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PubMed2002

Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs.

PURPOSE: To compare gene expression profiles and drug permeability differences in Caco-2 cell culture and human duodenum. METHODS: Gene expression profiles in Caco-2 cells and human duodenum were determined by GeneChip analysis. In vivo drug permeability measurements were obtained through single-pass intestinal perfusion in human subjects, and correlated with in vitro Caco-2 transport permeability. RESULTS: GeneChip analysis determined that 37, 47, and 44 percent of the 12,559 gene sequences were expressed in 4-day andl6-day Caco-2 cells and human duodenum, respectively. Comparing human duodenum with Caco-2 cells, more than 1,000 sequences were determined to have at least a 5-fold difference in expression. There were 26, 38, and 44 percent of the 443 transporters, channels, and metabolizing enzymes detected in 4-day, 16-day Caco-2 cells, and human duodenum, respectively. More than 70 transporters and metabolizing enzymes exhibited at least a 3-fold difference. The overall coefficient of variability of the 10 human duodenal samples for all expressed sequences was 31% (range 3% to 294%) while that of the expressed transporters and metabolizing enzymes was 33% (range 3% to 87%). The in vivo / in vitro drug permeability measurements correlated well for passively absorbed drugs (R2 = 85%). The permeability correlation for carrier-mediated drugs showed 3- 35-fold higher in human above the correlation of passively absorbed drugs. The 2- 595-fold differences in gene expression levels between the Caco-2 cells and human duodenum correlated with the observed 3- 35-fold difference in permeability correlation between carrier-mediated drugs and passively absorbed drugs. CONCLUSIONS; Significant differences in gene expression levels in Caco-2 cells and human duodenum were observed. The observed differences of gene expression levels were consistent with observed differences in carrier mediated drug permeabilities. Gene expression profiling is a valuable new tool for investigating in vitro and in vivo permeability correlation.

Adult↗

PubMed1999

Correlation between high-pass resolution perimetry and standard threshold perimetry in subjects with glaucoma and ocular hypertension.

PURPOSE: To evaluate the correlation between High-Pass Resolution Perimetry (HRP) and standard threshold perimetry in patients with glaucoma or ocular hypertension. METHODS: 31 glaucomatous patients and 37 ocular hypertension subjects with previous perimetric examination experience were consecutively recruited and only one eye for each patient was selected at random. Glaucomatous patients were classified as having primary open angle glaucoma when they had an abnormal visual field and/or an abnormal optic nerve head (ONH)/retinal nerve fiber layer (RNFL) typical of glaucoma, open angle at gonioscopy and no clinically apparent secondary cause for their glaucoma. Ocular hypertension subjects were defined as having intraocular pressure >21 mm Hg on no treatment, normal visual field, normal ONH and RNFL, elevated intraocular pressure without any treatment. All the subjects were examined with Humphrey Field Analyzer (HFA) 640, 'program central 30-2' (Humphrey Systems, San Leandro, CA, USA) and with High-Pass Resolution Perimeter (HRP), Ophthimus version 2.4,'ring program' (Nikon-HighTech Vision, Goteborg, Sweden). Visual field indices were obtained with both systems: for HFA mean deviation (MD), corrected pattern standard deviation (CPSD) and short term fluctuation (SF), while for HRP global deviation (GD), local deviation (LD), form index (FI) and neural capacity (NC). The data were analyzed by descriptive analysis, Student's t test with Bonferroni's correction or Mann-Whitney non-parametric test and Pearson or Spearman's correlation coefficient. RESULTS: A significant correlation was found between MD and GD (r = -0.81), CPSD and LD (r = 0.87), PSD and LD (r = 0.72). NC was significantly correlated with MD (r = 0.76), GD (r = -0.94). FI was significantly correlated with PSD (r = -0.58), CPSD (r = -0.72), LD (r = -0.56). When the same data were analyzed for the glaucomatous group only, similar results were found; in the ocular hypertensive group no significant correlation was found except between NC and MD (r = 0.52). CONCLUSION: HRP indices vary comparably with HFA indices. Parameters as NC and FI were significantly correlated with standard visual field indices of both HFA and HRP. Although the clinical applications for FI are not clear yet, NC could detect both early glaucomatous damage and age related changes.

Disease Progression↗

PubMed2004

Correlation times and adiabatic barriers for methyl rotation in SNase.

The relation of rotational correlation times to adiabatic rotational barriers for alanine methyl groups in staphylococcal nuclease (SNase) is investigated. The hypothesis that methyl rotational barriers may be useful probes of local packing in proteins is supported by an analysis of ten X-ray crystal structures of SNase mutants. The barrier heights are consistent across a set of ten structures of a native SNase and mutants containing single-point mutations or single or double insertions, most in a ternary SNase complex. The barriers for different methyls have a range of 7.5 kcal/mol, which at 300 K would correspond to a five-order-of-magnitude range in correlation time. It is demonstrated that adiabatic rotational barriers can fluctuate significantly during an MD simulation of hydrated SNase, but that a Boltzmann weighted average is predictive of rotational correlation times determined from correlation functions. Even if a given methyl is on average quite sterically hindered, infrequently sampled low-barrier conformations may dominate the Boltzmann distribution. This result is consistent with the observed uniformity of NMR correlation times for (13)C-labeled methyls. The methyl barriers in simulation fluctuate on multiple time scales, which can make the precise relationship between methyl rotational correlation time and methyl rotation barriers complicated. The implications of these issues for the interpretation of correlation times determined from NMR and simulation are discussed.

Alanine↗

PubMed2003

Implant stability and histomorphometry: a correlation study in human cadavers using stepped cylinder implants.

The aim of the present study was to determine the correlation between the primary stability of dental implants placed in edentulous maxillae and mandibles, the bone mineral density and different histomorphometric parameters. After assessing the bone mineral density of the implant sites by computed tomography, 48 stepped cylinder screw implants were installed in four unfixed human maxillae and mandibles of recently deceased people who had bequeathed their bodies to the Anatomic Institute I of the University of Erlangen-Nuremberg for medical-scientific research. Peak insertion torque, Periotest values and resonance frequency analysis were assessed. Subsequently, histologic specimens were prepared, and bone-to-implant contact, the trabecular bone pattern factor (TBPf), the density of trabecular bone (BV/TV) and the height of the cortical passage of the implants were determined. The correlation between the different parameters was calculated statistically. The mean resonance frequency analysis values (maxilla 6130.4+/-363.2 Hz, mandible 6424.5+/-236.2 Hz) did not correlate with the Periotest measurements (maxilla 13.1+/-7.2, mandible -7.9+/-2.1) and peak insertion torque values (maxilla 23.8+/-2.2 N cm, mandible 45.0+/-7.9 N cm) (P=0.280 and 0.193, respectively). Again, no correlations could be found between the resonance frequency analysis, the bone mineral density (maxilla 259.2+/-124.8 mg/cm(3), mandible 349.8+/-113.3 mg/cm3), BV/TV (maxilla 19.7+/-8.8%, mandible 34.3+/-6.0%) and the TBPf (maxilla 2.39+/-1.46 mm-1, mandible -0.84+/-3.27 mm-1) (P=0.140 and 0.602, respectively). However, the resonance frequency analysis values did correlate with bone-to-implant contact of the oral aspect of the specimens (maxilla 12.6+/-6.0%, mandible 35.1+/-5.1%) and with the height of the crestal cortical bone penetrated by the implants in the oral aspect of the implant sites (maxilla 2.1+/-0.7 mm, mandible 5.1+/-3.7 mm) (P=0.024 and 0.002, respectively). The Periotest values showed a correlation with the height of the crestal cortical bone penetrated by the implants in the buccal aspect of the implant sites (maxilla 2.5+/-1.2 mm, mandible 5.4+/-1.2 mm) (P=0.015). The resonance frequency analysis revealed more correlations to the histomorphometric parameters than the Periotest measurements. However, it seems that the noninvasive determination of implant stability has to be improved in order to give a more comprehensive prediction of the bone characteristics of the implant site.

Aged↗

PubMed1993

Correct and incorrect interpretations of correlations between risk perceptions and risk behaviors.

Correlations between risk perceptions and risk behaviors are used by investigators to answer 2 important and easily confused questions: Are individuals' perceptions of their personal risk accurate, correctly reflecting their precautions and their risk-increasing behaviors? and Does recognition of high personal risk cause people to adopt precautions to reduce that risk? Researchers who use survey data to investigate these questions often look at the wrong correlations to get their answers. Furthermore, as members of a population adopt precautions and change their risk status, correlations between perceived risk and risk behavior in this population also change. A mathematical model of precaution adoption--allowing a bidirectional relationship between perception and behavior--is used to illustrate the different correlations between risk perception and risk behavior that can be examined and the changes in correlations that can occur with the passage of time. Recommendations are provided concerning the correlations most appropriate for answering each of the 2 preceding questions. Which correlation is appropriate to answer the second question varies depending on whether a study is begun before people have taken precautions or after ample time to take precautions has already passed.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Learning modes, feature correlations, and memory-based categorization.

Several pairs of correlated features were embedded in descriptions that had a wealth of exemplar-specific (i.e., idiosyncratic) information, and sensitivity to these correlations was examined as a function of intentional and incidental encoding conditions. Participants in incidental conditions were able to access information about several embedded correlations, even when the correlations involved 3 rather than 2 dimensions, and when complex inferences were required to recover correlations. In intentional conditions, however, little access to correlations was observed. The richness of the stimuli made it difficult to detect correlations at encoding, and the representations that resulted from analysis appeared too impoverished to allow covariations to be recovered. The results are discussed in terms of the advantages of storing examples for addressing unanticipated needs and goals.

Female↗

PubMed1998

Coding of visual information by precisely correlated spikes in the lateral geniculate nucleus.

Correlated firing among neurons is widespread in the nervous system. Precisely correlated spiking, occurring on a millisecond time scale, has recently been observed among neurons in the lateral geniculate nucleus with overlapping receptive fields. We have used an information-theoretic analysis to examine the role of these correlations in visual coding. Considerably more information can be extracted from two cells if temporal correlations between them are considered. The percentage increase in information depends on the degree of correlation; the average increase is approximately 20% for strongly correlated pairs. Thus, precise temporal correlation could be used as an additional information channel from thalamus to visual cortex.

Action Potentials↗

PubMed1979

Correlation between cancer mortality and alcoholic beverage in Japan.

Geographical correlations between standardized, mortality ratios (SMRs) of cancers and consumption of different types of alcoholic beverages (saké synthetic saké, shochu, beer, wine, and whisky), of cigarettes, and urbanization were examined for all 46 prefectures in Japan. Suggestive correlations were observed between cancer of the oesophagus in males and both shochu and whisky (r = 0.27 and 0.22 respectively), between cancer of the rectum in males and wine (r = 0.45), and between cancer of the prostate and shochu (r = 0.50). These correlations were also confirmed in the partial correlations between SMRs of cancers and consumption of alcoholic beverages, controlling for the two variables urbanization and consumption of cigarettes. Alhtough cancers of other sites were also correlated with certain types of alcoholic beverages, their associations seemed to be secondary to other factors. The validity of higher-order partial correlations and the problems of correlation study are also referred to.

Alcohol Drinking↗

PubMed1992

A study of interlocus allozyme heterozygosity correlations: implications for neutral theory.

Using a database of allozyme studies, correlations in heterozygosity between selected enzyme loci (MDH, alpha GPDH, IDH, 6PGDH, LDH, SOD, AAT, PGM, EST, PGI) were calculated across vertebrate species. Large and positive correlations were observed with untransformed heterozygosity values. However, after transformation to correct for mean species heterozygosity, correlations were substantially reduced and median values were closer to zero. Some enzymes were more often involved in significant correlations than others, and correlations calculated across species within vertebrate classes were significant for different enzyme pairs in different classes. There was no evidence that significant correlations occurred primarily between functionally related enzymes. It is suggested that the observed correlations are best explained by variation between enzyme loci in functional constraint and effective neutral mutation rate.

Animals↗

PubMed1993

Correlation between the individual heterozygosity of parents and their offspring.

Specific formulations are derived for the correlation between the heterozygosity of a randomly mating parent and its offspring for a diallelic locus, and for the correlation when multiple loci are considered. The expected correlation is maximal, approaching r = 0.50, when allelic frequencies are highly asymmetric, and it is zero when the allelic frequencies are equal to 0.50. Parent-offspring correlations, up to a maximum of 0.50 for diallelic loci, indicate that levels of heterozygosity can respond to selection. Multilocus allozyme data from limber pine, Pinus flexilis, and from horses of standardbred and thoroughbred breeds are used to demonstrate correlations between a parent and its offspring. The Spearman rank correlation between the heterozygosity of a limber pine and the mean heterozygosity of her offspring is r = 0.45. Correlations in the horses range from r = 0.16 to 0.32.

Animals↗

PubMed2005

Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression.

Angiogenesis and lymphangiogenesis are essential for breast cancer progression and are regulated by vascular endothelial growth factors (VEGF). To determine clinical and molecular correlates of these processes, we measured blood and lymphatic vascular microvessel density in 29 invasive carcinomas (22 ductal, six lobular, one papillary), using the vascular marker CD31 and the novel lymphatic marker D2-40. Microvessel density was assessed microscopically and by image cytometry, and was compared with tumor histology, grade, stage, lymph node metastasis, hormone receptors, HER2/neu status, and expression of VEGF, VEGF-C and VEGF-D by immunohistochemistry or quantitative RT-PCR. Strong correlation was observed between visual and image cytometric microvessel density using D2-40 but not CD31 (P=0.016 and 0.1521, respectively). Image cytometric CD31 microvessel density correlated with tumor size, grade, stage and lymph node metastasis (P=0.0001, 0.0107, 0.0035 and 0.0395, respectively). D2-40 microvessel density correlated with tumor stage (P=0.0123 by image cytometry) and lymph node metastasis (P=0.0558 by microscopy). Immunohistochemical VEGF signal in peritumoral blood vessels correlated with image cytometric CD31 and D2-40 microvessel density (P=0.022 and 0.0012, respectively), consistent with the role of VEGF in blood and lymphatic vascular growth. Intratumoral VEGF-C and VEGF-D expression by quantitative RT-PCR correlated with D2-40 (P=0.0291 by image cytometry) but not with CD31 microvessel density, which could suggest a selective role of VEGF-C and VEGF-D in lymphangiogenesis. CD31 and D2-40 microvessel density correlated significantly with several prognostic factors, including lymph node metastasis. Thus, measurements of angiogenesis and lymphangiogenesis may have utility for breast cancer pathology, particularly for estimation of metastatic risk.

Adult↗

PubMed1998

Plasma levels of selenium, selenoprotein P and glutathione peroxidase and their correlations to fish intake and serum levels of thyrotropin and thyroid hormones: a study on Latvian fish consumers.

OBJECTIVE: To study the relationships between fish intake and different markers of selenium status and thyroid hormone function. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: Sixty-eight men (age 24-79 years) were recruited among coastal fishermen and inland subjects from Latvia. None of the subjects was on selenium medication or had any known endocrine disease. MAIN OUTCOME MEASURES: Correlations between fish intake, plasma levels of selenium, selenoprotein P, glutathione peroxidase, organic mercury in erythrocytes and TSH in serum. RESULTS: Selenium in plasma ranged from 0.30 to 1.56 micromol/l, selenoprotein P from 0.54 to 2.21 arbitrary units relative to pooled plasma, and glutathione peroxidase from 1.20 to 5.73 mg/l. The number of fish meals per month was correlated with plasma selenium, selenoprotein P and glutathione peroxidase (r = 0.63, r = 0.62 and r = 0.50, respectively; P<0.001). Plasma selenium was correlated with selenoprotein P and glutathione peroxidase (r = 0.88 and r = 0.67, respectively; P < 0.001), and also selenoprotein P and glutathione peroxidase were correlated (r = 0.63, P < 0.001). The mean plasma selenium level in those with a high fish intake (21-50 fish meals/month), was 81% higher than in those with lowest fish intake. TSH in serum was inversely correlated with plasma selenium and selenoprotein P. Thyroid hormone levels were not correlated with plasma selenium, selenoproteins or fish intake. CONCLUSIONS: In this study group, selenium from fish intake had a marked impact on all variables studied on selenium status. No impact of selenium status on T3 and T4 levels was observed. The slightly negative correlation of selenium status with TSH levels might indicate a higher TSH secretion at low selenium status.

Adult↗

PubMed2004

Familial correlations and inter-relationships of four asthma-associated quantitative phenotypes in 320 French EGEA families ascertained through asthmatic probands.

Asthma is a complex disease, associated with biological and physiological phenotypes including immunoglobulin E (IgE) levels, sum of positive skin prick tests to allergens (SPTQ), eosinophil counts (EOS) and percent predicted forced expiratory volume in 1 s (%FEV1). We investigated the patterns of familial correlations and the inter-relationships of these four quantitative phenotypes, using the general class D regressive model, in 320 French EGEA nuclear families ascertained through 204 offspring (set A) and 116 parents (set B). Familial correlations of IgE and SPTQ were consistent with a model including no spouse correlation and equal parent-offspring and sib-sib correlations (rhoPO = rhoSS = 0.25 for IgE and 0.15 for SPTQ), this model being compatible with an additive polygenic model in the whole sample and the two family subsets A and B. Different patterns of familial correlations of EOS and %FEV1 were observed in these two sets. In set A, the best fitting model included no spouse correlation and equality of parent-offspring and sib-sib correlations (rhoPO = rhoSS = 0.14 for EOS and 0.23 for %FEV1). In set B, EOS had only a significant rhoSS of 0.28, while %FEV1 had significant rhoMO of 0.28 and rhoSS of 0.16. Analysis of shared familial determinants between these phenotypes indicated an overlap of at most 30% in rhoFO for IgE and SPTQ and in both rhoFO and rhoMO for IgE and EOS, while determinants of %FEV1 and atopy-related phenotypes appear distinct. These results may have implications for further linkage and association studies with genetic markers.

Adolescent↗

PubMed2006

Realized correlated responses to artificial selection on pre-adult life-history traits in a butterfly.

We use artificial selection experiments targeted on egg size, development time or pupal mass within a single butterfly population followed by a common-garden experiment to explore the interactions among these life-history traits. Relationships were predicted to be negative between egg size and development time, but to be positive between development time and body size and between egg size and body size. Correlated responses to selection were in part inconsistent with these predictions. Although there was evidence for a positive genetic correlation between egg and body size, there was no support for genetic correlations between larval development time and either egg size or pupal mass. Phenotypic correlations among the three target traits of selection gave comparable results for the relationships between egg mass and development time (no association) as well as between egg mass and pupal mass (positive association), but not for the relation between development time and pupal mass (negative phenotypic correlation). In summary, correlated responses to selection as well as phenotypic correlations were rather unpredictable. The impact of variation in acquisition and allocation of energy as well as of the benign conditions used deserve further investigation.

Animals↗

PubMed2007

Environmental influence on the genetic correlations between life-history traits in Caenorhabditis elegans.

Empirical evidence is mounting to suggesting that genetic correlations between life-history traits are environment specific. However, detailed knowledge about the loci underlying genetic correlations in different environments is scant. Here, we studied the influence of temperature (12 degrees C and 24 degrees C) on the genetic correlations between egg size, egg number and body mass in the nematode Caenorhabditis elegans. We used a quantitative trait loci (QTL) approach based on a genetic map with evenly spaced single nucleotide polymorphism markers in an N2 x CB4856 recombinant inbred panel. Significant genetic correlations between various traits were found at both temperatures. We detected pleiotropic or closely linked QTL, which supported the negative correlation between egg size and egg number at 12 degrees C, the positive correlation across temperatures for body mass, and the positive correlation between body mass and egg size at 12 degrees C. The results indicate that specific loci control the covariation in these life-history traits and the locus control is prone to environmental conditions.

Animals↗

PubMed2002

Correlation of year-to-year magnetic field exposure metrics among children in a leukemia survival study.

The Childhood Leukemia Survival Study is examining the possible association between magnetic field exposure and survival of children with newly diagnosed acute lymphocytic leukemia (ALL). We report the results of serial 24-h personal magnetic field monitoring for 412 US and Canadian children and present the correlations between annual values. The mean time-weighted average (TWA) and geometric mean (GM) were similar for first, second, and third year measurements [TWA: 0.11 microT (n = 412), 0.13 microT (n = 304), and 0.12 microT (n = 134), respectively]. There were no consistent differences in mean TWA or GM based on age or gender. Significantly lower mean TWA and GM were found for children living in rural areas. Higher exposures were noted among children living in urban areas, among apartments dwellers, and those living in rental homes. Measurements taken during summer months and among children residing in the northeast and Canada also tended to be higher. Correlations for most metrics were increased among children who had annual measurements performed during the same season. The metric with the highest year-to-year correlation was the GM. The lowest correlations were found for metrics estimating field intermittency and temporal stability. First to second year GMs were well correlated when taken in the same home (Spearman rank correlation = 0.70), but a lower correlation (0.44) was noted among residentially mobile children. Our findings suggest that summarizing exposure using a single measurement of GM can estimate exposures for residentially stable children, but is not a good predictor of personal exposures among children who change residence during the study interval.

Age Factors↗

PubMed1997

Serum angiotensin-converting enzyme activity correlates positively with plasma angiotensin II: a population-based study of ambulatory blood pressure and the renin-angiotensin system.

A population-based study was performed in order to study the interrelationships of the circulating components of the renin-angiotensin system during basal conditions and their relations to blood pressure (BP), age and gender. One hundred and four women and 95 men, 16-70 years old, evenly age distributed and randomly selected from the population of Linköping, Sweden, participated. Venous blood was drawn at 08.00 hours and ambulatory BP recording was then performed. Serum angiotensin-converting enzyme (ACE) activity correlated with plasma angiotensin II (r = 0.20, P = 0.004), but when calculated separately according to gender, the correlation remained significant only in men (r = 0.33, P = 0.001). Plasma renin activity (PRA) correlated negatively with age (r = -0.30, P < 0.0001), but immunoreactive active renin (IRR) and angiotensin II did not. PRA and IRR correlated negatively with BP in women but correlations disappeared after age adjustment. The 23 women on oestrogen medication did not differ from the remaining 81 with respect to age (P = 0.5), IRR (P = 0.96) or angiotensin II (P = 0.4) levels, but PRA was higher (2.2 +/- 1.4 ng Ang l/ml/h and 1.5 +/- 0.9 ng Ang l/ml/h, respectively, P = 0.004). PRA (r = 0.38, P < 0.0001) and IRR (r = 0.49, P < 0.0001) correlated positively with the levels of angiotensin II. In conclusion the fact that PRA, but not IRR, declined with age and was higher among oestrogen-treated women, although angiotensin II was unaffected suggests IRR to be a more robust marker of angiotensin II levels than is PRA in a population-based setting. ACE correlates positively with angiotensin II in men.

Adolescent↗

PubMed2006

Correlation of skeletal maturation stages determined by cervical vertebrae and hand-wrist evaluations.

The aim of this study was to assess the correlation between the Fishman maturation prediction method (FMP) and the cervical vertebral maturation (CVM) method for skeletal maturation stage determination. Hand-wrist and lateral cephalograms from 79 subjects (52 females and 27 males) were used. Hand-wrist radiographs were analyzed using the FMP to determine skeletal maturation level (advanced, average, or delayed) and stage (relative position of the individual in the pubertal growth curve). Cervical vertebrae (C2, C3, and C4) outlines obtained from lateral cephalograms were analyzed using the CVM to determine skeletal maturation stage. Intraexaminer reliability (Intraclass correlation coefficient [ICC]) for both methods was calculated from 10 triplicate hand-wrist and lateral cephalograms from the same patients. An ICC coefficient of 0.985 for FMP and an ICC of 0.889 for CVM were obtained. A Spearman correlation value of 0.72 (P < .001) was found between the skeletal maturation stages of both methods. When the sample was subgrouped according to skeletal maturation level, the following correlation values were found: for early mature adolescents 0.73, for average mature adolescents 0.70, and for late mature adolescents 0.87. All these correlation values were statistically different from zero (P < .024). Correlation values between both skeletal maturation methods were moderately high. This may be high enough to use either of the methods indistinctively for research purposes but not for the assessment of individual patients. Skeletal level influences the correlation values and, therefore, it should be considered whenever possible.

Adolescent↗