications, together with the emergence of new, nonpharmacological approaches to the treatment of arrhythmias, has led some to question the future of antiarrhythmic drug therapy. Antiarrhythmic drugs are quite effective in terminating a variety of arrhythmias, including atrioventricular (AV) node re-entrant and AV tachycardias (particularly calcium antagonists and adenosine), atrial flutter (class III agents) and atrial fibrillation (class IA and IC drugs. The chronic use of antiarrhythmic drugs has been increasingly limited by a fear of adverse effects (especially proarrhythmia) and the availability of highly effective nonpharmacological alternatives (particularly ablation for re-entrant tachycardias involving the AV node and bypass tracts and cardiovertor/defibrillators for malignant ventricular arrhythmias. Atrial fibrillation (AF) continues to be a therapeutic challenge for which there is no safe and curative nonpharmacological therapy. Antiarrhythmic drugs of classes IA, IC and III show efficacy in preventing recurrence of AF but there are concerns about possible pro-arrhythmic complications. In the future, antiarrhythmic agents will continue to be used acutely to terminate a broad range of sustained arrhythmias. Chronic use is likely to depend on the development of safer and/or more effective compounds, as well as on improved ways of predicting which patients are likely to develop pro-arrhythmic reactions. The development of molecular electrophysiology will allow for the identification of agents with selected ion channel blocking profiles which may prove efficacious with a lower risk of complications. Finally, an improved understanding of arrhythmia substrates may permit the identification of therapy that prevents arrhythmias by acting on the underlying substrate, rather than simply trying to modify the electrical end product.

Anti-Arrhythmia Agents↗
PubMed1998

Selective impairment in GLUT4 translocation to transverse tubules in skeletal muscle of streptozotocin-induced diabetic rats.

We previously reported that insulin induces the translocation of GLUT4 to both the plasma membrane and the transverse tubules (T-tubules) in rat skeletal muscle (Am J Physiol 270:E667-E676, 1996). The aim of the present study was to investigate whether the insulin-resistant glucose utilization of skeletal muscle from streptozotocin (STZ)-induced diabetic rats is linked to an impaired translocation of GLUT4 to the plasma membrane, the T-tubules, or both surface compartments. Whole-body insulin-mediated glucose disposal, assessed during a hyperinsulinemic-euglycemic clamp, was reduced by 48% (P < 0.01) in diabetic rats as compared with controls. Subcellular membrane fractions enriched with plasma membranes, T-tubules, or GLUT4-enriched intracellular membranes were isolated from hindlimb muscles of control and insulin-stimulated rats, and GLUT4 content was measured by Western blot analysis. In the absence of insulin (unstimulated), GLUT4 content in muscle of diabetic rats was markedly lower (by approximately 40%) in both the T-tubules and the intracellular membrane fraction as compared with controls. In contrast, the transporter protein levels were similar in the plasma membrane fraction. In skeletal muscle of control animals, the hyperinsulinemic clamp induced GLUT4 translocation from the intracellular membrane pool to both the plasma membrane and the T-tubule-enriched fractions (approximately 2.2-fold to approximately 2.5-fold). Surprisingly, insulin increased plasma membrane GLUT4 content to comparable levels in control and diabetic rat skeletal muscle. However, insulin-mediated GLUT4 translocation to the T-tubules was significantly reduced in the same muscle. Whole-body insulin action was significantly correlated with GLUT4 protein levels in the T-tubules, but not with the transporter content in either plasma membranes or intracellular membranes. These results strongly suggest that peripheral resistance to insulin action on glucose disposal in STZ-induced diabetic rats is caused by a selective impairment of GLUT4 translocation to skeletal muscle T-tubules.

Animals↗
PubMed1998

Benign superior vena cava syndrome due to suppurative mediastinal lymphadenitis: anterior mediastinoscopic management.

The benign superior vena cava syndrome is an uncommon medical emergency. We describe a case of the superior vena cava syndrome caused by suppurative mediastinal lymphadenitis. The organisms isolated from various cultures were group C beta-hemolytic Streptococcus, Fusobacterium species, Corynebacterium species, Eikenella corrodens, and Streptococcus milleri. These anaerobic bacteria are part of the normal flora of the upper respiratory tract and the oral cavity. Anterior mediastinoscopy through the right parasternal approach was used to drain the anterior mediastinal abscess and to establish the etiologic factor.

Adult↗
PubMed1998

Adhesion of Aeromonas hydrophila to water distribution system pipes after different contact times.

Scanning electron microscopy observation was used to investigate the ability of Aeromonas hydrophila to attach to various water distribution pipe surfaces, such as stainless steel, copper, and polybutylene, after different contact times at ambient and storage temperatures. Surface energy value of each surface was estimated by contact angle measurements using water, alpha-bromonaphthalene, and dimethyl sulfoxide. Our results indicated that Aeromonas cells could easily attach to all surface types after exposures as short as 1 or 4 h at both temperatures (4 and 20 degrees C). Polybutylene, a low-energy surface (41.2 mJ.m-2), followed by stainless steel (65.7 mJ.m-2), was most colonized by Aeromonas cells, whereas few cells were observed on copper, which has a surface energy of 45.8 mJ.m-2. Extracellular materials could also be observed on polybutylene surfaces, especially after 1 and 4 h of exposure at the refrigeration temperature.

Aeromonas hydrophila↗
PubMed1998

Craniocervical dural fistula associated with cervical myelopathy: angiographic demonstration of normal venous drainage of the thoracolumbar cord does not rule out diagnosis.

We report a case of craniocervical dural arteriovenous fistula with perimedullary venous drainage associated with cervical myelopathy in which spinal angiography showed a normal venous phase after injection of the artery of Adamkiewicz. We conclude that because of the complex venous drainage of the spinal cord, a dural arteriovenous fistula with spinal drainage cannot be ruled out solely because a normal venous phase is seen in the lower part of the cord, as has previously been suggested.

Aged↗