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Biomedical subjects

J D Hudson

Publications and source records attributed to J D Hudson.

13 recordsLinked to original sources

The disparity between hypothermic coagulopathy and clotting studies.

Hypothermic patients commonly develop coagulopathy, but the effects of hypothermia on coagulation remain unclear because clinical laboratories routinely perform clotting tests only at 37 degrees C. Measurements of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on plasma from normothermic and hypothermic rats at a range of temperatures (25 degrees-37 degrees C) to assess the effects of hypothermia on apparent clotting factor levels and clotting factor activities. In general, clotting times were more severely prolonged when test temperatures were hypothermic than when body temperatures were hypothermic. Indeed, little to no prolongation resulted from body hypothermia alone. These findings reveal the observed disparity between clinically evident hypothermic coagulopathy and near-normal clotting studies. Clotting studies performed at 37 degrees C will not confirm hypothermic coagulopathy. These results indicate that the appropriate treatment for hypothermia-induced coagulopathy is rewarming rather than administration of clotting factors.

Animals

stf1: a new suppressor of the mitotic control gene, cdc25, in Schizosaccharomyces pombe.

A novel element in the mitotic control, stf1, has been identified genetically by its ability to rescue cdc25-22 as well as a gene disruption of cdc25. This is the first phenotypically non-wee mutation shown to do so. stf1-1 functions additively with cdc2-1w, cdc2-3w, or wee1-6 to rescue cdc25. The available data are consistent with the wild-type gene product operating either on the same pathway as cdc25 or to stimulate cdc2 by a pathway independent of cdc25 or wee1. The stf1 gene has been cloned and sequenced and encodes a putative protein of 50-65 kD, depending on whether a potential intron is present. It is a novel protein with no homology detected in the current data bases. When challenged with hydroxyurea, stf1-1 acts additively with cdc2-3w in rescuing cdc25 mutants and in allowing mitosis to occur without DNA synthesis. It does not appear to play a role in the nutritional sensing pathway nor in the pathway mediating radiation-induced G2 delay.

Alleles

stf1: non-wee mutations epistatic to cdc25 in the fission yeast Schizosaccharomyces pombe.

In Schizosaccharomyces pombe, cdc25 is a cell cycle regulated inducer of mitosis. wee1 and phenotypically wee alleles of cdc2 are epistatic to cdc25. Mutant alleles of a new locus, stf1 (suppressor of twenty-five), identified in a reversion analysis of conditionally lethal cdr1-76 cdc25-22 and cdr2-96 cdc25-22 double mutant strains, also suppress both temperature-sensitive and gene disruption alleles of cdc25. These mutants, by themselves, are phenotypically indistinguishable from wild type strains; hence they represent the first known mutations that are epistatic to cdc25 and do not display a wee phenotype. stf1 genetically interacts with other elements of mitotic control in S. pombe. stf1-1 is additive with wee1-50, cdc2-1w and cdc2-3w for suppression of cdc25-22. Also, like wee1- and cdc2-w, stf1- suppression of cdc25 is reversed by overexpression of the putative type 1 protein phosphatase bws1+/dis2+. Interaction with various mutants and plasmid overexpression experiments suggest that stf1 does not operate either upstream or downstream of wee1. Similarly, it does not operate through cdc25 since it rescues the disruption. stf1 appears to encode an important new element of mitotic control.

Alleles

Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels.

Previous studies of hypothermia and blood coagulation have focused on alterations in the levels of blood clotting elements using coagulation tests performed under normothermic conditions. However, because of the enzymatic nature of activated clotting factors, hypothermia should also be expected to affect clotting factor activities. Multiple determinations of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on commercially available normal human plasma at assay temperatures similar to those encountered clinically (25-37 degrees C). Both the APTT and the PT were significantly prolonged at temperatures below 35 degrees C (P less than 0.05). Clotting time correlated significantly with assay temperature in a negative exponential fashion for all three tests (r = -0.97 for APTT, -0.93 for PT, -0.71 for TT, P less than 0.001 for all regressions). Clotting time prolongation appears proportional to the number of enzymatic steps involved. These data indicate that the coagulopathy observed during hypothermia is, in part, independent of clotting factor levels.

Blood Coagulation

Comparison of serologic screening tests for brucellosis.

The slide agglutination test (SAT), microagglutination test (MAT), and card agglutination test (CAT) were compared with each other, using the tube agglutination test (TAT) as the standard method, by two reference laboratories to determine effectiveness as screening tests for human brucellosis. TAT titers of 1,253 sera tested in both laboratories were compared. In one laboratory, 1,270 sera were tested by the TAT and SAT, while the other laboratory tested 1,261 sera by both methods. Of these sera, 1,155 were tested in one laboratory by the CAT and 187 sera were tested by the MAT. Compared with that of the TAT (greater than or equal to 160 positive), the sensitivities were 97 to 100% (SAT), 90% (CAT), and 88% (MAT). The specificities were 88 to 89% (SAT), 98% (CAT), and 88% (MAT). For populations with a low prevalence of disease, increased specificity offers higher predictive value, so the CAT and MAT are preferable for screening purposes and the choice between tests depends on the number and frequency of tests performed. All sera reactive in the CAT and MAT should be retested with the TAT.

Agglutination Tests

Evaluation of MUREX SUDS Toxo test.

The SUDS Toxo test (MUREX Corp., Norcross, Ga.) was compared with the indirect hemagglutination test (IHA) and the indirect fluorescent-antibody test (IFA) by examining 404 serum specimens, including 64 (15.8%) specimens with IFA titers of greater than or equal to 1:2. When SUDS was compared with IHA, sensitivity (96.4%), specificity (97.9%), and negative predictive value (99.4%) indicated that there were similar reactivities between the two tests. When an IFA titer of greater than or equal to 1:16 was considered significant and IHA and SUDS were compared with IFA, IHA was slightly less sensitive but had a higher positive predictive value than did SUDS; however, there was no statistical difference between the tests. When SUDS was compared with IFA, in which a titer of greater than or equal to 1:16 was considered significant, the high negative predictive value (100%), excellent sensitivity (100%) and specificity (98.3%), and ease of performance made SUDS an attractive alternative to IHA for screening single serum specimens for toxoplasmosis.

Animals

Evaluation of the Bio-EnzaBead test for syphilis.

The sensitivity and specificity of the Bio-EnzaBead test for syphilis and the fluorescent treponemal antibody-absorption (FTA-ABS) test were determined by examining 262 serum samples, including 202 serum samples from patients with confirmed syphilis in various stages. Overall correlation with patient history was 95.8% with both tests. False-negative Bio-EnzaBead tests occurred in 9 of 86 (10.5%) cases of late-latent syphilis (greater than 2 years) and in 1 of 38 (2.6%) cases for which the stage of disease could not be determined. False-negative FTA-ABS tests occurred in 5 of 86 (5.8%) cases of late-latent syphilis (greater than 2 years) and in 2 of 38 (5.3%) cases for which the stage of disease could not be determined. One false-positive test occurred with Bio-EnzaBead, and the cause could not be determined. The reproducibility of the Bio-EnzaBead test was excellent when spectrophotometric readings were calibrated against either air or substrate blanks. The Bio-EnzaBead test for syphilis is a suitable alternative to the FTA-ABS test.

Enzyme-Linked Immunosorbent Assay

Effects of pesticides and drugs on working memory in rats: continuous delayed response.

Effects of four pesticides (carbaryl, propoxur, chlordimeform, and deltamethrin) and four reference drugs (physostigmine, scopolamine, methscopolamine, and chlordiazepoxide) were measured in two delayed response, working memory procedures: go-no go alternation in which rats initiated their own trials, and spatial reversals. Four of these compounds (carbaryl, propoxur, physostigmine, and scopolamine) were also tested in a go-no go alternation procedure in which animals did not initiate their trials. The pesticides and physostigmine did not selectively affect working memory in any of the procedures: low doses only moderately decreased response accuracy, whereas higher doses suppressed responding indiscriminately. The pesticides and physostigmine had similar effects on go-no go alternation (i.e., working memory) and analogous go-no go discrimination performance. Effects on go-no go alternation performance did not depend on whether the animals initiated their own trials. Scopolamine, in contrast, appeared to disrupt working memory. It profoundly disrupted accuracy at doses that only moderately decreased over-all responding and impaired go-no go alternation accuracy much more than discrimination accuracy.

Animals

Effects of pesticides and drugs on working memory in rats: continuous non-match.

Effects of four pesticides (carbaryl, propoxur, chlordimeform, and deltamethrin) and two reference drugs, physostigmine and chlordiazepoxide, were measured on the performance of rats trained on a continuous non-match (CNM) delayed comparison, working memory procedure. These same compounds were also tested in analogous, large and small stimulus difference discrimination (i.e., non working-memory) procedures. The effects of the pesticides and physostigmine on CNM performance were qualitatively similar, and also similar to their effects on discrimination performance. As dosage of these compounds increased, only small effects on accuracy were observed, followed at still larger doses by an abrupt and non-selective decrease in all responding. The pesticides and physostigmine did not selectively affect working memory: the magnitude of their effects did not increase with intertrial interval, and the compounds were equally effective in disrupting discrimination and CNM performance. Effects of chlordiazepoxide on performance in the CNM and discrimination control procedures differed qualitatively from those of the pesticides and physostigmine.

Animals