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Biomedical subjects

R Cooper

Publications and source records attributed to R Cooper.

At least 55 records · Page 3Linked to original sources
PubMed2000

Correlates of blood pressure in an urban Zimbabwean population and comparison to other populations of African origin.

We have evaluated the relationship between systolic blood pressure (SBP) and age, body mass index (BMI), waist circumference, sodium to potassium ratio (Na/K), and tobacco use in an urban African population. We conducted a random, population-based, cross-sectional survey of people 25 years and older in Marondera, Zimbabwe, with over-sampling in older age groups (n = 775), using a method comparable to that used in International Collaborative Study on Hypertension in Blacks (ICSHIB). The age-adjusted prevalences of hypertension in Marondera (SBP >/=140/DBP >/=90/antihypertensive medication) were 30% for women and 21% for men. The average BMI was 26.3 kg/m2 for women and 21.4 kg/m2 for men. The prevalence of hypertension had a steep association with age and in women ranged from 15% (25-34 years) to 63% (55 years and over) and in men from 9% to 47%. No tobacco use in women and greater Na/K ratio in spot urines in men were significantly associated with an increased SBP. In both men and women the levels of hypertension and SBP were strongly positively associated with BMI, although the relationship appeared to plateau in women with a BMI greater than >/=25 kg/m2. At a given BMI, men and women had similar SBPs and prevalences of hypertension. There is a very high prevalence of hypertension among urban Zimbabweans, particularly among women. Under the assumption the studies are comparable, the prevalence of hypertension in Zimbabwean women (41%) and men (26%) after age adjustment to the ICSHIB populations, appeared higher than almost all of the ICSHIB populations, including those with higher average body mass indexes. Journal of Human Hypertension (2000) 14, 65-73.

Adult↗
PubMed2000

Effects of dietary fibre and olestra on regional apparent viscosity and water content of digesta residue in porcine large intestine.

BACKGROUND: Increased consumption of non-digested, non-absorbed substrates, such as dietary fibre, can lead to an increase in colonic transit rate and stool output. The effects of dietary fibre and olestra on the consistency and water content of digesta residue within the large bowel were not known. AIM: The aim of this study was to determine the effects of dietary fibre and olestra on regional dehydration and apparent viscosity of digesta residue throughout the large bowel. METHODS: Seventy-eight pigs were fed diet alone (control) or supplemented with 40 g/day or 80 g/day dietary fibre or olestra and sacrificed 24, 48, 96 or 192 h after initiation of dosing. The large bowel was removed, divided into 13 segments, and the digesta residue/stool was analysed for apparent viscosity (peak force for extrusion) and percentage water content. RESULTS: In control animals, digesta residue occurred as a continuum, from liquid in the cecum (87.9% water) to solid in the rectum (71. 5% water). The relatively small decrease in percentage water content (16.4%) resulted in a marked increase in mean apparent viscosity (liquid = 87 g peak force; solid=3919 g peak force). Dietary fibre increased the percentage water content of digesta residue throughout the large bowel. In contrast, olestra decreased the percentage water content of digesta residue in the mid and distal large bowel. At 40 g/day, dietary fibre showed a significant (P < 0.05) digesta residue/stool softening effect for all time points, beginning at 24-h (single dose). Olestra 40 g/day did not significantly soften digesta residue/stool until 48 h (2 doses, P < 0.05), and was not different from control at 96 h. At 80 g/day, both dietary fibre and olestra significantly (P < 0.01) softened digesta residue/stool at all time points. There were no liquid or oily stools at any dose or time-point. CONCLUSIONS: Relatively small changes in water content result in large changes in digesta residue/stool apparent viscosity. Dietary fibre increased digesta residue/stool water content throughout the bowel, resulting in softer digesta residue/stool. In contrast, olestra decreased stool water content, yet had a similar stool softening effect compared to dietary fibre.

Animals↗
PubMed2000

Lack of association of the angiotensinogen-6 polymorphism with blood pressure levels in the comprehensive NHLBI Family Blood Pressure Program. National Heart, Lung and Blood Institute.

OBJECTIVE: To evaluate the association between the angiotensinogen-6 polymorphism (AGT-6) and blood pressure levels. DESIGN: Data were analysed from the first 4,322 subjects of the NHLBI Family Blood Pressure Program (FBPP), consisting of four networks (GenNet, GENOA, HyperGEN and SAPPHIRe), each conducting a multicentre observational family study to identify and characterize the genetic determinants of hypertension and blood pressure. The four studies use different designs (concordant sibpairs, discordant pairs, sibships, extended pedigrees), target different ethnic groups (Caucasian, African-American, Japanese, Chinese), and have different inclusion/exclusion criteria. However, the protocols and definitions were standardized across networks before data collection to allow maximum poolability. METHODS: Each network/racial group was analysed separately, using generalized linear models that accounted for the non-independence of family members and/or the confounding of anti-hypertensive medications as needed. The results were also pooled using a pre-planned meta-analysis technique. RESULTS: AGT-6 was not significantly associated with blood pressure in any network/racial group. In the meta-analysis, the pooled effect of AGT-6 was small [hazard ratio = 1.10, 95% confidence interval (CI) = 0.99-1.22, P= 0.0647 for systolic; hazard ratio = 1.04, 95% CI = 0.89-1.21, P= 0.6383 for diastolic]. A post-hoc analysis restricting to subjects meeting JNC VI criteria for Stage I hypertension (blood pressure > 140/90 mmHg or medicated) showed a stronger statistically significant relationship for systolic blood pressure (hazard ratio = 1.44, 95% CI = 1.04-2.00, P= 0.0283). CONCLUSIONS: AGT-6 has minimal to no effect on the inter-individual variation of blood pressure levels, and is at best a 'minor gene' for blood pressure in the population as a whole.

Adolescent↗
PubMed2000

Infant colic syndrome--maternal fantasies of aggression and infanticide.

This study examined the impact of infant colic on the emotional state of the mother. Subjects were 23 pairs of mothers and their colicky infants. Structured interviews were conducted with mothers to elicit details around the colic episode and included (1) the emotional state experienced by the mother, (2) the quality and content of the mother's fantasies in response to her infant, and (3) the emotional impact on the parents. Explicit aggressive thoughts and fantasies were revealed by 16 (70%) of the mothers while six (26%) admitted thoughts of infanticide during their infant's colic episodes, a finding notable because previously this has not been documented in medical literature. All mothers experienced physical and psychological symptoms in response to their infant's colic. More than 90% of the mothers with a colicky infant experienced significant marital tension and disruption in their social contacts. The findings suggest that physician receptivity and skill in uncovering the physical and psychological impact of colic on parents is essential for the physical and emotional well-being of the family. Active support and counseling by physicians is critical to diminish any potential for abuse and infanticide in these infants.

Adult↗
PubMed2000

Induction of mammary gland development in estrogen receptor-alpha knockout mice.

Mammary glands from the estrogen receptor-a knockout (alphaERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted ERalpha signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute to the alphaERKO mammary phenotype. We report that circulating PRL is reduced in the female alphaERKO mouse. Implantation of an age-matched, heterozygous ERalpha pituitary isograft under the renal capsule of 25-day-old or 12-week-old alphaERKO mice increased circulating PRL and progesterone levels, and induced mammary gland development. Grafted alphaERKO mice also possessed hypertrophied corpora lutea demonstrating that PRL is luteotropic in the alphaERKO ovary. By contrast, ovariectomy at the time of pituitary grafting prevented mammary gland development in alphaERKO mice despite elevated PRL levels. Hormone replacement using pellet implants demonstrated that pharmacological doses of estradiol induced limited mammary ductal elongation, and estradiol in combination with progesterone stimulated lobuloalveolar development. PRL alone or in combination with progesterone or estradiol did not induce alphaERKO mammary growth. Estradiol and progesterone are required for the structural development of the alphaERKO mammary gland, and PRL contributes to this development by inducing ovarian progesterone levels. Therefore, the manifestation of the alphaERKO mammary phenotype appears due to the lack of direct estrogen action at the mammary gland and an indirect contributory role of estrogen signaling at the hypothalamic/pituitary axis.

Animals↗
PubMed1999

Usefulness of triiodothyronine (T3) treatment after surgery for complex congenital heart disease in infants and children.

This is a study of the use of T3 infusion in the postoperative period in 6 pediatric patients who underwent complex cardiac surgical procedures under cardiopulmonary bypass. Normalization of serum T3 levels was reflected in a marked decrease in requirement of inotropic support, conversion to normal sinus rhythm, and progressively improving clinical course.

Child, Preschool↗
PubMed1999

The presence of novel amino acids in the cytoplasmic domain of stem cell factor results in hematopoietic defects in Steel(17H) mice.

Stem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF(248)) or membrane-associated (MA) (SCF(220)) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie (Sl(d)) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms. Steel(17H) (Sl(17H)) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl(17H) allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa's) in the SCF cytoplasmic domain with 28 novel aa's. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl(17H)-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl(17H) mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl(17H) isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCF(X9/D3)) SCF in Sl/Sl(17H) mutants results in a significant improvement in peripheral red blood cell counts in comparison to Sl/Sl(17H) mice.

Amino Acid Sequence↗
PubMed1999

Reversible immortalization of human myogenic cells by site-specific excision of a retrovirally transferred oncogene.

Myogenic cells have a limited life span in culture, which prevents expansion at clinically relevant levels, and seriously limits any potential use in cell replacement or ex vivo gene therapy. We developed a strategy for reversibly immortalizing human primary myogenic cells, based on retrovirus-mediated integration of a wild-type SV40 large-T antigen (Tag), excisable by means of the Cre-Lox recombination system. Myogenic cells were transduced with a vector (LTTN-LoxP) expressing the SV40 Tag under the control of an LTR modified by the insertion of a LoxP site in the U3 region. Clonal isolates of Tag-positive cells showed modified growth characteristics and a significantly extended life span, while maintaining a full myogenic potential. Transient expression of Cre recombinase, delivered by transfection or adenoviral vector transduction, allowed excision of the entire provirus with up to >90% efficiency. Cultures of Cre-treated (Tag-) or untreated (Tag+) myogenic cells were genetically labeled with a lacZ retroviral vector, and injected into the regenerating muscle of SCID/bg immunodeficient mice. Tag- cells underwent terminal differentiation in vivo, giving rise to clusters of beta-Gal+ hybrid fibers with an efficiency comparable to that of control untransduced cells. Tag+ cells could not be detected after injection. Neither Tag+ nor Tag- cells formed tumor in this xenotransplantation model. Reversible immortalization by Tag therefore allows the expansion of primary myogenic cells in culture without compromising their ability to differentiate in vivo, and could represent a safe method by which to increase the availability of these cells for clinical application.

3T3 Cells↗
PubMed1999

Platelet cytosolic calcium hyperresponsivity to serotonin in patients with hypertension and depressive symptoms.

BACKGROUND: Data from recent studies indicate that the presence of depression is an independent risk factor for cardiovascular and cerebrovascular events. The mechanism by which depression increases the morbidity and mortality risks in patients with comorbid vascular disease is currently the object of considerable research interest. Platelets may be involved in this pathological process. Although many investigators have extensively evaluated platelet biochemistry in depressed patients, there currently exists very little information regarding how the biochemical alterations might relate to an increased risk of cardiovascular events. In this study, we examined the responsivity of platelet cytosolic calcium concentrations ([Ca++]i) to serotonin stimulation in populations of hypertensive patients with or without comorbid depressive symptoms. METHODS: We utilized Fura-2 loaded platelets to compare changes in intracellular calcium levels (delta [Ca++]i) following serotonin stimulation among 48 patients with hypertension and varying degrees of depressive symptomatology. RESULTS: We found that those patients with higher scores on standardized depression rating scales showed significantly greater [Ca++]i (82.82 +/- 15.88 mmol/L) increase compared with [Ca++]i (60.10 +/- 22.65 mmol/L) patients with lower depression scores. CONCLUSIONS: The results of this study support the hypothesis that the enhanced platelet reactivity seen in patients with depressive symptoms may mediate the deleterious effects of depression on cardiovascular disease.

Aged↗
PubMed1999

Antihyperglycemic sesquiterpenes from Psacalium decompositum.

Psacalium decompositum was investigated for antihyperglycemic compounds using diabetic ob/ob mice as a model for type 2 diabetes. In vivo bioassay-guided fractionation of an aqueous extract from the roots of P. decompositum led to the isolation of two new eremophilanolides, 3-hydroxycacalolide (1a) and epi-3-hydroxycacalolide (1b). A 1:1 mixture of 1a/1b exhibited antihyperglycemic activity when tested at 1.09 mmol/kg in ob/ob mice. The known furanoeremophilanes, cacalone (2a) and epicacalone (2b), were also isolated from the aqueous extract and were inactive. The known furanoeremophilane, cacalol (3), was isolated from a CH2Cl2 extract of P. decompositum roots and possessed antihyperglycemic activity. The relative stereochemistry in 1a and 1b was assigned 3R,5S and 3S,5S, respectively, based on ROESY data, 3J H-H values, and molecular mechanics calculations. Complete 13C and 1H NMR chemical shifts were assigned for 1a, 1b, 2a, 2b, and 3, and several revisions in 13C NMR assignments for 2a and 3 were made. Results from the conformational analysis of 1a, 1b, 2a, and 2b indicate that each compound exists in one major conformation in solution with H3-12 in a pseudoaxial position.

Animals↗
PubMed1999

Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.

Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 candidate human genes for blood-pressure homeostasis and hypertension. We assayed 28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5' and 3' untranslated regions (UTRs), introns and coding sequence of these genes, for sequence differences in individuals of African and Northern European descent using high-density variant detection arrays (VDAs). We identified 874 candidate human SNPs, of which 22% were confirmed by DNA sequencing to reveal a discordancy rate of 21% for VDA detection. The SNPs detected have an average minor allele frequency of 11%, and 387 are within the coding sequence (cSNPs). Of all cSNPs, 54% lead to a predicted change in the protein sequence, implying a high level of human protein diversity. These protein-altering SNPs are 38% of the total number of such SNPs expected, are more likely to be population-specific and are rarer in the human population, directly demonstrating the effects of natural selection on human genes. Overall, the degree of nucleotide polymorphism across these human genes, and orthologous great ape sequences, is highly variable and is correlated with the effects of functional conservation on gene sequences.

3' Untranslated Regions↗