Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
1.
J Anim Sci ; 96(3): 941-949, 2018 Apr 03.
Article in English | MEDLINE | ID: mdl-29617863

ABSTRACT

Identifying traits associated with susceptibility or tolerance to heat stress (HS) is a prerequisite for developing strategies to improve efficient pork production during the summer months. Study objectives were to determine the relationship between the thermoregulatory and production responses to acute HS in pigs. Prepubertal gilts (n = 235; 77.9 ± 1.2 kg BW) were exposed to a thermoneutral (TN) period (P1, 24 h; 21.9 ± 0.5 °C, 62 ± 13% RH; fed ad libitum) followed immediately by a subsequent acute HS period (P2, 24 h; 29.7 ± 1.3 °C, 49 ± 8% RH; fed ad libitum). Rectal temperature (TR), skin temperature (TS), and respiration rate (RR) were monitored and BW and feed intake (FI) were determined. All pigs had increased TR, TS, and RR (0.80 °C, 5.65 °C, and 61.2 bpm, respectively; P < 0.01) and decreased FI and BW (29% and 1.10 kg, respectively; P < 0.01) during P2 compared to P1. Interestingly, body temperature indices did not explain variation in FI during P2 (R2 ≤ 0.02). Further, the percent change in BW during P2 was only marginally explained by each body temperature index (R2 ≤ 0.06) or percent change in FI (R2 = 0.14). During HS, TR was strongly correlated with P1 TR (r = 0.72, P < 0.01), indicating a pig's body temperature during TN conditions predicts the severity of hyperthermia during HS. Additionally, the change in TR (ΔTR, HS TR - TN TR) was larger in pigs retrospectively classified as susceptible (SUS) as compared to tolerant (TOL) pigs (1.05 vs. 0.51 °C, respectively; P < 0.01). In summary, thermoregulatory responses and production variables during acute HS are only marginally related. Further, changes in BW and FI were unexpectedly poorly correlated during acute HS (r = 0.34; P < 0.01). Collectively, suboptimal growth is largely independent on the thermoregulatory response and hypophagia during acute HS. Consequently, incorporating solely body temperature indices into a genetic index is likely insufficient for substantial progress in selecting HS tolerant pigs.


Subject(s)
Body Temperature Regulation , Heat-Shock Response/physiology , Swine/physiology , Animals , Body Temperature , Female , Hot Temperature/adverse effects , Respiratory Rate , Swine/growth & development , Thermotolerance
2.
J Anim Sci ; 93(5): 2587-96, 2015 May.
Article in English | MEDLINE | ID: mdl-26020353

ABSTRACT

Objectives were to investigate the effects of prolonged gestational and/or postnatal heat stress on performance and carcass composition of market weight pigs. Pregnant gilts were exposed to gestational heat stress (GHS, 28°C to 34°C, diurnal) or thermal neutral (18°C to 22°C, diurnal) conditions during the entire gestation or during the first or second half of gestation. At 14 wk of age (58 ± 5 kg), barrows were housed in heat stress (32°C, HS) or thermal neutral (21°C, TN) conditions. Feed intake and BW were recorded weekly, and body temperature parameters were monitored twice weekly until slaughter (109 ± 5 kg). Organs were removed and weighed, and loin eye area (LEA) and back fat thickness (BF) were measured after carcass chilling. Carcass sides were separated into lean, separable fat, bone, and skin components and were weighed. Moisture, lipid, and protein content were determined in the LM at the 10th rib. Data were analyzed using a split plot with random effect of dam nested within gestational treatment. Carcass measurements included HCW as a covariate to control for weight. Planned orthogonal contrast statements were used to evaluate the overall effect of GHS in the first half, second half, or any part of gestation. Gestational heat stress did not alter postnatal performance or most body temperature parameters (P > 0.10). However, ADFI in the finishing period was increased (P < 0.05) in response to GHS, particularly in pigs receiving GHS in the first half of gestation. Gestational heat stress during the first half of gestation decreased head weight as a percent of BW (P = 0.02), whereas GHS in the second half of gestation decreased bone weight as a percent of BW (P = 0.02). Heat stress reduced ADG, BW, and HCW (P < 0.0001). Lean tissue was increased in HS pigs on both a weight and percentage basis (P < 0.0001), but LEA was similar to TN carcasses (P = 0.38). Carcasses from HS barrows also had less carcass separable fat (P < 0.01) and tended to have less BF (P = 0.06) compared with those from TN barrows, even after controlling for HCW. However, percent intramuscular fat did not differ between treatments (P = 0.48). The LM from HS carcasses had a greater moisture to protein ratio (P = 0.04). HS barrows also had decreased heart (P < 0.001) and kidney (P < 0.0001) as a percent of BW compared with TN pigs. In summary, GHS may affect head and bone development, subsequently affecting carcass composition. Chronic HS during finishing results in longer times to reach market weight and a leaner carcass once market weight is achieved.


Subject(s)
Body Composition/physiology , Body Weight/physiology , Hot Temperature/adverse effects , Pregnancy, Animal/physiology , Stress, Physiological/physiology , Swine/physiology , Animal Husbandry/methods , Animals , Body Temperature/physiology , Female , Heat Stress Disorders/physiopathology , Housing, Animal , Hydrogen-Ion Concentration , Male , Pregnancy , Prenatal Exposure Delayed Effects/physiopathology , Swine/embryology
3.
Women Health ; 27(3): 17-35, 1998.
Article in English | MEDLINE | ID: mdl-9698635

ABSTRACT

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.


PIP: The relationship between acculturation, alcohol consumption, and AIDS-related risky sexual practices was investigated in a national probability sample of 533 African American women. Data were collected in 1991-92 as part of a follow-up survey to the 1984 US National Alcohol Survey. Acculturation--the extent of adaptation to US mainstream society--was measured through use of a 10-item questionnaire related to preference for African American mass media and reliance on an African American social network. Scores on this scale ranged from 1.00 (low acculturation) to 3.78 (high acculturation). Most respondents were 18-29 years of age and lived in urban areas. Among the 306 respondents (74%) who were sexually active in the preceding year, 60 (21%) had had multiple sex partners, 130 (43%) were in a nonmonogamous relationship, and 266 (91%) had not used condoms consistently. 109 women (41%) abstained from alcohol consumption, 107 (36%) were moderate drinkers, and 90 (22%) consumed 5 or more drinks per day. When sociodemographic factors, religiosity, and attitudes toward sex were controlled, it was found that high-risk sexual practices were most prevalent among respondents with high levels of both acculturation and alcohol consumption. Heavy drinking alone was not a risk factor. Multivariate analysis indicated that women in the high acculturation/heavy drinking group were 13 times more likely to have multiple sex partners than their low acculturation/alcohol abstinent counterparts. These findings suggest the need for AIDS prevention programs for African American women that address alcohol treatment and assertiveness training.


Subject(s)
Acculturation , Acquired Immunodeficiency Syndrome/ethnology , Alcohol Drinking/ethnology , Black or African American/statistics & numerical data , Cultural Characteristics , Sexual Behavior/statistics & numerical data , Acquired Immunodeficiency Syndrome/etiology , Adolescent , Adult , Alcohol Drinking/adverse effects , Chi-Square Distribution , Data Collection , Female , Humans , Incidence , Logistic Models , Middle Aged , Multivariate Analysis , Risk Factors , Risk-Taking , Sampling Studies , Software , United States
4.
Health Soc Work ; 23(3): 186-94, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9702550

ABSTRACT

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.


Subject(s)
Acquired Immunodeficiency Syndrome/prevention & control , Black or African American , Contraception Behavior/ethnology , Health Behavior/ethnology , Hispanic or Latino , White People , Adolescent , Adult , Chi-Square Distribution , Contraception Behavior/statistics & numerical data , Female , Health Knowledge, Attitudes, Practice , Health Surveys , Humans , Interviews as Topic , Logistic Models , Sampling Studies , United States
5.
Addiction ; 93(2): 183-203, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9624721

ABSTRACT

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.


Subject(s)
Alcohol Drinking/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Follow-Up Studies , Health Status , Humans , Longitudinal Studies , Male , Mental Health , Middle Aged , Prospective Studies , Risk Factors , Social Class , Sweden/epidemiology , Temperance , United States/epidemiology
6.
Addiction ; 93(2): 205-18, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9624722

ABSTRACT

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.


Subject(s)
Alcohol Drinking/mortality , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Humans , Logistic Models , Longitudinal Studies , Male , Middle Aged , Risk Factors , Social Class , Sweden/epidemiology , Temperance , United States/epidemiology
7.
Addiction ; 93(2): 219-29, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9624723

ABSTRACT

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.


Subject(s)
Alcohol Drinking/mortality , Adult , Age Factors , Aged , Female , Humans , Logistic Models , Longitudinal Studies , Middle Aged , Risk Factors , United States/epidemiology
8.
AIDS Educ Prev ; 9(3): 219-37, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9241389

ABSTRACT

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.


Subject(s)
Alcohol Drinking/ethnology , Black or African American/psychology , Cross-Cultural Comparison , HIV Infections/ethnology , Hispanic or Latino/psychology , Sexual Partners/psychology , White People/psychology , Adolescent , Adult , Alcohol Drinking/adverse effects , Condoms , Female , Gender Identity , HIV Infections/prevention & control , HIV Infections/transmission , Health Knowledge, Attitudes, Practice , Humans , Male , Risk-Taking , Sampling Studies
9.
Am J Physiol ; 271(1 Pt 1): L61-9, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8760133

ABSTRACT

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.


Subject(s)
Fibronectins/pharmacology , Interleukin-1/metabolism , Monocytes/drug effects , Monocytes/metabolism , Receptors, Interleukin-1/antagonists & inhibitors , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Humans , Interleukin-1/genetics , Protein Precursors/biosynthesis , RNA, Messenger/metabolism
10.
Am J Health Promot ; 10(1): 27-36, 1995.
Article in English | MEDLINE | ID: mdl-10155656

ABSTRACT

PURPOSE: To examine the relationship between alcohol use and sexual activity in a sample of young adults. DESIGN: Data were collected as part of a 1990 survey of a multistage area household probability sample. SETTING: In-home interviews were conducted by experienced interviewers. SUBJECTS: In total, 1006 persons from 18 to 30 years of age living in the contiguous United States were contacted. MEASURES: Detailed information was collected on alcohol use and sexual behavior. To minimize the reluctance of respondents to answer queries on sexual behavior, those questions were contained in a self-administered questionnaire. RESULTS: At the population level, having had multiple sexual partners in the past year was more likely among men who consumed five or more drinks per sitting. Condom use was less likely among respondents who had consumed five or more drinks on at least one occasion in the past year. In multivariate analyses, the amount of alcohol consumed at the new partner event was not associated with condom use with a new partner. When the effects of other demographic and psychosocial factors were removed, the number of drinks consumed during the heaviest drinking event was a significant predictor of engaging in sex for women but not for men. CONCLUSION: In young adults, alcohol use with sex does not necessarily lead directly to lapses in judgment about safe sexual practices. Alcohol is but one of a number of factors that play an important role in determining the riskiness of a particular sexual encounter.


Subject(s)
Alcohol Drinking/epidemiology , Risk-Taking , Sexual Behavior , Sexually Transmitted Diseases/prevention & control , Adult , Chi-Square Distribution , Condoms , Female , Humans , Male , Multivariate Analysis , Sexual Partners , United States/epidemiology
11.
Biochemistry ; 34(26): 8422-32, 1995 Jul 04.
Article in English | MEDLINE | ID: mdl-7599133

ABSTRACT

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.


Subject(s)
Bacteriophage T4/enzymology , Escherichia coli/enzymology , Glutamic Acid , Hydroxymethyl and Formyl Transferases , Protein Conformation , Thymidylate Synthase/chemistry , Thymidylate Synthase/metabolism , Transferases/chemistry , Transferases/metabolism , Amino Acid Sequence , Binding Sites , Catalysis , Cloning, Molecular , Conserved Sequence , Electrochemistry , Folic Acid Antagonists/chemistry , Folic Acid Antagonists/metabolism , Kinetics , Models, Theoretical , Mutagenesis, Site-Directed , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism
12.
Fam Plann Perspect ; 27(1): 18-22, 33, 1995.
Article in English | MEDLINE | ID: mdl-7720848

ABSTRACT

Data on substance use and sexual activity from a nationally representative, probability-based sample of young adults aged 18-30 in 1990 indicate that 86% of respondents had had sex in the previous 12 months, with three-fourths reporting no more than one sexual partner. Seventy-five percent of respondents had consumed alcohol in the past 12 months, 40% had smoked cigarettes and 20% had used marijuana. After adjustment for demographic factors, both sexual activity and a history of multiple partners were positively associated with some measures of substance use. Respondents who drank more frequently, those who were heavy drinkers, those who smoked cigarettes and those who used marijuana in the past year were more likely than others to be sexually active. Those who consumed five or more drinks at a sitting and those who used marijuana were more likely than others to have had more than one sexual partner. Heavy drinkers were also less likely to use condoms; however, the results showed no association between having sex under the influence of alcohol and engaging in unsafe sexual practices.


Subject(s)
Alcohol Drinking/psychology , Sexual Behavior , Substance-Related Disorders/psychology , Adolescent , Adult , Age Factors , Condoms/statistics & numerical data , Female , Humans , Male , Odds Ratio , Risk-Taking , Sexual Partners , Surveys and Questionnaires , United States
13.
Biochemistry ; 33(44): 13049-56, 1994 Nov 08.
Article in English | MEDLINE | ID: mdl-7947710

ABSTRACT

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)


Subject(s)
Bacteriophage T4/enzymology , Fluorodeoxyuridylate/chemistry , Hydroxymethyl and Formyl Transferases , Transferases/chemistry , Tritium/metabolism , Catalysis , Electrophoresis, Polyacrylamide Gel , Escherichia coli/enzymology , Fluorodeoxyuridylate/metabolism , Kinetics , Mutation/genetics , Protein Binding/genetics , Transferases/genetics , Transferases/metabolism
14.
Biochemistry ; 33(34): 10521-6, 1994 Aug 30.
Article in English | MEDLINE | ID: mdl-8068692

ABSTRACT

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.


Subject(s)
Hydroxymethyl and Formyl Transferases , Transferases/metabolism , Bacteriophage T4/enzymology , Catalysis , Deoxycytidine Monophosphate/analogs & derivatives , Deoxycytidine Monophosphate/biosynthesis , Deoxycytidine Monophosphate/chemistry , Folic Acid/analogs & derivatives , Folic Acid/pharmacology , Kinetics , Magnetic Resonance Spectroscopy , Models, Chemical , Molecular Structure , Oxygen/metabolism , Oxygen Isotopes , Tetrahydrofolates/pharmacology
15.
Ann Epidemiol ; 3(6): 605-13, 1993 Nov.
Article in English | MEDLINE | ID: mdl-7921308

ABSTRACT

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.


Subject(s)
Cholesterol/blood , Coronary Disease/epidemiology , Dietary Fats , Adult , Aged , Dietary Fats/metabolism , Energy Intake , Female , Humans , Male , Middle Aged , Minnesota/epidemiology , Nutrition Surveys , Urban Population
16.
Biochemistry ; 31(42): 10315-21, 1992 Oct 27.
Article in English | MEDLINE | ID: mdl-1420151

ABSTRACT

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.


Subject(s)
Aspartic Acid , Bacteriophage T4/enzymology , Cysteine , Escherichia coli/enzymology , Hydroxymethyl and Formyl Transferases , Mutagenesis, Site-Directed , Transferases/genetics , Transferases/metabolism , Alleles , Amino Acid Sequence , Bacteriophage T4/genetics , Cloning, Molecular , Deoxyuracil Nucleotides/metabolism , Escherichia coli/genetics , Hydrogen Bonding , Kinetics , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Transferases/isolation & purification
17.
J Virol ; 66(8): 4824-33, 1992 Aug.
Article in English | MEDLINE | ID: mdl-1629957

ABSTRACT

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.


Subject(s)
Gene Expression Regulation, Viral , Protein Biosynthesis , RNA Splicing , RNA, Messenger/genetics , RNA, Viral/genetics , Simian Immunodeficiency Virus/genetics , Animals , Base Sequence , Blotting, Western , Introns , Macaca mulatta , Molecular Sequence Data , Nucleic Acid Conformation , Oligodeoxyribonucleotides , Plasmids , RNA, Messenger/analysis , RNA, Messenger/metabolism , RNA, Viral/analysis , RNA, Viral/metabolism , Transcription, Genetic
18.
Am J Public Health ; 82(1): 79-84, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1311152

ABSTRACT

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.


Subject(s)
Dietary Fats/administration & dosage , Dietary Fiber/administration & dosage , Nutritional Sciences/education , Patient Education as Topic/methods , Primary Health Care/methods , Self Care/methods , Teaching Materials/standards , Adult , Black or African American , Educational Status , Energy Intake , Feeding Behavior , Health Behavior , Humans , North Carolina , Surveys and Questionnaires
19.
Pacing Clin Electrophysiol ; 14(10): 1514-27, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1721134

ABSTRACT

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.


Subject(s)
Biosensing Techniques , Cardiac Pacing, Artificial/methods , Oximetry/instrumentation , Pacemaker, Artificial , Animals , Blood Flow Velocity , Body Temperature , Carboxyhemoglobin , Dogs , Electrodes, Implanted , Equipment Design , Female , Heart Rate , Heart Ventricles , Hematocrit , In Vitro Techniques , Male
20.
J Am Diet Assoc ; 91(3): 321-4, 1991 Mar.
Article in English | MEDLINE | ID: mdl-1997555

ABSTRACT

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.


Subject(s)
Nutritional Requirements , Sports Medicine , Adolescent , Attitude to Health , Educational Status , Humans , Schools , Surveys and Questionnaires , Teaching
SELECTION OF CITATIONS
SEARCH DETAIL
...