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M O'Brien

Publications and source records attributed to M O'Brien.

At least 73 records · Page 4Linked to original sources
PubMed2000

Analysis of the role of HLA-G in preeclampsia.

Preeclampsia (PE) is a multisystem disorder of human pregnancy, occurring in 5%-10% of all population births and represents the leading cause of both fetal and maternal morbidity and mortality in pregnancy. Although the disorder only becomes clinically apparent late in pregnancy, the underlying pathology indicates that invasion of fetal trophoblasts into maternal spiral arteries during early pregnancy is shallow or absent in PE. A large number of epidemiologic studies have been carried out and they demonstrate that the disorder is highly heritable and occurs with a high incidence in all populations. Studies have shown that PE is largely under genetic control, but the mode of its inheritance remains unclear. Genetic studies have been carried out using both large scale linkage analysis and candidate gene approaches; however, the genetic mechanisms underlying the disorder have yet to be determined. We focus on the potential role of HLA-G, a nonclassical class I HLA located on chromosome 6, which appears to be a key component in trophoblast invasion. We examine the hypothesis that HLA-G may have a key role in both genetic susceptibility to, and pathogenesis of, PE.

Female↗
PubMed2000

The X1 box of HLA-G promoter is a target site for RFX and Sp1 factors.

HLA-G gene regulation was investigated with regards to homologies among the pathways regulating both classical MHC class I and MHC class II gene expression. They include four conserved cis-acting regulatory elements located in the proximal promoter region referred to as the W/S/Z box, the X box that is comprised of the X1 and X2 halves, and the Y box with an inverted CCAAT site. The X1 box is the binding site for the ubiquitous RFX complex consisting of three subunits; the X2 box is bound by the X2BP/ATF/CREB family factors. The basic S-X-Y regulatory module interacts with CIITA, which is expressed constitutively in APCs, but may be inducible in others cell types by IFN-gamma. Within HLA-G gene promoter the only conserved motifs are S and X1 boxes. We thus investigated the binding capacity of the HLA-G X box in comparison to that of HLA-DRA and HLA-E. We demonstrate that X2 box mutations in HLA-G promoter affect the binding of ATF/CREB family factors and may privilege the X2 box to access by other shared factors. The X1 box is the target for RFX complex and an additional factor we identified as Sp1. We propose that the X region in the HLA-G gene promoter might participate to the combination of factors which play a role in HLA-G gene activation.

Cell Extracts↗
PubMed2000

Mild renal failure is associated with adverse outcome after cardiac valve surgery.

The present study was performed to ascertain whether the presence of mild renal failure (defined as a serum creatinine concentration of 1. 5 to 3.0 mg/dL) is an independent risk factor for adverse outcome after cardiac valve surgery. An extensive set of preoperative and postoperative data was collected in 834 prospectively evaluated patients undergoing cardiac valve surgery at 14 Veterans Affairs Medical Centers. Univariate and multivariable analyses were performed to determine whether an independent association of mild renal dysfunction with adverse outcomes was present. Patients with mild renal failure had significantly greater 30-day mortality rates (P = 0.001; 16% versus 6%) and frequency of postoperative bleeding (P = 0.023; 16% versus 8%), respiratory complications (P = 0.02, 29% versus 16%), and cardiac complications (P = 0.002; 18% versus 7%) than patients with normal renal function (serum creatinine <1.5 mg/dL) when controlling for multiple other variables. The presence of a serum creatinine concentration of 1.5 to 3.0 mg/dL is significantly and independently associated with adverse outcomes after cardiac valve surgery.

Age Factors↗
PubMed2000

Parents' attitudes about children: associations with parental life histories and child-rearing quality.

This study examined relations among parents' perceptions of their childhood, attitudes about life, expectations for child behavior, attitudes about their child's behavior, and the child-rearing environment parents provide. Eighty mothers of 1- to 5-year-olds were interviewed about perceptions of receiving harsh parenting as children, current attitudes about life, developmental expectations, and views of intentionality and severity of their child's misbehavior. The home environment was measured using the Home Observation for Measurement of the Environment (R. H. Bradley & B. Caldwell, 1979) scale. Mothers who reported harsh parenting as children, negative attitudes about life, and unrealistic developmental expectations had negative attitudes about their own child. These attitudes were related to provision of lower quality home environments. Results support a constructivist approach to understanding parental social cognitions and behavior.

Attitude↗
PubMed2000

Genetic analysis of insulin-like growth factor II and HLA-G in pre-eclampsia.

Pre-eclampsia (PE) is uniquely a disease of pregnancy and is the major cause of foetal and maternal morbidity and mortality. Epidemiological studies show that PE is highly heritable, with a high incidence in all populations. The underlying pathology indicates that absent or shallow invasion of foetal trophoblasts into maternal arteries is a feature of true PE. The objective of this study was to determine the genetic factors influencing PE. A large number of mother-father-baby trios were collected in which the first pregnancy was complicated by severe PE. After careful examination of the epidemiology and pathology of the disease, two plausible candidate genes, namely insulin-like growth factor II (IGF-II) and HLA-G, were analysed for association with PE. No association was found between a commonly occurring polymorphism in IGF-II and PE. Three polymorphisms in HLA-G were analysed in the sample cohorts. No association was found between three polymorphisms in HLA-G and PE. However, the frequency of the HLA-G insertion/deletion polymorphism in exon 8 deviated significantly from Hardy-Weinberg expectations in PE off-spring, reflecting an excess of heterozygotes for these polymorphisms in PE offspring. The significance of this deviation is not clear and further genetic analysis will be necessary to confirm this finding and to explore further the candidacy of HLA-G in PE.

Adult↗
PubMed2000

Trends in treated opiate misuse in Dublin: the emergence of chasing the dragon.

AIMS: To examine trends in treated opiate misuse and identify factors associated with route of heroin use. DESIGN: Cross-sectional survey. SETTING: Services providing addiction treatment in Dublin. PARTICIPANTS: Individuals making their first ever contact seeking treatment for current opiate misuse, between January 1991 and December 1996. MEASUREMENTS: Data on socio-demographics and current drug use. FINDINGS: The study population was 3981. Over the 6-year period, there was a 330% increase in the number of new attenders. The proportion of females increased. The mean age of first opiate use declined and users began presenting earlier in their opiate-using careers, causing a decline in the age profile of new attenders. Heroin users were more likely to smoke (chase) rather than inject after 1994 (odds ratio 3.3, 95% confidence interval 2.4-4.5). Apart from year of presentation, the other significant independent predictors of chasing as the preferred route of heroin use were being in employment, shorter history of use, less frequent use, younger age, longer period in education and absence of polydrug use. Gender did not independently predict route of use. CONCLUSIONS: Ireland has joined the growing number of European countries witnessing a movement towards heroin chasing. This has coincided with a surge in the number of people entering treatment. We are concerned that the greater acceptability of this route of use may be drawing increased numbers of individuals into heroin use.

Adult↗
PubMed2000

Have lessons been learned from the UK bovine spongiform encephalopathy (BSE) epidemic?

History is full of examples of public health, commerce and politics in conflict. In recent years attempts to protect UK egg producers, after the discovery of Salmonella enteritidis (phage type 4) in hens' eggs, strained previously good working relationships between medical and veterinary epidemiologists and ended the political career of a government minister who spoke out in defence of the public health. Against the background lessons of earlier high profile public health problems in the UK conflict should have been avoided when bovine spongiform encephalopathy (BSE) started. It might have been expected that its significance for human health could have been recognized and researched earlier. Public announcements about it could have been timely and clear. Unfortunately this was not the case and it looks as though similar mistakes are going to be repeated over genetically modified foods.

Animal Husbandry↗
PubMed2000

NK-1 antagonist reduces colonic inflammation and oxidative stress in dextran sulfate-induced colitis in rats.

Although substance P (SP) has been implicated as a mediator of neurogenic inflammation in the small intestine, little information is available regarding the role of SP in the pathogenesis of chronic ulcerative colitis. In this study, our aim was to investigate whether the intraperitoneal administration of a nonpeptide neurokinin-1 (NK-1) antagonist, CP-96345, which antagonizes the binding of SP to its NK-1 receptor, results in the attenuation of colonic inflammation induced in rats by 5% dextran sodium sulfate (DSS) in drinking water for 10 days compared with an inactive enantiomer, CP-96344. Disease activity was assessed daily for 10 days, after which colonic tissue damage was scored and myeloperoxidase activity and colon and urinary 8-isoprostanes were measured. Animals receiving DSS exhibited marked physical signs of colitis by day 5 compared with controls. Chronic administration of the NK-1 antagonist significantly reduced the disease activity index, mucosal myeloperoxidase activity, colonic tissue damage score, and mucosal and urinary levels of 8-isoprostanes compared with inactive enantiomer- or vehicle-injected (saline) animals receiving DSS alone. These data indicate that the administration of an NK-1 antagonist can attenuate colonic inflammation and oxidative stress and suggest a novel therapeutic approach in the treatment of chronic ulcerative colitis.

Animals↗
PubMed2000

Ticlopidine plus aspirin for coronary thrombosis in Kawasaki disease.

Selective inhibitors of the adenosine 5'-diphosphate pathway of platelet activation have been used rarely in children in the United States. We report the successful use of ticlopidine, together with aspirin, in a 7-month-old infant with Kawasaki disease complicated by a thrombus in a giant coronary aneurysm that failed to resolve with thrombolytic therapy. Kawasaki disease, coronary aneurysms, antithrombotic therapy, ticlopidine, children.

Aspirin↗
PubMed2000

The safety of intravenous iron dextran (Dexferrum) during hemodialysis in patients with end stage renal disease.

The National Kidney Foundation recently published guidelines stating that regular use of intravenous iron therapy will prevent iron deficiency and promote better erythropoiesis than oral iron therapy in patients with end stage renal disease (ESRD) who are undergoing hemodialysis. Although intravenous iron dextran has been shown to be clinically effective in maintaining iron stores in such patients, some clinicians are concerned about the incidence of adverse events associated with this mode of iron supplementation. We conducted a retrospective review of adverse events associated with the use of Dexferrum (American Regent Laboratories, Inc., Shirley, NY) in ESRD patients at an outpatient dialysis clinic. During the 6-month study period, only 1 patient out of 62 (1.6%) experienced adverse events (hypotension, chest pain) related to treatment with Dexferrum. No patients developed anaphylactoid reactions.

Adolescent↗
PubMed2000

The influence of coordinate overexpression of glutathione phase II detoxification gene products on drug resistance.

Glutathione (GSH), glutathione S-transferases (GSTs), and the multidrug resistance-associated protein 1 (MRP1) have been independently studied for their contributions to drug resistance. Single cDNA transfection experiments have provided inconsistent and disparate conclusions with respect to the importance of GSH and GST in conferring a resistant phenotype. Because these three proteins can act as a concerted coordinated pathway, we reasoned that equivalent increases may be required for enhanced resistance to be expressed. We have assembled these proteins together, or in various combinations, to determine whether they show cooperativity in determining drug response. Increased expression through single cDNA transfection of GSTpi, gamma-glutamylcysteine synthetase (gamma-GCS) (regulatory plus catalytic subunits), or MRP1 enhanced resistance to a number of anticancer drugs. Cotransfection of GSTpi and GCS, gave higher resistance to doxorubicin, etoposide, and vincristine than with either alone. Resistance toward chlorambucil and ethacrynic acid was similar in cells overexpressing either component or overexpressing GST alone. Coexpression of GSTpi with MRP1 conferred significant resistance above that seen for MRP1 alone to chlorambucil, etoposide, ethacrynic acid, and vincristine. The combination of GCS and MRP1 did not afford additional resistance above MRP1 alone. When all three were transfected, significantly higher levels of resistance were found for doxorubicin and etoposide. These results support the concept that coordinate enhancement of focal thiol elements of detoxification pathways provides a more efficient protective phenotype than do single components alone.

3T3 Cells↗
PubMed2000

Influence of HLA matching and associated factors on aortic valve homograft function.

BACKGROUND AND AIM OF THE STUDY: Evidence suggests that the implanted aortic valve homograft suffers eventual loss of function due to early donor-specific antibody and T cell-mediated responses to human leukocyte antigens (HLA). The association between rejection/dysfunction and donor/recipient HLA mismatch for vascularized organ homografts has not been revealed for aortic valve homografts. An aortic valve homograft recipient cohort was studied to determine whether HLA mismatch and associated factors predicted homograft dysfunction. METHODS: Both donor and recipient HLA type was obtained for 162 recipients of cryopreserved aortic valve homografts between 1986 and 1998. Structural deterioration of the homograft was defined by echocardiography as at least moderate aortic stenosis or regurgitation. Patients' records were searched for postoperative fever, ABO blood type disparity, and other associated factors. HLA class 1 (A and B antigens) were typed serologically, and HLA class 2 (DR antigens) by molecular genotyping. Associations were analyzed using chi-square tests and Kaplan-Meier curves of freedom from structural deterioration in all patients, and in those with > or =5 years of follow up. Cox regression was used to determine independent predictors of structural deterioration. RESULTS: Class 2 antigen mismatch had a significant association (p = 0.04) with decrease in cryopreserved aortic valve homograft freedom from structural deterioration in patients with long-term follow up (> or =5 years). In addition, there was an important difference in frequency of postoperative fever in recipients with two DR mismatches (31.2%), and in those with no or one DR mismatch (16.9%; p = 0.051). Significant associations were not found between homograft dysfunction and HLA mismatch at the class-1 loci. Young age at operation and short time (<4 h) between homograft procurement and cryopreservation were associated with an increase in structural deterioration. CONCLUSION: The association between aortic valve homograft dysfunction and HLA DR mismatch suggests that elements of the anti-donor immune response penetrate and damage the homograft. A similar link to postoperative fever indicates that immune stimulation may be an early event. Further investigation will reveal the exact pathways by which this occurs and by which therapy (immunosuppression of the recipient, genetic engineering of the donor graft, or other techniques) this recipient anti-donor response can be modified.

ABO Blood-Group System↗
PubMed1999

Inhibition of the broad spectrum nonmetallocarbapenamase of class A (NMC-A) beta-lactamase from Enterobacter cloacae by monocyclic beta-lactams.

beta-Lactamases hydrolyze beta-lactam antibiotics, a reaction that destroys their antibacterial activity. These enzymes, of which four classes are known, are the primary cause of resistance to beta-lactam antibiotics. The class A beta-lactamases form the largest group. A novel class A beta-lactamase, named the nonmetallocarbapenamase of class A (NMC-A) beta-lactamase, has been discovered recently that has a broad substrate profile that included carbapenem antibiotics. This is a serious development, since carbapenems have been relatively immune to the action of these resistance enzymes. Inhibitors for this enzyme are sought. We describe herein that a type of monobactam molecule of our design inactivates the NMC-A beta-lactamase rapidly, efficiently, and irreversibly. The mechanism of inactivation was investigated by solving the x-ray structure of the inhibited NMC-A enzyme to 1.95 A resolution. The structure shed light on the nature of the fragmentation of the inhibitor on enzyme acylation and indicated that there are two acyl-enzyme species that account for enzyme inhibition. Each of these inhibited enzyme species is trapped in a distinct local energy minimum that does not predispose the inhibitor species for deacylation, accounting for the irreversible mode of enzyme inhibition. Molecular dynamics simulations provided evidence in favor of a dynamic motion for the acyl-enzyme species, which samples a considerable conformational space prior to the entrapment of the two stable acyl-enzyme species in the local energy minima. A discussion of the likelihood of such dynamic motion for turnover of substrates during the normal catalytic processes of the enzyme is presented.

Anti-Bacterial Agents↗
PubMed1999

Health-related quality of life as a predictor of mortality following coronary artery bypass graft surgery. Participants of the Department of Veterans Affairs Cooperative Study Group on Processes, Structures, and Outcomes of Care in Cardiac Surgery.

CONTEXT: Health-related quality of life has not been evaluated as a predictor of mortality following coronary artery bypass graft (CABG) surgery. Evaluation of health status as a mortality predictor may be useful for preoperative risk stratification. OBJECTIVE: To determine whether the Physical and Mental Component Summary scores from the preoperative Short-Form 36 (SF-36) health status survey predict mortality following CABG surgery after adjustment for known clinical risk variables. DESIGN: Prospective cohort study conducted between September 1992 and December 1996. SETTING: Fourteen Veterans Affairs hospitals. PATIENTS: Of the 3956 patients undergoing CABG surgery only and who were enrolled in the Processes, Structures, and Outcomes of Care in Cardiac Surgery study, the 2480 who completed a preoperative SF-36. MAIN OUTCOME MEASURE: All-cause mortality within 180 days after surgery. RESULTS: A total of 117 deaths (4.7%) occurred within 180 days of CABG surgery. The Physical Component Summary of the preoperative SF-36 was a statistically significant risk factor for 6-month mortality after adjustment for known clinical risk factors for mortality following CABG surgery. In multivariate analysis, a 10-point lower SF-36 Physical Component Summary score had an odds ratio (OR) of 1.39 (95% confidence interval [CI], 1.11-1.77; P=.006) for predicting mortality. The SF-36 Mental Component Summary score was not associated with 6-month mortality in multivariate analyses (OR, 1.09; 95% CI, 0.92-1.29; P=.31). CONCLUSIONS: The Physical Component Summary score from the preoperative SF-36 is an independent risk factor for mortality following CABG surgery. The baseline Mental Component Summary score does not appear to be predictive of mortality. Preoperative patient self-report of the physical component of health status may be helpful for risk stratification and clinical decision making for patients undergoing CABG surgery.

Coronary Artery Bypass↗
PubMed1999

Digital fluoroscopic assessment of the scapulohumeral rhythm.

Previous studies have shown that abnormal rotation of the scapula is associated with shoulder pathology. Among the methods which have been proposed, planar x-ray measurements are probably the only methods, which enable clinicians to assess accurately and objectively the scapulohumeral function in vivo. The aim of this study was to develop a method for the assessment of scapulohumeral kinematics using digital fluoroscopy. Anteroposterior images of the right glenohumeral joint were taken, in thirty-four healthy males, with the arm at rest, 30 degrees, 60 degrees, 90 degrees, 120 degrees, 150 degrees and maximum abduction, in the scapular plane. High inter- and intra-examiner reliability was observed regarding the arm and scapular angle measurements (ICC = 0.92-0.99). The positioning of the arm at the proposed angles was also highly accurate (< 2.3 degrees misplacement) and reproducible (CV% < 5.3%). The mean radiation dose was 0.075 mSv (+/- 0.027 mSv). At the resting position the scapula was in slight downward rotation (-2.4 degrees +/- 4.3 degrees) and the arm in slight abduction (1.5 degrees +/- 6.6 degrees). The mean maximum scapular rotation and the mean maximum arm abduction was 61.4 degrees (+/- 5.2 degrees) and 162.4 degrees (+/- 6.6 degrees) respectively. A curvilinear relationship was found between the arm angle (AA) and the scapular angle (SA) (p < 0.0001). The AA:SA ratio for the entire range of abduction was 2.5:1. The greatest contribution of the scapula (1.7:1) achieved at 30 degrees-60 degrees of arm. The high accuracy and reliability of our method and the low radiation recordings suggests that digital fluoroscopy may be considered for further investigation of the scapulohumeral kinematics in both healthy and pathological shoulders.

Adolescent↗
PubMed1999

Multicenter study of stentless valve replacement in the small aortic root.

OBJECTIVE: A clinical study was conducted to evaluate the results of stentless porcine valves in patients with a small aortic root (19- and 21-mm aortic anulus). METHODS: Of 567 patients, from 4 surgical institutions, 171 patients (30.1%) had a small aortic root, comprising 163 cases with calcified aortic stenosis and 8 cases with predominant valvular insufficiency. Sixty patients had associated mitral or coronary lesions. Mean age was 72 +/- 4.2 years. Forty-seven patients with a small aortic root had a 19-mm anulus, and 124 patients had a 21-mm anulus. The body surface area was, respectively, 1.55 +/- 0.2 m2 and 1.78 +/- 0.45 m2. Hemodynamic evaluation of the stentless valve comprised serial measures of mean gradients, effective orifice area, and left ventricular mass reduction. Complication rates for secondary events were evaluated over a 6-year period. RESULTS: The hospital mortality rate was 3.5%. The mean gradients after the first year were 9 +/- 2 mm Hg and 6 +/- 1.7 mm Hg in patients with a 19-mm and a 21-mm anulus, respectively. Effective orifice area was 1.45 +/- 0.3 cm2 and 1.72 +/- 0.4 cm2. Gradients and surfaces remained stable throughout the study period. Aortic regurgitation was zero to trace. Left ventricular mass at discharge and at 1 year were, respectively, 296 +/- 127 g and 215 +/- 102 g for patients with a 19-mm anulus and 281 +/- 75 g and 236 +/- 15 g for patients with a 21-mm anulus. CONCLUSIONS: Stentless valves are a suitable device for elderly patients with small aortic roots, which leave only mild residual obstruction.

Aged↗
PubMed1999

Primary renal tumours in cats: 19 cases (1992-1998).

A search from databases of four veterinary colleges and one private referral practice between January 1992 and April 1998 provided 20 cases diagnosed with primary renal neoplasia. Review of these cases revealed 19 primary renal tumours, excluding lymphoma. Of the 20 histologically reviewed cases, the diagnosis was amended in eight. There were 13 renal carcinomas (11 tubular and two tubulopapillary), three transitional cell carcinomas, one malignant nephroblastoma, one haemangiosarcoma and one adenoma. The haemangiosarcoma is, to our knowledge, the first reported case of this tumour type as a primary renal tumour in the cat. Most cats were presented for non-specific clinical signs such as anorexia and weight loss. One cat presented with tumour-associated polycythaemia which has not, to our knowledge, been reported previously. The metastatic rate for cats with complete staging was 64%, and 100% for transitional cell carcinomas.

Adenoma↗