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R Cooper

Publications and source records attributed to R Cooper.

At least 91 records · Page 5Linked to original sources
PubMed1998

Estimating African American admixture proportions by use of population-specific alleles.

We analyzed the European genetic contribution to 10 populations of African descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45% between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8% (Jamaica) to 22.5% (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3%-2.7%). We also estimated the male and female European contribution to African Americans, on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater than the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental populations.

Africa↗
PubMed1998

Angiotensinogen levels and obesity in four black populations. ICSHIB Investigators.

BACKGROUND: The relationship between circulating levels of angiotensinogen and hypertension in the epidemiologic setting has not been studied much. Recent findings related to the association between hypertension and polymorphisms of the angiotensinogen gene have generated new interest in this potential pathway to hypertension. OBJECTIVES: To examine environmental factors associated with levels of circulating angiotensinogen as determinants of hypertension in populations of African origin. METHODS: We recruited 1557 participants from communities in Nigeria (n = 611), Zimbabwe (n = 161), Jamaica (n = 476), and Maywood, Illinois, USA (n = 309). RESULTS: Mean angiotensinogen levels varied widely across groups (Nigeria 1381 ng/ml angiotensin I generated, Zimbabwe 1638 ng/ml angiotensin I generated, Jamaica 1808 ng/ml angiotensin I generated, and Maywood 2039 ng/ml angiotensin I generated). Average body mass index was highly correlated to angiotensinogen level across the population samples, accounting for 90% of the between-sample variation. At the individual level the correlation between body mass index and angiotensinogen level was substantially smaller, in the range 0.04-0.15, although the association attained statistical significance for all but one of the populations. Women had higher levels of angiotensinogen and mean levels in subjects of both sexes declined in late middle age. Hypertensives also had significantly higher levels of angiotensinogen and we noted correlations to blood pressure for two of the four populations. CONCLUSION: Obesity, sex and age would all appear to be important modifiers of circulating angiotensinogen levels. The variation in level across populations was substantially larger than that which has been found previously in association with known genetic polymorphisms within populations, suggesting the possibility that environmental effects are more important than had previously been recognized.

Adult↗
PubMed1998

Effects of castration and chronic steroid treatments on hypothalamic gonadotropin-releasing hormone content and pituitary gonadotropins in male wild-type and estrogen receptor-alpha knockout mice.

Testicular androgens are integral components of the hormonal feedback loops that regulate circulating levels of LHbeta and FSH. The sites of feedback include hypothalamic areas regulating GnRH neurons and pituitary gonadotropes. To better define the roles of androgen receptor (AR), estrogen receptor-alpha (ERalpha), and estrogen receptor-beta (ERbeta) in mediating feedback effects of sex steroids on reproductive neuroendocrine function, we have determined the effects of castration and steroid replacement therapy on hypothalamic GnRH content, pituitary LHbeta and FSHbeta messenger RNA (mRNA) levels, and serum gonadotropins in male wild-type (WT) and estrogen receptor-alpha knockout (ERKO) mice. Hypothalami from intact WT and ERKO males contained similar amounts of GnRH, whereas castration significantly reduced GnRH contents in both genotypes. Replacement therapy with estradiol (E2), testosterone (T), or dihydrotestosterone (DHT) restored hypothalamic GnRH content in castrated (CAST) WT mice; only the androgens were effective in CAST ERKOs. Analyses of pituitary function revealed that LHbeta mRNA and serum LHbeta levels in intact ERKOs were 2-fold higher than those in intact WT males. Castration increased levels of LHbeta mRNA (1.5- to 2-fold) and serum LHbeta (4- to 5-fold) in both genotypes. Both E2 and T treatments significantly suppressed LHbeta mRNA and serum LH levels in CAST WT males. However, E2 was completely ineffective, and T was only partially effective in suppressing these two indexes in the CAST ERKO males. DHT treatments stimulated a 50% increase in LHbeta mRNA and serum LH levels in WT males, whereas serum LH was significantly suppressed in DHT-treated ERKO males. Although the pituitaries from intact ERKO males contained similar amounts of FSHbeta mRNA, serum FSH levels were 20% higher than those in the intact WT males. Castration increased FSHbeta mRNA levels only in WT males, but significantly increased serum FSH levels in both genotypes. Both E2 and T treatments significantly suppressed serum FSH in CAST WT males, whereas only E2 suppressed FSHbeta mRNA. DHT treatments of CAST WT mice stimulated a small increase in serum FSH, but failed to alter FSHbeta mRNA levels. None of the steroid treatments exerted any significant effect on FSHbeta mRNA or serum FSH levels in CAST ERKOs. These data suggest that hypothalamic GnRH contents can be maintained solely through AR signaling pathways. However, normal regulation of gonadotrope function requires aromatization of T and activation of ERalpha signaling pathways in the gonadotrope. In addition, serum FSH levels in male ERKOs appear to be regulated largely by nonsteroidal testicular factors such as inhibin. Finally, these data suggest that hypothalamic ERbeta may not be involved in mediating the negative feedback effects of T on serum LH and FSH in male mice.

Animals↗
PubMed1998

Montserrat. Managing health care in a volcanic crisis.

The volcano on Montserrat, after being dormant for over 400 years, has been active for the past two years, last erupting on 27 June, 1997. With the capital, Plymouth, in the unsafe zone, major dislocation of people, facilities and services has occurred. The Health Department is splintered over five sites across an eight mile span and the temporary 30 bed hospital, sited at a primary school, is separated from its Casualty and Out-patient Department and Operating Theatre by 0.25 mile. In order to maintain continuity of care for communities, efforts have been made to keep evacuated clients and their community health workers as close together as possible. The mass emigration has depleted the health services, creating severe stress for those remaining. Elderly relatives have frequently been left behind, necessitating the establishment of special geriatric care facilities to cater to their needs. Increased and continuous health surveillance and mass media education have been integral to the prevention of major disease outbreak--particularly with added challenges to food safety, and management of liquid and solid waste disposal. Cooperation from neighbouring states, particularly Antigua, Barbados and Guadeloupe, as well as from the United Kingdom, has been critical in the management of the continuing crisis.

Aged↗
PubMed1997

Overexpression of human stem cell factor impairs melanocyte, mast cell, and thymocyte development: a role for receptor tyrosine kinase-mediated mitogen activated protein kinase activation in cell differentiation.

Stem cell factor (SCF) is synthesized as both soluble (S) and membrane-associated (MA) proteins. Indirect insight into the function of MA and S isoforms of SCF has come from studies performed in Steel (Sl) mutant mice. However, the physiologic role(s) of these two isoforms remain unknown. In an attempt to better understand the in vivo role of c-kit/SCF interactions on various cell lineages, transgenic mice were generated that overexpress MA isoform of human SCF (hSCF). In murine cells, hSCF behaves as an antagonist to normal SCF function, due to interference with the interaction between endogenous murine SCF and its receptor, c-kit, encoded by the dominant white spotting (W) gene. Mice expressing the hSCF transgene display a variety of phenotypic abnormalities, which are accentuated when combined with W alleles. Here we show that mice homozygous for the hSCF transgene demonstrate a coat color deficiency seen in some mice homozygous for mild W alleles. Specifically, homozygous hSCF transgenic mice (hSCF220) display a pronounced forehead blaze, with additional white spots over the cervical region, as well as a very large belly spot. Doubly heterozygous animals that carry both a mutated W allele and the hSCF transgene also display an unusual pigment defect and a dramatic reduction in the number of dermal mast cells. Furthermore, overexpression of MA hSCF in the thymus results in abnormal thymocyte differentiation and proliferation, which is associated with reduced mitogen activated protein (MAP) kinase activation. Thus, MAP kinase activation by a receptor tyrosine kinase, such as c-kit, may be critical for the differentiation of thymocytes in vivo.

Animals↗
PubMed1997

Hypertension, serum angiotensinogen, and molecular variants of the angiotensinogen gene among Nigerians.

BACKGROUND: We evaluated the association among the M235T and T174M variants of the angiotensinogen (AGT) gene, plasma AGT, and hypertension status in a sample of Nigerians. METHODS AND RESULTS: Participants were selected from the extremes of the blood pressure distribution obtained from the population survey of 2509 men and women aged 25 to 74 years. Cases (hypertensive subjects) were individuals who had high blood pressure or were taking antihypertensive medication, and control subjects were individuals with low blood pressure who had never taken antihypertensive medication. We found a significant association between the M235T variant and plasma AGT level. Hypertensive subjects had higher plasma AGT levels compared with control subjects. The allele frequencies of the two variants were similar in the hypertensive patients and the control subjects. CONCLUSIONS: The consistent relationships observed between the M235T variant and the protein product and between plasma level of the protein and hypertension status in different ethnic groups provide some evidence for a biochemical mechanism linking DNA variation in the renin-angiotensin system with the hypertension phenotype.

Adult↗
PubMed1997

Bovine beta-lactoglobulin at 1.8 A resolution--still an enigmatic lipocalin.

BACKGROUND: beta-Lactoglobulin (beta-Lg) is the major whey protein in the milk of ruminants and many other mammals. Its function is not known, but it undergoes at least two pH-dependent conformational changes which may be important. Bovine beta-Lg crystallizes in several different lattices, and medium-resolution structures of orthorhombic lattice Y and trigonal lattice Z have been published. Triclinic lattice X and lattice Z crystals grow at pH values either side of the pH at which one of the pH-induced conformational changes occurs. A full understanding of the structure is needed to help explain both the conformational changes and the different denaturation behaviour of the genetic variants. RESULTS: We have redetermined the structure of beta-Lg lattice Z at 3.0 A resolution by multiple isomorphous replacement and have partially refined it (R factor = 24.8%). Using the dimer from this lattice Z structure as a search model, the triclinic crystal form grown at pH 6.5 (lattice X) has been solved by molecular replacement. Refinement of lattice X at 1.8 A resolution gave an R factor of 18.1%. The structure we have determined differs from previously published structures in several ways. CONCLUSIONS: Incorrect threading of the sequence in the published structures of beta-Lg affects four of the nine beta strands. The basic lipocalin fold of the polypeptide chain is unchanged, however. The relative orientation of the monomers in the beta-Lg dimer differs in the two lattices. On raising the pH, there is a rotation of approximately 5 degrees, which breaks a number of intersubunit hydrogen bonds. It is not yet clear, however, why the stability of the structure should depend so heavily upon the external loop around residue 64 or the beta strand with the free thiol, each of which shows genetic variation.

Amino Acid Sequence↗
PubMed1997

Heritability of plasma leptin in a population sample of African-American families.

The aim of this study was to examine familial patterns of plasma leptin levels and the potential association with cardiovascular risk factors in a population sample of African-American families recruited from metropolitan Chicago. The study included 68 mothers, 31 fathers, 143 daughters, and 119 sons, for a total of 361 individuals from 118 families. Leptin levels were adjusted for the effect of age separately for mothers, fathers, daughters, and sons. Residuals were then standardized before estimating familial correlation using the maximum-likelihood method available in SEGPATH. With the exception of height, plasma leptin level was strongly correlated with all measured anthropometric variables. Familial effect (i.e., heritability) of leptin levels was estimated as 39% in this population at high risk for over weight. A significant sex difference was observed, and most of the estimated familial effect may be attributed to genetic influences since the spouse correlation was not statistically different from zero. A strong nonshared environmental effect is also suggested, however.

Anthropometry↗
PubMed1997

Carbon regulation of the cuticle-degrading enzyme PR1 from Metarhizium anisopliae may involve a trans-acting DNA-binding protein CRR1, a functional equivalent of the Aspergillus nidulans CREA protein.

The pr1 gene of the entomopathogenic fungus Metarhizium anisopliae encodes a serine protease that is highly active towards the insect cuticle and whose synthesis is subject to both carbon and nitrogen repression. The pr1 promoter region was sequenced revealing the presence of putative CREA- and AREA-binding sites. In vitro bandshift experiments demonstrated that an Aspergillus nidulans GST-CREA fusion protein was capable of binding to two of the three putative CREA sites. Using a PCR-based strategy the M. anisopliae crr1 gene was identified; it encodes a putative C2H2-type DNA-binding protein with significant sequence similarity to A. nidulans CREA. Complementation experiments with an A. nidulans strain carrying creA204 demonstrated that CRR1 can partially substitute for CREA function.

Amino Acid Sequence↗
PubMed1997

The angiotensin converting enzyme and blood pressure in Jamaicans.

An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme gene influences the level of serum angiotensin converting enzyme activity and has been associated with risk of several cardiovascular conditions. The relationship to blood pressure remains uncertain, however. We conducted a population-based survey in Kingston, Jamaica, to examine the association between angiotensin converting enzyme genotype, angiotensin converting enzyme serum activity and blood pressure. Serum angiotensin converting enzyme activity was measured and genotyping performed for the I/D polymorphism in 500 community residents. The overall prevalence of the D allele was 59.3%. Angiotensin converting enzyme genotype was not significantly related to blood pressure (P = .16), although it did influence angiotensin-converting enzyme activity, leading to an increase of 35% among individuals with the DD as compared with II genotype. Angiotensin converting enzyme levels were significantly higher in hypertensives as compared with normotensives (P < .05). A modest correlation was observed between blood pressure and angiotensin converting enzyme activity among untreated individuals (r = 0.11; P = .04), although this did not persist in multivariate analysis. A relationship between body mass index and angiotensin converting enzyme activity was identified in both men and women that was independent of genotype. These data demonstrate findings among blacks which are consistent with other studies and suggest a relationship between angiotensin converting enzyme genotype, and serum activity which is influenced by both genetic and environmental factors. The potential role of ACE on blood pressure control in the population remains uncertain.

Adult↗
PubMed1997

Hypertension in blacks.

The excess of hypertension among blacks has been recognized since early in this century and explains a substantial portion of the black health disadvantage. In a cohort study begun in the 1970s, hypertension accounted for 20% of all-cause mortality among blacks, compared to 10% among whites. National data on trends in hypertension (140/90 mm Hg or treatment) prevalence from 1960 to 1990 suggest a decline from 44% to 32%, although differences in survey technique likely account for this pattern. During this period the prevalence ratio of black:white remained constant at 1.5, suggesting that secular trends in causal factors, if any, effected both groups equally. Recent data demonstrate a gradient in risk across the African diaspora, with standardized prevalences of 14% in West Africa and 26% in the Caribbean, compared to 33% in the US. This pattern parallels the gradient in known risk factors, with obesity alone accounting for a third of the excess in the US compared to Africa. Why the black excess of hypertension in the US? Despite widespread speculation, unique characteristics of hypertension among blacks have yet to be established. Consistent evidence demonstrates a similar impact of the known risk factors in all population groups. Epidemiologic evidence likewise suggests that a similar risk of complications exists with blood pressure elevation among blacks and whites, level for level. Although the genetic epidemiology of hypertension is still in its infancy, no clear cross-population differences are yet apparent. Pathophysiologic traits that are known to be part of the causal etiologic pathway have not been shown to vary across groups. Unique features of this condition among blacks are likely to be restricted to the different mixes and intensities of risk factors. In the absence of evidence to support the hypothesis, it is perhaps surprising that credence continues to be given to the notion of black exceptionalism. Am J

Black People↗
PubMed1997

ACE, angiotensinogen and obesity: a potential pathway leading to hypertension.

The renin-angiotensin system (RAS) plays a crucial role in the regulation of fluid volume, thereby influencing blood pressure (BP). Obesity is an important risk factor for hypertension, however the physiologic basis for this relationship has not been clarified. In a population survey we examined the potential relationship between the RAS and obesity. Based on community sampling, 449 individuals were recruited from metropolitan Kingston, Jamaica. Serum angiotensin-converting enzyme (ACE) and circulating angiotensinogen levels were measured and the associated genes were typed for previously described polymorphisms. Obese individuals (body mass index > 31) had significantly higher serum ACE and angiotensinogen levels, this relationship persisted for ACE in multivariate analyses controlling for BP, hypertension status, age, and gender. The insertion/deletion polymorphism of the ACE gene was associated with variation in the levels of ACE, but inconsistently with body mass index. Variants of the angiotensinogen gene leading to amino acid substitutions at positions 174 and 235 did not influence levels either of angiotensinogen or obesity. These data suggest that obesity may alter the levels of ACE and angiotensinogen, and provide a potential pathway through which obesity leads to elevation of BP.

Adult↗
PubMed1997

Simultaneous monitoring of heart rate and motion to assess energy expenditure.

Measurement of energy expenditure in free-living individuals represents a methodologic challenge in epidemiologic research. Heart rate monitors, while closely tied to energy expenditure at high levels of energy output, provide much less predictive power at low levels; however, measurement of motion may improve the predictive ability. This study was undertaken to determine the usefulness of simultaneously monitoring heart rate and motion for the estimation of energy expenditure. Ten subjects were studied during simulated activities of daily living (ADLC) and submaximal treadmill tests. Compared to direct measurement, the motion sensor predicted oxygen consumption poorly (r2 = 0.53) for both tests. Heart rate measured simultaneously yielded an r2 of 0.81 for ADLC and 0.90 for the treadmill. Addition of motion data increased the r2 value for the ADLC for all but one individual and increased the group mean from 0.81 to 0.86. This improvement was not observed for the treadmill, confirming the hypothesis that the principle value of monitoring motion occurs at lower heart rates.

Activities of Daily Living↗
PubMed1997

Differential physiology and morphology of phasic and tonic motor axons in a crayfish limb extensor muscle

The main leg extensor muscle of the crayfish Procambarus clarkii is innervated by two excitatory motor axons (phasic and tonic) and by the common inhibitory axon. The axons and their terminals were investigated using vital fluorescent dyes, antibodies and electron microscopy. Correlative physiological observations were made using intracellular microelectrodes and focal 'macro-patch' electrodes. The excitatory axons innervate the muscle fibres more extensively than does the inhibitory axon. Striking morphological and physiological differences between the two excitatory axons were discerned. The tonic motor axon contains many mitochondria and has varicose junctional terminals; the phasic axon has fewer mitochondria and thin terminals. In freely moving animals, the tonic axon is very active, whereas the phasic axon is inactive but fires in brief bursts during walking. Throughout the muscle, tonic excitatory postsynaptic potentials (EPSPs) are very small at low frequencies and facilitate greatly at higher frequencies. The EPSPs of the phasic axon are larger at low frequencies and depress with maintained stimulation. At identified tonic terminals, quantal content at 1&shy;10 Hz is very low, whereas at identified phasic terminals, quantal content is 50- to 200-fold greater. The results indicate that transmitter release is regulated differently at the synapses of the two axons.

Journal Article↗
PubMed1997

The prevalence of hypertension in seven populations of west African origin.

OBJECTIVES: This study was undertaken to describe the distribution of blood pressures, hypertension prevalence, and associated risk factors among seven populations of West African origin. METHODS: The rates of hypertension in West Africa (Nigeria and Cameroon), the Caribbean (Jamaica, St. Lucia, Barbados), and the United States (metropolitan Chicago, Illinois) were compared on the basis of a highly standardized collaborative protocol. After researchers were given central training in survey methods, population-based samples of 800 to 2500 adults over the age of 25 were examined in seven sites, yielding a total sample of 10014. RESULTS: A consistent gradient of hypertension prevalence was observed, rising from 16% in West Africa to 26% in the Caribbean and 33% in the United States. Mean blood pressures were similar among persons aged 25 to 34, while the increase in hypertension prevalence with age was twice as steep in the United States as in Africa. Environmental factors, most notably obesity and the intake of sodium and potassium, varied consistently with disease prevalence across regions. CONCLUSION: The findings demonstrate the determining role of social conditions in the evolution of hypertension risk in these populations.

Adult↗