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Biomedical subjects

D A Dawson

Publications and source records attributed to D A Dawson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Development of an internal restriction control in the PCR detection of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation.

BACKGROUND: Detection of the presence of 677C/T allele in the human MTHFR gene is easily achieved by amplification using primers designed to span this region. Hinf I digestion, occurring only in the 677T allele, subsequently discriminates between the two alleles. Existing methods, however, do not control for failed restriction endonuclease digestion. METHODS AND RESULTS: A new forward, modified primer was designed and placed further upstream to create a Hinf I site, which, because it is present in both alleles, would serve as an internal restriction control. CONCLUSIONS: By allowing an additional restriction to take place in both the normal and mutated alleles, the use of the new primer provided for an internal restriction control.

Alleles↗
PubMed1999

Endothelin receptor antagonist preserves microvascular perfusion and reduces ischemic brain damage following permanent focal ischemia.

Synthesis and release of the potent vasoconstrictor peptide endothelin-1 (ET-1) increases following cerebral ischemia and has previously been shown to mediate the delayed hypoperfusion associated with transient global ischemia. In this study we assessed the impact of ET-1 on perfusion and infarct volume in a focal model of cerebral ischemia by use of the selective ET(A) receptor antagonist Ro 61-1790 (affinity for ET(A) receptor 1000 fold greater than ETB receptor). Control rats subjected to permanent middle cerebral artery occlusion (MCAO) showed extensive reductions in microvascular perfusion 4 h post-MCAO that were significantly attenuated by Ro 61-1790 pretreatment (10 mg/kg, i.v.). Ro 61-1790 concomitantly and significantly reduced the ischemic lesion volume in the same animals. This effect was maintained 24 h post-MCAO providing that the animals received additional i.v. injections of 5 mg/kg Ro 61-1790 at 5 h and 8 h after MCAO. These findings demonstrate that ET(A) receptor antagonism partially preserves tissue perfusion following focal ischemia and that this effect is associated with significant neuroprotection. The results also support the hypothesis that vasoactive mediators, and ET-1 in particular, are important contributors to the pathogenesis of cerebral ischemic injury.

Animals↗
PubMed1999

The isolation and mapping of 19 tetranucleotide microsatellite markers in the chicken.

Microsatellites consisting of tetranucleotide repeats are more easily, and consequently efficiently, scored than loci consisting of dinucleotides. However, they are much less frequent in the genome. A hybridisation selection protocol was therefore employed to generate a chicken genomic library enriched for inserts containing the tetranucleotide repeat motif (TTTC)n. Forty-five new microsatellite sequences were isolated that mainly consisted of perfect repeats of the tetranucleotide (TTTC) motif. Nineteen markers were mapped in one or both of the East Lansing and Compton international chicken reference populations.

Animals↗
PubMed1999

Development of an internal restriction control in the PCR detection of the prothrombin 20210A mutation.

Detection of the presence of the 20210A/G allele in the human prothrombin gene is easily achieved by amplification using primers designed to span this region. The downstream primer creates a HindIII restriction site if the 20210A variant is present. A new forward upstream primer was designed to incorporate a naturally occurring HindIII site that, as it is present in both alleles, serves as an internal restriction control. Using this technique, the DNA of 292 unselected patients with venous thromboembolic disease was analysed. Of the 149 white patients, 4.7% were heterozygous for this mutation but none of the African Black patients were positive.

3' Untranslated Regions↗
PubMed1999

Cerebrovascular hemodynamics and ischemic tolerance: lipopolysaccharide-induced resistance to focal cerebral ischemia is not due to changes in severity of the initial ischemic insult, but is associated with preservation of microvascular perfusion.

Lipopolysaccharide (LPS), administered 72 hours before middle cerebral artery (MCA) occlusion, confers significant protection against ischemic injury. For example, in the present study, LPS (0.9 mg/kg intravenously) induced a 31% reduction in infarct volume (compared with saline control) assessed 24 hours after permanent MCA occlusion. To determine whether LPS induces true tolerance to ischemia, or merely attenuates initial ischemic severity by augmenting collateral blood flow, local CBF was measured autoradiographically 15 minutes after MCA occlusion. Local CBF did not differ significantly between LPS- and saline-pretreated rats (e.g., 34 +/- 10 and 29 +/- 15 mL x 100 g(-1) x min(-1) for saline and LPS pretreatment in a representative region of ischemic cortex), indicating that the neuroprotective action of LPS is not attributable to an immediate reduction in the degree of ischemia induced by MCA occlusion, and that LPS does indeed induce a state of ischemic tolerance. In contrast to the similarity of the initial ischemic insult between tolerant (LPS-pretreated) and nontolerant (saline-pretreated) rats, microvascular perfusion assessed either 4 hours or 24 hours after MCA occlusion was preserved at significantly higher levels in the LPS-pretreated rats than in controls. Furthermore, the regions of preserved perfusion in tolerant animals were associated with regions of tissue sparing. These results suggest that LPS-induced tolerance to focal ischemia is at least partly dependent on the active maintenance of microvascular patency and hence the prevention of secondary ischemic injury.

Animals↗
PubMed1999

Combined osteolathyric effects of beta-aminopropionitrile and penicillamine on Xenopus embryos: statistical comparison with dose-addition and independence.

The combined osteolathyric effects of beta-aminopropionitrile (beta APN) and penicillamine (PNC) on developing Xenopus embryos were determined and compared with theoretical effects for the dose-addition and independence models. The testing protocol utilized a 1.2-factor matrix design that generated two single chemical and seven mixture concentration-response curves within 36 treatments. Testing was for 96-h with daily solution removal and replacement. The chi 2 goodness-of-fit test was used to compare experimental responses with theoretical responses. Response curve analyses indicated, in general, a combined effect between that expected for dose-addition and that for independence, which is a combined effect typical of chemicals acting dissimilarly.

Aminopropionitrile↗
PubMed1998

Beyond black, white and Hispanic: race, ethnic origin and drinking patterns in the United States.

This study used data on 42,862 U.S. adults, including 18,352 past-year drinkers, to describe differentials by race and national origin in U.S. drinking patterns. Age-sex standardized estimates were presented within 21 categories of ethnic origin for whites and within five categories each for individuals of black and other races. Of the three racial groups, whites were the most likely to drink, but blacks had the highest volume of intake and frequency of heavy drinking. Differences by ethnic origin within racial categories were as marked as differentials between races. Compared to whites of European origin, those of Hispanic and native American origin were less likely to drink but consumed more alcohol on days when they drank. Whites of Southern and Eastern European origin drank proportionately more wine and demonstrated more moderate drinking patterns (lower intake per drinking day and/or less frequent heavy drinking) than those of Northern or Central European origin. Hispanics of Caribbean origin were less prone to heavy drinking than other white Hispanics; similarly, blacks from the English-speaking Caribbean showed more moderate drinking patterns than other blacks. Individuals of Asian origin, in particular those of non-Japanese origin, had the most moderate drinking patterns within the category of other race. Although the black/white differentials in volume of intake and frequency of heavy drinking disappeared after adjusting for marital status, education and income, most of the differences by ethnic origin retained their statistical significance if not their original magnitudes. These findings indicate that cultural forces exert a strong effect on drinking behavior. Differences among European whites with respect to prevalence of drinking, beverage preference and frequency of heavy drinking suggest that the association between ethnic origin and drinking behavior may persist even after many generations of presumed acculturation.

Acculturation↗
PubMed1998

Symptoms and characteristics of individuals with different types of recovery from DSM-IV alcohol dependence.

Symptoms and criteria for DSM-IV alcohol dependence and demographic and drinking characteristics are compared for three groups. Group I (N = 1,044) consists of persons who formerly met the criteria for dependence but were abstinent in the past year, Group II (N = 2,325) consists of persons who were formerly dependent but did not meet the criteria for abuse or dependence in the past year despite drinking, and Group III (N = 22,204) consists of persons who never met the criteria for dependence. Members of Group II lay between members of Groups I and III in terms of the numbers of prior dependence symptoms and criteria, past level of intake, degree of familial alcoholism and history of alcohol treatment. Both groups of former alcoholics were equally likely to have experienced withdrawal, drinking more/longer than intended and tolerance. The criteria that most strongly distinguished the groups were continued use despite physical or psychological consequences, time spent drinking and activities given up, all of which were far more common in Group I than in Group II. Members of Group II had earlier onsets of heavy drinking and dependence than members of Group I, supporting the existence of a developmentally limited subtype of alcoholism that is subject to spontaneous remission in early adulthood without treatment. The paper compares three options for tightening the criteria for dependence, all of which remove more members from Group II (28% to 41% depending on option) than from Group I (12% to 19%).

Adult↗
PubMed1998

Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey.

The purpose of this study was to examine the relationship between early onset drug use and the development of lifetime DSM-IV drug abuse and dependence using a representative sample of the U.S. population. Prevalences of lifetime drug abuse and dependence were estimated for each year of age of onset of drug use from ages 13 and younger to 21 and older for the overall sample of drug users by race and gender. Linear logistic analyses were conducted to assess the relationship between age of drug use onset and lifetime drug use disorders controlling for important covariates. The major finding of this study was that early onset drug use is a significant predictor of the subsequent development of drug abuse over the life course. Early onset drug use was also a significant predictor of the subsequent development of lifetime alcohol dependence among males, females, and nonblacks, but not among blacks. After adjusting for important model covariates, the likelihood of lifetime drug abuse and dependence among the total sample of lifetime drug users was reduced by 4% and 5% with each year drug use onset was delayed. Implications of these findings are discussed in terms of the importance of collecting national data on drug use, abuse and dependence and the need for further research and its integration with prevention efforts.

Adolescent↗
PubMed1998

Alcoholic beverage preference and risks of alcohol-related medical consequences: a preliminary report from the National Longitudinal Alcohol Epidemiologic Survey.

In studying the alcohol-morbidity association, a substantial amount of attention and efforts has been focused on volume of alcohol intake. Considerably less is known about the differential health effects of beverage types. The present study used a most recent national household survey of the U.S. general population on drinking practices, alcohol use disorders, and their associated disabilities. The prevalence of a broad range of alcohol-related diseases was examined with respect to preferred beverage type, as well as consumption level. Our findings showed a reduced health risk associated with beer and wine drinking for a number of physical disorders, and a somewhat favorable cardiovascular effect of these two beverage types in relation to abstention. Among preferrers of beer, wine, and liquor, the results indicate that liquor preference is associated with elevated morbidity for several medical consequences. However, interpretation of results and the public health implications of these findings need to be taken cautiously, because sociodemographic and other behavioral characteristics were not considered in this preliminary report.

Adolescent↗
PubMed1998

Enzyme-linked immunosorbent assay for detection of feline herpesvirus 1 IgG in serum, aqueous humor, and cerebrospinal fluid.

Feline herpesvirus 1 (FHV) is an important cause of feline ocular and respiratory disease, but the role the virus plays in central nervous system disease of cats has not been explored. The study described here was performed to validate an indirect enzyme-linked immunosorbent assay (ELISA) to detect FHV-specific IgG antibodies for use in feline epidemiologic, ocular, and central nervous system disease studies. The indirect IgG ELISA was applied to serum, aqueous humor, and cerebrospinal fluid from cats. Serum FHV IgG ELISA results were compared with those of serum neutralization in client-owned cats and laboratory-housed cats following vaccination. Of the 100 client-owned cats tested by ELISA, 97 had detectable FHV IgG; 95 had titers >32. The FHV IgG ELISA was more sensitive than serum neutralization and could be used with aqueous humor and cerebrospinal fluid. Cats with inflammatory central nervous system or ocular diseases had significant leakage of serum proteins into aqueous humor and cerebrospinal fluid, necessitating use of cutoff values derived from serum when these fluids were assessed.

Animals↗
PubMed1998

Volume of ethanol consumption: effects of different approaches to measurement.

OBJECTIVE: Eight different approaches to measuring alcohol consumption were compared in terms of average daily volume of ethanol intake, selected percentiles of the volume distribution, the proportion of drinkers exceeding a volume-based cutpoint for moderate drinking and the estimated association between volume of intake and alcohol use disorders. METHOD: Data were drawn from the 1988 National Health Interview Survey and the 1992 National Longitudinal Alcohol Epidemiologic Survey. The eight approaches compared overall and beverage-specific questions, reference periods of varying lengths, and measures based solely on usual intake with those that incorporated different aspects of atypical heavy drinking. RESULTS: Average daily ethanol intake ranged from 0.43 oz based on two questions on current usual frequency and quantity of drinking (assuming 0.5 oz of ethanol per drink) to 0.72 oz based on 21 questions that included usual and heaviest consumption of beer, wine and distilled spirits in the year preceding interview. CONCLUSIONS: Estimated volume was highly sensitive to the number and types of questions upon which it was based, and changes in formulation that resulted in relatively small increases in mean volume often were associated with much larger increases in the proportion of drinkers exceeding some specified level of intake and in the estimated association between consumption and alcohol use disorders. These issues should be considered when deciding on the consumption items to be included in alcohol surveys.

Adolescent↗
PubMed1998

Family history of alcoholism and gender: their combined effects on DSM-IV alcohol dependence and major depression.

OBJECTIVE: Data from a representative sample of U.S. adults were used to assess the extent of familial alcoholism, to examine its association with the odds of DSM-IV lifetime alcohol dependence, major depression, and their comorbid occurrence, and to determine whether the magnitude of this association was different for men and women. METHOD: Self-report data from a sample of 42,862 U.S. adults (25,043 women) 18 years of age and over were analyzed by means of multiple logistic regression models that predicted the odds of various combinations of DSM-IV alcohol dependence and major depression. RESULTS: After adjusting for potential confounders through multiple logistic regression, family history saturation was associated with increased odds of dependence only, depression only, and all primary-secondary-concurrent combinations of these two disorders. The estimated effects were greatest for comorbid dependence and depression, next highest for dependence only and lowest for depression only. Differences in odds ratios among these groups increased with degree of family history saturation but were statistically significant at all levels of saturation. The effects of family history were greater for men than women for the outcome of primary depression followed by secondary dependence, but only at the higher levels of saturation. Among persons with lifetime major depression, family history of alcoholism had a positive independent association with the conditional odds of having experienced comorbid alcohol dependence. It had a weaker but still significant association with the odds of comorbid depression, conditional upon having experienced dependence, and this association was stronger among men than among women. For most outcomes, family history effects were stronger for paternal male and maternal female relatives than for paternal female and maternal male relatives. CONCLUSIONS: These findings supported prior research showing more familial alcoholism among persons with comorbid dependence and depression than among those with dependence alone. Gender differences were supportive of the proposed distinction between pure depression and depressive-spectrum disease.

Adult↗
PubMed1998

Phase III interlaboratory study of FETAX, Part 2: interlaboratory validation of an exogenous metabolic activation system for frog embryo teratogenesis assay--Xenopus (FETAX).

Interlaboratory validation of an exogenous metabolic activation system (MAS) developed for the alternative, short-term developmental toxicity bioassay, Frog Embryo Teratogenesis Assay-Xenopus (FETAX) was performed with cyclophosphamide and caffeine. Seven study groups within six separate laboratories participated in the study in which three definitive concentration-response experiments were performed with and without the MAS in a side-by-side format for each chemical. Since both chemicals had been previously tested in FETAX, the test concentrations were provided to each laboratory prior to testing. Interlaboratory coefficient of variation (CV) values for unactivated cyclophosphamide (no MAS) were 15%, 15%, 29%, and 25% for the 96-hr LC50, 96-hr EC50 (malformation), Minimum Concentration to Inhibit Growth (MCIG), and Teratogenic Index (TI) values, respectively. Addition of the MAS increased the CV values of each endpoint at least 3.9-fold. Interlaboratory CV values for unactivated caffeine were 31%, 18%, 31%, and 46% for the 96-hr LC50, 96-hr EC50 (malformation), MCIG, and TI values, respectively. Addition of the MAS decreased the CV values of each respective endpoint by at least 1.6-fold. Results indicated that bioactivated toxicants may be prone to greater variability in response amongst laboratories than compounds, which are detoxified. Even though more variability was noted with activated cyclophosphamide, results were within interlaboratory variation expected for other aquatic-based bioassays. Thus, results from these studies warrant the continued use and further refinement of FETAX for alternative developmental toxicity assessment.

Abnormalities, Drug-Induced↗
PubMed1997

Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat.

Microcirculatory impairments have theoretically been proposed as a potential factor in the development of ischemic injury, but few attempts have been made to directly assess microvascular patency following stroke. To address this issue we investigated the temporal changes in microvascular perfusion induced by permanent focal ischemia. Halothane-anesthetized spontaneously hypertensive rats were subjected to middle cerebral artery occlusion (MCAO) of 5 min to 4 h duration. Two fluorescent tracers (FITC-dextran and Evans blue) were then sequentially administered i.v. and allowed to circulate for 10 and 5 s respectively. Tissue sections were examined by fluorescent microscopy, and the mean number of perfused microvessels/mm2 calculated for cortical areas representing non-ischemic (Region A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham-operated controls, virtually all microvessels perfused with tracer within 5 s. In contrast MCAO induced significant reductions in the number of perfused microvessels in Regions B and C. The most marked impairments in perfusion were observed in core MCA territory (e.g. 2-10% of control values for 5 s circulation period) while, initially, the deficit was less severe in penumbral cortex. However, a secondary perfusion impairment developed over time in the perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than at earlier time points (e.g. 72%, 71% and 22% of control value for 0.5, 1 and 4 h MCAO respectively; 10 s circulation period). In conclusion, MCAO induced severe impairments in microcirculatory perfusion within the core ischemic region, and to a lesser extent in the penumbra. However, the development of a more severe perfusion deficit in the penumbra within 4 h of MCAO supports the hypothesis that microcirculatory failure in this region contributes to its recruitment to the ischemic infarct.

Analysis of Variance↗
PubMed1997

Changes of cytoskeletal protein immunostaining in myelinated fibre tracts after focal cerebral ischaemia in the rat.

Breakdown of the cytoskeleton has been proposed to be a central event in the evolution of ischaemic brain damage. Alterations in the immunostaining of cytoskeletal proteins, particularly microtubule-associated protein (MAP) 2, have been suggested to be sensitive markers of ischaemic damage in the somatodendritic compartment. However, axons are also subjected to the adverse conditions created by an ischaemic challenge, but MAP2 is not located in the axonal compartment. The purpose of the present study was to examine immunostaining of beta-tubulin, MAP1a and MAP5, all of which are located in axons as well as perikarya, specifically in myelinated fibre tracts in rats subjected to unilateral middle cerebral artery (MCA) occlusion. In sham-operated control rats immunostaining of all three antibodies in myelinated fibre tracts had a smooth, regular appearance. Two hours after MCA occlusion there were striking changes in the patterns of immunostaining of all three antibodies in myelinated fibre tracts within the MCA territory. These were particularly noticeable in beta-tubulin- and MAP5-stained sections where the pattern in white matter had a rough, globular appearance. This pattern was accentuated at 6 h after MCA occlusion and the presence of "bulb-like" profiles in white matter tracts was notable particularly in the MAP5-stained sections. Thus, the changes in the patterns of staining at 2 h after MCA occlusion may represent the early stages of axonal disconnection, and immunostaining of microtubular proteins may represent a sensitive method to assess ischaemically induced damage to myelinated fibre tracts.

Animals↗
PubMed1997

Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey.

Data from 27,616 current and former drinkers interviewed in the 1992 National Longitudinal Alcohol Epidemiologic Survey were used to examine the relationship between age at first use of alcohol and the prevalence of lifetime alcohol abuse and alcohol dependence, among all U.S. adults 18 years of age and over and within subgroups defined by sex and race. The rates of lifetime dependence declined from more than 40% among individuals who started drinking at ages 14 or younger to roughly 10% among those who started drinking at ages 20 and older. The rates of lifetime abuse declined from just over 11% among those who initiated use of alcohol at ages 16 or younger to approximately 4% among those whose onset of use was at ages 20 or older. After using multivariate logistic regression models to adjust for potential confounders, the odds of dependence decreased by 14% with each increasing year of age at onset of use, and the odds of abuse decreased by 8%. These findings are discussed with respect to their implications for prevention policies and the need to integrate epidemiological and intervention research.

Adolescent↗