Biomedical subjects

B F Gilmore

Publications and source records attributed to B F Gilmore.

11 recordsLinked to original sources

PubMed2006

Peptides containing acylated C-terminal gem diamines: novel irreversible inactivators of the cysteine and serine proteinases.

This study reports on the synthesis of peptides containing C-terminal acylated gem-diamines and their utilization for the preparation of irreversible inactivators of the serine and cysteine proteinases. We have succeeded in obtaining an inhibitor Acetyl-Val-Pro-g-Val-CO-O-C(6)H(4)-NO(2) of neutrophil and pancreatic elastases that functions in a time-dependent manner, indicative of the action of an irreversible inactivator, functioning, most probably, through the formation of a long-lived acyl enzyme intermediate. In addition, we have demonstrated the irreversible inhibition of the cysteine proteinase bovine cathepsin B, by chloroacetyl and bromoacetyl derivatives of a dipeptide gem-diamine, Cbz-Phe-g-Ala-CO-CH(2)Hal (Hal = Br, Cl).

Animals↗

PubMed2005

The inactivation of bovine cathepsin B by novel N-chloro-acetyl-dipeptides: application of the Houghten 'tea bag' methodology to inhibitor synthesis.

In this study, a series of N-chloro-acetylated dipeptides were synthesised by the application of Houghten's methodology of multiple analog peptide syntheses (MAPS). The peptides, all of which contain a C-terminal free acid, were tested as inactivators of bovine cathepsin B, in an attempt at exploiting the known and, amongst the cysteine proteinases, unique carboxy dipeptidyl peptidase activity of the protease. We have succeeded in obtaining a number of effective inactivators, the most potent of which-chloroacetyl-Leu-Leu-OH, inactivates the enzyme with an apparent second-order rate constant of 3.8 x 10(4)M(-1)min(-1). In contrast, the esterified analog, chloroacetyl-Leu-Leu-OMe, inactivates the enzyme some three orders of magnitude less efficiently, lending credence to our thesis that a free carboxylic acid moiety is an important determinant for inhibitor effectiveness. This preliminary study has highlighted a number of interesting features about the specificity requirements of the bovine proteinase and we believe that our approach has great potential for the rapid delineation of the subsite specificities of cathepsin B-like proteases from various species.

Acetylation↗

PubMed1993

Matrix effects and the accuracy of cholesterol analysis.

We found evidence of bias due to matrix effect in 70% of 37 instrument/reagent-specific systems analyzing the total cholesterol content of a lyophilized proficiency testing material. We used a computational method to remove bias due to matrix effect from the proficiency testing database. After correction for matrix effect bias and when compared with the reference method, 92% to 93% of results for three lyophilized proficiency testing samples analyzed in 1989 and 1990 met the 1992 National Cholesterol Education Program total error goal of 8.9%, and 94% to 95% met the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) goal of 10%. However, compared with the definitive method for total cholesterol, the calibration bias of 41% of 37 peer groups exceeded the 1992 National Cholesterol Education Program goal for bias of 3%. Because the calibration bias of the method is incorporated into the peer group mean, use of peer group means as target values to assess result acceptability hinders advancement of the state of the art in interlaboratory comparability and the clinical effectiveness of laboratory testing. The prevalence of matrix effects has prevented successful application of accuracy-based evaluation of cholesterol test proficiency. The establishment of predictable recovery, preferably complete recovery, of cholesterol from reference materials is an important priority for cholesterol test methods. However, adjustment of proficiency testing results to remove the average bias due to matrix effects can help assess the actual state of the art in cholesterol test accuracy.

Bias↗

PubMed1988

Multiprogram characterization of laboratory bias, precision, and total error. Proposal for improved assessment with shared external and expanded internal (regional) quality control pools.

We establish that, for the analytes aspartate aminotransferase, glucose, phosphorus, and potassium, there is significant correlation between laboratory performance as determined by College of American Pathologists-sponsored external (Surveys) and expanded internal (regional) quality control (Quality Assurance Service) programs. However, relatively low parametric and nonparametric correlation coefficients and significant departure of linear regression slopes from unity reflect major differences in the calculated parameters of absolute bias, precision, and total error obtained through internal and external quality control. Significantly better performance in both Surveys and the Quality Assurance Service was documented for laboratories participating in the College of American Pathologists Laboratory Accreditation Program. Multiple descriptors of laboratory quality, as indicated here, are superior in describing laboratory performance to proficiency testing alone. As a bridge between external and internal quality control, shared pools of quality control materials are described for use as unknown Survey challenges and subsequent distribution for regional quality control. Such programs, which can be configured to serve thousands of laboratories, could offer cost savings, better quality assurance, and improved characterization of laboratory performance by minimizing interprogram differences in control matrix and method classification and providing greater reliability of target values.

Academies and Institutes↗

PubMed1983

Contemporary quality control practices for antimicrobial susceptibility tests: a report from the microbiology portion of the College of American Pathologists (CAP) surveys program.

The evaluation of quality control (QC) practices from the College of American Pathologists (CAP) Microbiology Surveys demonstrates a trend away from daily controls similar to that first noted in 1980. Previous recommendations for more relevant cost-containment oriented weekly QC procedures are discussed, and the 1982 CAP Surveys statistics confirm earlier comparability between the daily and weekly QC participant groups. Each QC practice subgroup (daily or weekly) had nearly identical mean disk inhibitory zone diameters, and the performance accuracy on two 1982 challenge strains were very similar. Generally, disk zone diameter from those laboratories using weekly QC were smaller, but the frequency of minor and major (false-resistant) errors was only slightly increased. The authors recommend the conversion to weekly QC of disk or dilution antimicrobial susceptibility tests after an acceptable daily QC performance has been established (See criteria in discussion).

Drug Resistance, Microbial↗

PubMed1983

Stability of mean assay values of magnesium and iron in lyophilized quality control serum: a study based on data from the quality assurance service (QAS) of the College of American Pathologists.

Data from magnesium and iron analyses of pools of lyophilized quality control serum were used to evaluate stability of analyte mean values in the pre-reconstitution period. Information was received from laboratories in Regional Quality Control Programs between 1977 and 1981, using CAP Quality Assurance Service data processing. For magnesium, 28 of 41 (68%) pool-method combinations were stable, 11 (27%) showed decreases, and 2 (5%) showed increases. Decreases averaged 0.008 mg/dL/month (all methods). A pronounced effect of method (automated methylthymol blue) and year correlated with decreases in measurable magnesium. For iron, 45 of 56 (80%) pool-method combinations were stable, 8 (15%) showed decreases, and 3 (5%) showed increases. Decreases averaged 0.349 g/dL (all methods). In most cases, changes in measured concentrations are attributed to methodologic factors, rather than intrinsic changes in analyte concentrations.

Autoanalysis↗

PubMed1983

Interlaboratory survey of enzyme analyses: V. A simplified method of reporting participants' data.

The College of American Pathologists' Enzyme Survey continues to provide a valuable measure of the analytic quality of clinical enzymology for its participants and for the laboratory community. An updated reporting format for the participants simplifies the interpretation of Enzyme Survey data and should make it more valuable for detecting short- and long-term changes in accuracy and precision. A short-term CV of 3% and a long-term CV of 6% are recommended as analytic goals for the five enzymes described here. The upper limit of normal used by many laboratories is appropriate for a given enzyme yet remains as an area requiring urgent further study.

Adult↗

PubMed1982

Glucose stability in lyophilized chemistry quality control serum. A study of data from the quality assurance service (QAS) program of the College of American Pathologists.

Data from 2.5 million glucose analyses on pools of lyophilized human quality control serum were used to evaluate analyte stability in the prereconstitution phase. Input information was from laboratories in Regional Quality Control Programs that use CAP Quality Assurance Service (QAS) data processing. Of 31 pools in use between 1977 and 1981, decreasing glucose concentration was detected by, at least, one method in 26 pools, and by two or more methods in 21 pools. Method-associated average decrease in concentration varied from 0.13 mg/dL/month (glucose oxidase-electrode) to 0.19 mg/dL/month (automated glucose oxidase-colorimetric). Bidirectional instability as a function of analytic method, i.e., increase with "mild" methods, decrease with "rigorous" methods that was noticed previously with pools analyzed between 1973 and 1977, was no longer seen. Dominant directional changes in the later pools were downward by all methods, when statistically significant trends were demonstrated.

Blood Glucose↗

PubMed1982

Analytic clinical laboratory precision. State of the art for selected enzymes.

Results of precision estimates are reported for selected enzyme analytes. Laboratories that participated in regional quality control programs supplied data to a centralized data processing service (College of American Pathologists Computer Center). These data, representing several regional groups which used different commercial sources of control serum, were statistically analyzed by regression of coefficient of variation (CV) upon concentration of analyte using a modified polynomial regression technic. Tolerance limits for long-term within-laboratory precision were developed from this data. Estimated CVs were extracted at selected analyte concentrations, and tolerance limits for CVs at these concentrations were developed. In addition, selected individual methods within the larger groups were individually examined to evaluate effect of control material matrix upon clinical estimates of enzyme precision. Differences in selected method groups are discussed.

Alanine Transaminase↗

PubMed1981

Quality control of agar diffusion susceptibility tests. Data from the Quality Assurance Service Microbiology Program of the College of American Pathologists.

During the period from January 1979 through January 1981, 155 active participants in the Microbiology Program of the College of American Pathologists Quality Assurance Service (QAS) submitted approximately two million individuals determinations on three quality control reference strains. Of these determinations, 83% were obtained using the standardized disc-diffusion procedure of Bauer and co-workers, and, 6% using the agar overlay modification of Barry and associates. The mean and standard deviation for data obtained using these procedures were similar to those for data collected from the inception of the program in 1974 through December 1978. The number of individual determinations falling above or below existing control limits, however, was significantly less for the present data than for that previously reported. These differences result from a change in computation procedures. In the current report percentages of daily values exceeding the NCCLS limits were calculated using actual counts, whereas in the previous reports these percentages were estimated by accepting an assumption of Gaussian distribution.

Ampicillin↗

PubMed1981

Stability of sodium and potassium in lyophilized quality control serum. A study of data from the Quality Assurance Service Program of the College of American Pathologists.

The long-term prereconstitution stability of sodium and potassium in large pools of lyophilized quality control serum used in Regional Quality Control Programs, conducted between 1977 and 1980 is reviewed. In approximately one third of 27 pools studied, minimal but significant increases in sodium concentration were detected, these increases averaged less than 0.50 per year and confirmed our previously reported results from pools analyzed between 1973 and 1976. Results relating to potassium stability have been inconsistent. The previously reported tendency for potassium to increase in some pools was again suggested by data obtained from laboratories using automated flame-emission photometry procedures. This was not confirmed, however, by the data reflecting manual/semi-automated flame-emission photometry procedures or automated electrode methods. It is postulated, that the source of sodium causing the increases in concentration is the glass containers in which control materials are stored between the time of manufacture and reconstitution. Regression analysis against time of monthly interlaboratory means, from participants in Regional Quality Control Programs, is a useful tool for evaluating postmanufacture stability of analytes in pools used for daily internal quality control procedures.

Blood Preservation↗