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Biomedical subjects

G R Cooper

Publications and source records attributed to G R Cooper.

At least 55 records · Page 3Linked to original sources

An international collaborative study on standardization of apolipoproteins A-I and B. Part II. Evaluation of contributions of antisera to among-laboratory variance components.

Local antisera (LA) were compared with a common interim reference antiserum (IRA) to examine the antiserum component of the among-laboratory variation in an international collaborative study with 28 laboratories evaluating a candidate international Reference Material (apo-RM) for apolipoproteins A-I (apo A-I) and B (apo B). Measurement of the relative concentration of lyophilized preparations differed by less than 1% for LA and IRA. The percentage of the total variation in measurement of the concentration of apo-RM that was contributed by antisera among laboratories was 5% and 8% for apo A-I and B, respectively. Estimated differences from overall mean concentrations for the five different immuno-methods were greater for apo B (range: +22% to -23.5%) than for apo A-I (range +14% to -14%), but were similar within a method for LA and IRA. The results indicated that antisera are not a major source of error among laboratories and, indeed, are responsible for relatively little of the total variability.

Apolipoprotein A-I↗

Quality control of biochemical data in the Multiple Risk Factor Intervention Trial: Central Laboratory.

The acquisition of quality biochemical data in the MRFIT was enhanced by writing detailed protocols, instituting strict rules for collecting and shipping specimens, setting high goals for analytical performance, using reliable means to transfer data, employing dedicated and competent analysts, and having a director of the Central Laboratory who believed in and enforced an effective quality control system. A Laboratory Quality Control Subcommittee was formed to work with this director in solving laboratory problems, with the Coordinating Center in conducting appropriate monitoring, with the Quality Control Committee in documenting the quality of data and investigating any laboratory problems, and with other committees of the directors and Program Office in responding to any questions raised about laboratory aspects of the trial. All of these efforts culminated in reliable biochemical data.

Cholesterol↗

Quality control in the MRFIT local screening and clinic laboratory.

Quality control was emphasized in the screening and clinic laboratory during the early stages of the trial to cover all aspects of screening, and in the later stages to cover local testing used to monitor the participant in the clinic and to guarantee collection of valid specimens to be shipped to the Central Laboratory. Special attention throughout the trial was focused on techniques for collection of specimens, since it was recognized that analytical results could not be better than the quality of the specimens. Training courses, on-site visits, and newsletters were used to sensitize the staff of the clinic laboratory about the necessity to follow protocol. Any monitoring evidence of carelessness, use of deteriorated supplies, failure to follow safety rules, and deviation from directions in the MRFIT Manual of Operations resulted in memoranda from the Coordinating Center or the Central Laboratory.

Cholesterol↗

Interlaboratory testing of the transferability of a candidate reference method for total cholesterol in serum.

In 1975 the Centers for Disease Control, in cooperation with the American Association for Clinical Chemistry Cholesterol Reference Method Study Group, began an investigation to develop a reference method for total cholesterol. Five potential reference methods were compared with the definitive method developed by the National Bureau of Standards before the chemical method of Abell et al. (J Biol Chem 1952;195:357-66) was selected as the recommended reference method. Because acceptance of a proposed reference method depends so greatly on the method's capability for transfer to other laboratories by written specifications and instructions, a transferability testing study was designed and conducted with 14 laboratories. The study consisted of preliminary testing of readiness of equipment, reagents, and personnel followed by transferability testing with eight runs on 10 serum pools. Laboratoires that did not meet readiness specifications had higher CVs in the transferability testing. The study demonstrated that the proposed method permits laboratories to attain a CV of less than 1.5% for one laboratory and of less than 3.0% among laboratories. The mean percent bias value was less than 1.0% for six of the 14 laboratories, less than 1.5% for 12, and less than 3.0% for all 14 laboratories.

Calibration↗

The ratio of plasma high-density lipoprotein cholesterol to total and low-density lipoprotein cholesterol: age-related changes and race and sex differences in selected North American populations. The Lipid Research Clinics Program Prevalence Study.

The distribution of the ratios of plasma high-density lipoprotein cholesterol (HDL-C) to total cholesterol (TC) and of HDL-C to low-density lipoprotein cholesterol (LDL-C) are presented for 6900 white and 495 black examinees greater than 4 years old. Measurements were obtained during the visit 2 survey of the Lipid Research Clinics (LRC) Program Prevalence Study, and correspond to a 15% random sample of 60,502 participants screened during the LRC visit 1 survey. Age-specific means, medians, and selected percentiles are given by sex and by gonadal hormone use in white women. Apparent in these cross-sectional data was a consistent age-related decline in the ratio of HDL-C to TC for white male participants, from a mean of 0.360 in the age group 5 to 9 to a mean of 0.211 in the age group 50 to 54. Thereafter the mean ratio increased slightly. In white women not using gonadal hormones the age-related decline in the ratio was only evident starting at the age group 35 to 39, from which it declines from 0.329 to 0.258 in the age group 55 to 59. White women using gonadal hormones showed very minor age-related changes in the HDL-C/TC ratio, varying around a mean of 0.300. The number of blacks examined was low and thus the racial comparisons must be interpreted with caution. For each gender, age-related trends were similar in black and white study participants. Black men, however, had a higher percentage of TC carried as HDL-C than white men in all age groups examined. Black women had a higher percentage of TC in HDL-C than white women only below age 20; in the adult age range no appreciable differences were seen. Pearson correlation coefficients between the lipid, lipoprotein, and lipoprotein ratios are presented. The ratio HDL-C/TC correlated highly with the ratio HDL-C/LDL-C (greater than 0.92 for all groups) and the former may be a more conveniently determined surrogate for the latter. Although not exhaustive regarding the information it conveys about a lipid pattern, the ratio HDL-C/TC has the advantage of summarizing complex associations into a single numerical approximation.

Adolescent↗

Standardization of lipid and lipoprotein determinations for pediatric screening procedures.

Standardization of lipid and lipoprotein measurements is of concern to laboratories that serve pediatric as well as adult populations, since preventive measures taken during pediatric years can help control atherosclerotic cardiovascular problems that can arise during adult years. Multiple analytical and physiologic problems that exist inherently in the lipids and lipoproteins and in application of measurements to the pediatric population must be controlled to gain standardization and produce highly precise and accurate results. Reference values from well-described, observed pediatric populations have been published for use in interpreting analytical results. In collaboration with NHLBI, the CDC has offered lipid and lipoprotein standardization services for the United States since 1957 and, on an international scale, has cooperated with WHO since 1962. Standardization activities have been primarily concerned with total and HDL cholesterol and triglyceride determinations for cardiovascular epidemiologic and clinical trial investigations.

Adolescent↗

International survey of apolipoproteins A1 and B measurements (1983-1984).

We report here results of a worldwide survey of apolipoprotein (apo) A1 and B measurements. A lyophilized pool of human serum was developed for the survey to test its suitability as a candidate Reference Material. Seventy-five laboratories from 18 countries responded to invitations to participate. Using several methods, they evaluated the mass concentration of apo A1 and B in the proposed Reference Material. The bias between laboratories and between analytical methods was then characterized. Fifty-five laboratories reported results before the deadline on measurement of at least one apolipoprotein by one method. Variation in apo A1 and B among collaborators constituted the largest source of error in the study (68% of the total variation for apo A1, 73% for apo B). Variation among method means was not significant for apo A1, but for apo B it constituted 20% of the total variation. Differences due to vials or in replicate measurements within vials were found to constitute 6% or less of the total variability. Within-laboratory, among-vial, and among-replicate CV values were less than 5% for the study. These results suggest that future standardization efforts can be successful.

Apolipoprotein A-I↗

Stability of dopamine in an in vitro incubation system using Medium 199.

This study investigated the stability of exogenous dopamine (DA) in vitro in a commercially available medium (Medium 199), with and without additional ascorbic acid, during incubation with pituitary halves in prolactin secretion experiments. After a 3-h incubation period, 26 and 15% of the starting concentrations of DA were degraded in the absence and presence of 1 mM ascorbic acid, respectively; in the absence of pituitary tissue, these reductions in DA concentration were 19% and 0%, respectively. In contrast, 98% of DA was degraded after 3 h of incubation in Krebs-Henseleit bicarbonate buffer which contained no tissue or no antioxidants. A number of antioxidants (including a low concentration of ascorbic acid) which are already present in Medium 199 are most likely responsible for the relative stability of DA in this medium. The loss of DA during incubation in Medium 199 is considered small for this type of study, and additional ascorbic acid only marginally improves DA stability in this medium. We have concluded that there is no need to be overly concerned about the degradation of exogenous DA in vitro for some incubation experiments using Medium 199, and the addition of extra ascorbic acid (which may be deleterious) is not necessary.

Animals↗

Some considerations of methodology and standardization of apolipoprotein B immunoassays.

Apolipoprotein B, the major protein component of very-low-density (VLDL) and low-density (LDL) lipoproteins in serum, is being widely measured in serum, to help assess risk of cardiovascular disease. Standardization has proven difficult because of the physical and immunochemical heterogeneity of LDL and VLDL, the masking of antigenic determinants of LDL and VLDL, the insolubility of apolipoprotein B, the instability of lipoprotein reference materials, and the multiplicity of analytical methods. Here we have examined the literature and collected current information from lipoprotein scientists to determine the problems--and the ways investigators have attempted to solve them--in preparation, storage, and use of standards and anti-apolipoprotein B sera, analytical procedures and reagents, and the nature of apolipoprotein B in serum. Standardization appears possible with development of stable reference materials that are applicable to the various analytical methods, controlled immunochemical reaction conditions, and establishment of a selected interim reference method for use as a point of reference.

Adult↗

Some considerations of methodology and standardization of apolipoprotein A-I immunoassays.

Apolipoprotein A-I (apo A-I) is the major protein of high-density lipoprotein. Compelling evidence suggests that measurement of concentrations of apo A-I in serum may be useful in predicting and assessing ischemic heart disease. The following review of methods of isolation, characterization, and assay of apo A-I has been developed to assess the possibility of standardizing apo A-I immunoassays. We consider the properties of apo A-I that have an effect on its quantification, such as self-association, polymorphism, and stability characteristics. We attempt to review critically the various methods presented, but more information about the physicochemical properties of the protein is required before definitive recommendations can be made.

Adult↗

Somatostatin inhibits prolactin secretion in the estradiol primed male rat.

Somatostatin inhibits not only growth hormone secretion, but also the secretion of several other hormones. The role of somatostatin in prolactin (PRL) secretion has not been clearly demonstrated. The present study was undertaken to examine the effects of somatostatin on rat PRL secretion in several different circumstances where the circulating PRL level is elevated: (1) the estradiol primed intact male rat, (2) normal and (3) estradiol primed rats pretreated with pimozide, (4) normal and (5) estradiol primed hypophysectomized male rats with adenohypophyses grafted under the kidney capsule (HAG rat). Blood samples (70 microL) were taken every 2 min via an indwelling atrial cannula from conscious, unrestrained animals. In the estradiol primed intact rats, a bolus injection of somatostatin (10, 100, and 1000 micrograms/kg) lowered PRL levels in a dose-dependent manner. When the PRL concentration was elevated by the administration of pimozide (3 mg/kg), a dopaminergic receptor blocking agent, somatostatin was ineffective in decreasing plasma PRL concentration but the PRL concentration was lowered by somatostatin when the rat had been primed with estradiol. Somatostatin had no effect on the normal HAG rats, but lowered the plasma PRL concentration in the estradiol primed HAG rats. Since somatostatin inhibits PRL secretion only in the estradiol primed rats, it is suggested that estradiol priming creates a new environment, presumably via new or altered receptors, which can be inhibited by somatostatin.

Animals↗