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Biomedical subjects

D Roy

Publications and source records attributed to D Roy.

At least 73 records · Page 4Linked to original sources
PubMed2001

GD1a in phospholipid bilayer: a molecular dynamics simulation.

Molecular dynamics simulation of ganglioside GD1a attached to the upper layer of a fully hydrated lipid bilayer of dimyristoyl phosphatidyl choline (DMPC) at room temperature under periodic boundary conditions was performed. The time average conformation of GD1a reveals that the terminal sialic acid is more exposed into the solvent than the internal branched one. Many interresidual contacts between N-acetyl galactosamine-internal branched sialic acid; external Gal-external sialic acid; N-acetyl galactosamine-internal gal are also observed. The conformation of the GD1-hexasaccharide is stabilized by a number of intra molecular hydrogen bonds that were previously observed experimentally. The simulation results indicate that the presence of a single GD1a molecule has local effects on the bilayer. A local disorder in the arrangement of the acyl chains as well as the head groups is evident in the upper layer due to the presence of GD1a.

Acetylgalactosamine↗
PubMed2001

Frequent allelic imbalance on chromosome 6 and 17 correlate with radiation-induced neoplastic transformation of human breast epithelial cells.

The development of human breast cancer is a complex multi-step process that depends on various exogenous and endogenous factors that modulate the transformation of normal human breast epithelial cells into neoplastic ones. Using a spontaneously-immortalized human breast epithelial (MCF-10F) cell line, we have shown previously that radiation, in combination with estrogen, induces a stepwise neoplastic transformation of this cell line. In the present study, we investigate the incidence of microsatellite instability and loss of heterozygosity using a battery of markers on chromosomes 6 and 17, we correlate the genetic alteration with the malignant transformation of the MCF-10F cell line ranging from altered morphology to increase in proliferative rate, anchorage independent growth and tumorigenicity in nude mice. Microsatellite markers were selected from the hot spot regions (6q21-q27, 17p12-p13.3 and 17q12-q21) of both chromosomes. We found that the frequency of allelic imbalance occurs at the different stages of tumor progression with a range of 21 to 50% depending on the marker studied. The relatively high rate of allele imbalance at all these loci suggests the presence and inactivation of one or more tumor suppressor genes in these regions. Thus, the present data will be useful for systematic studies to identify the cellular and molecular changes associated with radiation-induced breast carcinogenesis.

Allelic Imbalance↗
PubMed2001

Neck-bridge device for endovascular treatment of wide-neck bifurcation aneurysms: initial experience.

PURPOSE: To report the authors' initial experience in treating patients with wide-neck aneurysms with assistance from a recently developed neck-bridge device (TriSpan; Target Therapeutics/Boston Scientific, Fremont, Calif). MATERIALS AND METHODS: Twenty-five patients were examined. Aneurysms were most frequently at the basilar bifurcation (n = 19). Sixteen aneurysms were treated electively: six aneurysms that recurred after coil-only embolization and 10 nontreated aneurysms (including four that had failed coil-only embolization). Nine aneurysms were treated acutely following subarachnoid hemorrhage. All lesions except one had a wide neck. A dual-catheter technique was used in 23 patients. Immediate angiographic results, technical incidents, and complications were recorded. Follow-up angiography was performed in 16 patients. Clinical follow-up ranged from 1 to 12 months. RESULTS: Neck-bridge device-assisted coil packing was successfully performed in 23 lesions, with complete obliteration in three, residual necks in 13, and a minimal residual sac in seven patients. Parent vessel protection failed, with coil protrusion and arterial occlusion, in one of these patients. Other complications that were not directly related to use of the neck-bridge device included retroperitoneal hematoma, rebleeding, coil perforation, and transient embolic arterial occlusion. One patient died of vasospasm and heart failure. Follow-up angiography revealed complete obliteration in four, a residual neck in one, a persistent residual sac in four, and recurrent aneurysm in seven patients. One patient had a small occipital infarction 5 weeks after treatment. CONCLUSION: The described neck-bridge device is useful for assisting coil embolization of wide-neck bifurcation aneurysms.

Adult↗
PubMed2001

Endovascular treatment of unruptured aneurysms.

BACKGROUND AND PURPOSE: We sought to better define the morbidity of endovascular Guglielmi detachable coil (GDC) treatment of unruptured cerebral aneurysms and to discuss its role in the prevention of subarachnoid hemorrhage. METHODS: We conducted an observational study from August 1992 to June 1999 of 125 unruptured aneurysms treated with GDC in 116 patients: 91 women (78.4%) and 25 men (21.6%), aged 30 to 78 years (mean age, 50.6 years). Immediate and late clinical results were recorded for any neurological event or hemorrhage related to the treated unruptured aneurysm. Angiographic results are reported as immediate, early (2 to 12 months), intermediate (12 to 30 months), and late follow-up (>30 months). RESULTS: Immediate angiographic results showed complete obliteration (class 1) in 59 (47.2%) or residual neck (class 2) in 53 aneurysms (42.4%), leaving 6 residual aneurysms (4.8%) and 7 failures (5.6%). Early follow-up angiograms, available in 100 treated aneurysms (84%), revealed class 1 in 52% and class 2 in 41%. Intermediate angiograms, available in 53 aneurysms (44.5%), showed class 1 in 47.2% and class 2 in 43.4%, while late results, available in 37 lesions (31.1%), had class 1 and 2 in 48.6% and 37.8%, respectively. Six patients suffered a permanent neurological deficit at last follow-up (5.2%), with a good outcome in 5 patients and fair outcome in 1 patient. There was no mortality. There was no aneurysmal rupture during a mean clinical follow-up of 32.1 months. CONCLUSIONS: Endovascular treatment with GDC for unruptured aneurysms is relatively safe. Its role in the prevention of aneurysmal rupture remains to be determined, preferably by a randomized study.

Adult↗
PubMed2001

Cyclical regulation of GnRH gene expression in GT1-7 GnRH-secreting neurons by melatonin.

The pineal hormone melatonin plays an important role in the neuroendocrine control of reproductive physiology, but its effects on hypothalamic GnRH neurons are not yet known. We have found that GT1-7 GnRH-secreting neurons express membrane-bound G protein-coupled melatonin receptors, mt1 (Mel-1a) and MT2 (Mel-1b) as well as the orphan nuclear receptors ROR alpha and RZR beta. Melatonin (1 nM) significantly downregulates GnRH mRNA levels in a 24-h cyclical manner, an effect that is specifically inhibited by the melatonin receptor antagonist luzindole (10 microM). Repression of GnRH gene expression by melatonin appears to occur at the transcriptional level and can be mapped to the GnRH neuron-specific enhancer located within the 5' regulatory region of the GnRH gene. Using transient transfection of GT1-7 cells, downregulation of GnRH gene expression by melatonin was further localized to five specific regions within the GnRH enhancer including -1827/-1819, -1780/-1772, -1746/-1738, -1736/-1728, and -1697/-1689. Interestingly, the region located at -1736/-1728 includes sequences that correspond to two direct repeats of hexameric consensus binding sites for members of the ROR/RZR orphan nuclear receptor family. To begin to dissect the mechanisms involved in the 24-h cyclical regulation of GnRH transcription, we have found that melatonin (10 nM) induces rapid internalization of membrane-bound mt1 receptors through a beta-arrestin 1-mediated mechanism. These results provide the first evidence that melatonin may mediate its neuroendocrine control on reproductive physiology through direct actions on the GnRH neurons of the hypothalamus, both at the level of GnRH gene expression and through the regulation of G protein-coupled melatonin receptors.

Animals↗
PubMed2001

Role of a home care team in paediatric day-case tonsillectomy.

The feasibility of paediatric day-case tonsillectomy (PDCT) depends on its safety and acceptance by parents and patients. The purpose of our retrospective study of paediatric day-case tonsillectomy was to review the role of the home care team (HCT) in improving the safety and acceptance of the procedure. Between January 1997 and June 1999, 352 consecutive children underwent day-case tonsillectomy. The notes and HCT assessment sheets were reviewed for telephone calls made by HCT or by parents, home visit by HCT, types of complication and their outcome. The primary haemorrhage rate was 0.6 per cent. The effective day-case rate was 97 per cent. The unplanned admission rate was three per cent. The HCT visited about 25 per cent of patients at home. We conclude that paediatric day-case tonsillectomy is associated with high morbidity and considerable parental anxiety that can be dealt with by timely reassurance, support and advice by a dedicated HCT.

Adenoidectomy↗
PubMed2001

Extramedullary plasmacytoma of the submandibular gland.

Extramedullary plasmacytoma in the submandibular region is rare and on initial evaluation must be distinguished from multiple myeloma. The diagnostic evaluation includes appropriate radiological and pathological studies including immunohistochemistry. We report a case of extramedullary plasmacytoma in the submandibular gland. A review of the literature suggests that it has a good prognosis, if multiple myeloma is excluded. This patient was treated by surgical excision followed by radiotherapy.

Adult↗
PubMed2001

Base sequence-specific attack of stilbene estrogen metabolite(s) on the mitochondrial DNA: implications in the induction of instability in the mitochondrial genome in the kidney of Syrian hamsters.

We have demonstrated previously that diethylstilbestrol is metabolized to diethylstilbestrol reactive metabolites by mitochondrial enzymes in vitro. In vitro, these reactive intermediates bind to mitochondrial DNA. Here we have investigated the in vivo formation of diethylstilbestrol adducts with mitochondrial DNA, the nature of mitochondrial DNA-diethylstilbestrol adducts, and the influence of diethylstilbestrol adduction on in vitro replication of a mitochondrial gene. Diethylstilbestrol administration to male hamsters produced several adducts in mitochondrial DNA of both kidney and liver. The total relative adduct levels were 5- to 6-fold higher in mitochondrial DNA than in nuclear DNA. The chromatographic mobility of mitochondrial DNA adducts formed in vivo were similar to that of dGMP-DES quinone adducts formed in vitro. The identity of mitochondrial DNA adducts formed in vivo was further confirmed as dGMP-diethylstilbestrol quinone adducts by rechromatography and cochromatography. Using a DNA polymerase arrest assay we found that the DES quinone attack on a mitochondrial respiratory gene, i.e., the gene for subunit III of cytochrome c oxidase (COIII), was specific for guanine residues that were adjacent to cytosine residues. Long-term treatment with diethylstilbestrol produced tumors in the kidney, and the level of COIII transcripts was 5- to 10-fold higher in tumor samples than age-matched control kidneys. These findings suggest that i) mitochondrial DNA appears more susceptible to formation of diethylstilbestrol adducts than nuclear DNA, ii) the DNA adducts formed by DES were predominantly with guanines, iii) the adducted bases stopped DNA polymerase-mediated in vitro replication of the COIII gene, and iv) long-term exposure of hamsters to diethylstilbestrol elevated the expression of COIII mRNA. These results suggest that obstruction of replication of the mitochondrial genes by covalent modifications of the mitochondrial DNA by diethylstilbestrol may produce mitochondrial genomic instability in vivo and may provide an explanation for the DES-induced mitochondrial structural abnormality.

Animals↗
PubMed2001

The biphasic stimulation of proliferation of Leydig cells by estrogen exposure.

In this study, we have examined the influence of diethylstilbestrol (DES) and 17 beta-estradiol on the proliferation of TM3 Leydig cells, a normalized mouse cell line. Cells were treated with seven different concentrations (1 pg-1 microg/ml) of DES or 17 beta-estradiol, and cell growth was measured at 24-, 48-, and 72-h periods. DES treatment resulted in a significant (p<0.05) stimulation of cell proliferation. We observed two independent peaks of cell proliferation, one at 1 pg/ml DES (186.87%) and the other at 100 ng/ml DES (248.23%). Cytotoxicity was noted at all time periods with 1 microg/ml DES treatment. 17 beta-estradiol treatment resulted in a significant stimulation of cell proliferation (p<0.05) with a trend similar in response to that of DES treatment, as peak proliferation was noted with 1 pg/ml 17 beta-estradiol (125.27%) and 10 ng/ml 17 beta-estradiol (138.31%). Based on these data, it appears that DES is more mitogenic in these Leydig cells compared to 17 beta-estradiol. Furthermore, for the first time, we detected that both DES and 17 beta-estradiol were able to stimulate proliferation of Leydig cells in a biphasic fashion. Cell cycle kinetic analysis revealed that cell entry into the S-phase was higher in the DES treated cells compared to the controls, and doubling times of DES exposed cells were significantly reduced (p<0.05). Co-administration of tamoxifen at a concentration 1000-fold higher than either DES or 17 beta-estradiol resulted in complete inhibition of cell proliferation. Analysis of expression of ER alpha and ER beta by RT-PCR in untreated Leydig cells, as well as Leydig cells exposed to 1 pg/ml DES, revealed that the transcripts of ER alpha and ER beta were not detectable even after 40 cycles of amplification. A 100-ng/ml dose of DES induced ER alpha expression by 20-fold. These data suggest that estrogen exposure-mediated increases in cell proliferation, coupled with the decrease in cell cycle time, may allow greater accumulation of DNA damage to occur in the testicular target cells compared to untreated cells under normal cell cycle control. In addition, an unidentified estrogen receptor may be responsible for the mitogenic activity of estrogens at low levels.

Animals↗
PubMed2001

Distal superior cerebellar artery aneurysm presenting with cerebellar infarction: report of two cases.

SUMMARY: We report two cases of aneurysm of the distal branches of the superior cerebellar artery presenting with cerebellar infarction. In both cases, the diagnosis required close correlation of the findings from different imaging techniques, as catheter angiography failed to opacify the lesions. In one patient endovascular parent vessel occlusion was performed, whereas in the second patient the aneurysm thrombosed spontaneously. We describe the clinical and radiologic presentation of these aneurysms and discuss their pathogenesis, diagnosis, and treatment.

Adult↗
PubMed2001

Occupational exposure to endocrine-disrupting pesticides and the potential for developing hormonal cancers.

It is suspected that endocrine-disrupting pesticides are involved in the development of several cancer and noncancer health risks in humans and wildlife. A large number of pesticides show endocrine-disrupting activities. The potential for human and animal exposure to such pesticides is very high. Farmers, as a group, may be particularly at risk, because they are subject to higher-than-average levels of exposure to pesticides over longer-than-average periods. Recent studies have shown that the incidence of hormone-related organ cancers, or hormonal cancers, is elevated among farmers. Exposure to endocrine-disrupting pesticides, particularly to DDT and phenoxy herbicides, is suspected of involvement in some of these hormonal cancers. There is a clear need for a refined epidemiological study that focuses on specific pesticides, accurately assesses exposure, and then examines any association between pesticides and hormonal cancers among farmers.

Agriculture↗
PubMed2000

Cryothermal ablation of the slow pathway for the elimination of atrioventricular nodal reentrant tachycardia.

BACKGROUND: We report the first successful slow pathway ablation using a novel catheter-based cryothermal technology for the elimination of atrioventricular nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: Eighteen patients with typical AVNRT underwent cryoablation. Reversible loss of slow pathway (SP) conduction during cryothermy (ice mapping) was demonstrated in 11 of 12 patients. Because of time constraints, only 2 sites were ice mapped in 1 patient. Seventeen of 18 patients had successful cryoablation of the SP. One patient had successful ice mapping of the SP, but inability to cool beyond -38 degrees C prevented successful cryoablation. A single radiofrequency lesion at this site eliminated SP conduction. No patient has had recurrent AVNRT over 4.9+/-1.7 months of follow-up. During cryoablation, accelerated junctional tachycardia was not seen and was therefore not available to guide lesion delivery. Adherence of the catheter tip during cryothermy (cryoadherence) allowed atrial pacing to test for SP conduction. Cryoablation in the anterior septum produced inadvertent transient PR prolongation consistent with loss of fast pathway conduction in 1 patient and transient (6.5 seconds) 2:1 AV block in another. On rewarming, the PR interval returned to normal, and the AV nodal effective refractory period was unchanged in both. Accelerated junctional tachycardia was seen on rewarming in both but not during cryothermy. CONCLUSIONS: Cryothermal ablation of the SP was achieved in patients with this novel technique. Successful ice mapping of both the SP and fast pathway was demonstrated. The ability to test the functionality of specific ablation sites before production of a permanent lesion may eliminate inadvertent AV block.

Adult↗
PubMed2000

Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation.

Patients with atrial fibrillation (AF) report impaired health-related quality of life (QOL). Differences between men and women with AF have not been described and personality attributes such as somatization (tendency to amplify benign bodily sensations) may mediate potential gender differences in QOL. Patients with AF (n = 264, 59% men) who participated in the Canadian Trial of Atrial Fibrillation (n = 403) completed validated QOL questionnaires at baseline, 3 months, and 12 months after antiarrhythmic drug treatment. Women were significantly older than men and a greater proportion had hypertension, but other cardiac variables did not differ between women and men. At baseline, after controlling for significant clinical and demographic factors, women reported worse physical health (p = 0.002) and functional capacity (p < 0.001), but not mental health or general well-being. Women also had more frequent and severe cardiac symptoms than men (both p < 0.001). Physical health improved significantly from baseline to 3 months for women (p = 0.002), but not for men (p = 0.066). Conversely, mental health improved for men (p = 0.007), but not for women. Cardiac symptom frequency and severity improved over time for women and men (all p < 0.001). Tendency to somatize predicted poor QOL, and women had higher scores than men (p = 0.023). However, after controlling for somatization, women still had worse physical function, functional capacity, and symptom burden than men. Independent of cardiac disease severity and age, women with AF had significantly more impaired QOL than men, specifically on domains related to physical rather than emotional functioning. Personality attributes may have a role in influencing QOL outcomes.

Age Factors↗
PubMed2000

Molecular differentiation of Bifidobacterium species with amplified ribosomal DNA restriction analysis and alignment of short regions of the ldh gene.

The differentiation of Bifidobacterium species was performed with specific primers using the PCR technique, the amplified ribosomal DNA restriction analysis (ARDRA) technique based on reports on the sequence of the 16S rRNA gene and speciation based on a short region of the ldh gene. Four specific primer sets were developed for each of the Bifidobacterium species, B. animalis, B. infantis and B. longum. The use of the ARDRA method made it possible to discriminate between B. infantis, B. longum and B. animalis with the combination of BamHI, TaqI and Sau3AI restriction enzymes. The ldh gene sequences of 309-312 bp were determined for 19 Bifidobacterium strains. Alignment of these short regions of the ldh gene confirmed that it is possible to distinguish between B. longum and B. infantis but not between B. lactis and B. animalis.

Amino Acid Sequence↗
PubMed2000

Learning and the theory of games.

The potential for Game Theory in the Practice of Psychiatry is outlined. The deficiences of current Learning Theory in explaining observed phenomena are highlighted and the potential for a Game Theory analysis highlighted. The extension to "Game Learning" is of broad application.

Game Theory↗
PubMed2000

Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators.

BACKGROUND: The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. METHODS: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation. RESULTS: Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06). CONCLUSIONS: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.

Aged↗