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Biomedical subjects

A A Reilly

Publications and source records attributed to A A Reilly.

13 recordsLinked to original sources

Estimating serum polychlorinated biphenyl levels in highly exposed workers: an empirical model.

A regression model estimating high-homolog polychlorinated biphenyl (PCB) serum concentration on the basis of job exposure categorizations was developed. The model assumes first-order kinetics with a half-life determined empirically and uses variables that incorporate both intensity and duration of exposure over a 30-yr period. In order to compare the efficiency of these regression-based exposure estimates relative to often-used epidemiological parameters, models with dichotomized, ordinal, and continuous exposure surrogates were also investigated. Among the alternative exposure categorizations the most straightforward measure, ever versus never direct, was a particularly poor predictor of serum PCB level (r2 = .01). Nearly all of the candidate exposure measures we tried predicted serum levels poorly. The best of these after the fact was with total months employed in direct-exposure jobs (r2 = .43). None of the logical deductive models approached the predictability of the empirical model developed here (r2 = .69).

Adult

Observational study of erythrocyte protoporphyrin screening test for detecting low lead exposure in children: impact of lowering the blood lead action threshold.

We examined a retrospective sample of 1800 children on whom both erythrocyte protoporphyrin (EP) and blood lead (BPb) measurements were taken. The primary objective was to ascertain whether EP is a cost-effective screening test for low but increased BPb concentrations and to establish the optimal thresholds. The data did not provide evidence of an EP threshold at low BPb concentrations; however, the data did show a significant age effect. A subset of 500 children for whom both EP and hematocrit data were available showed no correlation between those variables. Age-specific operating characteristic curves, total error, and cost analyses are presented. The latter sets bounds on the relative cost of EP testing, above which only BPb determination should be performed. The implications of these findings are discussed in light of impending changes in U.S. federal guidelines for preventing lead poisoning in young children.

Aging

An expectation maximization (EM) algorithm for the identification and characterization of common sites in unaligned biopolymer sequences.

Statistical methodology for the identification and characterization of protein binding sites in a set of unaligned DNA fragments is presented. Each sequence must contain at least one common site. No alignment of the sites is required. Instead, the uncertainty in the location of the sites is handled by employing the missing information principle to develop an "expectation maximization" (EM) algorithm. This approach allows for the simultaneous identification of the sites and characterization of the binding motifs. The reliability of the algorithm increases with the number of fragments, but the computations increase only linearly. The method is illustrated with an example, using known cyclic adenosine monophosphate receptor protein (CRP) binding sites. The final motif is utilized in a search for undiscovered CRP binding sites.

Algorithms

Evidence that the interferon-induced Daudi cell human lupus inclusions are de novo synthesized complexes of ribonucleoprotein and membrane.

Quantitative electron microscope autoradiography has been used to define the macromolecular composition of the interferon-induced human lupus-type inclusions (LI) in the human B lymphoblastoid cell line, Daudi. LI were first apparent in Daudi cell cultures 12 h after the addition of 100 units/ml of the purified recombinant human leukocyte interferon, IFLrA. Radiolabels were added at this time and allowed to incorporate over the following 12 h during which an estimated greater than 99% of the LI material present at 24 h was formed. The LI-incorporated radiolabels were present only during this discrete 12-h period after the interferon activation of LI cell pathways in order to detect LIs de novo synthesized macromolecular components. The estimate relative specific activities of the LI-incorporated radiolabels were: choline at 4.042, mannose at 2.631, uridine at 0.664, glucosamine at 0.578, and amino acids at 0.477. With thymidine the estimated LI specific activity was 0.000. LI isolated from whole cells retained the tubular elements and the interwoven membrane network. These results provide direct evidence that the interferon-induced Daudi cell LI are de novo synthesized complexes of ribonucleoprotein and membrane.

Amino Acids

Fluoroimmunoassay studies with solubilized antigens from Borrelia burgdorferi.

Sodium deoxycholate-solubilized Borrelia burgdorferi antigen was prepared for use in a solid-phase fluoroimmunoassay (FIA-L) to detect antibodies in Lyme disease. Serum specimens were tested by FIA-L and by a microimmunofluorescence test. The FIA-L results are comparable to those of the standard microimmunofluorescence test. The overall agreement was 0.98. Moreover, the FIA-L procedure is simple and rapid; fluorescence is objectively determined and is proportional to antibody titer.

Antibodies, Bacterial

An interlaboratory comparison of control materials for use with hematofluorometers.

This interlaboratory study was conducted to examine four erythrocyte protoporphyrin control materials from Aviv Biomedical, Helena Laboratories, Kaulson Laboratories, and the New York State Department of Health for use with hematofluorometers. Our principal aims were to monitor the stability of these materials at three different storage temperatures (room, refrigerator, freezer) and, where appropriate, to validate the manufacturer's target values. Measurements for the study were generated in three reference laboratories that used a total of five hematofluorometers, three from Environmental Science Associates and two from Aviv Biomedical. Each instrument was calibrated against a consensus acetic acid-ethyl acetate extraction procedure. We found the materials from Aviv to be the most stable, followed by the New York State material. However, the target values assigned by Aviv were not within the acceptable range determined by consensus. The target values assigned by Kaulson Laboratories for their materials did fall within the acceptable consensus range, but they were the least stable of the materials evaluated. The materials from Helena Laboratories were originally designed for use as calibrators with Helena's "ProtoFluor Z" hematofluorometer, which reports in different units. They were deemed unsuitable for use as control materials with the Aviv or Environmental Science Associates hematofluorometers because of the narrow range of values and the wide scatter of results.

Acetates

Patterns of blood-vessel invasion by mammary tumor cells.

Rat mammary tumor TMT-081 was employed as a model for blood vessel invasion because its mode of metastasis resembles that of human tumors. The invasive mechanism was studied with two methods of serial transplantation: transfer of enzymatically dispersed solid tumors, and transfer of buffy coat containing circulating tumor cells. The latter method produced greater invasion of blood vessels, including larger veins and occasionally arteries, perhaps by obviating damage to tumor cells during enzyme treatment. The course of migration was traced by three-dimensional examination in the high voltage electron microscope, as well as the light microscope. Two broad patterns were found for the course of invasion of small and large vessels respectively.

Animals

Maximum likelihood estimation of subsequence conservation.

A statistical method is presented for comparing protein sequences by partitioning the polymers and estimating each subsegment's degree of conservation. Conservation is measured as a function of the number of transitions occurring in the underlying time homogeneous Markov process assumed to govern amino acid mutations. The Markovian assumption also permits estimation of the ancestral sequence. Partitioning and estimation are carried out via maximum likelihood. The method is contrasted with the commonly utilized percent homology measure. A moving likelihood ratio plot to aid in identifying regions of high conservation is suggested as an analogue to moving hydrophobicity plots. An application is presented which identifies highly conserved regions in thymidylate synthase from L. casei and E. coli.

Amino Acid Sequence

Mortality patterns of New York State Vietnam Veterans.

Mortality odds ratios (MORs) comparing veterans with Vietnam service who died in New York State to veterans of the Vietnam era with no Vietnam service were estimated (N = 1,496). The most elevated MORs and their confidence intervals were non-motor vehicular injuries of transport (MOR = 2.18, (1.19, 3.96)), other accidents and burns (MOR = 1.37, (0.95, 1.98)), and homicide (MOR = 1.59, (0.86, 2.94).

Accidents

Prolonged incubation period of AIDS in intravenous drug abusers: epidemiological evidence in prison inmates.

Fourteen heterosexual inmates who developed acquired immunodeficiency syndrome (AIDS) while incarcerated in New York state prisons were studied. All 14 had regularly used illicit drugs intravenously in New York City prior to imprisonment. Leukocyte counts on admission to the state prison system--when all of these inmates were well--were depressed by one-third when compared with those in matched intravenous drug-using inmates used as controls (mean leukocyte counts, 4,430 vs. 6,320 cells/mm3, respectively; P less than .005); twelve (86%) of the 14 inmates who developed AIDS had counts of less than 5,000 cells/mm3, compared with only six (14%) of the 42 controls (P less than .00001). The 14 inmates developed AIDS symptoms a mean of 22.6 +/- 9.6 months after imprisonment. We conclude that leukopenia is frequently to be found in presymptomatic AIDS infection and that the minimum mean incubation period of AIDS in intravenous-drug abusers is quite prolonged.

Acquired Immunodeficiency Syndrome

Trihalomethanes in drinking water and human colorectal cancer.

The relation of trihalomethanes (THM) to colorectal cancer was evaluated. A total of 395 colorectal cancer deaths among white women teachers in New York State was compared to an equal number of deaths of teachers from noncancerous causes. Cumulative chloroform (CHCl3) exposure was estimated by the application of a statistical model to operational records from the individual water treatment facilities that served the home and work addresses of each study subject during the 20 years prior to death. The odds of exposure to a surface source containing little or no THM was no greater for cases than for controls. The odds ratio = 1.07; the 90% confidence interval = 0.79-1.43; and the P = .68. The distribution of CHCl3 exposure was not significantly different between cases and controls (rated by Wilcoxon signed rank statistic = -0.52; P = .60). No effect of cumulative CHCl3 exposure on outcome was seen in a logistic analysis controlling for average source type, population density, marital status, age, and year of death (likelihood ratio test statistic = 0.047; P = .83).

Aged

Regression line analysis of neutrophil chemotaxis.

Polymorphonuclear leukocyte chemotaxis and chemokinesis, in the micropore filter assay, have been evaluated using Regression Line Analysis. The method discriminates between migration rate and the number of migrating cells by statistical comparison of the slope of the regression line and the y-intercept, respectively. The derivation of this new method of assessment of cell migration is reported. This report also includes critical evaluation of the chemokinesis dose/response curve and the directional component of chemotaxis. The effect of inhibitors of chemotaxis were evaluated using the new method. Colchicine was found to effect the directional component of chemotaxis, as indicated by decreased rate of locomotion in chemotaxis experiments, and had no effect on random migration and chemokinesis. Cytochalasin B had a general inhibitory effect upon cell locomotion by depressing the rate of random migration and chemotaxis. 1-Tosylamide-2-phenylethyl chloromethylketone (TPCK) had the apparent effect of uncoupling the receptor and effector mechanisms of chemotaxis or altering the binding of the chemotactic ligand, since random migration was unaffected but the rate of chemotaxis and chemokinesis were depressed. Ionophore A23187 had a generalized inhibitory effect on the cell rate under all three conditions; however, at low concentrations it induced an increase in the number of migrating cells. These studies indicate that the method of regression line analysis is effective in differentiating in vitro the mechanisms of chemotaxis inhibition. The method may be used effectively in the assessment of defective neutrophil chemotaxis in disease states and may prove a useful adjunct to the study of cell locomotory mechanisms.

Calcimycin

A rapid, semi-automated procedure for the evaluation of leukocyte locomotion in the micropore filter assay.

A commerically available bacterial colony counter has been modified to allow rapid, accurate, semi-automated evaluation of cell numbers in the micropore filter assay for chemotaxis. The method is valuable for objective, rapid evaluation of cell counts at various levels through the filter, as well as counts on the distal surface of the filter. Coupled with a programmable calculator, this instrument had made feasible a new method of assessing random migration by the regression line analysis, which discriminates between migration rate and mass migration of cells. This combination of equipment may thus serve as a considerable time saving accessory to laboratories engaged in cell locomotion research, but also will allow more rigorous assessment of differences among specific populations of cells.

Analysis of Variance