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Biomedical subjects

K L Graves

Publications and source records attributed to K L Graves.

At least 19 recordsLinked to original sources
PubMed1998

Alcohol consumption and mortality. I. Characteristics of drinking groups.

AIMS: This is the first of a set of three papers evaluating drinking status and mortality risk. Analyses of multiple studies describe associations of drinking patterns with characteristics hypothesized to confound the relationships between drinking status and mortality. Characteristics which both significantly differentiate drinking groups and are consistent across studies would suggest that mortality studies not controlling for them may be compromised. DESIGN AND PARTICIPANTS: Associations are evaluated from the raw data of 10 general population studies which contained mortality data. Long-term abstainers are compared to former drinkers, long-term abstainers and former drinkers are compared to light drinkers (by quantity, frequency and volume in separate analyses) and moderate to heavy drinkers are compared to light drinkers. Tetrachoric correlation coefficients assess statistical significance; meta-analysis determines if associations are homogeneous across studies. MEASUREMENTS: Measures of alcohol consumption are quantity, frequency and volume; long-term abstainers are differentiated from former drinkers. Multiple measures of health, social position, social integration and mental health characteristics are evaluated. FINDINGS: Across studies, adult male former drinkers are consistently more likely to be heavier smokers, depressed, unemployed, lower SES and to have used marijuana than long-term abstainers. Adult female former drinkers are consistently more likely to be heavier smokers, in poorer health, not religious, and unmarried than long-term abstainers. Both types of abstainers tend to be of lower SES than light drinkers and report poorer health (not consistent). Female abstainers are more likely to be of normal or overweight than light drinkers. CONCLUSIONS: Characteristics of two groups of abstainers, other than their non-use of alcohol, may confound the associations found between drinking and mortality risk.

Adolescent↗
PubMed1998

Alcohol consumption and mortality. II. Studies of male populations.

AIMS: This is the second of a set of three papers evaluating drinking status and mortality risk. Analysis of eight general population surveys of men evaluated all-cause mortality rates by drinking pattern. DESIGN AND PARTICIPANTS: Raw data from three studies of youth and five studies of adults were evaluated. Logistic regression models controlled for confounding characteristics. Meta-analysis combined study results. MEASUREMENTS: Drinking pattern was alternatively defined by quantity, frequency and volume of drinking. Final models included drinking pattern (as well as abstinence in the youth models and long-term abstainers and former drinkers in adult models), age and other confounding variables. Models also evaluated interactions of age and, respectively, long-term abstinence and former drinking. FINDINGS: No evidence was found for the hypothesis that abstinence is associated with greater mortality risk than light drinking. In the youth samples, abstainers had a lower risk of dying than those drinking less than 15 times per month. One study of the adult samples showed a significant age by former drinker interaction; this did not alter the lack of association of former drinking with mortality risk or the homogeneity of results across studies for this finding. The most consistent finding was the association of heavy drinking with mortality among youth. Among adults, drinking 43 or more drinks per month and drinking 21 or more times per month were associated with increased mortality risk. Quantity per occasion was not significantly associated with mortality risk among adults. CONCLUSIONS: That frequent drinking was related to mortality risk, whereas heavier quantity was unrelated, is inconsistent with the belief that daily consumption of a few glasses of wine has salutary effects. Empirically, however, this pattern tends to be unusual. Findings were homogeneous across studies lending generalizability to results.

Adolescent↗
PubMed1998

Alcohol consumption and mortality. III. Studies of female populations.

AIMS: This is the third of a set of three papers evaluating drinking status and mortality risk. Analysis of three general population surveys of women evaluated all-cause mortality rates by drinking pattern. DESIGN AND PARTICIPANTS: Raw data from three studies of adult women were evaluated. Logistic regression models controlled for confounding characteristics. Meta-analysis combined study results. MEASUREMENTS: Drinking pattern was alternatively defined by quantity, frequency and volume of drinking. Final models included drinking pattern (including long-term abstainers and former drinkers) as well as age and other confounding variables. Models also evaluated interactions of age and, respectively, long-term abstinence and former drinking. FINDINGS: In models in which age was controlled, odds of death for long-term abstainers and former drinkers (defined by volume or quantity) were greater than those for light drinkers; odds of death for moderate and heavy drinkers (defined by quantity) were greater than those for light drinkers. When other psychosocial attributes were controlled, odds of death were similar for abstainers and light drinkers. When other psychosocial attributes were controlled, odds of death for heavy drinkers (defined by volume and quantity) were greater than those for light drinkers. When interactions of age and the two forms of abstinence were introduced, one study showed a significant effect of age and former drinking. CONCLUSIONS: Results were consistent with the hypothesis that characteristics of abstainers other than their non-use of alcohol may account for their higher mortality risk. With the exception of former drinkers compared to light drinkers, when interactions were introduced into models (for measures of quantity and frequency) findings were homogeneous across studies, lending generalizability to results.

Adult↗
PubMed1998

AIDS protection and contraception among African American, Hispanic, and white women.

The goal of this study was to examine behaviors related to AIDS protection and contraception among African American, Hispanic, and white women. Data were collected in 1991 and 1992 as part of a large-scale National Alcohol Survey in which respondents were asked questions about AIDS-related sexual behavior and attitudes in face-to-face interviews. Results indicated that a significant proportion of women and their partners in each ethnic group did not use any form of protection during their most recent sexual encounter. The findings suggest that it may be useful to combine efforts to reduce unintended pregnancies with efforts for AIDS protection.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Acculturation, alcohol consumption and AIDS-related risky sexual behavior among African American women.

The present study examined the relationship between acculturation, alcohol consumption and AIDS-related risky sexual behavior in a national probability sample of 533 African American women. Results indicated that women who were the heaviest drinkers were also the least acculturated. However, women most likely to engage in risky sexual behavior, including having multiple partners, being nonmonogamous or in a nonmonogamous relationship, and being nonmonogamous or in a nonmonogamous relationship and not using a condom consistently, were high in acculturation rather than low. Alcohol use proved related to risky sexual behavior when considered in conjunction with respondents' level of acculturation. Women at risk for contracting AIDS were not low acculturated African American women who drank heavily, but high acculturated African American women. Findings from this study extend our understanding of risk and contain implications for research and prevention efforts in the area of alcohol use and AIDS-related sexual behavior among African American women.

Acculturation↗
PubMed1997

Ethnic differences in the association between behavior with a new partner: an event-based analysis.

The relationship of alcohol consumption to risky sexual behavior at the most recent encounter with a new sexual partner in representative samples of white, Hispanic, and black adults was examined. Drinking at the new partner event was more prevalent among whites than either blacks or Hispanics. Multivariate analyses indicated that drinking in the event was an important predictor on having a casual partner and using condoms with a casual partner for men but not for women. For women, drinking during the event predicted failure to use a condom. Some of these associations were dependent on ethnicity. Hispanics who consumed alcohol at the encounter were more likely to engage in protected sex than whites or blacks. These findings suggest that alcohol is but one of many influences regulating the riskiness of a particular encounter with a new partner and that the interplay of personal, situational, and behavioral factors with risky sex are culturally dependent.

Adolescent↗
PubMed1996

Fibronectin modulates expression of interleukin-1 beta and its receptor antagonist in human mononuclear cells.

Identification of factors that regulate production of proinflammatory cytokines may provide insight into mechanisms governing lung inflammation. One potential regulatory factor highly expressed in inflamed tissues is fibronectin (FN). To determine the potential effects of FN on interleukin (IL)-1 beta production, we exposed human peripheral blood mononuclear cells to soluble FN. This treatment resulted in the accumulation of IL-1 beta mRNA and enhancement of IL-1 beta protein synthesis and secretion. This effect was dose dependent and appeared to be mediated by the integrin alpha 5 beta 1. Treatment with FN also increased production of IL-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of IL-1 function. However, the stimulatory effect of FN on IL-1ra production was abolished by costimulation with type I collagen. We conclude that the increased deposition of FN in injured tissues may enhance the expression of IL-1 beta mRNA and augment the production and release of IL-1 beta protein by mononuclear cells. Differential expression of IL-1 beta and IL-1ra resulting in a high IL-1 beta-to-IL-1ra ratio in response to mixed matrices containing FN and type I collagen may be an important regulatory point in inflammation.

Cells, Cultured↗
PubMed1995

Electrostatic guidance of catalysis by a conserved glutamic acid in Escherichia coli dTMP synthase and bacteriophage T4 dCMP hydroxymethylase.

Thymidylate synthase (TS) and dCMP hydroxymethylase (CH) are homologous enzymes which catalyze the alkylation of C5 of pyrimidine nucleotides. One of the first catalytic steps is isomerization of the alkyl donor, methylenetetrahydrofolate, from its N5,N10 bridged form to the N5 iminium ion upon enzyme binding. Glu58 in TS has been postulated [Matthews et al. (1990) J. Mol. Biol. 214, 937-948] to be involved in this isomerization and the deprotonation of C5 of the nucleotide. Substitution by Asp or Gln of Glu58 in Escherichia coli TS, or of the corresponding Glu60 in CH from phage T4, decreases the activity of either enzyme. Alkylation is slowed much more than deprotonation, indicating uncoupling of steps which are tightly coupled for the wild-type enzymes. The data support minor roles for Glu58/60 in nucleotide binding and in isomerization of methylenetetrahydrofolate, but no major roles in nucleotide deprotonation, product dissociation, or hydration catalyzed by CH. The primary role of Glu58/60 is to accelerate bond cleavage between N5 of tetrahydrofolate and the methylene being transferred. The influence of Glu58/60 on the rate of bond cleavage is proposed to arise from electrostatic destabilization due to the proximity of the glutamyl carboxylate, of the anionic species formed when C5 of the nucleotide is deprotonated. The proposal explains the uncoupling of deprotonation and alkylation with the Glu58/60 variants and the reduced kinetic isotope effect on hydride transfer for TS(Glu58Gln). The inability of 5-deazatetrahydrofolate to stimulate enzyme-catalyzed tritium exchange from [5-(3H)]nucleotides into solvent suggests that N5 of tetrahydrofolate is the base which deprotonates the nucleotide.

Amino Acid Sequence↗
PubMed1994

Kinetic and equilibrium alpha-secondary tritium isotope effects on reactions catalyzed by dCMP hydroxymethylase from bacteriophage T4.

Deoxycytidylate (dCMP) hydroxymethylase (CH) catalyzes the formation of 5-(hydroxymethyl)-dCMP, essential for DNA synthesis in phage T4, from dCMP and methylenetetrahydrofolate (CH2THF). The nucleotide analog 5-fluorodeoxuridylate (FdUMP) stoichiometrically inactivates CH by formation of a covalent complex containing enzyme, FdUMP, and CH2THF. Similar FdUMP complexes are formed by dTMP synthase and dUMP hydroxymethylase, enzymes which are homologous to CH. Both the association and the dissociation rate of the FdUMP complex are shown to be increased by the mutation of active site Asp179 to Asn. The mutated enzyme, CH(D179N), has an altered substrate preference, favoring dUMP rather than dCMP [Graves, K. L., et al. (1992) Biochemistry 31, 10315]. A value of 0.8 was determined for the alpha-secondary tritium equilibrium isotope effect on the binding of [6-3H]FdUMP to wild-type CH and to CH(D179N), using a mixture of 2-14C- and 6-3H-labeled FdUMP. These effects, similar to that found for TS, indicate that C6 of the nucleotide is saturated (i.e., sp3 hybridized) in the covalent complex of CH, FDUMP, and CH2THF. This strongly suggests that catalysis by CH proceeds via sequential sp2-->sp3-->sp2 hybridization changes at C6 of substrate nucleotides, and it is consistent with a transient covalent linkage of C6 to the thiol of an essential CH residue, Cys148. The values of the alpha-secondary 3H kinetic isotope effect (KIE) on kcat/KM for CH-catalyzed formation of Hm5dCMP caused by 6-3H-substitution of dCMP, with both wild-type CH and CH(D179N), were very close to 1.0. However, the KIE for CH-(D179N) with dUMP was 0.82.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophage T4↗
PubMed1994

Evidence from 18O exchange studies for an exocyclic methylene intermediate in the reaction catalyzed by T4 deoxycytidylate hydroxymethylase.

18O exchange experiments were designed to identify the final intermediate in the catalytic mechanism of bacteriophage T4 deoxycytidylate (dCMP) hydroxymethylase (CH). CH catalyzes the formation of 5-(hydroxymethyl)-dCMP (HmdCMP) from dCMP and methylenetetrahydrofolate (CH2-THF). CH resembles thymidylate synthase (TS), an enzyme of known three-dimensional structure, in both amino acid sequence and the reaction catalyzed. The final intermediate in the reaction catalyzed by TS or CH has been proposed to be the nucleotide with an exocyclic 5-methylene group covalently linked to the enzyme. This intermediate is then hydrated to HmdCMP (by CH) or reduced to deoxythymidylate (by TS). We report here that CH catalyzes the incorporation of 18O from solvent water into the product, HmdCMP, in the presence of tetrahydrofolate (THF). The cause of this exchange is a reverse reaction followed by a resynthesis. CH also catalyzes the exchange of 18O from solvent water into HmdCMP in the absence of exogenous THF and in the presence of THF analogues that lack N-5. N-5 is the nitrogen that is likely to be bound to the methylene as it is transferred to dCMP. A CH variant that lacks the nucleophilic Cys 148 is incapable of promoting these 18O exchange reactions. The THF analogues lacking N-5 do not promote a CH-catalyzed reverse reaction. Rather, we propose that the CH-catalyzed 18O exchange reaction promoted by these THF analogues occurs via 5-methylene-dCMP linked to the enzyme through Cys 148. We conclude here that enzyme-bound 5-methylene-dCMP is the final intermediate during catalysis by CH, as has also been proposed for TS and dUMP.

Bacteriophage T4↗
PubMed1993

Contribution of dietary lipid change to falling serum cholesterol levels between 1980 to 1982 and 1985 to 1987 in an urban population. The Minnesota Heart Survey.

We assessed dietary intake and serum total cholesterol trends during the 1980s, in the Minneapolis-St. Paul (Twin Cities) metropolitan area. Twin Cities residents 25 to 74 years old participated in independent, cross-sectional, population-based surveys of risk factors for cardiovascular disease in 1980 to 1982 (n = 1611) and 1985 to 1987 (n = 2231). Age-adjusted total energy intake was similar in 1980 to 1982 and 1985 to 1987: 2528 kcal (10.6 MJ) versus 2574 kcal (10.8 MJ) for men and 1683 kcal (7.1 MJ) versus 1689 kcal (7.1 MJ) for women. However, significant changes were observed in macronutrient intake. The percent of energy from total fat intake decreased from 39.3 to 38.1% in men and 38.9 to 36.6% in women (both P < 0.01). The composition of fat consumed changed, such that the Keys score, an index of dietary fat and cholesterol, decreased by 3.3 units in both sexes (both P < 0.01). The predicted changes in serum total cholesterol (Keys score) were generally consistent with observed declines of 5.4 mg/dL (0.1 mmol/L) in men and 5.8 mg/dL (0.15 mmol/L) in women during this time period. These data suggest that members of this community are on average modifying their fat consumption and that these dietary changes are resulting in more favorable serum total cholesterol levels.

Adult↗
PubMed1992

Roles of Cys148 and Asp179 in catalysis by deoxycytidylate hydroxymethylase from bacteriophage T4 examined by site-directed mutagenesis.

The proposed roles of Cys148 and Asp179 in deoxycytidylate (dCMP) hydroxymethylase (CH) have been tested using site-directed mutagenesis. CH catalyzes the formation of 5-(hydroxymethyl)-dCMP, essential for DNA synthesis in phage T4, from dCMP and methylenetetrahydrofolate. CH resembles thymidylate synthase (TS), an enzyme of known three-dimensional structure, in both amino acid sequence and the reaction catalyzed. Conversion of Cys148 to Asp, Gly, or Ser decreases CH activity at least 10(5)-fold, consistent with a nucleophilic role for Cys148 (analogous to the catalytic Cys residue in TS). In crystalline TS, hydrogen bonds connect O4 and N3 of the substrate dUMP to the side-chain amide of an Asn; the corresponding residue in CH is Asp179. Conversion of Asp179 to Asn reduces the value of kcat/KM for dCMP by (1.5 x 10(4))-fold and increases the value of kcat/KM for dUMP by 60-fold; as a result, CH(D179N) has a slight preference for dUMP. Wild-type CH and CH(D179N) are covalently inactivated by 5-fluoro-dUMP, a mechanism-based inactivator of TS. Asp179 is proposed to stabilize covalent catalytic intermediates, by protonating N3 of the pyrimidine-CH adduct.

Alleles↗
PubMed1992

Role of TAR RNA splicing in translational regulation of simian immunodeficiency virus from rhesus macaques.

The untranslated leader sequences of rhesus macaque simian immunodeficiency virus mRNAs form a stable secondary structure, TAR. This structure can be modified by RNA splicing. In this study, the role of TAR splicing in virus replication was investigated. The proportion of viral RNAs containing a spliced TAR structure is high early after infection and decreases at later times. Moreover, proviruses containing mutations which prevent TAR splicing are significantly delayed in replication. These mutant viruses require approximately 20 days to achieve half-maximal virus production, in contrast to wild-type viruses, which require approximately 8 days. We attribute this delay to the inefficient translation of unspliced-TAR-containing mRNAs. The molecular basis for this translational effect was examined in in vitro assays. We found that spliced-TAR-containing mRNAs were translated up to 8.5 times more efficiently than were similar mRNAs containing an unspliced TAR leader. Furthermore, these spliced-TAR-containing mRNAs were more efficiently associated with ribosomes. We postulate that the level of TAR splicing provides a balance for the optimal expression of both viral proteins and genomic RNA and therefore ultimately controls the production of infectious virions.

Animals↗
PubMed1992

Evaluation of a self-help dietary intervention in a primary care setting.

BACKGROUND: Dietary intervention to reduce fat consumption and increase fiber consumption has been recommended by the National Cancer Institute, but there is little evidence concerning the effectiveness of self-help materials. The purpose of this study was to evaluate such self-help materials, introduced by a nurse in a primary care setting. METHODS: A randomized controlled trial involving 242 subjects was conducted in two primary care clinics in Chapel Hill, NC, in 1987. Changes in fat and fiber consumption in the intervention and control groups during the 3-month interval between interviews were compared using analysis of covariance. RESULTS: The estimated reduction in fat was 3.8g larger for the intervention group than for the control group, but the confidence interval included zero. For those individuals who had some responsibility for meal preparation there was a larger difference (-6.9g) in favor of the intervention group, although the difference using calorie-adjusted values was -3.8g with a 95% confidence interval (-7.1, -0.4). The differences for fiber change were smaller. CONCLUSIONS: We found significant small but consistent differential changes associated with a minimal self-help intervention, but we cannot rule out the possibility of some response bias. Nonetheless, this study demonstrates that the use of self-help materials for dietary change is feasible, and may be effective.

Adult↗
PubMed1991

In vivo and in vitro studies of a chronic oxygen saturation sensor.

An oxygen saturation sensor, for the purpose of chronically controlling the heart rhythm produced by a pacemaker, should be specific to oxygen saturation and should be minimally affected by the harsh blood environment. For the sensor type we tested we found: (1) one sensor failure in 205.5 canine-months of chronic implantation (n = 11, range 4 to 50 months); (2) hematocrit-induced error of less than 5 percentage points of SvO2 over the range of 50% to 80% SvO2 and 15% to 45% hematocrit; (3) carboxyhemoglobin (HbCO)-induced error of less than 4 percentage points of SvO2 with HbCO up to 20%; (4) a fibrotic sheath-induced error of less than 3 percentage points of SvO2 in the range of 50% to 80% SvO2 due to fibrotic sheath thicknesses up to 0.22 mm; (5) no significant error induced by velocity variations local to the sensor; (6) no significant error due to temperature in the range of 30 degrees to 42 degrees C; and (7) that the sensor could be as close as 0.3mm to the ventricular wall and still only produce an error of 5% SvO2.

Animals↗
PubMed1991

Nutrition training, attitudes, knowledge, recommendations, responsibility, and resource utilization of high school coaches and trainers.

Because misconceptions about nutrition are prevalent in athletics, we assessed the knowledge of sports-related nutrition concepts of high school athletic personnel. A questionnaire was mailed to all athletic directors and teacher athletic trainers in North Carolina high schools. Of the 821 surveys sent, 303 were returned (a response rate of 37%). The sample was grouped into three categories on the basis of the perceived role of the respondent: coach (n = 152), trainer (n = 91), and dual coach-trainer (n = 29). Thirty-one individuals who indicated that they held administrative positions with little or no contact with students were omitted from the analysis. One-way analysis of variance or chi 2 was used to examine differences in questionnaire responses among the three groups. In comparison with high school coaches, trainers had taken more workshops or courses related to nutrition (2.9 compared with 1.8) and had more frequently used professional meetings (62% vs 39%), workshops (64% vs 41%), and textbooks (75% vs 50%) as sources of information. Trainers were more knowledgeable about nutrition (9.6 correct responses vs 8.9 for coaches) and recommended desirable nutrition practices more often than coaches (7 of 9 vs 6 of 9). There was some disagreement between coaches and trainers in their perceptions of who was more important in dispensing nutrition information. Future nutrition education efforts should take into account the differences among these groups.

Adolescent↗
PubMed1985

Nutrient intakes among selected North American populations in the Lipid Research Clinics Prevalence Study: composition of fat intake.

Components of fat and their relationship to total energy are described for 2,368 white male and 2,200 white female adults, aged 20-59 years, for whom 24-hour dietary recalls were completed between 1972 and 1975 in nine North American populations as a part of the Lipid Research Clinics (LRC) Program Prevalence Study. Men had higher absolute intakes of total fat and cholesterol than women, although both sexes consumed diets similar in relative composition of polyunsaturated, saturated, and monounsaturated fatty acids. Marked geographical differences in intakes of energy, total fat, and dietary cholesterol were observed. Compared with data from dietary surveys conducted in the 1960's the LRC data showed that consumption of cholesterol had decreased by the early 1970's, whereas consumption of polyunsaturated fatty acids appears to have increased, resulting in a higher ratio of polyunsaturated to saturated fatty acids. However, comparison of current dietary guidelines with these data, which are based on a single dietary recall, showed that few LRC participants met the recommendations of the Senate Select Committee on Nutrition and Human needs for dietary fat intake.

Adult↗