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Biomedical subjects

W B Strong

Publications and source records attributed to W B Strong.

At least 19 recordsLinked to original sources

Preliminary profile of the Cryptosporidium parvum genome: an expressed sequence tag and genome survey sequence analysis.

Cryptosporidium parvum is a protozoan enteropathogen that infects humans and animals and causes a pronounced diarrheal disease that can be life-threatening in immunocompromised hosts. No specific chemo- or immunotherapies exist to treat cryptosporidiosis and little molecular information is available to guide development of such therapies. To accelerate gene discovery and identify genes encoding potential drug and vaccine targets we constructed sporozoite cDNA and genomic DNA sequencing libraries from the Iowa isolate of C. parvum and determined approximately 2000 sequence tags by single-pass sequencing of random clones. Together, the 567 expressed sequence tags (ESTs) and 1507 genome survey sequences (GSSs) totaled one megabase (1 mb) of unique genomic sequence indicating that approximately 10% of the 10.4 mb C. parvum genome has been sequence tagged in this gene discovery expedition. The tags were used to search the public nucleic acid and protein databases via BLAST analyses, and 180 ESTs (32%) and 277 GSSs (18%) exhibited similarity with database sequences at smallest sum probabilities P(N)< or =10(-8). Some tags encoded proteins with clear therapeutic potential including S-adenosylhomocysteine hydrolase, histone deacetylase, polyketide/fatty-acid synthases, various cyclophilins, thrombospondin-related cysteine-rich protein and ATP-binding-cassette transporters. Several anonymous ESTs encoded proteins predicted to contain signal peptides or multiple transmembrane spanning segments suggesting they were destined for membrane-bound compartments, the cell surface or extracellular secretion. One-hundred four simple sequence repeats were identified within the nonredundant sequence tag collection with (TAA)(> or =6)/(TTA)(> or =6) and (TA)(> or = 10)/(AT)(> or =10 ) being the most prevalent, occurring 40 and 15 times, respectively. Various cellular RNAs and their genes were also identified including the small and large ribosomal RNAs, five tRNAs, the U2 small nuclear RNA, and the small and large virus-like, double-stranded RNAs. This investigation has demonstrated that survey sequencing is an efficient procedure for gene discovery and genome characterization and has identified and sequence tagged many C. parvum genes encoding potential therapeutic targets.

Amino Acid Sequence↗

Cloning and sequence analysis of a highly polymorphic Cryptosporidium parvum gene encoding a 60-kilodalton glycoprotein and characterization of its 15- and 45-kilodalton zoite surface antigen products.

The apicomplexan parasite Cryptosporidium parvum is a major cause of serious diarrheal disease in both humans and animals. No efficacious chemo- or immunotherapies have been identified for cryptosporidiosis, but certain antibodies directed against zoite surface antigens and/or proteins shed by gliding zoites have been shown to neutralize infectivity in vitro and/or to passively protect against, or ameliorate, disease in vivo. We previously used monoclonal antibody 11A5 to identify a 15-kDa surface glycoprotein that was shed behind motile sporozoites and was recognized by several lectins that neutralized parasite infectivity for cultured epithelial cells. Here we report the cloning and sequence analysis of the gene encoding this 11A5 antigen. Surprisingly, the gene encoded a 330-amino-acid, mucin-like glycoprotein that was predicted to contain an N-terminal signal peptide, a homopolymeric tract of serine residues, 36 sites of O-linked glycosylation, and a hydrophobic C-terminal peptide specifying attachment of a glycosylphosphatidylinositol anchor. The single-copy gene lacked introns and was expressed during merogony to produce a 60-kDa precursor which was proteolytically cleaved to 15- and 45-kDa glycoprotein products that both localized to the surface of sporozoites and merozoites. The gp15/45/60 gene displayed a very high degree of sequence diversity among C. parvum isolates, and the numerous single-nucleotide and single-amino-acid polymorphisms defined five to six allelic classes, each characterized by additional intra-allelic sequence variation. The gp15/45/60 single-nucleotide polymorphisms will prove useful for haplotyping and fingerprinting isolates and for establishing meaningful relationships between C. parvum genotype and phenotype.

Alleles↗

Ethnicity and socioeconomic status: impact on cardiovascular activity at rest and during stress in youth with a family history of hypertension.

OBJECTIVE: The purpose of the present study was to examine the potential interaction of ethnicity and SES on hemodynamic functioning at rest and during acute stress in normotensive adolescents with a family history of essential hypertension (EH). DESIGN: The influences of ethnicity and socioeconomic status (SES) on cardiovascular function were evaluated at rest and in response to five different laboratory stressors. METHODS: 110 (50 female) Caucasian and 162 (85 female) African-American normotensive youth (initial age 11.2+/-2.4 years) with a family history of essential hypertension (EH) were tested on two occasions, an average of 2.5 years apart. Based on previous findings, it was predicted that African Americans, particularly those of low SES, would exhibit higher resting blood pressure (BP) and greater cardiovascular reactivity to acute laboratory stressors than would Caucasians. RESULTS: As predicted, African-American youth exhibited higher resting diastolic blood pressure (DBP) and total peripheral resistance (TPR) than Caucasians on both visits (both Ps<.04). African Americans exhibited greater systolic blood pressure (SBP) reactivity than did Caucasians to the video game stressor during both lab visits (both Ps<.02) and greater heart rate reactivity during the first lab visit (P<.01). African Americans exhibited greater SBP and/or DBP, and TPR reactivity to the cold pressor during the first lab visit and the parent-child discussion during the second visit (all Ps<.03). CONCLUSION: As predicted, African Americans exhibited higher resting BP and TPR, and greater cardiovascular reactivity than Caucasians. Although not in the predicted direction, a pattern of interactions began to emerge on the second evaluation. For example, upper SES youth exhibited greater heart rate reactivity compared to all other groups on the social competence interview and parent-child discussion stressors. Further study is needed to clarify the role cardiovascular reactivity may play in the link between ethnicity, SES, and cardiovascular disease risk.

Adolescent↗

Patterns of body fat deposition in youth and their relation to left ventricular markers of adverse cardiovascular prognosis.

The patterns of body fat deposition in healthy youth and their relation to future development of cardiovascular disease remain incompletely understood. To further evaluate these patterns, we measured indirect indexes of central and general fat deposition in healthy adolescents (mean age 15.4+/-2.3 years) with family histories of hypertension. We examined the relation between these indexes and echocardiographic markers of adverse prognosis as well as the effect of gender and ethnicity. All 225 subjects (64% black and 48% female) had > or =1 biologic parent and 1 grandparent with hypertension. Skinfold thicknesses, waist-to-hip girth ratio, Quetelet index, Ponderal index, conicity, and Z score weight - Z score height were measured. Left ventricular (LV) mass, indexed LV mass, relative wall thickness (RWT), and midwall fractional shortening (MFS) were determined using echocardiography. In both black and white subjects, the adiposity indexes were significantly correlated with posterior wall thickness, total LV mass, and indexed LV mass (p <0.05 for all). Additionally, in black subjects, central adiposity was inversely related to MFS and directly related to RWT and septal thickness. General adiposity independently predicted indexed and nonindexed LV mass, whereas central adiposity predicted MFS and RWT. Compared with subjects with normal LV geometry, those with abnormal geometry were heavier and fatter based on every index of obesity (p <0.03 for all). Thus, indexes of fat deposition are significantly correlated with LV markers of adverse prognosis in healthy youth.

Adolescent↗

Effects of race, sex, and socioeconomic status upon cardiovascular stress responsivity and recovery in youth.

Cardiovascular (CV) responsivity to and recovery from acute laboratory stressors, as derived from aggregate scores of CV functioning during and after postural change, video game challenge, social competence interview, and parent-child conflict discussion, were evaluated in 272 youths [mean age 13.5 +/- 2.6 years; 162 Blacks (77 males, 85 females), 110 Whites (60 males, 50 females)], all with a positive family history of essential hypertension. Blacks demonstrated greater systolic and diastolic blood pressure (SBP, DBP) and lower heart rate responsivity compared to Whites (all P values < 0.05). A race by neighborhood socioeconomic status (SES) interaction for SBP responsivity was also observed where low SES Whites and high SES Blacks had the greatest responsivity compared to their same race cohorts. Additionally, upper SES Whites had the lowest total peripheral resistance responsivity. For recovery, Blacks and males exhibited higher SBP during recovery compared to Whites and females, respectively. These findings extend previous studies and provide further support for the hypothesis that recovery from stress is a potentially informative component of the contribution of stress responsivity to cardiovascular disease.

Adolescent↗

Predictors of future ambulatory blood pressure in youth.

OBJECTIVE: The objective of this study was to determine the predictors of future ambulatory blood pressure in normotensive youths with family histories of essential hypertension. STUDY DESIGN: Eighty-eight healthy youths (mean age 10.9 +/- 2.5 years; 52 blacks, 36 whites; 45 boys) were studied. During an initial visit anthropometric variables and hemodynamics were measured at rest and before, during, and after three laboratory stressors: postural change, forehead cold, and video game challenge. The subjects' ambulatory blood pressure was monitored for 24 hours as part of a follow-up evaluation an average of 2.5 years later. RESULTS: Anthropometric and demographic variables and measures of reactivity to laboratory stressors were related to future daytime and nighttime ambulatory blood pressure. CONCLUSION: These findings provide important information on the predictors of ambulatory blood pressure and underscore the importance of resting blood pressure and adiposity. These results support the guidelines of the Second Task Force, which recommend the measurement of blood pressure and adiposity in the context of ongoing health care.

Blood Pressure↗

Central adiposity and hemodynamic functioning at rest and during stress in adolescents.

OBJECTIVE: To examine the impact of central adiposity upon hemodynamic functioning at rest and during stress in adolescents. DESIGN: Cross-sectional, correlational study. SUBJECTS: 46 White and 49 Black normotensive adolescents with family histories of essential hypertension. MEASUREMENTS: Systolic and diastolic blood pressure (SBP, DBP), cardiac output and total peripheral resistance responses were assessed at rest, during postural change, video game challenge and forehead cold stimulation. Specific lower and higher waist-to-hip ratio (WHR) tertiles were created for each gender and then integrated for analyses. This resulted in a lower WHR tertile of 11 Whites and 21 Blacks and an upper WHR tertile of 15 Whites and 17 Blacks. RESULTS: No differences in age, gender or ethnicity proportions were found between tertile groups (all P > 0.21). The upper WHR group showed greater body weight, waist and hip circumferences, body mass index (BMI), triceps skinfold and body surface area (all P < 0.001). Controlling for peripheral (that is, triceps skinfold) and overall (that is, BMI) adiposity, the upper WHR group exhibited greater SBP (that is, peak response minus mean pre-stressor level) to all three stressors and greater DBP reactivity to postural change and cold pressor (all P < 0.05). CONCLUSION: Central adiposity appears to adversely influence hemodynamic functioning during adolescence. Underlying mechanisms responsible for these associations require exploration.

Adipose Tissue↗

Prediction of left ventricular mass in youth with family histories of essential hypertension.

To determine predictors of left ventricular mass (LVM) and hypertrophy (LVH), 56 black and 30 white normotensive healthy youths (mean age 12.6 +/- 2.3 years at initial visit) were studied twice, 2.5 years apart. During the initial visit, anthropometric variables and hemodynamics were measured at rest and before, during, and after 4 physical and behavioral stressors. 2-D directed M-mode echocardiography was performed to derive LVM. Hierarchical multiple regression analyses indicated that follow-up LVM was predicted by initial LVM, weight, height (ht), and gender (males > females; total model R2 = 0.77, P < 0.0001). Predictors of LVM/ht2.7 were initial LVM/ht2.7, weight, ethnicity (blacks > whites), and the aggregate index of blood pressure reactivity (total model R2 = 0.66, P < 0.0001). Youth with LVH at follow-up were taller, heavier, and exhibited greater blood pressure reactivity at initial evaluation. These findings are important since interventional strategies can be developed that target obesity and exaggerated reactivity to stress.

Adolescent↗

The role of maternal hostility and family environment upon cardiovascular functioning among youth two years later: socioeconomic and ethnic differences.

Two hundred sixty-eight African-American and white children and their biological mothers participated in the study. The purpose of the study was to examine the potential collective impact of maternal hostile coping styles and perceptions of family functioning upon youths' cardiovascular (CV) functioning 2.4 years later, within the context of SES and ethnicity. The mother completed a set of questionnaires that included the Cook-Medley Hostility Scale and three scales from the Family Environment Scale (FES). Childrens' systolic and diastolic blood pressure (SBP and DBP) and impedance cardiography derived total peripheral resistance (TPR) was measured at rest two years later. Mothers with lower SES and African-American mothers reported higher levels of hostility compared to those with higher SES and white mothers, respectively. Lower SES mothers reported lower levels of family cohesion and expressiveness than higher SES mothers. Whites reported more family conflict and expressiveness than African Americans. African-American and lower SES youth exhibited higher SBP and DBP values than whites and higher SES youth. Among lower SES African-American youth, CV functioning tended to be impacted negatively when their mothers rated themselves high in hostility. Findings suggest that ethnicity and SES may have independent as well as interactive impacts on the influence of maternal coping styles on the CV functioning of their children, particularly those from lower SES backgrounds.

Adaptation, Psychological↗

Relationships between children's cardiovascular stress responses and resting cardiovascular functioning 1 year later.

Resting cardiovascular parameters were predicted from anthropometric data, resting baseline cardiovascular data, and cardiovascular responses to three laboratory stressors completed 1 year earlier. Subjects were 106 male and female children (72 Whites, 34 Blacks) aged 6-7 years at the initial evaluation. During initial testing, blood pressure, heart rate, cardiac output, and total peripheral resistance were assessed at rest and also during a forehead cold pressor task, postural change, and treadmill exercise. The same cardiovascular parameters were then assessed at rest 1 year later. After controlling for significant anthropometric measures and the pertinent previous year's resting data, systolic and diastolic responses to the cold pressor were predictive of respective follow-up resting levels. Postural change heart rate responses were predictive of follow-up resting heart rate after controlling for initial resting levels. Exercise cardiac index reactivity predicted follow-up cardiac index after controlling for earlier resting levels and adiposity. Follow-up total peripheral resistance index was predicted by earlier resting levels.

Blood Pressure↗

Prediction of resting cardiovascular functioning in youth with family histories of essential hypertension: a 5-year follow-up.

Two hundred forty-six children (96 Whites, of whom 51 were males; 150 African- Americans, of whom 69 were males) with a familial history of essential hypertension (EH) were re-evaluated 5 years after an initial evaluation. During the initial visit anthropometric, demographic, and resting cardiovascular (CV) parameters (designated initial baseline levels) were assessed. These CV parameters (systolic and diastolic blood pressure [BP], heart rate, cardiac output index [CI], and total peripheral resistance index [TPRI] were also measured during postural challenge, a video game challenge, and a cold pressor task. At follow-up, resting CV parameters were again evaluated, and designated as follow-up resting levels. Moderate temporal stability (r range = .43-.56) was observed for all resting CV parameters. Mean stress responses for each CV parameter for all 3 stressors during the initial visit were positively related to the respective CV follow-up resting level. BP stress responses to postural change and video game challenge to be significant independent predictors of future resting BP after controlling for standard EH risk factors. Follow-up resting CI was not predicted by any stress responses, whereas follow-up resting TPRI was predicted by TPRI responses to the video game after controlling for standard Eh risk factors. These results contrast with those from an earlier 1-year follow-up, where stress responses for neither CI nor TPRI predicted follow-up resting levels. It appears that, as children get older, TPRI stress responses play a stronger role in vasoconstrictive function.

Journal Article↗

Anthropometric, demographic, and cardiovascular predictors of left ventricular mass in young children.

Left ventricular (LV) mass is a strong independent predictor of cardiovascular morbidity and mortality. Few longitudinal studies have examined predictors of LV mass in children. This study assessed the contributions of anthropometric, demographic, and cardiovascular parameters (at rest and after exposure to laboratory stressors) as predictors of LV mass 3.6 years after the initial examination in a sample of 68 Caucasian and African-American children 7.9 +/- 0.7 years old. At the initial examination, all subjects had standard anthropometrics measured and hemodynamics assessed at rest and during 3 stressors: postural change, forehead cold stimulation, and treadmill exercise. On the follow-up examination 3 to 4 years later, echocardiographic evaluations were conducted to estimate LV mass and related LV geometry. LV mass and LV internal diameter in diastole were adjusted for linear growth (LV mass/height2.7 and LV internal dimension during diastole/height0.80, respectively). Hierarchical stepwise multiple regression analyses were conducted using parameters significant in univariate comparisons (p < 0.05). Initial weight (R2 = 0.38), height (R2 = 0.42), and cardiac output reactivity to standing and treadmill exercise (final model R2 = 0.55) were significant predictors of LV mass, whereas LV mass/height2.7 was predicted by initial adiposity (R2 = 0.07) and cardiac output and systolic pressure reactivity to postural change (final model R2 = 0.25). Follow-up relative wall thickness was significantly predicted by ethnicity (African-Americans greater than Caucasians, R2 = 0.15), adiposity (R2 = 0.20), and systolic pressure reactivity to postural change (final model R2 = 0.28). These findings suggest the potential benefit of weight control in childhood as a primary prevention for later onset of cardiovascular disease.

Anthropometry↗

Calf blood pressure: clinical implications and correlations with arm blood pressure in infants and young children.

OBJECTIVE: Indirect measurement of lower extremity blood pressure is often used in the clinical setting, although normative data after the newborn period are not readily available. METHODS: Indirect blood pressure (BP) measurement was obtained in the right arms and right calves of 148 healthy infants and young children 2 weeks to 3 years of age. All measurements were made using an oscillometric device. The infants and children are quiet or asleep and in the supine position. A BP cuff of proper size was chosen. Three measurements were made in both extremities; the average of the second and third measurements was used for all analyses. RESULTS: Age correlated better with calf systolic blood pressure (SBPc) than with arm SBP (SBPa) (r = .52 vs .17). Calf diastolic blood pressure (DBPc) and calf mean blood pressure (MBPc) correlated moderately poorly with age (r = .37 and .39, respectively). There was no order effect. SBPc correlated best with height (r = .53), then age (r = .52), and, finally, weight (r = .51). The correlation between BPc and BPa was moderately low. The correlation of SBPc with SBPa was r = .46; that of DBPc with DBPa was r = .37; and that of MBPc with MBPa was r = .41. From birth to 6 months, SBPc was slightly lower than SBPa (1 to 3 mm Hg). SBPc increased linearly relative to SBPa and began to exceed SBPa at 6 months of age. The pattern of DBP and MBP was similar. Wide variability of blood pressure parameters was noted between the infants and children at all ages. CONCLUSIONS: Reference data are presented for BPc and the difference between BPc and BPa in healthy infants and children from 2 weeks to 3 years of age. BPc is not equivalent to BPa and should not be arbitrarily substituted. Because of the wide variability among healthy infants and children, SBPc measurements should be interpreted with caution when evaluating for coarctation of the aorta.

Arm↗

Young children's cardiovascular stress responses predict resting cardiovascular functioning 2 1/2 years later.

BACKGROUND: Since the pathogenesis of coronary heart disease (CHD) has its origins in childhood, researchers have increasingly evaluated CHD risk factors in youth. In this study we examined the hypothesized behavioral risk factor of cardiovascular responsivity as a predictor of very young children's resting cardiovascular functioning 2 1/2 years later. SUBJECTS AND METHODS: During an initial visit to the laboratory, 97 children (30 blacks and 67 whites, 45 boys and 52 girls) aged 6-7 years completed three laboratory stressor tests (forehead cold pressor, postural change, and treadmill exercise). A comprehensive cardiovascular assessment was conducted during the tests. Resting cardiovascular activity (baseline values) was also assessed. Follow-up resting cardiovascular parameters were measured in the laboratory 2 1/2 years later. RESULTS: Cardiovascular stress responses were predictive of cardiovascular follow-up resting levels 2 1/2 years later. Multiple regression was used to evaluate the independent predictive power of stress responses after controlling for traditional risk factors. Follow-up resting systolic blood pressure (SBP) was predicted by the SBP response to postural change and treadmill exercise. Follow-up resting diastolic blood pressure (DBP) was predicted by the DBP response during treadmill exercise, particularly for blacks. The follow-up resting heart rate was predicted by the heart rate response to the forehead cold pressor and treadmill exercise. CONCLUSION: These results show that in very young children, stress responses are predictive of resting cardiovascular functioning 2 1/2 years later. Further developmental and longitudinal investigations will determine whether such responses are predictive of later preclinical manifestations of cardiovascular disease. If so, incorporation of stress testing in a standardized risk identification protocol might aid the design and practice of cardiovascular preventive medicine.

Analysis of Variance↗

Moderators of ethnic differences in vasoconstrictive reactivity in youth.

Three hundred and forty-one children (170 males and 171 females: 155 whites and 186 blacks) with a mean age of 11.2 years completed laboratory stressors of forehead cold and a video game. Impedance cardiography was used to assess total peripheral resistance indexed by body surface area (TPRI) at rest and during the stressors. Black youths exhibited greater TPRI and mean arterial pressure (MAP) reactivity to both stressors. It was hypothesized that anthropometric, demographic, lifestyle, and psychosocial variables might partially account for ethnicity differences in vasoconstrictive reactivity. Black youths' higher resting MAP and TPRI and greater MAP and TPRI reactivity to forehead cold were accounted for by anthropometric characteristics, physical activity, sedentary behavior (i.e., TV viewing) and family cohesion. The ethnic differences in TPRI and MAP video game reactivity were not accounted for by the various parameters.

Black or African American↗