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Biomedical subjects

D A Boudreau

Publications and source records attributed to D A Boudreau.

At least 19 recordsLinked to original sources

CDKN2A promoter methylation in gastric adenocarcinomas: clinical variables.

The CDKN2A gene encodes a cyclin-dependent kinase inhibitor, p16, which promotes cell cycle arrest. Methylation of the promoter region of the gene transcriptionally inactivates the gene. We have analyzed the methylation status of the promoter region of the CDKN2A gene in gastric adenocarcinomas using methylation-specific polymerase chain reaction. We also examined the tumors by immunohistochemistry for p16 protein. Of 114 gastric adenocarcinomas analyzed by immunohistochemistry, 34 cases (30%) were negative for p16 protein. Twenty-four of these 34 cases (71%) had methylation of the promoter region of the CDKN2A gene. Methylation of the promoter was strongly associated with loss of p16 protein by immunohistochemistry (P <0.0001). Neither stage, grade, anatomic site, or histologic subtype of the tumor nor age, gender, ethnic origin, or survival time of the patient were significantly different between the groups characterized by tumors with and without methylation. CDKN2A promoter methylation was not significantly associated with microsatellite instability.

Adenocarcinoma↗

Epstein-Barr virus in gastric adenocarcinomas: association with ethnicity and CDKN2A promoter methylation.

AIMS: It has been shown previously (by immunohistochemistry) that gastric adenocarcinomas harbouring Epstein-Barr virus (EBV) frequently lose p16 protein. This study aimed to examine the mechanisms of inactivation of the CDKN2A gene and correlate the results with clinicopathological features. METHODS: Methylation specific polymerase chain reaction was used to detect CDKN2A promoter methylation in gastric adenocarcinomas from American patients. In addition, immunohistochemistry was used to detect the loss of the p16 protein and in situ hybridisation was used to detect the presence of EBV. The tumours were also analysed for the presence of microsatellite instability. RESULTS: Eleven (10%) of 107 tumours harboured EBV in the malignant cells. In gastric cancers without EBV, 32% exhibited CDKN2A promoter methylation and 26% had p16 protein loss. In contrast, 91% of the tumours containing EBV had CDKN2A promoter methylation (p = 0.0003) and 90% showed p16 protein loss (p = 0.0001). The presence of EBV was also associated with male sex (p = 0.03) and was more common in tumours from Texas Hispanics than from non-Hispanic whites or African-Americans (p = 0.01). EBV was not associated with microsatellite instability, histological subtype, stage, or grade of the tumour, or age or survival time of the patient. CONCLUSIONS: The presence of EBV in gastric adenocarcinomas is strongly associated with CDKN2A inactivation by promoter methylation. In addition, these findings suggest that there are ethnic differences in tumour virology and pathogenesis.

Adenocarcinoma↗

Apolipoprotein E and atherosclerosis in Greenland Inuit.

Arterial, liver, and serum specimens were collected from Greenland Inuit at autopsy and apolipoprotein E genotyping was done on 42 females (mean age = 61.3 years) and 56 males (mean age = 56.8 years). Estimates of the allele frequencies of the apo E, derived from the observed frequencies of the six common apolipoprotein E genotypes, are E2: 0.015+/-0.009; E3: 0.776+/-0.030; and E4: 0.209+/-0.029. No significant difference was found between these frequencies and those previously reported for Greenland Inuit, Canadian Inuit, or Alaska natives; however, differences were observed in comparison with frequencies reported for Japan, Norway, Sweden, USA-Blacks and USA-Whites. Anthropometric data (body mass index, panniculus adiposus thickness), blood analyte levels (total serum cholesterol, HDL-cholesterol, LDL + VLDL-cholesterol, and glycohemoglobin), and prevalence and extent of atherosclerotic lesions in the aorta and coronary arteries were analyzed for any associations with apolipoprotein E genotype. The occurrence of apolipoprotein E2 alleles are very rare and the E4 alleles are slightly more frequent in the Greenland Inuit population as compared to other populations. No significant association between apolipoprotein E genotypes and the extent of atherosclerotic lesions in the aorta and coronary arteries were found, and there does not appear to be any strong evidence for an association of either serum lipids, glycohemoglobin levels, or adiposity measurements to apolipoprotein E genotype in Greenland Inuit.

Adult↗

Diabetes and obesity in the Louisiana Coushatta Indians.

OBJECTIVE: In order to assist their community in planning intervention and prevention programs, prevalence rates for diabetes and obesity were examined among the Louisiana Coushatta. RESEARCH DESIGN AND METHODS: Coushatta individuals participated in a health survey (questionnaires and physical examinations). Those without known diabetes underwent oral glucose tolerance testing and were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes mellitus (DM). Those with known DM had the diagnosis confirmed by history and/or elevated hemoglobin A1c. Waist-to-hip ratio (WHR), body mass index (BMI), and percent body fat (%BF) were determined as measures of central adiposity and obesity. Prevalence rates of diabetes and obesity among those examined were calculated. The prevalence of those with more than one anthropometric index positive for obesity was also determined. RESULTS: The prevalence of DM was 30% and IGT was 17% among the first 151 Coushatta participants. For males, the prevalence of obesity was 62%, 57%, and 52%, and for females, 59%, 54%, 45%, as determined by the BMI, %BF, and WHR, respectively. Obesity was more prevalent among those with glucose intolerance (IGT + DM) than those with NGT, and those who were obese had the highest prevalence of glucose intolerance. A greater percentage of those with glucose intolerance had more than one positive obesity measure as compared to those with NGT, and those with more than one index consistent with obesity had a greater prevalence of IGT + DM. CONCLUSIONS: Prevalence rates of DM and obesity are high among the Louisiana Coushatta, and obesity is associated with glucose intolerance. Clustering of the three obesity measures occurs in a high percentage of individuals. Data from the current survey are providing information that is being used by the Coushatta community for health planning and development of intervention and prevention programs.

Adolescent↗

Arterial calcification as a marker for atherosclerosis in three Arctic populations.

Accumulation of calcification in the arterial wall in the course of the atherogenic process is considered to be a manifestation of advanced atherosclerosis. In this study of autopsy specimens from Alaska non-Natives, Alaska Natives, and Greenland Natives, comparisons were made of the prevalence and extent of arterial calcification with that of all raised (advanced) lesions in the thoracic aorta, abdominal aorta, right coronary artery, and left anterior descending coronary artery, to determine the degree to which calcified lesions track the development of advanced lesions. Calcification was determined quantitatively from radiograph images of the fixed specimens; advanced lesion data on these specimens were available from prior studies. Findings show that the prevalence and extent of calcified lesions closely follows the pattern of prevalence and extent of advanced lesions among the groups. We conclude that calcification is a good marker for comparisons of the prevalence and may also provide a good measure of the extent of atherosclerosis in these populations.

Adolescent↗

Genetic variation of recent Alu insertions in human populations.

The Alu family of interspersed repeats is comprised of over 500,000 members which may be divided into discrete subfamilies based upon mutations held in common between members. Distinct subfamilies of Alu sequences have amplified within the human genome in recent evolutionary history. Several individual Alu family members have amplified so recently in human evolution that they are variable as to presence and absence at specific loci within different human populations. Here, we report on the distribution of six polymorphic Alu insertions in a survey of 563 individuals from 14 human population groups across several continents. Our results indicate that these polymorphic Alu insertions probably have an African origin and that there is a much smaller amount of genetic variation between European populations than that found between other population groups.

Base Sequence↗

Lipoprotein (a) levels in African-Americans with NIDDM.

OBJECTIVE: The purpose of this study was to investigate possible relationships between lipoprotein (a) [Lp(a)] levels and NIDDM in African-Americans. The objectives were to identify associations between Lp(a) levels of subjects with and without NIDDM and to determine the influence of glycemic control, determined by GHb, and of mode of therapy on Lp(a) levels. RESEARCH DESIGN AND METHODS: We studied [4] African-American subjects, 103 with NIDDM and 38 without NIDDM. Their Lp(a) levels, GHb levels, and apolipoprotein (a) [apo(a)] isoforms were determined. Clinical information, including mode of therapy (sulfonylurea, insulin, or no pharmacological therapy), date of diagnosis, and medical history, was obtained by chart review and patient interview. RESULTS: There was no significant difference in median Lp(a) levels between the non-NIDDM (25.5 mg/dl) and NIDDM (24.0 mg/dl) study subjects. No statistically significant difference was found in Lp(a) levels when NIDDM patients with GHb < 12.3% were compared to those with GHb > or = 12.3% (P = 0.096). An inverse relationship was found between apo(a) root-mean-square isoform size and Lp(a) level (r2 = 0.091, P = 0.0035). Analysis of the cases by mode of therapy indicates that there is evidence of an increased median level of Lp(a) in African-Americans with NIDDM on insulin therapy relative to those on sulfonylurea (34.0 vs. 16.0 mg/dl; P = 0.013) and to nondiabetic subjects (34.0 vs. 25.5 mg/dl; P = 0.043). CONCLUSIONS: We conclude that the level of plasma Lp(a) is higher in African-Americans with NIDDM who are being treated with insulin when compared to those on sulfonylurea therapy and to those who are non-NIDDM subjects, and this does not seem to be due to genetic variance or method bias.

Adult↗

Apolipoprotein E and atherosclerosis in Alaska Natives.

Arterial, liver, and serum specimens were collected from 130 Alaska Natives who underwent forensic necropsy (mean age, 36.9 years; age range, 9-85 years; 38 females and 92 males). Based upon the observed frequencies of the six common apo E genotypes, the estimates of the relative frequencies of the corresponding alleles in the population are 0.020 +/- 0.009 for E2, 0.787 +/- 0.026 for E3 and 0.193 +/- 0.025 for E4. Analysis showed significant differences, by apo E genotype, in the extent of total surface lesion involvement in both the right and left coronary arteries. In all but the abdominal aorta, the pattern of lesion involvement by genotype is consistent with a decrease in lesions for genotypes with the E2 allele and an increase in lesions for the genotypes with the E4 allele, relative to the E3 homozygotes. After adjustment for low + very low density lipoprotein cholesterol (LDL + VLDL-C), the differences fell below statistically significant levels. Analysis by genotype of total serum cholesterol, high density lipoprotein cholesterol (HDL-C) and LDL + VLDL-C showed no statistically significant differences in analyte levels among genotypes. However, evidence is seen of a pattern in which total cholesterol and VLDL + LDL-C is less in genotypes with the E2 allele and greater in those with the E4 allele. We conclude that there does appear to be an effect by apo E genotype upon extent of atherosclerosis in the coronary arteries of Alaska Natives and this effect is likely due to the previously reported effect of apo E polymorphisms on serum cholesterol, particularly LDL + VLDL-C.

Adolescent↗

A comprehensive evaluation of the performance of duplicate prothrombin time and activated partial thromboplastin time assays.

An evaluation of the performance of duplicate prothrombin time (PT) and activated partial thromboplastin time (aPTT) assays was undertaken to develop analytical duplicate performance criteria in order to quantitate the risks associated with singlet versus duplicate procedures. Data were retrospectively collected from two hospital laboratories using two different coagulation systems. Included in the study were 6,391 patient samples; 3,047 PT, 3,334 aPTT, for a total of 12,782 data points. If a difference between duplicates of 5% or less is deemed analytically (or clinically) insignificant for PT, then fewer than 1% of the samples analyzed by either laboratory would require duplicates. If a difference between duplicates of 15% or less is deemed analytically (or clinically) insignificant for aPTT, then fewer than 2% of samples would exceed this limit for laboratory A, but 6.0% of samples from laboratory B exceeded this limit.

Blood Coagulation Tests↗

In vitro aggregation of normal platelets: a hypothetical first-approximation model for light extinction in platelet-rich plasma.

Aggregometer tracings of light transmission through platelet-rich-plasma are routinely used for the clinical evaluation of platelet function. The analytical relation between the changing aggregometer curve tracings of the light extinction and the aggregation process remains unknown. A first-approximation equation for this relation is proposed, based upon a highly simplified view of the in vitro aggregation process for normal platelets. The model described is capable of generating curves which show strong resemblance to those predicted by light scattering theory as well as those observed experimentally, including biphasic structures.

Adenosine Diphosphate↗

Laboratory equipment maintenance contracts.

The increasing level of technical sophistication and complexity found in clinical laboratory instrumentation today more than ever demands careful attention to maintenance service needs. The time-worn caution for careful definition of requirements for acquisition of a system should also carry over to acquisition of maintenance service. Guidelines are presented for specifications of terms and conditions for maintenance service from the perspective of the laboratorian in the automated clinical laboratory.

Commerce↗

Zero base approach to fiscal management of the laboratory.

Lab administrators who face the challenge of providing quality care while cutting costs need a way to periodically re-evaluate all lab functions and services. The guidelines presented here, based on the Zero Base Budget approach, formulate a management strategy for the lab that could lead to better fiscal planning.

Budgets↗

Estimating supply requirements for implementing a laboratory information system.

The implementation of a new laboratory information system requires the total commitment of all laboratory personnel. Difficulties both within and external to the lab are to be expected as the lab and the hospital staff learn to use the system. Proper planning prior to implementation will avert additional problems that can arise due to an inadequate supply inventory. The purpose of this paper is to discuss methods of estimating supply requirements, as well as to point out other operational considerations related to system start-up.

Computers↗