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Biomedical subjects

J E O'Brien

Publications and source records attributed to J E O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1997

Origin of extracellular matrix synthesis during coronary repair.

BACKGROUND: Coronary injury triggers differentiation of activated adventitial fibroblasts to myofibroblasts, which may contribute to neointimal formation and vascular remodeling. Accordingly, the purpose of this study was to examine the cellular origin of the enhanced synthesis of extracellular matrix proteins during coronary repair. METHODS AND RESULTS: The time course and localization of collagen and elastin expression were examined by in situ hybridization and immunohistochemistry in porcine coronary arteries after balloon-induced injury. Procollagen-alpha 1(I) transcripts and intracellular type I procollagen protein increased in the adventitia within 2 days after injury. This was followed by a sustained synthesis of type I procollagen in neointima beginning at 7 days and the extracellular accumulation of type I collagen in both layers. The origin of synthetic cells was further examined by colocalization of type I procollagen and bromodeoxyuridine labeling to activated adventitial cells, which translocated to neointima. Neointimal cells exhibited sustained synthetic activity manifested by the presence of type I procollagen and elastin at 3 months after injury. In contrast, the media showed only minor changes in the synthesis of collagen or elastin throughout coronary repair. CONCLUSIONS: Activated adventitial fibroblasts are endowed with synthetic capabilities after coronary injury. They express type I procollagen, with some of them translocating to the intima, where they continue to synthesize procollagen. The accumulation of type I collagen is evident in the adventitia and neointima, whereas elastin accumulates mainly in neointima. These findings support the involvement of adventitial fibroblasts in coronary repair and remodeling after endoluminal injury.

Angioplasty, Balloon↗
PubMed1997

Comparison of teaching the basic electrocardiographic concept of frontal plane QRS axis using the classical versus the orderly electrocardiogram limb lead displays.

This study compares the effectiveness of teaching the calculation of frontal plane QRS axis with the use of the classical versus the orderly electrocardiographic limb lead display. Eighty-three students from two environments were randomized into two groups and were taught to determine frontal plane axis with one of the methods. The accuracy and time to determine the axis were tested on 10 electrocardiograms. In the United States the group using the classical display achieved 4.2 (+/-2.7) correct answers, whereas those using the orderly method achieved 6.8 (+/-3.0) (p = 0.0006). The classical group used 9.2 (+/-2.8) minutes to complete the test, whereas the orderly group needed 7.2 (+/-2.0) minutes (p = 0.015). The results achieved in Sweden were similar. The use of the orderly electrocardiographic limb lead display results in greater diagnostic accuracy in less time than the classical display when determining the frontal plane QRS axis.

Adult↗
PubMed1997

Wound healing around and within saphenous vein bypass grafts.

BACKGROUND: Myofibroblasts are a prominent cell type in wound healing. The goal of this study was to examine the extent to which myofibroblasts contribute to structural changes in saphenous vein bypass grafts. METHODS AND RESULTS: Control veins and reversed saphenous vein bypass conduits of porcine carotid arteries were examined 2 to 4, 7 to 14, and 30 to 90 days after surgery with immunohistochemical markers of cellular proliferation (proliferating cell nuclear antigen), cytoskeletal protein production (alpha-smooth muscle actin and desmin), and histochemistry (Verhoeff's stain). Control veins demonstrated an extremely low level of cellular proliferation and no evidence of myofibroblasts in the adventitia, media, or intima. After bypass grafting, cellular proliferation was followed by myofibroblast formation, which occurred in the perivascular area and within the media. This was evidenced by a dense, but transient, expression of alpha-smooth muscle actin and a variable expression of desmin at 1 to 2 weeks, and with a significant increase in collagenous tissue by 1 to 3 months. Major cytoskeletal protein changes also occurred in the intima, with the appearance of alpha-smooth muscle actin positive cells at 7 to 14 days. alpha-Smooth muscle actin was still present in the neointima at 1 to 3 months, which is compatible with a persistent myofibroblast formation. CONCLUSION: Myofibroblast formation occurs around and within saphenous veins after bypass grafting. This phenomenon is associated with significant remodeling of the vein grafts. The histologic changes are strikingly similar to events that occur during wound healing and may have implications for the development of neointimal hyperplasia and late vein graft disease.

Animals↗
PubMed1997

Race-ethnicity-specific variation in multiple-marker biochemical screening: alpha-fetoprotein, hCG, and estriol.

OBJECTIVE: To identify any race-ethnicity-specific differences in serum alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3) levels in women between 14 and 21 weeks' gestation. METHODS: Data from the 3-year period 1992-1994 were analyzed from 208,257 women who had AFP screening, of whom 155,142 also had hCG and 62,121 also had E3 screened, between 14 and 21 weeks' gestation. Subjects were categorized into four groups: white, black, Asian, and Hispanic. RESULTS: There was a consistent pattern of analyte differences across gestational ages. Levels for AFP were generally higher in Asian and black women than in Hispanic and white women (median AFP at 16 weeks-31.2, 30.9, 27.4, 27.3, respectively), and levels of hCG and E3 were highest in Asians (hCG at 16 weeks-34.7, 30.3, 28.2, 26.8, respectively). Weight correction for AFP, hCG, and E3 levels did not compensate for the ethnic differences. CONCLUSIONS: Because hCG and E3 demonstrate the same general pattern of differences as AFP among ethnic groups, averaging values for all ethnic groups tends inappropriately to lower calculated Down syndrome risks for black and Asian women. Additionally, the slopes of the curves are not parallel, such that separate data bases are preferable to multiplicative correction factors. Separate data bases should be used in laboratories with volume sufficient to permit the establishment of race-ethnicity-specific regressions. Use of separate data bases should result in more accurate screening.

Chorionic Gonadotropin↗
PubMed1996

Relation between estrogen replacement therapy and restenosis after percutaneous coronary interventions.

OBJECTIVES: We attempted to determine the relation between estrogen replacement therapy and the rate of restenosis after coronary angioplasty and atherectomy. BACKGROUND: Although estrogen replacement therapy in women has been associated with a reduction in cardiovascular events and improvement in endothelial function, no study has examined whether estrogen reduces restenosis rates after percutaneous coronary interventions. METHODS: A total of 204 women enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial with angiographic follow-up were contacted, and their menopausal and estrogen replacement status was determined. Late loss in minimal lumen diameter, late loss index, minimal lumen diameter, rate of restenosis > 50% and actual percent of stenosis were compared in estrogen users and nonusers by quantitative coronary angiography at 6-month follow-up. RESULTS: Late loss in minimal lumen diameter was significantly less in women using estrogen than in nonusers (-0.13 vs. -0.46 mm, p = 0.01). A regression analysis of the determinants of late loss in minimal lumen diameter revealed that estrogen use was the single most important predictor of subsequent late loss (F = 13.38, p = 0.0006). Formal testing revealed a highly significant interaction between the use of estrogen and intervention (angioplasty or atherectomy). Women undergoing atherectomy who received estrogen had a significantly lower late loss index (0.06 vs. -0.63, p = 0.002), less late loss (0.06 vs. -0.61 mm, p = 0.0006), larger minimal lumen diameter (p = 0.044) and lower restenosis rates (p = 0.038 for > 50% stenosis) than those not using estrogen. In contrast, estrogen had minimal effects on restenosis end points after angioplasty. CONCLUSIONS: This study demonstrates the potential for estrogen replacement therapy to reduce angiographic measures of restenosis in postmenopausal women after coronary intervention, particularly in those undergoing atherectomy.

Aged↗
PubMed1996

Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries.

BACKGROUND: The adventitia undergoes remodeling changes after a deep medial coronary injury. Because this process is associated with the formation of adventitial myofibroblasts, which resemble medial smooth muscle (SM) cells, we have examined myofibroblast involvement in the development of neointima. METHODS AND RESULTS: In a porcine model, severe endoluminal coronary injury resulted in fibroblast proliferation and adventitial remodeling. Significant adventitial responses were associated with increased neointimal formation (P < .01). To examine the contribution of adventitial cells to the development of neointima, proliferating cells were labeled with bromodeoxyuridine (BrdU) at 12 and 24 hours after injury, and their subsequent localization was determined by immunohistochemistry (n = 24). At 2 to 3 days after severe injury, the adventitia contained numerous BrdU-labeled cells (37 +/- 4%), whereas the media demonstrated infrequent labeled cells (4 +/- 1%). Adventitial cells lacked alpha-SM actin and desmin, which distinguished them from medial SM cells. At 7 to 8 days, some labeled cells acquired characteristics of myofibroblasts expressing alpha-SM actin. They were found to translocate to the gap between dissected media and contributed to the formation of neointima (76 +/- 19%). At 18 to 35 days, labeled cells were abundant in the neointima (86 +/- 5%). They showed uniform immunostaining for alpha-SM actin but not for desmin, thereby differing from medial SM cells and blood-borne cells. CONCLUSIONS: This study demonstrates translocation of adventitial fibroblasts to neointima, their phenotypic modulation to myofibroblasts, and distinct characteristics of myofibroblasts within neointima after severe endoluminal coronary injury. These findings suggest the significance of vascular fibroblasts in the process of arterial repair.

Animals↗
PubMed1996

Transforming growth factor-beta 1 expression and myofibroblast formation during arterial repair.

Transforming growth factor-beta 1 (TGF-beta 1) plays a central role in tissue repair owing to its modulating effects on cell growth and the synthesis of extracellular matrix. We have previously shown that adventitial fibroblasts differentiate to myofibroblasts after endoluminal injury, thereby contributing to arterial remodeling. Since TGF-beta 1 exerts several biologic actions attributed to myofibroblasts, we examined its role in myofibroblast formation in a porcine model of balloon overstretch coronary artery injury. TGF-beta 1 transcripts were induced in numerous adventitial cells 2 days after injury (47 +/- 10%, P < .001 versus control). These cells displayed no smooth muscle (SM) markers, i.e., alpha-SM actin or desmin, which suggested their fibroblastic origin. This was further corroborated by the rare presence of macrophages in the injured adventitia (3 +/- 1%). At 7 to 8 days, most TGF-beta 1-expressing cells demonstrated alpha-SM actin immunoreactivity. Their myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments (stress fibers) and a well-developed rough endoplasmic reticulum. The distribution of TGF-beta 1 transcripts by in situ hybridization was paralleled by the immunolocalization of intracellular and extracellular TGF-beta 1 epitopes. At later times (> 14 days after injury), the decrease in TGF-beta 1 coincided with the disappearance of adventitial myofibroblasts, whereas the neointima exhibited longer TGF-beta 1 expression. In conclusion temporal and spatial relationships between TGF-beta 1 and myofibroblast formation suggest an important role for autocrine TGF-beta 1 in the phenotypic modulation of vascular fibroblasts. Induction of TGF-beta 1 expression may provide a differentiation signal for adventitial fibroblasts to become myofibroblasts, which affect arterial remodeling via their mechanical and synthetic properties.

Animals↗
PubMed1995

MOMs (multiples of the median) and DADs (discriminant aneuploidy detection): improved specificity and cost-effectiveness of biochemical screening for aneuploidy with DADs.

OBJECTIVE: Our purpose was to assess the efficacy of double- and triple-screening paradigms for Down syndrome and to develop a more logical, statistical approach to risk prediction that will decrease the cost of screening and allow the incorporation of new parameters appropriately weighted for their contribution. STUDY DESIGN: Data from 24,504 patients who had biochemical screening for Down syndrome by single (alpha-fetoprotein), double (alpha-fetoprotein, beta-human chorionic gonadotropin), or triple screening (alpha-fetoprotein, beta-human chorionic gonadotropin, unconjugated estriol) who had complete outcome information were analyzed by (1) existing gaussian-based methods, (2) the Glasgow ratio method, and (3) a new statistical approach (i.e., directly adjusted data sets for discriminant aneuploidy detection [DADs]) RESULTS: By use of individual risk-based thresholds for "at risk" status, both double and triple screening performed far better than single screening, but the percentages of patients at risk varied widely. When the percentages at risk were held constant, the sensitivity of double and triple screenings was similar, suggesting that there are no benefits of using estriol as a third marker. For 25,000 patients the use of only alpha-fetoprotein and beta-human chorionic gonadotropin would save about $500,000, with no decrease in sensitivity. With the DADs approach a statistically sound model giving more stable estimates was developed that permits each factor to be analyzed for its own explained proportion of variance and allows each parameter to have different weighting. For this data set the same sensitivity was seen with, conservatively, a 1% reduction in the percentage of patients at risk, which would reduce by 250 the number of amniocenteses, at a further savings of about $400,000. CONCLUSIONS: By use of existing methods, double screening is equally as effective as triple screening, so that the expense of estriol is unnecessary. The DADs approach, by allowing for variable weighting of parameters, lowers the at risk percentage and will permit a much more flexible approach as new parameters become available. Changing to DADs and eliminating estriol should achieve higher specificity for the same sensitivity and save, conservatively, about $900,000 in this series. Extrapolated nationally, if confirmed, the annual savings could approach $72,000,000.

Adolescent↗
PubMed1994

Localization of branchio-oto-renal (BOR) syndrome to a 3 Mb region of chromosome 8q.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant condition of branchial arch anomalies, deafness and renal dysplasia. Clinical manifestations tend to have considerable intrafamilial and interfamilial variability. Previous linkage studies had localized the gene responsible for BOR syndrome to a broad region of chromosome 8q. Using 10 microsatellite markers, we have further refined the localization of this disorder by establishing tight linkage to two markers, D8S279 and D8S530 (Zmax = 3.91 and Zmax = 2.83 respectively at theta = 0.00). These markers are within 1 cM of one another. Multipoint analysis, involving 7 loci, placed the gene between these markers, with a lod-1 confidence interval 0.7 cM proximal to D8S530 and 0.6 cM distal to D8S279.

Branchial Region↗
PubMed1994

Biochemical screening.

The goal of screening both low and high risk obstetrics populations for chromosomally abnormal fetuses continues to be developed in many centers worldwide. Advances in the past year have been multifocal in their approach--neural tube detection, the development of new markers for aneuploidy, and attempts to move screening into the first trimester.

Chromosome Aberrations↗
PubMed1993

Development of valve dysfunction in adolescents and young adults with Down syndrome and no known congenital heart disease.

We performed examinations and echocardiographic studies in 35 patients with Down syndrome (aged 20 +/- 4.2 years) with no known intracardiac disease. Sixteen patients (46%) had mitral valve prolapse; two of these also had tricuspid valve prolapse. Two had aortic regurgitation. Valve regurgitation was present in 4 (17%) of 23 patients more than 18 years of age but in none of the 12 patients 18 years of age or younger. We recommend screening of adolescent and young adult patients with Down syndrome for the development of valve dysfunction, especially before dental or surgical procedures.

Adolescent↗
PubMed1992

High-performance liquid chromatographic method for the simultaneous measurement of remacemide (a novel anticonvulsant and cerebroprotectant) and an active metabolite in human plasma.

A high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of both remacemide (a novel anticonvulsant and cerebroprotectant) and an active, major metabolite in human plasma. After the addition of an internal standard, the analytes were extracted from the plasma by ion-exchange solid-phase extraction and measured by an isocratic HPLC system with ultraviolet detection at 210 nm. The recovery of the analytes was > 90%. The standard curves were linear over the range of quantitation of approximately 10-500 ng/ml for remacemide itself and 15-250 ng/ml for the metabolite. Both intra-day and inter-day accuracy and precision data were excellent. Remacemide and its metabolite were shown to be stable in human plasma for at least a year when stored at -20 degrees C.

Acetamides↗
PubMed1992

Prenatal biochemical screening.

Most fetal abnormalities occur in low-risk pregnancies. Screening techniques have been developed to help determine who in the low-risk group may actually be at high risk. Biochemical screening for chromosomal abnormalities and neutral tube defects have significantly increased their detection, but there is still considerable room for improvement.

Amniocentesis↗
PubMed1990

Idioms and mental imagery: the metaphorical motivation for idiomatic meaning.

We conducted three experiments to investigate the mental images associated with idiomatic phrases in English. Our hypothesis was that people should have strong conventional images for many idioms and that the regularity in people's knowledge of their images for idioms is due to the conceptual metaphors motivating the figurative meanings of idioms. In the first study, subjects were asked to form and describe their mental images for different idiomatic expressions. Subjects were then asked a series of detailed questions about their images regarding the causes and effects of different events within their images. We found high consistency in subjects' images of idioms with similar figurative meanings despite differences in their surface forms (e.g., spill the beans and let the cat out of the bag). Subjects' responses to detailed questions about their images also showed a high degree of similarity in their answers. Further examination of subjects' imagery protocols supports the idea that the conventional images and knowledge associated with idioms are constrained by the conceptual metaphors (e.g., the MIND IS A CONTAINER and IDEAS ARE ENTITIES) which motivate the figurative meanings of idioms. The results of two control studies showed that the conventional images associated with idioms are not solely based on their figurative meanings (Experiment 2) and that the images associated with literal phrases (e.g., spill the peas) were quite varied and unlikely to be constrained by conceptual metaphor (Experiment 3). These findings support the view that idioms are not "dead" metaphors with their meanings being arbitrarily determined. Rather, the meanings of many idioms are motivated by speakers' tacit knowledge of the conceptual metaphors underlying the meanings of these figurative phrases.

Adult↗
PubMed1987

Increased nickel concentrations in body fluids of patients with chronic alcoholism during disulfiram therapy.

Nickel concentrations were measured by electrothermal atomic absorption spectrophotometry in body fluids of 61 patients with chronic alcoholism during disulfiram treatment (tetraethylthiuram disulfide, 250 mg/day, po). Nickel concentrations in serum, whole blood, and urine were significantly increased at 12 hours after the initial dose of disulfiram. In serum and whole blood, the Ni concentrations reached a plateau after two weeks of treatment; in urine, the Ni concentrations increased progressively during the initial four months of treatment. During the interval from four months to three years of disulfiram treatment, the median concentrations of nickel in serum, whole blood, and urine were elevated 17-, 15-, and 39-fold, respectively, compared to pretreatment values. The effects of disulfiram on nickel metabolism evidently involve chelation of dietary nickel by diethyldithiocarbamate (DDC), a disulfiram metabolite, and gastrointestinal absorption of the Ni-DDC complex. Since animal studies have demonstrated cerebral uptake of the lipophilic Ni-DDC complex, nickel may possibly accumulate in brain cells of disulfiram-treated patients; physicians should therefore be cautious in administering disulfiram to persons with nickel-containing orthopedic prostheses or occupational exposures to nickel.

Adult↗