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Biomedical subjects

C E Davis

Publications and source records attributed to C E Davis.

At least 109 records · Page 6Linked to original sources

Distributions of hemostatic variables in blacks and whites: population reference values from the Atherosclerosis Risk in Communities (ARIC) Study.

The Atherosclerosis Risk in Communities Study measured hemostatic variables in nearly 16,000 men and women, aged 45 to 64 years, from four US communities. This report, based on the first 12,681 participants, presents distributions of fibrinogen concentration, factor VII activity, factor VIII activity, von Willebrand factor antigen, protein C antigen, antithrombin III activity, and activated partial thromboplastin time. Many of the hemostatic variables differed between blacks and whites, and by sex and age. For example, compared to whites, blacks had higher mean values of fibrinogen, factor VIII, von Willebrand factor, and antithrombin III, and lower mean values of protein C. Some seasonal fluctuations in hemostatic variables were noted; most notably, mean values of factor VII were lowest and protein C were highest in subjects examined in the summer compared to those examined during the other seasons. These results provide population-based reference values on blacks and whites for those interested in the relation of hemostasis to disease.

Arteriosclerosis↗

Body mass index and body girths as predictors of mortality in black and white women.

BACKGROUND: The high prevalence of obesity in black women has been hypothesized to contribute to higher rates of coronary heart disease and total mortality. Investigators have recently refined the study of obesity by differentiating anatomic patterns of the physical location of adipose tissue on the body. We examined fat patterning as a predictor of mortality in black women. METHODS: Body mass index (BMI) and body girths were examined as predictors of all-cause and coronary heart disease mortality during 25 to 28 years of follow-up in black and white women in the Charleston Heart Study. RESULTS: The BMI was associated with all-cause and coronary heart disease mortality in white, but not black, women. After controlling for differences in BMI, the risk of all-cause mortality was greater in white women with larger chest and abdominal girths, while midarm girths were inversely associated with mortality. The hazard at the 85th percentile relative to the 15th percentile of abdomen/midarm ratio was 1.44 in models that included BMI, education, and smoking as covariates. In black women, the girths were not predictive of either all-cause or coronary heart disease mortality. CONCLUSIONS: The failure of BMI and fat patterning to predict mortality in black women challenges previously held assumptions regarding the role of overweight in the higher mortality experienced by black women.

Adult↗

Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors.

Recent prospective investigations have reported that higher plasma fibrinogen concentrations and higher factor VII coagulant activity are associated with greater risk of cardiovascular disease. To discover what characteristics may influence fibrinogen and factor VII, we analyzed data from the Atherosclerosis Risk in Communities Study obtained from over 12,000 men and women, aged 45-64 years, from four communities in December 1986 to June 1989. Fibrinogen was higher in blacks than whites and in women than men; in general, it increased with age, smoking, body size, diabetes, fasting serum insulin, LDL cholesterol, lipoprotein(a), leukocyte count, and menopause, and it decreased with ethanol intake, physical activity, HDL cholesterol, and female hormone use. Factor VII was higher in women than men and, in women, increased with age; in both sexes, it increased with body size, triglycerides, LDL cholesterol, and HDL cholesterol, and it decreased with ethanol intake. These findings indicate that elevations in fibrinogen and factor VII may be modifiable through appropriate lifestyle changes.

Body Constitution↗

Myosin isoform transitions and physiological properties of regenerated and re-innervated soleus muscles of the rat.

Soleus muscles in young female rats were destroyed by the local injection of the crude venom of the Australian tiger snake, Notechis scutatus and allowed to regenerate. The regenerated muscles consisted almost exclusively of type I muscle fibres, and histograms of fibre cross-sectional area were unimodal. In contrast the normal contralateral muscles consisted of a mixture of type I and IIa fibres, and histograms of fibre cross-sectional area were bimodal. There was no change in the ability of the regenerated muscles to generate tension in response to indirect stimulation, and muscle fibre number and motor unit index were similar to controls. The regenerated muscles often contained split muscle fibres, but if re-innervation of the regenerated muscles was delayed, splitting did not occur. The principal features of the regenerated muscles (fibre type homogeneity, unimodal histograms of muscle fibre area, normal numbers of muscle fibres and normal motor unit index) were reproduced in soleus muscles that were simply denervated by nerve crush and allowed to re-innervate. We conclude that the phenotypic homogeneity of the regenerated muscles is a consequence of the temporary disconnection of muscle from nerve, rather than of the cycle of degeneration/regeneration, and suggest that this disconnection results in the reprogramming of the soleus motor neurones.

Animals↗

Expression and deletion analysis of the Trypanosoma brucei rhodesiense cysteine protease in Escherichia coli.

Trypanosoma brucei, the cause of African sleeping sickness, differentiates in the mammalian bloodstream from a long, slender trypanosome into a short, stumpy trypanosome. This event is necessary for infection of the tsetse fly and maintenance of the life cycle. We have previously shown that the stumpy form contains 10- to 15-fold-greater cysteine protease activity than either the slender form or the insect midgut procyclic, and we have isolated a cDNA encoding the protease. In order to determine whether the cDNA encodes the developmentally regulated cysteine protease, we have purified the protease from trypanosomes and have made a polyclonal antiserum against it. The trypanosomal protease gene was then expressed in Escherichia coli with three different methionines within the pre- and propeptides acting as initiation sites. In each case, a protein was synthesized that was recognized by an antiserum specific for the developmentally regulated trypanosomal cysteine protease. The protein synthesized from the more upstream initiation site within the propeptide was proteolytically active. The recombinant protease and the trypanosomal enzyme were identical with respect to peptide substrates and protease inhibitors. The protein remained active when synthesized in a truncated form lacking the nine consecutive prolines and carboxy-terminus extension, indicating that the terminal 108 amino acids are not necessary for proteolytic activity.

Amino Acid Sequence↗

A single cholesterol measurement underestimates the risk of coronary heart disease. An empirical example from the Lipid Research Clinics Mortality Follow-up Study.

In prospective epidemiologic studies of coronary heart disease, a single measurement of cholesterol is made to assess its relationship to the risk of coronary disease. Statistical theory states that if this measurement is subject to within-individual variability, the strength of the relationship will be underestimated. This is empirically shown for the example of plasma cholesterol. For the Lipid Research Clinics Follow-up Study population (comprising 2170 white men over 30 years of age), the age-adjusted coronary heart disease mortality regression coefficient increases from .453 to .496 if the average of two cholesterol measurements is used instead of a single measurement. Since the correlation between the two repeated cholesterol measurements is .815, an increase in the regression coefficient up to .556 would be expected if the true cholesterol values were available. Thus, epidemiologic studies have substantially underestimated the strength of the relationship between cholesterol levels and the risk of coronary disease by calculating the relationship on the basis of a single cholesterol determination.

Adult↗

The assessment of muscle fibre loss after the injection of the venom of Notechis scutatus (Australian tiger snake).

We have used the W.H.O. International Reference Venom from the Australian tiger snake, Notechis scutatus, to study possible methods for the assessment of local myonecrosis caused by this venom. We made subcutaneous injections of various doses (0.25-20.0 micrograms) of venom into the antero-lateral aspect of the rat hind limb. The soleus muscle was removed after 24 hr and muscle fibre loss calculated from photo-montages of histological sections. Muscle tissue which had been either frozen or wax-embedded was preferable to resin-embedded tissue for making muscle fibre counts. There was a dose-dependent relationship between muscle fibre loss and the amount of venom inoculated. One microgramme of crude venom caused the loss of 50% of muscle fibres from the soleus muscle. This dose of venom neutralized by 1.5 microliters of the W.H.O. International Standard Antivenom for Notechis scutatus. Muscle wet weight increased following the inoculation of venom, to reach a peak of 42% at a dose of 0.5 microgram. There was no correlation between fibre loss and increase in wet weight. Biochemical analysis of both the venom-damaged muscle and the plasma showed that there was a strong linear correlation (r = 0.95) between loss of muscle aspartate aminotransferase and muscle fibre loss. There was a non-linear relationship between muscle fibre loss and the increase of plasma aspartate aminotransferase (EC 2.6.1.1). There was no correlation between either the loss of muscle creatine kinase or the increase of plasma creatine kinase and muscle fibre loss. We conclude that direct measurements are required to calculate muscle fibre loss with precision, but that the loss of muscle aspartate aminotransferase AST and its release into the plasma may also be important criteria to be used when studying local necrosis.

Animals↗

Empirical Bayes estimates of subgroup effects in clinical trials.

At the completion of a clinical trial it is often desirable to compare the treatments within subgroups of patients. The results of the subgroup analysis are usually reported for the subgroups within which sizable treatment differences are found. This practice can lead to an overestimate of the difference between treatments within the subgroups reported. One way of adjusting for this bias is to use empirical Bayes methods which shrink the extreme estimates toward the overall measure of treatment difference. Both point and interval estimates can be obtained. The computations are illustrated with an example using subgroup data from the Lipid Research Clinics Coronary Primary Prevention Trial.

Bayes Theorem↗

Identification of a developmentally regulated cysteine protease of Trypanosoma brucei.

Trypanosoma brucei undergoes dramatic metabolic changes during differentiation from the mammalian bloodstream form into the procyclic form of the insect midgut. Because modulation of protein degradation is likely to be important during this process we studied T. brucei for life cycle mediated proteolysis. We detected an increase in the activity of a 28 kDa protease as pleomorphic GUTat 3.1 trypanosomes differentiate in the mammalian bloodstream from long slenders into short stumpies. Short stumpy trypanosomes hydrolyse z-Phe-Arg-AMC 12 fold more actively than either long slenders or procyclics. The 28 kDa protease is activated by dithiothreitol and is inhibited by trans-epoxysuccinyl-L-leucyl-amido(4-guanidino) butane (E-64), indicating that it is a cysteine protease. The proteolytic activity of monomorphic ILTat 1.4 trypanosomes does not increase during mammalian parasitemia. If monomorphic ILTat 1.4 trypanosomes are induced to differentiate into short stumpies by exposure to difluoromethylornithine, however, the activity of the 28 kDa cysteine protease increases 8 fold. This suggests that polyamine depletion induces the 28 kDa cysteine protease and that its expression may be regulated by mechanism not previously described in protozoa.

Animals↗

Comparisons of cause of death verification methods and costs in the lipid research clinics program mortality follow-up study.

Classification of causes of death by a nosologist is standardized and relatively inexpensive, although the quality of the data recorded on death certificates has been subjected to criticism and the level of detail may not allow examination of specific circumstances of the death. A costly alternative is classification by a panel of physicians reviewing additional clinical information. The costs associated with both methods of classification as utilized by the Lipid Research Clinics Program Mortality Follow-up Study are presented along with their advantages and disadvantages. For deaths among the elderly (65 years or older), determination of the underlying cause of death may be difficult, especially as regards cardiovascular disease causes of death using only the death certificate, and impossible for classifying sudden death. Both classification methods are compared for 268 deaths among the elderly and 155 deaths among the nonelderly males and females participating in the study. The kappa statistics for observer agreement indicate moderate agreement (k = 0.58) and were not significantly different between the two age-groups (p greater than 0.10). Thus, the agreement between the methods was not affected significantly by the age of the deaths being classified. However, examination of the agreement chart showed a preference by the nosological classification for cardiovascular classification in the elderly population. The effect of the different classifications upon the analysis of the predictive value of high-density lipoprotein cholesterol on coronary heart disease mortality showed little difference between both methods of classification.

Adult↗

myc-related proteins and DNA sequences in Trypanosoma brucei.

The cAMP content of Trypanosoma brucei increases in parallel with ascending mammalian parasitemia to very high levels just before differentiation of the long-slender to the short-stumpy bloodstream form. Because expression of myc oncogenes is required for vertebrate cells to interpret proliferation signals and declines in response to cAMP mediated differentiation, we investigated whether T. brucei also harbored myc-like proteins and genes. Accordingly, we probed lysates of long-slenders, short-stumpies and procyclics (insect midgut stage) with antibody to myc proteins and also hybridized myc gene family sequences to procyclic DNA. We found that antibody to myc-family proteins of mammals reacts with 40 kDa and 55 kDa proteins in all three life cycle stages, and that procyclic DNA contains three EcoRI fragments that are homologous to a v-myc probe. One of these fragments also hybridizes to a synthetic 25-mer oligonucleotide deduced from a consensus sequence in the second exon of the myc family and expresses a 3.2 kb mRNA transcript in Northern blots of procyclic RNA. The conservation of myc-family homologous across the broad phylogenetic gap between mammals and trypanosomes illustrates ancient evolutionary relationships and raises the possibility of stage-specific expression of myc genes during the life cycle of T. brucei.

Animals↗

Formulation of malaria treatment policy for children in Côte d'Ivoire as chloroquine resistant Plasmodium falciparum spreads into west Africa.

To develop a malaria treatment policy for children with Plasmodium falciparum, an in vivo and in vitro chloroquine (CQ) sensitivity study was conducted in Côte d'Ivoire in September 1986. The efficacy of a single dose of CQ (10 mg base kg-1, C10) was tested with assessment of subjects on Days 2 and 7 after treatment; 108 (99%) of 109 children were aparasitaemic on Day 7. Of 33 isolates of P. falciparum tested in vitro, two (6%) were resistant to CQ. Although C10 appeared effective clinically and parasitologically in Côte d'Ivoire, a treatment dose of 25 mg of CQ base kg-1 (C25), over three days, was recommended as first-line therapy for malaria. This was because in vivo CQ-resistance will soon spread into other West African countries including Côte d'Ivoire, the C25 dose still retains clinical effectiveness in most partially-immune persons living in areas with low-level chloroquine resistance, and alternate drugs are more expensive.

Animals↗

Effects of electrical stimulation on the post-mortem biochemical changes and texture of broiler pectoralis muscle.

A study was conducted to determine the influence of electrical stimulation (50,200, or 350 V ac) on biochemical and textural changes in broiler breast muscle. Sixty-four broilers were stunned (50 V ac) prior to kill, and all but a control group were pulse stimulated during bleeding. After processing, carcasses were held in 10-C water for 1 h, then in 2-C ice/water slush for 1 h prior to muscle removal at 2 h post-mortem (PM). Bagged samples were held at 2 C for 24 h, then cooked. The pH, R value (ratio of adenine nucleotides to inosine nucleotides), cook yield, fluids and solids lost (F&S), and objective texture were measured. In addition, 16 broilers processed in the same manner were used in producing a profile of sarcoplasmic protein/enzyme changes in the breast muscle by cation exchange fast protein-liquid chromatography at 10 min, 2, and 24 h PM. The R values and soluble protein were also determined. Stimulation at 200 and 350 V accelerated the onset of rigor noted by lower pH values at 10 min and 1 h PM, and higher R values at 2 h PM. Muscle stimulated at 350 V exhibited the lowest cook yield and highest percentage of F&S lost, suggesting both the loss of functional properties and muscle integrity due to this treatment. All control and stimulated samples exhibited shear values in excess of what would be considered tender. Hardness and chewiness values increased as stimulation voltage levels increased. Only one of the seven principal chromatographic peaks decreased in response to increased electrical stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Regulation of activated macrophage antimicrobial activities. Identification of lymphokines that cooperate with IFN-gamma for induction of resistance to infection.

Macrophages exposed to lymphokines (LK) before exposure to parasites develop the capacity to resist infection with amastigotes of Leishmania major. Activity of LK for induction of this activated macrophage effector function is abrogated by depleting the LK of IFN-gamma, yet IFN-gamma is incapable of inducing the activity by itself. To identify the factors in LK that serve as second signals for induction of resistance to infection, we exposed macrophages to the following cytokines available as recombinant or highly purified reagents: CSF-1, granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-1, -2, -3, -4, and -5, and IFN-alpha/beta. None of these factors induced resistance to infection by themselves or in combination with each other; in the presence of 50 U/ml IFN-gamma, three cytokines were active: GM-CSF, IL-2, and IL-4. IFN-gamma was an essential component of the activation cascade but was insufficient by itself to induce the effector reaction. Cytokines that act as cofactors with IFN-gamma worked directly on macrophages and not through another cell in the peritoneal cell (PC) cultures. Activation of PC depleted of Thy-1.2+ cells (85 +/- 5% macrophages) and bone marrow-derived macrophages (100% macrophages) showed that 50% maximal doses of GM-CSF, IL-2, and IL-4 for these macrophage-enriched populations were not different than for untreated PC. Unlike other effector reactions of activated macrophages, bacterial LPS did not synergistically enhance the activity of any of the cytokines, alone or in combination with IFN-gamma. Antibody depletion of the active cytokines from LK, singly or in combination, failed to alter the dose response of the active factors in whole LK for induction of resistance to infection. Thus, multiple factors can provide the second signal for IFN-gamma in the induction of resistance to infection, namely, GM-CSF, IL-2, IL-4, and at least two additional undefined factors in whole LK. Resistance to infection may be the first example of an activated macrophage effector reaction that has an absolute requirement for more than one endogenous signal for its induction.

Adjuvants, Immunologic↗